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-- --- -v - • •■ --■ ■. • ; - - - : —k ■- ■ ■ p A BIBLIOGRAPHICAL SOURCEBOOK 
OF 
COMPRESSED AIR, DIVING 
AND SUBMARINE MEDICINE 
VOLUME III 
By 
,1 
Leon Jack Greenbaum, Jr. 
Commander, Medical Service Corps, U.S. Navy 
Naval Medical Research Institute 
Bethesda, Maryland 
and 
Ebbe Curtis Hoff, Ph.D., M.D. 
Ml 7 7 
Chairman, Division of Psychiatric Research 
Department of Psychiatry 
Medical College of Virginia 
Richmond, Virginia 
DECEMBER 1966 
OFFICE OF NAVAL RESEARCH 
AND 
BUREAU OF MEDICINE AND SURGERY 
DEPARTMENT OF THE NAVY 
WASHINGTON, D.C. DEDICATION 
TO 
THE SUBMARINERS, DIVERS, AND UNDERWATER SWIMMERS 
OF THE 
UNITED STATES NAVY 
• THIS VOLUME IS INSCRIBED 
IN RECOGNITION OF 
THEIR DISTINGUISHED SERVICE 
For sale by the Superintendent of Documents, U.S. Government Printing Office 
Washington, D.C., 20402 - Price $3.25 PREFACE 
THE first volume of A Bibliographical Source- 
book of Compressed Air, Diving and Sub- 
marine Medicine, published in February 
1948, constituted a reference source to the litera- 
ture in medical problems of diving, compressed 
air work and submarine operations from the be- 
ginning to 1 January 1946. Volume II of the 
Sourcebook constituted an analysis and review of 
pertinent unclassified reports and documents as 
well as published books, monographs and papers 
published between 1 January 1946 and 31 De- 
cember 1951. 
The reader will find that the contents the 
present volume have been dealt with consistently 
with the same policies that prevailed in assembl- 
ing the first two volumes. As in the case of tfie 
first two volumes, the observations, conclusions 
and opinions of the research workers and other 
authors have been set forth briefly and all aspects 
of controversial issues have been considered. In 
arranging and classifying the material we have 
been guided by our judgment as to research 
trends and areas of special pertinence and im- 
portance. 
In the present volume the coverage has pri- 
marily extended from 1 January 1952 to 31 De- 
cember 1961. In areas of particular significance 
and in fields where rapid advances have been 
made, such as pressure physiology and hyper- 
baric oxygen therapy, we have extended the 
coverage up to the end of 1964. 
With new developments in engineering science 
since Volumes I and II were published, there 
have been associated changes in the scope and 
emphasis of submarine medicine. These changes 
are reflected in the table of contents of the present 
volume. Many problems have been solved and 
with these solutions has come a shift in interests 
and research focus. 
ARRANGEMENT AND 
STYLE 
Readers familiar with Volumes I and II of this 
Sourcebook will recognize that in the present vol- 
ume the classification, arrangement and style con- 
form to the conventions observed in the first two 
volumes. Each entry has been assigned a serial 
number which is used in the index of authors 
and in the text to identify the reference. 
As in the previous volumes all journals and 
handbooks from which references have been 
taken are cited in a list given separately at the 
end of this volume. The arrangement of these 
items is in alphabetical order of their abbrevia- 
tions, followed in each case by the full name of 
the publication and most recent place of publica- 
tion. The system of abbreviations continues to 
conform to A World List of Scientific Periodicals 
published in the years 1900-1950, 3rd edition, 
New York and London. We have retained this 
system for the sake of consistency from volume to 
volume, 
In the present volume there is no index of 
sources for unpublished reports. The reader may 
use the index of such sources on pages 362-364 
of Volume II. 
The present volume was prepared under con- 
tract Nonr 1134(04), NR 102-527 between the 
Office of Naval Research and the Medical College 
of Virginia. It is desired to thank Dr. Leonard 
M. Libber, Head of the Physiology Branch, Of- 
fice of Naval Research for his encouragement, ad- 
vice and support. It is our privilege to express 
our appreciation to Dr. R. Blackwell Smith, Jr., 
President of the Medical College of Virginia and 
to the Staff of the College. We wish to record our 
gratitude to Mr. L. Daniel Crooks, Comptroller 
of the Medical College of Virginia and his staff. We particularly wish to thank Captain G. J. 
Duffner, (MC) U.S. Navy, presently medical of- 
ficer to the Commander-in-Chief, Atlantic Fleet. 
We were encouraged to undertake the prepara- 
tion of this third volume largely through the 
initiative of Captain Duffner, who in all of the 
phases of this project has helped and advised us. 
Captain Duffner’s interest in this work has been 
essential. 
We express our appreciation to Captain Joseph 
P. Pollard, (MC) U.S. Navy, Director, Research 
Division, Bureau of Medicine and Surgery, for 
his ongoing interest and support. Thanks are 
also expressed to Captain Robert D. Workman, 
(MC) U.S. Navy, and Captain Jack Kinsey, 
(MC) U.S. Navy for their scientific and technical 
advice as well as for making available to us their 
personal reference files. 
We owe a debt of graditude to Dr. Christian J. 
Lambertsen, Department of Pharmacology, Uni- 
versity of Pennsylvania School of Medicine, for 
technical and scientific suggestions as well as for 
his generosity in giving us access to his reference 
lists on oxygen. 
We desire to thank Lieutenant Lawrence R. 
Raymond, (MC) U.S. Navy, Naval Medical Re- 
search Institute, Bethesda, Maryland for review- 
ing the sections dealing with cold. Thanks are ex- 
pressed to Surgeon Captain F. P. Ellis, OBE, 
M.D., FRCP, Royal Navy Corps, for supplying 
reports and references from the British Admiralty. 
We are particularly grateful to our colleagues in 
the Royal Navy for this outstanding example of 
international cooperation. 
Most of the work of collecting and abstracting 
the literature found in this volume was carried 
out at the National Library of Medicine, Be- 
thesda, Maryland. We wish to thank Dr. Frank 
B. Rogers, then Director of the Library, for his 
helpfulness in placing the facilities of the library 
at our disposal for a period of about four years. 
Among the many members of the library staff 
who have helped us we wish especially to offer 
our thanks to Mr. Edward A. Miller, Chief of 
the Reference Section. 
We wish to thank Mrs. Mabel D. Clark, Li- 
brarian, Naval Medical Research Institute, Be- 
thesda, Maryland for making the resources of her 
library so readily available to us. 
We have pleasure in according thanks to Dr. 
William D. Blake, Head of the Department of 
Physiology, School of Medicine, University of 
Maryland, for his encouragement and for pro- 
viding space for some phases of the study. Thanks 
are also expressed to Captain Herschel C. Sud- 
duth, (MC), U.S. Navy, Commanding Officer, 
Naval Medical Research Institute, and Captain 
Edward L. Beckman, (MC) U.S. Navy, Head, 
Department of Physiology, Naval Research In- 
stitute, for their sustaining concern. 
Finally we wish to offer our sincere thanks to 
Mrs. Minna L. Hamner and Mrs. Mary Ita 
Greenbaum for the many hours of diligent effort 
which they gave in making ready the manuscript 
of this volume for the press. For this devoted 
work on the manuscript requiring such close at- 
tention to detail, we are deeply indebted. 
The opinions and assertions contained in this 
volume should not be construed as official or 
necessarly reflecting the view of the Department 
of the Navy or the Naval Service at large. We 
hope, however, that we have accurately con- 
veyed to the reader the substance and main ad- 
vances in the fields of compressed air, diving and 
submarine medicine. 
L. J. G., Jr. 
E. C. H. 
Naval Medical Research Institute 
Bethesda, Maryland 
Medical College of Virginia 
Richmond, Virginia Table of Contents 
Page 
PREFACE iii 
TECHNICAL PROCEDURES AND RESEARCH APPARATUS IN COMPRESSED AIR, 
DIVING AND SUBMARINE MEDICINE 1 
I. General studies in submarine medicine 1 
II. Gas analysis in air and blood 2 
III. Pressure chambers 7 
IV. General source literature 7 
SPECIAL ANATOMY, PHYSIOLOGY AND BIOCHEMISTRY OF COMPRESSED AIR, 
DIVING AND SUBMARINE MEDICINE 10 
I. Physiological effects of raised atmospheric pressures 10 
A. Heart and circulation 10 
B. Respiration 10 
C. Kidney 11 
II. Physiological effects of decompression 11 
A. Physiology of bubble formation 11 
B. Saturation and desaturation of gases in the body 12 
C. Fat and water content 13 
III. Physiological effects of low oxygen tensions of environmental air 13 
A. Low oxygen percentages without decompression 13 
1. Special senses . . . 13 
2. Nervous system 17 
3. Muscle 20 
4. Heart and circulation 20 
5. Blood 36 
6. Cerebrospinal fluid 38 
7. Respiration 39 
8. Alimentary tract 41 
9. Metabolism 41 
10. Endocrines 45 
11. Temperature 45 
12. Kidney 47 
13. Effects of carbon dioxide on hypoxia 48 
14. Acclimatization 49 
15. Pathology 50 
B. Low oxygen tensions due to decompression 51 
1. Nervous system 51 
2. Muscle 53 
3. Heart and circulation 54 
4. Blood 57 SPECIAL ANATOMY, PHYSIOLOGY, ETC.-Continued 
III. Physiological effects of low oxygen tensions—Continued 
B. Low oxygen tensions due to decompression—Continued 
5. Respiration 62 
6. Alimentary tract 64 
7. Metabolism 64 
8. Endocrines 66 
9. Temperature 68 
10. Kidney 69 
11. Tolerance 70 
12. Acclimatization 73 
13. Pathology 74 
IV. Physiological effects of high carbon dioxide content in environmental air 75 
A. General studies 75 
B. Nervous system 76 
C. Heart and circulation 83 
D. Blood 90 
E. Cerebrospinal fluid 94 
F. Respiration 95 
G. Metabolism 102 
H. Endocrines 106 
I. Sweating 109 
J. Kidney 109 
K Spleen 112 
L. Tolerance 112 
M. Acclimatization 112 
N. Pathological changes 113 
V. Inert gases 114 
A. General studies 114 
B. Nitrogen 115 
C. Xenon 119 
D. Krypton 119 
E. Helium 120 
VI. Heat and humidity problems 122 
A. Physiological effects of raised temperatures 122 
B. Performance 126 
VII. Cold exposure problems 127 
A. General physiological effects 127 
B. Acclimatization 154 
C. Effects of cold on performance 136 
D. Immersion in cold water 137 
VIII. Visual problems 138 
A. General considerations 138 
B. Acuity 138 
C. Color vision 138 
D. Visual performance 140 
E. Night vision and dark adaptation 141 
F. Underwater vision 141 
IX. Auditory problems 141 SPECIAL ANATOMY, PHYSIOLOGY, ETC.-Continued 
X. Noise 143 
A. General studies 143 
B. Physiological and pathological effects 143 
C. Hearing defects from exposure to noise 145 
D. Effects of noise on efficiency 147 
E. Sound communication in noise 148 
F. Protection against noise 148 
BIOLOGY OF VERY HIGH HYDROSTATIC PRESSURES 149 
DISEASES AND ACCIDENTS IN SUBMARINE PERSONNEL. DIVERS, AND COM- 
PRESSED AIR WORKERS 150 
I. Ear, nose and throat disturbances 150 
A. General studies of otorhinolaryngological disturbances 150 
II. Otitis externa therapy 151 
III. Decompression sickness 151 
A. General considerations 151 
B. Clinical picture 153 
C. Case reports 155 
D. Incidence, diagnosis and prognosis 158 
E. Etiology 168 
F. Pathological lesions 159 
G. Prevention and treatment, including preselection tests 160 
1. General studies 160 
2. Decompression procedures 160 
3. Helium-oxygen administration 166 
4. Oxygen administration 168 
5. Recompression treatment and procedures 170 
6. Preselection tests 175 
7. Drugs and hypothermia in the treatment of decompression sickness . . . 178 
IV, Explosive decompression 178 
A. General studies 178 
B. Heart and circulation 179 
C. Respiratory system 180 
D. Gastrointestinal system 180 
E. Lethal factors and pathological lesions 181 
F. Tolerance 181 
V. Explosive compression 182 
VI. Oxygen intoxication 182 
A. Effects of increased oxygen tension not in excess of one atmosphere 182 
1. General studies 182 
2. Effects on the special senses 183 
3. Effects on the cardiovascular system 184 
4. Effects on blood 187 
5. Effects on lymph 187 
6. Effects on respiration 188 
7. Effects on metabolism 190 
8. Effects on the endocrine glands 192 
9. Effects on cold thresholds 193 
10. Effects on mitosis 193 DISEASES AND ACCIDENTS, ETC.-Continued 
VI. Oxygen intoxication—Continued 
A. Effects of increased oxygen tension not in excess of one atmosphere—Continued 
11. Pathological effects 194 
12. Therapy 196 
B. Effects of oxygen tension in excess of one atmosphere 196 
1. General studies 196 
2. Effects on the central nervous system 198 
3. Effects on muscle 200 
4. Effects on heart and circulation 200 
5. Effects on the blood 202 
6. Effects on respiration 202 
7. Effects on blood and tissue gas tensions 203 
8. Effects on the alimentary tract 205 
9. Effects on metabolism 205 
10. Effects on the endocrine system 208 
11. Effects on body temperature 209 
12. Effects on the kidneys 210 
13. Tolerance 210 
14. Effects on performance 212 
15. Pathological effects 212 
16. Treatment: General studies 214 
17. Treatment: Vascular shock 218 
18. Pressure oxygenated solutions 218 
VII. Noxious agents 219 
A. Carbon monoxide 219 
1. General studies of carbon monoxide poisoning 219 
2. Carbon monoxide in submarines and other naval vessels 219 
3. Clinical picture, functional changes and pathological effects 221 
4. Mechanisms of carbon monoxide poisoning 222 
5. Uptake and elimination of carbon monoxide 223 
6. Tolerance and acclimatization to carbon monoxide 224 
7. Treatment 225 
B. Stibine 226 
C. Ozone 226 
D. Radon 229 
E. Tobacco smoke 229 
F. Air ions 231 
VIII. Motion sickness 234 
IX. Submarine escape procedures 234 
A. Breath holding 234 
B. Escape procedures 238 
C. Gas embolism 240 
D. Underwater blast injuries 245 
E. Drowning 246 
PROTECTION AND PRESERVATION OF PERSONNEL 251 
I. General studies 251 
II. Ventilation and air conditioning 251 
A. General studies 251 PROTECTION AND PRESERVATION OF PERSONNEL-Continued 
II. Ventilation and air conditioning—Continued 
B. Prevention of atmospheric pollution 252 
C. Elimination of dust, gases, fumes and odors from air 253 
D. Photosynthetic gas production and utilization 254 
E. Carbon dioxide absorption 254 
F. Oxygen generators 256 
III. Resuscitation 257 
SELECTION AND TRAINING OF SUBMARINE PERSONNEL, DIVERS AND COM- 
PRESSED AIR WORKERS 258 
I. Selection 258 
II. Performance—Submarine operations 261 
III. Human factors in engineering design 262 
SPECIAL PSYCHOLOGICAL AND PSYCHIATRIC PROBLEMS 264 
I. Duty and rest periods 264 
II. Sleep deprivation 265 
A. Physiological effects 265 
B. Effects of sleep deprivation on performance 268 
C. Effects of drugs and sleep deprivation 269 
III. Isolation, sensory deprivation and confinement 270 
SPECIAL PROBLEMS OF SCUBA DIVING 272 
I. General studies 272 
II. Nervous system 274 
III. Cardiovascular system 274 
IV. Respiration 274 
V. Kidney 275 
VI. Oxygen consumption 276 
VII. Spatial orientation 276 
VIII. Hazards from dangerous fish and other marine organisms 277 
IX. Underwater breathing apparatus 279 Technical Procedures and Research 
Apparatus in Compressed Air, 
Diving and Submarine Medicine 
I. GENERAL STUDIES IN 
SUBMARINE MEDICINE 
The changing pattern of submarine medicine 
has been reported by Alvis (7) 1958. The ad- 
vent of nuclear-powered submarines has greatly 
enhanced the scope and effectiveness of sub- 
marine operations and has consequently altered 
the medical submarine problem. Offshore may 
be the safest place during attack and exposure 
levels for most crew members may be less than 
for many people in situations not ordinarily 
classed as hazardous. Alvis reviews the physical 
and psychological screening procedures emphasiz- 
ing that personality evaluation may be difficult 
to standardize. Such evaluation, however, is of 
great importance and especially in nuclear-pow- 
ered submarines where there may be longer 
periods of isolation than in other craft. Since 
submarines operate in all climtaes it is essential 
that the environment be adjusted by air condi- 
tioning. Many or most of the old submarine 
medicine problems require and have received re- 
investigation within the new frame of reference 
of the nuclear-powered vessel. There are un- 
solved problems which challenge investigation 
for the future. 
On the same general subject Ebersole (P) 
1958, has outlined three important areas in which 
nuclear propulsion has added to the scope and 
depth of submarine medicine: 1) the environ- 
ment of the true submersible vessel, capable of 
prolonged submergence, must be carefully con- 
trolled; 2) there must be strict radiation control 
for in-port periods during the time when the 
reactor shield may be open to admit workmen; 
3) the submarine medical officer has become an 
assigned crew on board. The main problems of 
environmental control are the provision for a 
continuous supply of oxygen, the continuous 
removal of metabolic products such as carbon 
dioxide, and three, the prevention and removal 
of any toxic substances released to the boat’s 
environment. Carbon monoxide problems on 
fleet type subamrines arose from diesel 
fuel combustion, but on the nuclear reactor boats 
the principle source is cigarette smoking. The 
total safe concentration of carbon monoxide has 
been set at 100 ppm. Radon gas originating from 
luminescent radium-markers poses another prob- 
lem in closed submarines on long submergence. 
This gas level is recorded as a rise in beta ac- 
tivity after submergence: it rises to 10 counts 
per minute per cubic foot after four days. Radia- 
tion problems are a potential source of difficulty 
and therefore radiation surveillance must be 
rigidly maintained. If contamination occurs the 
situation is serious because the closed atmosphere 
allows for little dilution of air-borne radiation. 
Also there is insufficient space for decontamina- 
tion. In addition, the proximity of the living 
quarters to the reactor can pose a hazard. Sub- 
mariners’ work allows no possible off-site recuper- 
ation from exposure and air recirculation means 
that there would be a rapid spread of air-borne 
radioactivity from one spot to another. 
1. Alvis, H. J. The changing pattern of submarine 
medicine. Arch, industr. Hlth., 1958, 18: 195-199. 
2. Alvis, H. J. Ecology of ships of inner space. Ann. 
intern. Med., 1959, 51: 1329-1334. 
3. Behnke, A. R. Decompression sickness: high pres- 
sure atmospheres, pp. 222-225 in: Medical Physics. O. Glas- 
ser. Editor. Year Book Publishers, Chicago, 1960, 754 pp. 4-38 
TECHNICAL PROCEDURES 
4. Blanchard, A. J. Report of a survey of the sub- 
marine medical allowance and its usage. U.S. Navy. Sub- 
marine Base, New London, Conn. Medical research labora- 
tory. MRL Rept. 225, June 1953, 13 pp. 
5. Dobbins, R. F. Medical-physiological problems pe- 
culiar to nuclear-powered submarines, pp. 388-389 in: 
Man’s dependence on the earthly atmosphere. Edited by 
Karl E. Schaefer. New York, The MacMillan Company, 
1962,416 pp. 
6. Donald, K. W. J- S. Haldane’s contributions to ap- 
plied physiology in the armed forces, with special reference 
to diving, pp. 83-91 in: The regulation of human respira- 
tion. Edited by D. J. C. Cunningham and B. B. Lloyd. 
Blackwell Scientific Publications, Oxford, 1963, 591 pp. 
7. Ebersole, J. H. Radiation exposure patterns aboard 
the USS Nautilus. New Engl. J. Med., 1957, 256: 67-74. 
8. Ebersole, J. H. Submarine medicine on Nautilus 
and Seawolf. Arch, industr. Hlth., 1958, 18: 200-207. 
9. Ebersole, J. H. Submarine medicine on USS Nauti- 
lus and USS Seawolf. Proc. R. Soc. Med., 1958, 51: 63-74. 
10. Ebersole, J. H. Occupational health problems in 
space flight as experienced with nuclear power plants. 
Milit. Med., 1959, 124: 711-716. 
11. Ebersole, J. H. The new dimensions of submarine 
medicine. New Engl. J. Med., 1960, 262: 599-610. 
12. Elliot, A. Ubatshygien. Submarine hygiene. Medd. 
Flyg. Navalmed., 1961, 10: 20-24. 
13. Guillerm and Badre. Les probtemes physiologi- 
ques et physico-chimiques poses par la navigation sous- 
marine. Rev. Med. nav., 1952, 7: 105-140. 
14. Harter, J. R. R., G. M. Janney and T. L. 
Rakoskie. Interim report on the performance of under- 
water television using both natural and artificial illumina- 
tion. U.S. Navy. Naval weapons plant, EDU. Project SF 
015001-5CD, sub task no. 110, tests no. 33.1 and 3.3.2 
(formerly Project NE 020632 ST 2b), 2 June 1959, 21 pp. 
15. Hogan, B. W. The practice of submarine medi- 
cine. Med. Arts Sci., 1958, 12: 61-65. 
16. James A. D. and W. R. Sanborn. Potable water 
on submarines. Med. Tech. Bull., 1957, 8: 234-242. 
17. James, A. D. and W. R. Sanborn. Potable water 
on submarines. U.S. Forces med. J., 1957, 8: 1792-1800. 
18. Kinsey, J. L. A report of the use of the submarine 
exposure suit in cold weather operations. U.S. Navy. Sub- 
marine Base, New London, Conn. Medical research labora- 
tory. Project NM 002 013.01.01, 10 March 1952. 16 pp. 
19. Kaufman, L. R. Evaluation of the radarange for 
submarine use. U.S. Navy. Submarine base, New London, 
Conn. Medical research laboratory. Project NM 24 01 20.04, 
Rept. no. 2, 1957. 
20. Miles, S. Underwater medicine. Lippincott Com- 
pany, Philadelphia, 1962, 328 pp. 
21. Nall, M. L. Submarine habitability; A literature 
survey (1951-1959). Documentation Inc., Washington, D.C., 
1959, 31 pp. 
22. Norman, J. C. Appendicitis in submariners. U.S. 
Forces med. J., 1959,10: 689-692. 
23. Panjang, (n). Doctor under the sea. Med. World, 
Lond., 1961, 94: 460-464. 
24. Resner, E. P. and F. R. Statzula. The corpsman 
and nuclear submarines. Med. Tech. Bull., 1956, 7; 1-6. 
25. Shilling, C. W. and I. F. Duff. Surgical care on 
wartime operating submarines. Milit. Surg., 1953, 112: 
79-87. 
26. Soule, G. I. Independent duty aboard submarines. 
Med. Tech. Bull., 1957, 8: 137-138. 
27. Storms, J. R. The submarine hospital corpsman. 
Med. Tech. Bull., 1953. 4: 131-133. 
28. U.S. Department of Health, Education and 
Welfare. Public Health Service. Bibliography of space 
medicine. National Library of Medicine, Ref. Div., Wash- 
ington, D.C., 1958, 49 pp. 
29. U.S. Navy. Submarine habitability and clothing, 
pp. 266-283 in: Submarine medicine practice. U.S. Navy, 
BuMed. NAVMED — P 5054, Gov’t. Printing Office, Wash- 
ington, D.C., 1956, 357 pp. 
30. U.S. Navy. Medical problems in submarines, pp. 
298-310 in: Submarine medicine practice. U.S. Navy, 
BuMed. NAVMED - P 5054, Gov’t. Printing Office, Wash- 
ington, D.C., 1956, 357 pp. 
31. U.S. Navy. Curriculum for submarine medical 
officers (Diving medicine). U.S. Navy, BuPers, Washington, 
D.C., NAVPERS 92427, February 1957, 167 pp. 
32. Vogel, J. Submarine medicine. J. Mich. med. Soc., 
1961, 60: 82-84. 
33. Ziatiushkov, A. I., and B. G. Tsukerman. Us- 
loviia obitaemosti i zabolevaemosti lichnogo sostava na 
podvodnykj lodkakh. (Po dannym inostrannoi pechati.) 
[Living conditions and morbidity of personnel on sub- 
marines. (According to data in the foreign literature.)] 
Voennomed. Zh., 1958, 4: 74-80. 
II. GAS ANALYSIS IN AIR AND 
BLOOD 
The references below constitute the principal 
reports encountered in the compressed air, div- 
ing, and submarine medicine literature dealing 
with gas analysis in air and blood. These and 
other technical procedures are also referred to 
throughout this volume in other appropriate 
sections. 
34. Allen, T. H. and W. S. Root. Determination of 
carbon monoxide in blood and air. Fed. Proc., 1955, 14: 3. 
35. Anderson, O. S., K. J0rgensen and N. Naeraa. 
Spectrophotometric determination of oxygen saturation in 
capillary blood. Scand. J. din. Lab Invest., 1962, 14: 298- 
302. 
36. Astrup, P. and S. Schrpder. Apparatus for an- 
aerobic determination of the pH of blood at 38 degrees 
Centigrade. Scand. J. din. Lab. Invest., 1956, 8: 30-32. 
37. Awad, O. and R. J. Winzler. Electrochemical 
determination of the oxygen content of blood. J. Lab. din. 
Med., 1961, 58: 489-194. 
38. Baker, L, E. Rapidly responding narrow-band in- 
frared gaseous C02 analyzer for physiological studies. 
IEEE Trans, med. Electr., 1961, 8: 16-24. GAS ANALYSIS IN AIR AND BLOOD 
39-71 
39. Bechtel, F. Technique et interet de la mesure des 
gaz du sang lors de 1’examen de la fonction pulmonaire. 
France med., 1962, 25: 71-75. 
40. Bergman, N. A., H. Rackow and M. J. Frumin. 
The collision broadening effect of nitrous oxide upon in- 
frared analysis of carbon dioxide during anesthesia. Anes- 
thesiology, 1958,19: 19-26. 
41. Bernstein, L. and C. Yoshimoto. An electrical 
analyzer for carbon dioxide in respiratory gases. J. appl. 
Physiol, 1962, 17: 126-130. 
42. Bishop, J. M. and A. C. Pincock. A method of 
measuring oxygen tension in blood and gas using a covered 
platinum electrode. J. Physiol, Lond., 1959, 145: 20P-21P. 
43. Bitner, J. L. Analysis for ozone, pp. 82-87 in: 
The present status of chemical research in atmosphere 
purification and control on nuclear-powered submarines. 
U.S. Navy. Naval Research Laboratory, Washington, D.C. 
NRL Rept. 5630, July 1961, 134 pp. 
44. Blakemore, W. S., G. D. Ludwig, R. E. For- 
ster and D. L. Drabkin. Measurement of CO in blood 
and production of CO by the degradation of hemin. Fed. 
Proc., 1957, 16: 12. 
45. Brandi, G. C02 pressure in mixed venous blood 
measured incurrently. Int. Z. angew. Physiol, 1961, 19: 
126-129. 
46. Bray, A. P. and R. Burtles. A method of meas- 
uring arterial carbon dioxide tension during anesthesia. 
Brit. J. Anaesth., 1961, 33: 166-167. 
47. Brismar, J., C. M. Hesser and G. Matell. 
Breath-by-breath sampling of alveolar (end-tidal) gas. 
Acta physiol, scand., 1962, 56: 299-305. 
48. Broch, O. J., H. Dahl, J. Haarstad and E. 
Hatletveit. A new instrument for the continuous deter- 
mination of the oxygen saturation and dye dilution curves 
in circulating blood. Scand. J. din. Lab. Invest., 1962, 14: 
66-71. 
49. Buckley, J. J., F. H. Van Bergen, A. Heming- 
way, H. L. Demorest, F. A. Miller, P. T. Knight and 
R. L. Varco. A portable mass spectrometer for continu- 
ous alveolar gas analysis: certain technical considerations 
inherent in its use. Anesthesiology, 1952, 13: 455-464. 
50. Campbell, E. J. M. and J. B. L. Howell. The 
determination of mixed venous and arterial C02 tension 
by rebreathing techniques, pp. 101-118 in: A symposium 
on pH and blood gas measurement. Edited by R. F. Wool- 
mer. Churchill Ltd., London, 1959, 210 pp. 
51. Castillo, C. A., W. C. Zarnstorff and C. W, 
Crumpton. An improved transmission oximeter using in- 
terference filters. Amer. Heart ]., 1962, 64 : 221-227. 
52. Cater, D. B., A. F. Phillips and I. A. Silver. 
Apparatus and techniques for the measurement of oxida- 
tion-reduction potentials, pH and oxygen tension in vivo. 
Proc. roy. Soc., 1957, Ser. B., 146: 289-297. 
53. Cater, D. B., A. F. Phillips and I. A. Silver. 
The measurement of oxidation-reduction potentials, pH, 
and oxygen tension in tumors. Proc. roy. Soc., 1957, Ser. B., 
146: 382-399. 
54. Cater, D. B. and I. A. Silver. The measurement 
of oxygen tension in tumors. Brit. J. Radiol, 1958, 31: 340. 
55. Cater, D. B., I. A. Silver and G. M. Wilson. 
Apparatus and technique for the quantitative measure- 
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56. Charlton, G. A microelectrode for determination 
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57. Cieplinski, E. W., W. Averill and L. S. Ettre. 
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TECHNICAL PROCEDURES 
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78. Gleichmann, U. and D. W. Lubbers. Die Mes- 
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80. Gleichmann, U., D, W. Lubbers and W. Ring- 
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84. Gramer, L. Uber die Problematik der Methoden 
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88. Hertz, C. H. and B. Siesjd. A rapid and sensitive 
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91. Jaaskelainen, V. and R. Makitalo. The reliabil- 
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95. Jordan, J., E. Ackerman and R. L. Berger. 
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98. Kibrick, A. C., M. R. Ross and S. J. Skupp. 
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99. Koeff, S. T., M. U. Tsao, A. Vadnay, T. O. 
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100. Kreuzer, F., E. D. Harris, Jr. and C. G. Nes- 
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blood oxygen tension. J. appl. Physiol., 1960, 15: 77-82. 
101. Kreuzer, F. and C. G. Nessler, Jr. Method of 
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102. Kreuzer, F., T. R. Watson, Jr. and J, M. Ball. 
Comparative measurements with new procedure for meas- 
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1958,12: 65-70. 
103. Lowe, H. J. An electrometric determination of 
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16: 919-922. GAS ANALYSIS IN AIR AND BLOOD 
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105. Maio, D. A. and J. R. Neville. Polarographic 
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106. Markus, G. and J. P. Baumberger. Oxygen 
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107. Marotta, S. F., E. F. Robbins and J. P. Mar- 
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108. McArthur, K. T., L. C. Clark, Jr., C. Lyons 
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saturation in open-heart operations. Surgery, 1962, 51: 
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109. Meyer, J. S., F. Gotoh and Y. Tazaki. Con- 
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110. Michielsen, C. E., C. J. Hoffman, J. C. Kruse, 
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111. Minter, C. C. An instrument for the rapid and 
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113. Minter, C. C., S. F. Anderson and R. W. Dolk. 
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101 in: The present status of chemical research in atmos- 
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ton, D.C. NRL Rept. 5630, July 1961, 134 pp. 
114. Mook, G. A. and W. G. Zijlstra. On the princi- 
ples underlying the single scale procedure of Wood’s 
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115. Muysers, K., F. Sieboff and G. Worth. Blut- 
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116. Naylor, P. F. D. The polarographic measure- 
ment of oxygen tension. J. Physiol, Lond., 1959, 145: 3P. 
117. Nestler, F. H. M. Trace contaminants, sampling, 
and analysis, pp. 39-46 in: The present status of chemical 
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tory, Washington, D.C. NRL Rept. 5465, April 1960, 167 
pp. 
118. Neville, J. R. Polagraphic determination of 
oxygen content and capacity of blood. Fed. Proc., 1958, 
17: 117. 
119. Neville, J. R. A simple, rapid polarographic 
method for blood oxygen content determination. J. appl. 
Physiol., 1960,15: 717-722. 
120. Nielsel, W. and G. Thews. Ein neues Verfahren 
zur schnellen und genauen Aufnahme der Sauerstoffbin- 
dungskurve des Blutes und konzentrierter Hamoproteid- 
losungen. Pfliig. Arch. ges. Physiol., 1961, 273: 380-395. 
121. Parmeggiani, L., S. Cambruzzi and G. Co- 
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espirato come metodo pratico di accertamento diagnostic© 
della intossicazione acuta da CO. Med. d. Lavoro, 1958, 49: 
428-141. 
122. Penneys, R. Use of the Beckman oxygen micro- 
electrode in the intact human skin. Fed. Proc., 1964, 23: 
207. 
123. Polgar, G. and R. E, Foster. Measurement of 
oxygen tension in unstirred blood with a platinum elec- 
trode. J. appl. Physiol., 1960, 15: 706-711. 
124. Poth, E. J. A simplified apparatus for gas analy- 
sis. J. thorac. cardiov. Surg., 1961, 41: 699-700. 
125. Rahn, H. The sampling of alveolar gas. pp. 299- 
308 in: Studies in respiratory physiology. Second series. 
Chemistry, mechanics and circulation of the lung. Edited 
by H. Rahn and W. O. Fenn. Wright Air Development 
Center, Aero Medical Laboratory, Dayton, Ohio. WADC 
Tech. Kept. 55-357, Nov. 1955, 438 pp. 
126. Rhodes, P. G., K. M. Moser and W. R. Scar- 
borough. Sources of error in blood oxygen tension meas- 
urement. Fed. Proc., 1964, 23: 468. 
127. Riley, R. L., E. J. M. Campbell and R. H. 
Shepard. A bubble method for estimation of PC02 and 
P02 in whole blood. J. appl. Physiol., 1957,11: 245-249. 
128. Roberts, R. E., M. B. Cole and A. H. Lawton. 
A simple device for bedside measurement of carbon dioxide 
percentage in expired air. Proc. Soc. exp. Biol., N.Y., 1961, 
106: 692-693. 
129. Rooth, G., B. Christensson, A. Gustafson, E. 
Linder and M. Vannitamby. Direct intracardiac oxygen 
tension measurement with a Pt electrode. Acta med. scand., 
1961,170: 617-620. 
130. Said, S. I., C. M. Banerjee, R. K. Davis and 
J. L. Crosier. Continuous in vivo recording of arterial 
blood P02 using a needle electrode. Fed. Proc., 1961, 20: 422. 
131. Said, S. I., R. K. Davis and J. L. Corsier. Con- 
tinuous recording in vivo of arterial blood PD9 in dogs 
and man. J. appl. Physiol., 1961, 16: 1129-1132. 
132. Saling, E, and K. Damaschke. Neue Mikro- 
Schnell-Methode zur Messung des Bluesauerstoffes auf 
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133. Saunders, R. A. The role of infrared spectro- 
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status of chemical research in atmosphere purification and 
control on nuclear-powered submarines. U.S. Navy. Naval 
Research Laboratory, Washington, D.C. NRL Kept. 5465, 
April 1960, 167 pp. 
134. Scholander, P. F., L. Van Dam, C. L. Claff 
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of dissolved oxygen and nitrogen. Biol. Bull., Wood’s 
Hole, 1955,109: 328-334. 135-162 
TECHNICAL PROCEDURES 
135. Schwerd, W. Zur quantitativen Kohlenoxyd- 
bestimmung im Blut. Munch. Med. Wschr., 1954, 96: 
1098-1099. 
136. Severinghaus, J. W. Methods of measurement 
of blood and gas carbon dioxide during anesthesia. Anes- 
thesiology, 1960, 21: 717-726. 
137. Severinghaus, J. W. Respiratory system; Meth- 
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754 pp. 
138. Severinghaus, J. W. and A. F. Bradley. Elec- 
trodes for blood pO„ and pCO„ determination. J. appl. 
Physiol, 1958, 13: 515-520. 
139. Severinghaus, J. W., M. Stupfel and A. F. 
Bradley. Accuracy of blood pH and PC02 determinations. 
/. appl. Physiol, 1956. 9: 189-196, 
140. Siesjo, B. A method for continuous measurement 
of the carbon dioxide tension of the cerebral cortex. Acta 
physiol, scand., 1961, 51: 297-313. 
141. Siggaard, O., A. K. Engel, K. Jprgensen and 
P. Astrup. A micro method for determination of pH, 
carbon dioxide tension, base excess and standard bicarbo- 
nate in capillary blood. Scand. J. din. Lab. Invest., 1960, 
12:172-176. 
142. Skeggs, L. T., Jr. The determination of carbon 
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650-657. 
143. Smith, W. D. and J. E. Johnson. Concentra- 
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carbon sampling, pp. 70-78 in: The present status of chem- 
ical research in atmosphere purification and control on 
nuclear-powered submarines. U.S. Navy. Naval Research 
Laboratory, Washington, D.C. NRL Rept. 5630, July 1961, 
134 pp. 
144. Smith, W. D. and J. E. Johnson. Carbon sampl- 
ing of submarine atmospheres, pp. 63-66 in: The present 
status of chemical research in atmosphere purification and 
control on nuclear-powered submarines. U.S. Navy. Naval 
Research Laboratory, Washington, D.C. NRL Rept. 5814, 
August 1962, 97 pp. 
145. Snell, F. M. Electrometric measurement of C02 
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146. Sproule, B. J., W. F. Miller, I. E. Cushing 
and C. B. Chapman. Improved polarographic method 
for measuring oxygen tension in whole blood. J. appl 
Physiol, 1957,11: 365-370. 
147. Staub, N. C. A simple small oxygen electrode. 
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148. Steinbacher, von Th, Methode zur Bestimmung 
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149. Stine, P. T. and R. E. Koncen. Operational 
performance of the NRL thermistor-bridge gas leak detec- 
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Research Laboratory, Washington, D.C. NRL Rept. 5807, 
June 1962, 22 pp. 
150. Stow, R. W. A systematic error in infrared analy- 
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151. Stow, R. W., R. F. Baer and B. F. Randall. 
Rapid measurement of the tension of carbon dioxide in 
blood. Arch. phys. Med., 1957, 38: 646-650. 
152. Stubbs, R. A., A. C. Bryan and W. G. Leach. 
Physical evaluation of a polarographic P02 sensor and its 
application as a hypoxia warning device. Aerospace Med., 
1962, 33: 209-212. 
153. Thomas, F. S. The development of the atmos- 
phere analyzer for use in nuclear-powered submarines, 
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submarines. U.S. Navy. Naval Research Laboratory, Wash- 
ington, D.C. NRL Rept. 5465, April 1960, 167 pp. 
154. Thomas, F. S. Leak detectors, pp. 67-71 in: 
The present status of chemical research in atmosphere 
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NRT. Rept. 5814, August 1962, 97 pp. 
155. Thomas, F. S. Atmosphere analyzers, pp. 59-62 
in: The present status of chemical research in atmosphere 
purification and control on nuclear-powered submarines. 
U.S. Navy. Naval Research Laboratory, Washington, D.C. 
NRL Rept. 5814, August 1962, 97 pp. 
156. Thomas, F. S. The Mark IV atmosphere analyzer, 
pp. 37-40 in: The present status of chemical research in 
atmosphere purification and control on nuclear-powered 
submarines. Edited by H. W. Carhart and V. R. Piatt. 
U.S. Navy. Naval Research Laboratory, Washington, D.C. 
NRL Rept. 6053, December 1963, 65 pp. 
157. Tsao, M. U. and A. Vadnay. An electrode for 
continuous measurement of transient blood p02 in the 
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158. Turpin, F. H. and B. L. Roberts. A rapid 
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159. Umstead, M. E. Gas chromatography in the 
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U.S. Navy. Naval Research Laboratory, Washington, D.C. 
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166. Van Liew, H. D. Tissue pC2 and pC02 estima- 
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167. Van Liew, H. D. Tissue gas tensions by micro- 
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III. PRESSURE CHAMBERS 
Literature that follows represents a selection 
from a large number of reports on pressure 
chambers. For applications of such equipment 
in compressed air, diving, and submarine medi- 
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176. Boerema, I. An operating room with high atmos- 
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180. Molfino, F. and G. Odaglia. Risultati e rilievi 
in tema di decompressione terapeutica nelle malattie baro- 
traumatiche. Med. d. Lavoro, 1958, 49: 565-571. 
181. Pinkerton, H. H. The scope of a pressure 
chamber in surgery an anesthesia. Canad. Anesth. Soc. J., 
1962, 9: 389-398. 
182. Quemada, E. V. Etude relative a la ventilation 
des caissons de recompression. Marine Nationale. GERS, 
Toulon. September 1956, 14 pp. 
183. Anon. The hyperbaric oxygen chamber. Appl. 
therapeut., 1962, 4: 839. 
IV. GENERAL SOURCE LITERATURE 
A number of reports not classified elsewhere 
have been included in the list that follows. 
184. Andresen, D. and S. M. Tenney. The work of 
breathing and ventilatory response to muscular exercise. 
Fed. Proc., 1959, 18: 4. 
185. Balke, B., G. Wells and R. T. Clark, In-flight 
hyperventilation during jet pilot training. J. Aviat. Med., 
1957, 28: 241-248. 
186. Bartlett, R. G., Jr., H. F. Brubach and H. 
Specht. Oxygen cost of breathing. Fed. Proc., 1958, 17: II. 
187. Bartlett, R. G., Jr. and N. E. Phillips. Olfac- 
tory identification of liquid oxygen contaminants. Aero- 
space Med., 1961, 32: 621-629. 
188. Bartlett, R. G., Jr. and H. Specht. Energy cost 
of breathing determined with a simplified technique. 
Fed. Proc., 1957,16: 8. 
189. Barnett, T. B. and R. M. Peters. Unanesthe- 
tized dogs with increased respiratory dead space. J. appl. 
Physiol, 1960, 15: 838-842. 
190. Bates, D. V., W. F. Palmer, R. Donevan and 
C. J. Varvis. Factors influencing pulmonary diffusing 
capacity on exercise. Fed. Proc., 1958,17: 11. 
191. Bonnet, J. D., N. C. Hightower, Jr. and J. R. 
Rodarte. Correlation of blood and fecal radioactivity. 
J. Amer. med. Ass., 1962, 181: 35-37. 
192. Buettner, K. J. K. Diffusion of liquid water 
through human skin. J. appl. Physiol, 1959, 14: 261-268. 
193. Carter, R. L., E. T. Carter and F. A. Hitch- 
cock. A method for determining pulmonary ventilation 
efficiency. Fed. Proc., 1957, 16: 20. 194-228 
TECHNICAL PROCEDURES 
194. Commoner, B., J. J. Heise, B. B. Lippincott, 
R. E. Norberg, J. V. Passonneau and J. Townsend. 
Biological activity of free radicals. Science, 1957, 126: 
57-63. 
195. Cooper, E. A. Suggested methods of testing and 
standards of resistance for respiratory protective devices. 
J. appl. Physiol, 1960, 15: 1053-1061. 
196. Cooper, D. Y. and C. J. Lambertsen. Effect of 
changes in tidal volume and alveolar pC02 on physiological 
dead space. Fed. Proc., 1956, 15: 39. 
197. Danhof, I. E. and F. R. Steggerda. Factors af- 
fecting the volume and chemical composition of flatus in 
man with altitude. Fed. Proc., 1953, 12: 31. 
198. Earle, R. H., J. F. Perkins, Jr., J. Stanimiro- 
vitch, R. Evans, J. S. Byrne and W. E. Adams. C02 
retention in animals during hypoventilation, with ade- 
quate oxygenation. Fed Proc., 1957, 16: 33. 
199. Ernsting, J. The ideal relationship between in- 
spired oxygen concentration and cabin altitude. Aerospace 
Med., 1963, 34: 991-997. 
200. Ferris, B. G., Jr. and D. Pollard. Effect of shal- 
low and deep breathing on pulmonary compliance. Fed. 
Proc., 1958, 17: 46. 
201. Frumin, J. J., R. M. Epstein and G. Cohen. 
Apneic oxygenation in man. Anesthesiology, 1959, 20: 
789-798. 
202. Hall, A. L. and R. J. Martin. Prolonged ex- 
posure in the Navy full pressure suit at “space equivalent” 
altitudes. Aerospace Med., 1960, 31: 116-122. 
203. Hall, F. G. Physiologic factors which limit the 
minimal utilizable oxygen for rats in a microenvironment. 
Aerospace Med., 1960, 31: 649-653. 
204. Hettinger, T. and W. Beck. Die Reaktions- 
fahigkeit der peripheren Gefasse als dispositioneller Faktor 
fur die Entstehung von Gelenkerkrankungen. Int. Z. angew. 
Physiol, 1956, 16: 250-264. 
205. Huber, H. and H. Kolder. Beriumtitanat- 
Druckgeber fur Dekompressionversuche. Experientia, 1957, 
13: 202-204. 
206. lampietro, P. F., E. R. Buskirk, D. E. Bass 
and B. E. Welch. Effect of food, climate and exercise on 
rectal temperature during the day. J. appl. Physiol, 1957, 
11: 349-352. 
207. Johnson, R. F. and H. Y. C. Wong. Effects of 
training and competitive swimming on serum proteins. 
J. appl. Physiol, 1961,16: 807-809. 
208. Jones, G. M. Gastric secretomotor activity and 
renal excretion of uropepsinogen during periods of high 
intensity operational flight. Quart. J. exp. Physiol, 1957, 
42: 390-397. 
209. Jones, G. M. Theoretical middle ear gas compo- 
sition after flights breathing oxygen, air mix, air and 
combinations of these. Gt. Brit. FPRC. RAF Institute of 
aviation medicine. F.P.R.C. Memo 131, June 1960, 7 pp. 
210. Kagarise, R. E. and R. A. Saunders. The analy- 
sis of contaminants in aviators’ breathing oxygen. U.S. 
Navy. Naval Research Laboratory. NRL Rept. 5554, 19 
October 1960, 20 pp. 
211. Konikoff, J. J. Oxygen recovery systems for man- 
ned space flight. Aerospace Med., 1961, 32: 701-712. 
212. Lyons, H. A. and R. G. Dolce. Maximum 
breathing capacity during negative pressure. Fed. Proc., 
1961, 20: 428. 
213. Maritz, J. S., J. F. Morrison, J. Peter, N. B. 
Strydom and C. H. Wyndham. A practical method of 
estimating an individual’s maximal oxygen intake. Ergo- 
nomics, 1961, 4: 97-122. 
214. McGregor, M. and M. R. Becklake. The rela- 
tionship of oxygen cost of breathing to respiratory me- 
chanical work and respiratory force. ]. din. Invest., 1961, 
40: 971-980. 
215. McKerrow, C. B. Assessment of the mechanical 
function in ventilation. Proc. R. Soc. Med., 1953, 46: 532- 
535. 
216. Miles, S. Resistance to breathing; its application 
to breathing apparatus. Gt. Brit. MRC-RNPRC, UPS. 
R. 56/871, U.P.S. 158, June 1956, 3 pp. 
217. Milic-Emili, J. and J. M. Tyler. Relationship 
between PaC(,2 and respiratory work during external re- 
sistance breathing in man. Ann. N.Y. Acad. Sci., 1963, 109: 
908-914. 
218. Nahas, G. G. and S. W. Weitzner. Apneic oxy- 
genation with and without a C02 buffer (motion picture). 
Fed. Proc., 1959, 18: 111. 
219. Pepler, R. D. Warmth, glare and a background 
of quiet speech; a comparison of their effects on perform- 
ance. Ergonomics, 1960, 3: 68-73. 
220. Peterson, R. E. Plasma corticosterone and hydro- 
cortisone levels in man. J. din. Endocrin., 1957, 17: 1 ISO- 
1157. 
221. Pugh, L. G. C. and O. G. Edholm. The physiol- 
ogy of channel swimmers. Lancet, 1955, 2: 761-768. 
222. Pugh, L. G. C. E., O. G. Edholm, R, H. Fox, 
H W. Wolff, G. R. Hervey, W. H. Hammond, J. M. 
Tanner and R. H. Whitehouse. A physiological study 
of channel swimming. Clin. Sci., 1960,19: 257-273. 
223. Raison, J. C. A. Cerebral oedema; follow-on 
treatment after cardiac resuscitation and respiratory crisis. 
Lancet, 1957, 2: 984-985. 
224. Rennie, D. W., B. G. Covino, B. J. Howell, 
S. H. Song, B. S. Kang and S, K. Hong. Physical in- 
sulation of Korean diving women. J. appl. Physiol., 1962, 
17: 961-966. 
225. Riley, R. L., S. Permutt, S. Said, M. Godfrey, 
T. O. Cheng, J. B. L. Howell and R. H. Shepard. 
Effect of posture on pulmonary dead space in man. J. appl. 
Physiol., 1959,14: 339-344. 
226. Sisson, G. M. and M. J. Fregly. A simplified 
apparatus for chronic exposure of rats to low oxygen ten- 
sion. J. appl. Physiol, 1955-56, 8: 128-131. 
227. Stroud, R. C. Combined ventilatory and breath- 
holding evaluation of sensitivity to respiratory gases. U.S. 
Navy. Submarine Base, New London, Conn. Medical Re- 
search Laboratory. Project NM 24 02 20.01.02, 20 July 
1959, 4 pp. 
228. Stuart, D. G. and W. D. Ceilings. Comparison 
of vital capacity and maximum breathing capacity of 
athletes and nonathletes. J. appl. Physiol, 1959, 14: 507- 
509. GENERAL SOURCE LITERATURE 
229-235 
229. Suit, H. D. “Oxygen effect factor” of human skin. 
Radiology, 1962, 79: 118-119. 
230. Sunahara, F. A., F. Girling, R. A. Snyder and 
D. Topliff. Studies in hyperventilation at ground level 
and at simulated altitudes. J. Aviat. Med., 1957, 28: 13-18. 
231. Van Goor, H. Extrapulmonale gaswisseling. 
[Extra-pulmonary gas exchange.] Ned. Tijdschr. Geneesk., 
1953, 97: 147-149, 
232. White, C. E. Frequency response of condenser 
microphone at increased atmospheric pressures. U.S. Navy. 
Submarine base, New London, Conn. Medical research 
laboratory. Project NM 002 014.06, Kept. no. 2, 24 March 
1955. 
233. Wiinsche, O. Zur Pathogenese und Prophylaxe 
der Druckfallkrankheit des Hohenfliegers. III. Intravasale 
Gasblasenbildung im Drucksturzversuch nach Hohenak- 
komodation. Int. Z. angew. Physiol., 1960,18: 165-174. 
234. Zechman, F., F. G. Hall and W. E. Hull. 
Effects of graded resistance to tracheal air flow in man. 
J. appl. Physiol, 1957,10: 356-362. 
235. Zocche, G. P., H. W. Fritts, Jr. and A. Cour- 
nand. Fraction of maximum breathing capacity available 
for prolonged hyperventilation. J. appl. Physiol, 1960, 15: 
1073-1074. Special Anatomy, Physiology and 
Biochemistry of Compressed Air, 
Diving and Submarine Medicine 
I. PHYSIOLOGICAL EFFECTS OF 
RAISED ATMOSPHERIC PRESSURES 
A. HEART AND CIRCULATION 
It has generally been found that exposure to 
compressed air for long periods causes no en- 
during alterations in blood pressure or cardiac 
function. Thus Amorim (236) 1957, found only 
minor variations in the electrocardiogram of 20 
subjects exposed to pressures of 10.7, 21.4 and 
29.4 psi. It was found that the rhythm became 
less frequent in 93.5 percent of the cases and 
the P-R interval was lengthened in 74.06 percent. 
There was a higher respiratory frequency in 81.81 
percent of the subjects. 
236. Amorim, I. de. Air comprimido e electrocardio- 
grama. Arch. bras. Cardiol., 1957, 10: 355-370. 
237. Barthelemy, L. Etude des modifications du “test 
de Ruffier” en pression. Marine Nationale. GERS, Toulon. 
Kept. 9162 G.E.R.S., No. 557, 7 December 1962, 8 pp. 
238. Peterson, L. H. Cardiovascular performance un- 
der water, pp. 267-270 in: Second symposium on under- 
water physiology. Edited by C. J. Lambertsen and L. J. 
Greenbaum, Jr. National Research Council, Washington, 
D.C. N.R.C. Publication 1181, 1963, 296 pp. 
B. RESPIRATION 
Earlier studies on the effects of raised at- 
mospheric pressure on respiration have indicated 
that repeated exposure causes an increase in vital 
capacity. However, more recently there has been 
doubt as to whether this occurs or if it does, 
whether there is more than a slight change. 
Studies on human subjects have shown that there 
may be an increase in the breath holding time 
and a slowing of the respiratory rate. 
Buhlmann (240) 1963, has examined respira- 
tory resistance with hyperbaric gas mixtures. 
Studies were made on male volunteers on the 
respiratory response to different gas mixtures. 
The mixtures used were helium (90 ± 3 per- 
cent) plus oxygen at 9.7 atmospheres, nitrogen 
(90 ± 3 percent) plus oxygen at 19.4 atmos- 
pheres and argon (90 ± 3 percent) plus oxygen 
at 29.0 atmospheres. Each subject was tested 
twice. It was found that as the depth increased 
the flow resistance increased also. The highest 
increase was for argon and oxygen and the lowest 
for helium and oxygen. The respiratory work 
was increased as the depth increased, being high- 
est for argon and oxygen and lowest for helium 
and oxygen. Hesser and Holmgren (241) 1959, 
have also examined the effects of raised baro- 
metric pressures on respiration in man at pres- 
sures up to four atmospheres. These investiga- 
tions were carried out on eight healthy subjects 
at rest in a recompression chamber. The inde- 
pendent effects of changes in inspired oxygen 
and nitrogen pressures were studied by compar- 
ing data obtained on air, 100 percent oxygen 
and five percent oxygen in nitrogen at various 
ambient pressures. Breathing air with increasing 
ambient pressure caused the respiration to be- 
come progressively slower and deeper whereas 
at four atmospheres the effective alveolar venti- 
lation was slightly increased. At four atmos- 
pheres there was an average increase of 33 per- 
cent in the tidal volume, an average decrease 
in the respiratory rate of 27 percent, an increase 
in the respiratory minute volume of ten percent 
and an increase in the functional dead space/tidal 
volume ration of nine percent. There was no DECOMPRESSION PHYSIOLOGY OF BUBBLE FORMATION 
239-252 
demonstrable change in the expiratory reserve 
volume, or in the functional dead space and 
respiratory exchange ratio. The authors pro- 
vided evidence that the respiratory changes were 
caused by the combined effects of increased 
oxygen tension and of breathing resistance due to 
increased gas density. Thus nitrogen at high 
pressures up to 3.8 atmospheres exerted little 
if any depressant action on respiration. Mead 
(243) 1956, has reported that exposures to in- 
creased ambient pressures increases the inertance 
of the lungs roughly proportionally to the ambi- 
ent pressure, suggesting that inertance as meas- 
ured was predominantly of the gas stream. 
239. Bond, G. F. Prolonged exposure to high ambient 
pressure, pp. 29-33 in: Second symposium on underwater 
physiology. Edited by C. J. Lambertsen and L. J. Green- 
baum, Jr. National Research Council, Washington, D.C. 
N.R.C. Publication 1181, 1963, 296 pp. 
240. Buhlmann, A. A. Respiratory resistance with 
hyperbaric gas mixtures, pp. 98-107 in: Second symposium 
on underwater physiology. Edited by C. J. Lambertsen 
and L. J. Greenbaum, Jr. National Research Council, 
Washington, D.C. N.R.C. Publication 1181, 1963, 296 pp. 
241. Hesser, C. M, and B. Holmgren. Effects of 
raised barometric pressures on respiration in man. Acta 
physiol, scand., 1959, 47: 28-43. 
242. Mead, J. Resistance to breathing at increased 
ambient pressures, pp. 112-123 in: Proceedings of the un- 
derwater physiology symposium. Edited by L. G. Goff. 
National Research Council, Washington, D.C. N.R.C. 
Publication 311, 1955, 153 pp. 
243. Mead, J. Measurement of inertia of the lungs at 
increased ambient pressure. J. app. Physical., 1956, 9: 
208-212. 
244. Miles, S. The effect of increase in barometric 
pressure on maximum breathing capacity. Gt. Brit. MRC, 
RNPRC, UPS. Rept. R.N.P. 58/922, U.P.S. 174, April 1958, 
4 pp. 
245. Sensing, J. and H. C. Drube. Die Bedeutung 
der Hyperkapnie fiir das Auftreten des Tiefenrauches. 
Klin. Wschr., 1960, 38: 1088-1090. 
246. Sensing, J. and H. C. Drube. Die Kohlensaure 
als Gefahrenquelle beim Tauchen in grossere Tiefen. 
Hefte z.Unfallheilk., 1961, 66: 299-301. 
247. U.S. Navy. Pressure effects on body structure and 
function, pp. 40-49 in: Submarine medicine practice. U.S. 
Navy, BuMed. NAVMED — P 5054, Gov’t Printing Office, 
Washington, D.C., 1956, 357 pp. 
248. Wood, W. B. Ventilatory dynamics under hyper- 
baric states, pp. 108-123 in: Second symposium on under- 
water physiology. Edited by C. J. Lambertsen and L. J. 
Greenbaum, Jr. National Research Council, Washington, 
D.C. N.R.C. Publication 1181, 1963, 296 pp. 
249. Wood, W. B., L. H. Leve and R. D. Work- 
man. Ventilatory dynamics under hyperbaric states. U.S. 
Navy. EDU, Naval Station, Washington, D.C. Res. Rept. 
1-62, 15 May 1962, 23 pp. 
C. KIDNEY 
For a report on the effects of high pressures on 
renal function, a paper by Barthelemy ('250) 
1962, may be consulted. 
250. Barthelemy, P. V. Etude du ph£nom£ne d’ob- 
stacle de Donnagio en pression. Marine Nationale. GERS, 
Toulon. Rept. 1/62 G.E.R.S., No. 519, 27 November 1962, 
7 pp. 
II. PHYSIOLOGICAL EFFECTS OF 
DECOMPRESSION 
A. PHYSIOLOGY OF BUBBLE FORMATION 
Reference may be made to a report by Bishop, 
Walder and Van Liew (257) 1964, on the exit 
of oxygen and carbon dioxide from gas pockets 
during compression to 2 and 4 atmospheres. 
These authors have pointed out that the ac- 
cepted treatment for decompression sickness is 
recompression which not only reduces the size 
of bubbles, but presumably facilitates their re- 
absorption as well. Assuming that large sub- 
cutaneous gas pockets are analogous to bends 
bubbles the authors studied carbon dioxide and 
nitrogen in rats after compression to 2 and 4 
ATA. Compression at first increases the partial 
pressure of pocket gases. The P02 quadrupled 
with 4 atmospheres, but carbon dioxide left so 
rapidly that P COo never reached the predicted 
level. After two hours compression the pockets 
reached a new steady state with P0a and Pco2 
only slightly higher than controls, demonstrating 
that these levels of compression with air exert 
minimal effect on tissue P02 and PCC)2. The early 
exit of oxygen and carbon dioxide causes a bonus 
decrease in pocket volume and increases the frac- 
tion of nitrogen in the pocket which aids nitro- 
gen absorption. At 4 atmospheres the volume 
decrease is about seven percent giving seven per- 
cent increase of FN2. 
251. Bishop, B., P. Walder and H. D. Van Liew. 
Exit of 02 and C02 from gas pockets during compression 
to 2 and 4 atm. Fed. Proc., 1964, 23: 469. 
252. Harvey, E. N. Bubble formation, pp. 53-60 in: 
Proceedings of the underwater physiology symposium. 
Edited by L. G. Goff. National Research Council, Wash- 
ington, D.C. N.R.C. Publication 311, 1955, 153 pp. 253-273 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
253. Liebermann, L. Air bubbles in water. J. appl. 
Physics, 1957, 28: 205-211. 
B. SATURATION AND DESATURATION OF 
GASES IN THE BODY 
Duffner and Snider (262) 1958, have studied 
the effects of exposing human subjects to com- 
pressed air and helium-oxygen mixutres for 12 
hours at pressures of 2 to 2.6 atmospheres. Five 
Navy divers aged 21 to 34 years were exposed 
for 12 hours in a recompression chamber to in- 
creasingly greater pressures. The pressure in all 
cases was reduced at a rate of 25 feet per minute 
(11.12 pounds). The exposures were performed 
first while breathing compressed air and then 
later while breathing 80 percent helium and 20 
percent oxygen. Greater exposures were toler- 
ated with the helium-oxygen mixture than with 
air. The differences amounted to pressures 
equivalent to 3, 4, 6, 10 and 14 feet of sea water. 
Data on helium elimination disclosed that a large 
fraction (over 50 percent) of the dissolved 
helium is contained in a tissue component which 
desaturates very rapidly (half-time 1.5 to 5 
minutes). The existence of a slow component 
(half-time 95 to 115 minutes) appears likely. 
The use of helium-oxygen mixtures in mixed gas 
SCUBA and the utilization of a single mathe- 
matical expression to compute decompression 
stops are considered feasible by the authors. 
254. Aver’ianov, V. A., P. M. Gramenitskii and 
A. A. Savich. Izmeneniia velichiny predel’no deposti- 
mogo peresyshcheniia organizma azotom pri mnogokrat- 
nom povtorenii opytov. Changes in the value of maximal 
permissable nitrogen supersaturation in repeated experi- 
ments. Patol. Fiziol. eksp. Terap., 1961, 4: 50-53. 
255. Balke, B. Rate of gaseous nitrogen elimination 
during rest and work in relation to the occurrence of de- 
compression sickness at high altitude. USAF. Randolph 
Field, Texas. School of Aviation Medicine. Project No. 
21-1201-0014, Kept. No. 6, October 1954, 6 pp. 
256. Boothby, W. M., U. C. Luft and O. O. Ben- 
son, Jr. Gaseous nitrogen elimination. Experiments when 
breathing oxygen at rest and at work with comments on 
dysbaresin. J. Aviat. Med., 1952, 25: 141-158. 
257. Bouhuys, A. Influence of tissue nitrogen elimina- 
tion on analysis of pulmonary nitrogen clearance curves. 
Acta physiol, pharm. need., 1959, 8: 431-436. 
258. Brestkin, A, P. and A. G. Zhironkin. Otsenka 
razlichnykh sposobov primeneniia kisloroda pri dekotn- 
pressii vodolazov. [Evaluation of different methods of 
administration of oxygen for the decompression of divers.] 
Fiziol. Zh. SSSR Sechenov, 1959, 45: 865-871. 
259. Briscoe, W. A. Discussion: The physiological 
significance of the slow space as determined in nitrogen 
washout studies during oxygen breathing. Proc. XXII 
Inter. Physiol. Congr., 1962, Vol. I, Part I, p. 303. 
260. Gander, L. Solubility of inert gases in human 
lung tissue. /. appl. Physiol., 1959, 14: 538-540. 
261. Chinard, F. P., T. Enns and M. F. Nolan. 
Diffusion and solubility factors in pulmonary inert gas 
exchanges. J. appl. Physiol., 1961,16: 831-836. 
262. Duffner, G. J. and H. H. Snider. Effects of ex- 
posing men to compressed air and helium-oxygen mixtures 
for 12 hours at pressures of 2 — 2.6 atmospheres. U.S. Navy. 
Naval weapons plant, EDU. Project NS 186-201, sub task 
no. 2, test no. 2, 18 September 1958, 6 pp. 
263. Featherstone, R. M., W. Steinfeld, E. G. 
Gross and C. B. Pittinger. Distribution of the anesthe- 
tic gas xenon in dog tissues as determined with radioactive 
xenon. J. Pharmacol., 1952, 106: 468-474. 
264. Hardewig, A., D. F. Rochester and W. A. 
Briscoe. Measurement of solubility coefficients of krpyton 
in water, plasma and human blood, using radioactive Kr88. 
J. appl. Physiol., 1960,15: 723-725. 
265. Hickam, J. B., E. Blair and R. Frayser. An 
open-circuit helium method for measuring functional re- 
sidual capacity and defective intrapulmonary gas mixing. 
J. din. Invest., 1954, 55: 1277-1286. 
266. Kety, S. S. Theory and applications of the ex- 
change of inert gas at the lungs and tissues. Pharmacol. 
Rev., 1951, 5: 1-41. 
267. Kovalenko, E. A. and I. A. lurkov. O gazovom 
sostave puzyrei vysotnoi tkanevoi emfizemy. [On the gas 
composition of vesicles occurring in high altitude tissular 
emphysema.] Patol. Fiziol. eksp. Terap., 1961, 4: 26-29. 
268. Lundin, G. Nitrogen elimination during oxygen 
breathing. Acta physiol, scand., Suppl., 1953, 111: 130-143. 
269. Marbarger, J. P., W. Kadetz, J. Paltarokas, 
D. Variakojis, J. Hansen and J. Dickinson. Gaseous 
nitrogen elimination at ground level and simulated alti- 
tude and the occurrence of decompression sickness. U.S.A.F. 
Randolph Field, Texas. School of aviation medicine, Feb- 
ruary, 1956. 
270. Mead, J., H. B. Martin and C. D. Cook. Dead 
space and washout measurements made with helium and 
sulfur hexafluoride. Fed. Proc., 1958,17: 109. 
271. Pittinger, C. B., H. L. Conn, R. M. Feather- 
stone, E. Stickley, L. Levy and S. C. Cullen. Observa- 
tions on the kinetics of transfer of xenon and chloroform 
between blood and brain in dog. Anesthesiology, 1956, 17: 
523-530. 
272. Pittinger, C. B., R. M. Featherstone, E. G. 
Gross, E. E. Stickley and L. Levy, Xenon concentra- 
tion changes in brain and other body tissues of the dog 
during inhalation of the gas. /. Pharmacol., 1954, 110: 
458^62. 
273. Riggs, D. S. and A. Goldstein. Equation for 
inert gas exchange which treats ventilation as cyclic. J. 
appl. Physiol., 1961,16: 531-537. LOW OXYGEN PERCENTAGES—SPECIAL SENSES 
274-285 
274. Specht, H. Solubility or absorption, pp. 587-589 
in: Industrial hygiene and toxicology. Volume I. Edited 
by F. A. Patty, Interscience Publishers, Inc., New York 
1958,830 pp. 
275. Tokuyasu, K., A. Coblentz and H. R. Bier- 
man. Estimation of pulmonary ventilation with nitrogen 
and helium, using the mass spectrometer. J. appl. Physiol., 
1959,14: 499-506. 
276. Wittenberg, J. B. The secretion of inert gas into 
the swim-bladder of fish. J. gen. Physiol., 1957-58, 41: 
783-804. 
C. FAT AND WATER CONTENT 
Reference may be made to this subject in 
Volume II of this Sourcebook and to the refer- 
ences listed below. It has been pointed out that 
fats and water are so distributed in the body 
that during saturation much of the nitrogen 
absorbed by fat diffuses from the body fluid. 
During decompression following partial satura- 
tion, the diffusion of nitrogen from the rapidly 
saturating body fluids into slowly saturating 
lipoids and fats tends to equalize the partial 
pressure of nitrogen in the different tissues of 
the body. Following brief exposures to very 
high pressures the fat acts as a nitrogen absorb- 
ent during decompression and acts as a buffer 
against bubble formation in the blood stream. 
It has been suggested that obese subjects with 
adequate blood supply and circulation should be 
better suited for short exposures in compressed 
air than lean men. 
277. Allen, T. H. Measurement of human body fat: 
a quantitative method suited for use by aviation medical 
officers. Aerospace Med., 1963, 34: 907-909. 
278. Allen, T. H., H. J. Krywicki, W. S. Worth 
and R. M. Nims. Human body volumeter based on water 
displacement. U.S. Army. Med. res. nutr. Lab., Denver, 
Col. Project 6-60-11-001, Kept. no. 250, 24 September 
1960, 32 pp. 
279. Behnke, A. R. Relationship between basal me- 
tabolism, lean body weight and surface area. Fed. Proc., 
1953,12: 13. 
280. Behnke, A. R. Estimation of lean body weight 
from skeletal (x-ray) diameters. Fed. Proc., 1957, 16: 9. 
281. Buskirk, E. R. and H. L. Taylor. Relationships 
between maximal oxygen intake and components of body 
composition. Fed. Proc., 1954,13: 21. 
282. Gosselin, R. E., J. D. Gabourel, S. C. Kaiser 
and J. H. Wills. Carbon and water contents of mouse 
and rat tissues. Proc. Soc. exp. iol., N.Y., 1955, 90: 533-537. 
283. Keys, A. and J. Brozek. Body fat in adult man. 
Physiol. Rev., 1953, 33: 245-325. 
284. Picon-Reategui, E., R. Lozano and J. Val- 
divieso. Body composition at sea level and high altitudes- 
J. appl. Physiol, 1961, 16: 589-592. 
285. Siri, W. E. Fat, water and lean tissue studies. 
Fed. Proc., 1953,12: 133. 
III. PHYSIOLOGICAL EFFECTS OF 
LOW OXYGEN TENSIONS OF EN- 
VIRONMENTAL AIR 
A. LOW OXYGEN PERCENTAGES 
WITHOUT DECOMPRESSION 
1. SPECIAL SENSES 
Conditions of hypoxia have been shown to re- 
sult in a deterioration of functional acuity of 
the special senses. Although modern oxygen 
generating equipment in the submarines now 
obviate or minimize the hazard of reduction in 
oxygen percentage available to the submarine 
personnel, hypoxia problems may be a danger 
to divers using self-contained underwater breath- 
ing apparatus. There is, in general, never a prob- 
lem for divers using an air supply from the sur- 
face, unless gear failure occurs. Experimental 
studies of the effects of hypoxia at ambient pres- 
sures still remain of interest. 
Of interest are the effects of changes in arterial 
oxygen tension upon cochlear microphonics. 
Wing, Harris, Stover and Brouillette (295) 1953, 
have found in some cats that a reduction of 
arterial oxygen, from an average possible maxi- 
mum value of 14.1 volumes percent to six to nine 
volumes percent, is accompanied by a definite 
although reversible depression in microphonics. 
The effectiveness of less severe degrees of hypoxia 
in reducing microphonics in cats was variable in 
the several animals used. This was explained in 
part by variability of circulatory adjustments and 
incidental changes in arterial carbon dioxide. 
The percentage fall in microphonics during hy- 
poxia was unrelated to the initial magnitude of 
the cochlear response at the moderate levels 
elicited in this investigation. Complete recovery 
of microphonic output followed arterial concen- 
trations as low as two to three volumes percent 
maintained for as long as about one-half hour. 
There was no instance of complete recovery after 
hypoxia of sufficient severity to lower arterial 
oxygen significantly below two volumes percent 
with arterial oxygen tensions below three volumes 
percent. There was a direct relationship between 
the depression of arterial oxygen and the time 
required to reach maximum recovery. When 
the reduction in microphonics during hypoxia SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
exceeded 80 percent, subsequent recovery upon 
termination of hypoxia was reduced and its 
temporal course was greatly prolonged. The 
authors found that no more than eight to nine 
seconds need elapse between the inhalation of 
oxygen in room air and a significant increase in 
microphonics already depressed by hypoxia. 
Cochlear microphonics were found to be rever- 
sibly reduced by inspiration of carbon dioxide 
in oxygen or air in concentrations between 5.2 
and 25 percent. 
Davis, Tasaki, Smith and Deatherage (286) 
1955, have studied cochlear potentials after in- 
tracochlear injections as well as anoxia. They 
injected small quantities of salt solution into 
the scala media of the basal turn in the guinea 
pig while recording the endolymphatic DC po- 
tential through the injection pipette. Simultane- 
ously they recorded the cochlear microphonics 
(CM), the action potential (AP), and the sum- 
mating potential (SP) in response to 5000 cycles 
per second tone pips, recorded from other intra- 
cochlear electrodes. Injections of 0.2 cmm of 
artificial endolymph (with high potassium and 
low sodium) had little or no effect. Artificial 
perilymph containing sodium and potassium in 
the usual tissue fluid ratio was toxic but it 
affected CM much more than DC. Larger injec- 
tions and complete perfusions of the scala media 
were complicated by probable mechanical injury. 
They depressed AT, CM and DC, but low potas- 
sium solutions were relatively more injurious 
than those with high potassium. Cocaine de- 
pressed CM and AP but not DC. It was found 
that cessation of respiration abolished AP and 
considerably reduced CM and DC. Following 
a single gasp, DC regularly returned promptly 
from less than 50 percent back to its full normal 
value. The increase in DC occupied less than 
three seconds and paralleled the familiar revival 
of CM and AP. These results suggested to the 
authors a more immediate dependence of the 
endolymphatic DC potential on an oxidative 
mechanism than on ionic concentration differ- 
ences. The summating potential was greatly 
affected in complicated fashion by anoxia as well 
as by ionic changes, but was small or absent when 
the cochlea was presumably most normal. 
Studies of the effects of oxygen lack on cohlear 
potentials have also been carried out by Fer- 
nandez (287) 1955, Fernandez and Alzate (288) 
1959, and Konishi, Butler and Fernandez (290) 
1961. In their first paper these authors induced 
asphyxia in guinea pigs and cats to determine 
the survival time, recovery time and revival time 
for cochlear microphonics (CM) and action 
potentials (AP). Two phases of CM were identi- 
fied. On the basis of the rapid decline of the 
fast phase a high metabolic rate of the hair 
cells was inferred. Lack of dependence of this 
decline on stimulus intensity suggested equal 
oxygen requirements among the hair cell popu- 
lation. The short survival time of AP supported 
the view that the cochlear nerve has a high 
metabolic rate, close to that of the central nervous 
system. A definite dependence of the survival 
time of AP upon stimulus intensity indicated that 
there are groups of fibers with different oxygen 
requirements. A short recovery time of CM re- 
flects the rapid rate of physical chemical recon- 
struction of the hair cells after initial recovery 
of responses, a full recovery was generally ob- 
served and occasionally there was overshooting. 
Repetitive asphyxia usually produced cumulative 
depression, probably due to irreversible changes. 
The recovery time of AP was of the same order 
of magnitude as that of the central nervous sys- 
tem. The recovery time of AP varied as did sur- 
vival time with stimulus intensity. This was 
considered by the author to represent different 
rates of physico-chemical reconstruction among 
the primary cochlear neuron population. AP 
recovered fully and as a rule exhibited over- 
shooting, at times as high as 75 percent over 
normal. Fibers with lowest threshold were 
characteristically the most sensitive to repeated 
asphyxia. It was found that survival/revival time 
for asphyxia could not be determined since the 
animals died within seven minutes. Fernandez 
and Alzate found that cochlear responses de- 
pended upon an adequate oxygen supply. Neural 
components (Nx and N2) were most sensitive. 
Their survivals were 90 and 60 seconds, respec- 
tively when asphyxia or fulminating anoxia was 
imposed while cochlear microphonics (CMX) sur- 
vived about 300 seconds. Depressions of CMX, 
Njl and N2 seem to be related to those chemical 
reactions underlying the generation of energy. 
The recovery of cochlear responses after a bout 
of oxygen deprivation followed a definite order: LOW OXYGEN PERCENTAGES—SPECIAL SENSES 
CMX recovered within ten seconds; Nx lagged 
CM! by a few seconds; N2 was the last potential 
to reappear. Recovery seemed to depend upon 
factors such as duration and degree of oxygen 
lack, and was probably related to the reconstruc- 
tion properties of the generators of cochlear 
potentials. The authors found that exposures to 
asphyxia repeated at one hour intervals produced 
an apparently permanent depression of both 
cochlear microphonics and neural components, 
provided the duration of each bout was at least 
three minutes. In these guinea pigs no changes 
in their inner ear structure were found after 
hemotoxlin eosin stain and study with light 
microscopy. Unanesthetized guinea pigs exposed 
several times (30 to 45 minutes each) to gas mix- 
tures of N2 with 3 percent oxygen and kept alive 
for about six weeks, also revealed no histologic 
changes in the inner ear. Similarly the temporal 
bones of animals exposed once for a period of 
about two hours to the same gas mixture and 
kept alive for several days revealed no evidence 
of histologic change. Routine histologic methods 
such as hemotoxylin eosin stain and light mi- 
croscopy were believed to be inadequate for de- 
tecting changes in the inner ear structures of 
animals with apparently permanent depression of 
cochlear responses induced by repeated exposures 
to anoxia. Chronic experiments suggested that 
this depression was a reversible phenomenon. 
In the experiments of Konishi, Butler and 
Fernandez, the anterior inferior cerebellar artery 
of guinea pigs was occluded as a device for in- 
terrupting the blood supply to the cochlea and 
thus producing anoxia. Durations of occlusion 
ranged from 1 to 60 minutes. Cochlear micro- 
phonics, summating potential, action potential 
and endocochlear potential were recorded before, 
during and after occlusion. Differential effects 
of anoxia upon the various potentials was ob- 
served, as well as the appearance of large negative 
DC potential in the scala media as anoxia pro- 
gressed. For brief occlusion durations, the ampli- 
tudes of all potentials, except cochlear micro- 
phonics, became greater than normal soon after 
the blood supply was restored. Even for the 
longer anoxic periods, the summating potential 
and the endocochlear potential exhibited super 
normality during the recovery process. 
To evaluate the role played by endolymphatic 
hyoxia on deafness, Mizrahy, Shinnebarger and 
Arnold {291) 1958 made continued recordings 
of oxygen availability, action potential and micro- 
phonics taken during asphyxia, chronic hypoxia 
and after loud sounds. Their results showed that 
hypoxia may play an important contributory role 
in temporary losses of hearing following loud 
sounds. The possible mechanisms of auditory 
trauma may be mechanical injury and acoustic 
vibrations inducing change in the permeability 
of the basilar membrane allowing ionic potas- 
sium to leak from the scala media and block 
hair cells and nerve endings. Hypoxia may 
produce diffuse reversible or irreversible changes 
not necessarily accompanied by obvious structural 
changes. A great variety of other bio-medical 
changes may be involved, such as variations of 
carbon dioxide tension, pH, and accumulation of 
metabolites. Mizrahy, Spradley, Zinovich and 
Brooks (292) 1961 found that intense sound, 
hypoxia and kanamycin increased the perme- 
ability of cochlear partitions. 
In a study of the effects of environmental 
changes upon the cochlear response of the cat, 
Wing (294) 1962 used a sound stimulus of 4000 
cycles per second of constant intensity to pro- 
duce the cochlear response (CR). Completely 
reversible losses in CR were associated with 
hypercapnia (6.7 percent and 24 percent carbon 
dioxide in oxygen). This loss was not main- 
tained during exposure, indicating that carbon 
dioxide may not have been acting directly upon 
the “electrical generators”. Flooding the bulla 
with carbon dioxide and oxygen at room tempera- 
ture caused a significant and reversible reduc- 
tion in the CR in a matter of seconds. Produc- 
tion of hypoxia through tracheal clamping and 
low oxygen-nitrogen mixtures caused a reduc- 
tion of arterial oxygen from 14.1 to 6 to 9 volumes 
percent, often accompanied by definite and re- 
versible drops in the CR. Effects of minimal 
and moderate hypoxia on CR were variable. 
Proportional fall of CR was unrelated to the 
size of the initial response. The rate of fall 
varied with the percentage of final voltage 
decrement and complete recovery was possible 
after two to three volumes percent arterial oxygen 
for 30 minutes, but not below two volumes per- 
cent. If the CR dropped more than 80 percent 286-291 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
during hypoxia recovery was incomplete and pro- 
longed. With less severe hypoxia recovery began 
during exposure and the CR was greater after 
the hypoxia than before. Recovery was signifi- 
cant within 8-10 seconds post-hypoxia. With the 
bulla flooded with nitrogen or oxygen at at- 
mospheric pressure before clamping the trachea, 
it was found that the postmortem CR at the 
round window depends on the presence of 
oxygen. The author believed that postmortem 
CR was produced by aerobic chemical reactions 
and that no qualitative difference exists be- 
tween reactions generating CR antemortem or 
postmortem. 
Gisselson (289) 1954 has examined the litera- 
ture on the effect of oxygen-lack and decreased 
blood pressure on the microphonic response of 
the cochlear, and has also himself conducted ex- 
periments on the nature of the cochlear poten- 
tials. He believes that cumulative evidence argues 
strongly for the view that cochlear potentials are 
intimately related to the activity of the hair cells, 
that is to say that cochlear potentials can be 
demonstrated only in the presence of intact hair 
cells. The amplitude of the cochlear potentials is 
decreased by oxygen lack as well as by extreme 
reduction in blood pressure. Oxygen lack pro- 
duced by the administration of potassium 
cyanide, which inhibits cellular respiration but 
increases blood pressure, decreases the ampli- 
tude of cochlear potentials, the decrease varying 
roughly with the degree of anoxia. Oxygen 
deficiency caused by deprivation of air supply 
causes an initial decrease of the amplitude of the 
cochlear potentials and a simultaneous, transient 
slight fall in blood pressure. After one or two 
minutes the blood pressure increases and there 
is an accompanying further decrease in the ampli- 
tude of the cochlear potentials. Reintroduction 
of the supply of oxygen to the animal increases 
the blood pressure violently as well as the ampli- 
tude of the cochlear potentials. Blood pressure 
then gradually drops with a corresponding 
gradual decrease in the amplitude of the cochlear 
potentials. This biphasic decrease in the cochlear 
potentials suggests to the author that the poten- 
tials are made up of two factors, one sensitive to 
oxygen lack and the other to changes in blood 
pressure. The cochlear potentials are very sensi- 
tive to oxygen lack, about 30 seconds of de- 
privation of air supply being enough to cause 
reversible injury to the cochlea, and two minutes 
deprivation being enough to produce irreparable 
damage to the organ. 
Of interest is a paper by Rizzo and Cinquemani 
(293) 1959. This paper deals with the behavior 
of the oculo-cardiac reflex of dogs at sea level 
under conditions of hypoxia. The authors inves- 
tigated the behaviour of the ocular-cardiac reflex 
in normal conditions and with reduced oxygen 
supply in animals anesthetized with chloralose. 
Pulmonary ventilation was continuously recorded 
during the experiments and the oculo-cardiac re- 
flex elicited with gradually increased compression 
of the eyeballs by the imposition of weights from 
100 gms. to a maximum of 1000 gms. Each com- 
pression lasted for 15 seconds with one minute 
intervals between. In some animals reflex ex- 
haust-ability was examined by means of weights 
of 500 gms. imposed for ten second periods with 
ten second intervals only. Hypoxia was induced 
by low 02 mixtures (02 9%, N2 91%). There is a 
straight line relation between heart rate slowing 
and the weight used to elicit the oculo-cardiac re- 
flex. OCR positiveness is less evident during 
hypoxia than under normal conditions and the 
threshold is raised. Pulmonary ventilation always 
undergoes a decrease when the eyeballs are com- 
pressed under normal sea level breathing condi- 
tions while during hypoxia an increase is some- 
times found. 
286. Davis, H., I. Tasaki, C. A. Smith and B. H. 
Deatherage. Cochlear potentials after intracochlear in- 
jections and anoxia. Fed. Proc., 1955, 14: 35. 
287. Fernandez, C. The effect of oxygen lack on 
cochlear potentials. Ann. Otol., etc., St. Louis, 1955, 64: 
1193-1204. 
288. Fernandez, C. and R. Alzate. Modifications of 
cochlear responses by oxygen deprivation. Arch. Otolaryng., 
1959, 69: 82-94. 
289. Gisselsson, L. The effect of oxygen lack and de- 
creased blood pressure on the microphonic response of the 
cochlea. Acta oto-laryng., Stockh., 1954, 44: 101-118. 
290. Konishi, T., R. A. Butler and C. Fernandez. 
Effect of anoxia on cochlear potentials. J. acoust. Soc. 
Amer., 1961, 33: 349-356. 
291. Misrahy, G. A., E. W. Shinabarger and J. E. 
Arnold. Changes in cochlear endolymphatic oxygen avail- 
ability, action potential, and microphonics during and 
following asphyxia, hypoxia and exposure to loud sounds. 
J. acoust. Soc. Amer., 1958, 30: 701-704, LOW OXYGEN PERCENTAGES—NERVOUS SYSTEM 
292-295 
292. Misrahy, G. A., J. F. Spradley, S. Dzinovic 
and C. J. Brooks. Effects of intense sound, hypoxia and 
Kanamycin on the permeability of cochlear partitions. 
Trans. Amer. otol. Soc., 1961, 49: 125-138. 
293. Rizzo, P. and N. Cinquemani. Sul comporta- 
mento del riflesso oculo-cardiaco nel cane a livello del 
mare e in anossia. Riv. Med. aero., 1959, 22: 77-103. 
294. Wing, K. G. Effects of certain environmental 
changes upon the cochlear response of the cat. pp. 19-30 
in: Environmental effects on consciousness. Edited by Karl 
E. Schaefer, The MacMillan Company, New York, 1962, 
146 pp. 
295. Wing, K. G., J. D. Harris, A. Stover and 
J. H. Brouillette. Effects of changes in arterial oxygen 
and carbon dioxide upon cochlear microphonics. J. comp. 
Physiol. Psychol., 1953, 46: 352-357. 
2. NERVOUS SYSTEM 
Weller (334) 1959 reported the case of a 
SCUBA diver who used a cylinder accidentally 
filled with 99.5 percent nitrogen and 0.5 percent 
oxygen instead of air. He became unconscious 
after a few breaths and was rescued from the 
water about 30 seconds later. Artificial respira- 
tion by Schaefer’s method was begun and 02 given 
shortly after that. About 20 minutes after the 
accident behavior similar to that seen in re- 
covery from nitrous oxide anesthesia was ob- 
served. The level of consciousness rose to normal 
during the next 12 hours. Thirty-six hours after 
the accident the patient was discharged from the 
hospital and remained symptom free. The author 
recommended that all free divers using SCUBA 
gear breathe through the apparatus for a period 
of 60 seconds, observed by a companion, before 
entering the water. For other studies of the 
clinical aspects of cerebral anoxia, papers by 
Steigman (337) 1951 and Monrad-Krohn (332) 
1956 may be consulted. Kasamatsu (321) 1952 
has reported studies on the loss of consciousness 
induced by inhalation of nitrogen gas, and a 
paper by Malette (328) 1958 on cerebral anoxia 
resulting from hyperventilation may be con- 
sulted. 
Blocking of synaptic transmission occurs in 
anoxia. Studies on oxygen uptake of the crayfish 
Blocking of synaptic transmisison occurs in 
anoxia. Studies on oxygen uptake fo the crayfish 
cord and the effect of anoxia on synaptic trans- 
mission have been reported by Wiersma and 
Ramos (345) 1953. Synapses between the third 
root motor fibers and giant fibers were blocked 
irreversibly after 20-40 minutes in commercial 
nitrogen. This type of block was shown to be 
like that caused by alcohol. Whether the synaptic 
region is more sensitive to anoxia in this species 
than the axone remains undecided. Observations 
have been made on asphyxial and postasphyxial 
changes in electrical responses of motor neurons 
to antidromic stimulation by Lloyd {387) 1953. 
In these studies asphyxia was produced by sus- 
pending artificial respiration, ventilation being 
restored immediately after complete conduction 
block was established, thus permitting study of 
the postasphyxial state. The initial change is a 
central depolarization commencing after a latent 
period of one minute. There is a severe loss of 
somatic after-potential. Thus the dendrites ac- 
quire the ability to carry two volleys in rapid 
succession. Changes appear to reach completion 
within approximately 30 seconds. There then 
follows a period of convulsive activity. There 
is fluctuation in somatic responsitivity demon- 
strated by reciprocal amplitude changes in the 
responses of the axones and dendrites. Intermit- 
tent impulse discharge in ventral roots is seen; 
conduction block may develop slowly during the 
convulsions. There is frequently a definite in- 
stance when convulsive activity stops and rapid 
development of block begins. The recorded 
amplitude of the dendritic responses increases to 
a peak and then disappears. This peak represents 
a developing block and not an increased response. 
When fully established the asphyxial block is 
located at the junction of the initial and myeli- 
nated axone segments and is a depolarization or 
cathodal block. On restoration of ventilation a 
latency of greater than 20 seconds precedes the 
beginning of the postasphyxial change. The 
membrane potential recovers and overshoots the 
normal level within a few seconds. At a critical 
stage, motorneurons are capable of conducting 
impulses but again lapsed into block. New block 
is due to hyperpolarization and is anodal in type 
and somatic rather than axonal. Final recovery 
requires 20 minutes after the rapid transition 
from asphyxial block through normal to post- 
asphyxial, the motor neuron will upon re-asphyxi- 
ation pass through a new and completely 
asphyxial cycle. For other studies on asphyxial 
spinal cord potentials, papers by Kolmodin and 
Skoglund {325) 1959 and Van Harreveld and 
Biersteker (339) 1962 may be consulted. Van 296-305 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
Harreveld and Biersteker (340) 1964 have shown 
that oxygen lack causes an impedance increase 
of the spinal cord coinciding in time with the 
asphyxial potential which can be led off from 
the spinal gray matter against an indifferent 
electrode. After a circulatory arrest the latency 
of these changes is of the order of ten seconds. 
After ventilation of the preparation with nitro- 
gen the latency is 20-25 seconds. An asphyxial 
transport of chloride was demonstrated, passing 
into the dendrites of dorsal horn neurons and 
accompanied by a volume increase of these struc- 
tures. The electrolyte movement can account 
for the impedance increase by a loss of extra- 
cellular ions which are the main carriers of the 
measuring current. The observed ion move- 
ment, taken as an indication of depolarization, 
suggests to the authors that the asphyxial poten- 
tial is due to dendritic depolarization, the cell 
bodies and axones acting as source. This explana- 
tion is supported by the much slower decline 
of the spinal asphyxial potential, as compared 
with that of a similar potential which can be led 
off from the cerebral cortex. The difference in 
the rate of decline reflects the much slower 
asphyxial depolarization of the somas of spinal 
neurons as compared with that of cerebral nerve 
cell bodies previously observed. 
The sensitivity of a number of spinal cord 
structures to anoxia have been determined in the 
dog by Gelfan and Tarlov (314) 1953. Responses 
of neurons, as well as afferent inflow of impulses 
initiated in dorsal roots or peripheral nerves, 
were recorded from the dorsum of the cord. 
Reflex outflow in ventral roots was also recorded 
on the oscillograph or by observation of leg 
muscle responses or both. Interneuronal activity 
gradually ceases after a minimum latent period 
of about four minutes following either inhalation 
of 100 percent nitrogen or in the spinal animal, 
interruption of artificial respiration. The posi- 
tive component of the interneuronal wave com- 
plex is always the first to be abolished and the 
last to recover. Intramedullary afferent fibers 
continue to conduct impulses for some 15 minutes 
longer. The slower conducting ones being more 
resistant to anoxia. Dorsal root impulses con- 
tinue to arrive at the cord for an additional 15 
minutes and conduction in peripheral nerves is. 
retained still longer. Spinal reflexes are abruptly 
abolished after about 2y2 minutes at a time when 
some interneuronal activity is still present and 
probably relayed to higher centers. Ventral roots 
retain their ability to conduct for at least as long 
as dorsal roots. Vulnerability, degree and 
sequence in the cord, roots and peripheral nerves 
to aschemic anoxia is the same as in anoxic 
anoxia only when the ascending aorta is clamped 
in the respiring animal, thus causing complete 
ischemia of the cord. Incomplete ischemia alters 
the order and rate of abolition of function as 
well as recovery rate. A more complete report 
of differential vulnerability of spinal cord struc- 
tures to anoxia was given by Gelfan and Tarlov 
(315) in 1955. 
296. Amassian, V. E. Effect of hypoxia and ischemia 
on cortical, thalamic and midbrain reticular neurons. Fed- 
Proc., 1957,16: 3. 
297. Baumgartner, G., O. Creutzfeldt and R. Jung. 
Micro-physiology of cortical neurones in acute anoxia and 
in the retinal ischemia, pp. 5-34 in: Cerebral anoxia and 
the electroencephalogram. Edited by John Stirling Meyer 
and Henri Gastaut. Charles C. Thomas, Springfield, 1961, 
617 pp. 
298. Bellville, J. W. and W. S. Howland. Prog- 
nosis after severe hypoxia in man. Anesthesiology, 1957, 18: 
389-397. 
299. Bokonjic, N. and F. Buchthal, Postanoxic un- 
consciousness as related to clinical and EEG recovery in 
stagnant anoxia and carbon monoxide poisoning, pp. 
118-127 in: Cerebral anoxia and the electroencephalogram. 
Edited by John Stirling Meyer and Henri Gastaut. Charles 
C. Thomas, Springfield, 1961, 617 pp. 
300. Born, G. V. R., G. S. Dawes and J. C. Mott. 
Oxygen lack and autonomic nervous control of the foetal 
circulation in the lamb. J. Physiol., 1956, 134: 149-166. 
301. Cahn, J., P. Mathia, M. Herold, J. Alano, I. 
Van Holten and N. Barre. Effects of acute anoxia on 
EEG and brain metabolism in the rabbit and dog. pp. 
89-104 in: Cerebral anoxia and the electroencephalogram. 
Edited by John Stirling Meyer and Henri Gastaut. Charles 
C. Thomas, Springfield, 1961, 617 pp. 
302. Calma, I. The reflex activity of the respiratory 
center. J. Physiol., 1952, 117: 9-21. 
303. Cohen, P. J,, H. Wollman, S. C. Alexander, 
P. E. Chase, T. C. Smith, E. Melman, M. G. Behar 
and H. L. Price. Cerebral circulation, carbohydrate 
utilization, and the electroencephalogram of conscious 
man during hypoxia. Fed. Proc., 1964, 23: 521. 
304. Courville, C. B. Contributions to the study of 
cerebral anoxia. San Lucas Press, Los Angeles, 1953, 257 pp. 
305. Creutzfeldt, O., J. Bark and G. H. Fromm. 
Alterations in activity of cortical neurones during anes- 
thesia compared with hypoxia, pp. 35-45 in: Cerebral 
anoxia and the electroencephalogram. Edited by John 
Stirling Meyer and Henri Gastaut. Charles C. Thomas, 
Springfield, 1961, 617 pp. LOW OXYGEN PERCENTAGES—NERVOUS SYSTEM 
306-332 
306. Dell, P., A Hugelin and M. Bonvallet. Effects 
of hypoxia on the reticular and cortical diffuse systems, pp. 
46-58 in; Cerebral anoxia and the electroencephalogram. 
Edited by John Stirling Meyer and Henri Gastaut. Charles 
C. Thomas, Springfield, 1961, 617 pp. 
307. Fischgold, H. Discussion following presentation 
by Dr. Bokonjic and Dr. Buchthal. pp. 128-129 in: Cere- 
bral anoxia and the electroencephalogram. Edited by John 
Stirling Meyer and Henri Gastaut. Charles C. Thomas, 
Springfield, 1961, 617 pp. 
308. Floris, V., E. Failla, C. Morocutti and R. 
Nurchi. The inhalation of nitrogen in EEG activation, 
pp. 398-401 in: Cerebral anoxia and the electroencephalo- 
gram. Edited by John Stirling Meyer and Henri Gastaut. 
Charles C. Thomas, Springfield, 1961, 617 pp. 
309. Gastaut, H., F. Bostem, A. Fernandez- 
Guardiola, R. Naquet and W. Gibson. Hypoxic activa- 
tion of the EEG by nitrogen inhalation. I. Preliminary ob- 
servations in generalized epilepsy, pp. 343-354 in: Cere- 
bral anoxia and the electroencephalogram. Edited by John 
Stirling Meyer and Henri Gastaut. Charles C. Thomas, 
Springfield, 1961, 617 pp. 
310. Gastaut, H., F. Bostem, A. Fernandez- 
Guardiola, R. Naquet and W. Gibson. Hypoxic activa- 
tion of the EEG by nitrogen inhalation. II. Preliminary 
results in partial epilepsy, pp. 355-364 in: Cerebral anoxia 
and the electroencephalogram. Edited by John Stirling 
Meyer and Henri Gastaut. Charles C. Thomas, Springfield, 
1961, 617 pp. 
311. Gastaut, H., F. Bostem, A. Fernandez- 
Guardiola, R. Naquet and W. Gibson. Hypoxic activa- 
tion of the EEG by nitrogen inhalation. III. Preliminary 
results in patients suffering from cerebro-vascular disease 
(Application to the diagnosis of carotid artery insufficiency 
and atrophy of the hemisphere), pp. 365-382 in: Cerebral 
anoxia and the electroencephalogram. Edited by John 
Stirling Meyer and Henri Gastaut. Charles C. Thomas, 
Springfield, 1961,617 pp. 
312. Gastaut, H., H. Fischgold and J. S. Meyer. 
Conclusions of the international colloquium on anoxia and 
the EEG. pp. 599-617 in: Cerebral anoxia and the electro- 
encephalogram. Edited by John Stirling Meyer and Henri 
Gastaut. Charles C. Thomas, Springfield, 1961, 617 pp. 
313. Gastaut, H. and Y. Gastaut. Electroencephalo- 
graphic and clinical study of anoxic convulsions in chil- 
dren; their location within the group of infantile convul- 
sions and their differentiation from epilepsy. EEG din. 
Neurophysiol., 1958, 10: 607-620. 
314. Gelfan, S. and I. M. Tarlov. Sensitivity of 
spinal cord and its nerve roots to anoxia. Fed. Proc., 1953, 
12: 50. 
315. Gelfan, S. and I. M, Tarlov. Differential vul- 
nerability of spinal cord structures to anoxia. J. Neuro- 
physiol., 1955,18: 170-188. 
316. Grandpierre, R., C. Franck and R. Lemaire. 
Modifications of excitability of respiratory centers in the 
course of anoxemia. Consequences of modifications in the 
treatment of anoxemic syncope. J. Aviat. Med., 1952, 23: 
566-568. 
317. Grenell, R. G. Cerebral cortical potentials in 
anoxia Fed. Proc., 1952, 11: 59. 
318. Gronqvist, Y. K. J., T. H. Sheldon and A. 
Faulconer, Jr. Cerebral anoxia during anesthesia; diag- 
nostic significance of electroencephalographic changes. 
Ann. Chir. Gyn. Fenn., 1952, 41: 149-159. 
319. Holmberg, G. The electroencephalogram during 
hypoxia and hyperventilation. EEG din. Neurophysiol., 
1953, 5; 371-376. 
320. Kandel, E. R., F. J. Brinley, Jr. and W. H. 
Marshall. Some properties of the direct cortical response. 
EEG din. Neurophysiol., 1958, 10: 765. 
321. Kasamatsu, A. Studies on the loss of conscious- 
ness induced by inhalation of nitrogen gas. Psychiat. et 
Neurol, jap., 1942, 54: 575-604. 
322. Kasamatsu, A., Y. Saito, S. Endo and E. 
Koga. Single cortical unit discharge under hypoxia. 
Folia psychiat. neur. jap., 1956, Suppl. 3: 8-9. 
323. Kilmore, M. A., D. J. LaFia and H. F. Chase. 
Effects of respiratory obstruction on the brain. Fed. Proc., 
1959, 18: 410. 
324. Koga, E., Y. Saito, Y. Nakamura and Y. 
Shimazono. Patterns of cortical unit discharges evoked 
in visual cortex of cat and their variations induced with 
anoxia and anesthesia. EEG din. Neurophysiol., 1957, 
Suppl. 9: 39-40. 
325. Kolmodin, G. M. Skoglund. Influence of as- 
phyxia on membrane potential level and action potentials 
of spinal moto- and interneurons. Acta physiol, scand., 
1959, 45: 1-18. 
326. Konstantinov, V. A. Znachenie tormozhennia 
tsentral’noi nervnoi sistemy pri kislorodnom golodanii. 
The significance of the inhibition of the central nervous 
system in anoxia. Patol. Fiziol. eksp. Terap., 1960, 4: 58-62. 
327. Lloyd, D. P. C. Influence of asphyxia upon the 
responses of spinal motoneurons. J. gen. Physiol., 1953, 36: 
673-702. 
328. Malette, W. Cerebral anoxia resulting from hy- 
perventilation. Surg. Forum, 1958, 9: 208-211. 
329. Meyer, J. S. and A. G. Waltz. Arterial oxygen 
saturation and alveolar carbon dioxide during electro- 
encephalography. I. Comparison of hyperventilation and 
induced hypoxia in subjects without brain disease. Arch. 
Neurol, 1960, 2: 631-643. 
330. Meyer, J. S. and A. G. Waltz. Arterial oxygen 
saturation and alveolar carbon dioxide during electro- 
encephalography. II. Comparison of hyperventilation and 
induced hypoxia in subjects with epilepsy. Arch. Neurol., 
1960, 2: 644-656. 
331. Meyer, J. S. and A. G. Waltz. Relationship of 
cerebral anoxia to functional and electroencephalographic 
abnormality, pp. 307-328 in: Cerebral anoxia and the 
electroencephalogram. Edited by John Stirling Meyer and 
Henri Gastaut. Charles C. Thomas, Springfield, 1961, 
617 pp. 
332. Monrad-Krohn, G. H, The clinical aspect of 
cerebral anoxia. Acta psychiat. neural, scand., 1956, 31: 
87-1-5. 333-351 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
333. Naquet, R. and A. Fernandes-Guardiola. Ef- 
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cerebral activity in the cat. pp. 72-88 in: Cerebral anoxia 
and the electroencephalogram. Edited by John Stirling 
Meyer and Henri Gastaut. Charles C. Thomas, Springfield, 
1961, 617 pp. 
334. Rudomin, Z, P., D. Erlij and P. Eberstadt. 
Influencia de la hipoxia e hipoventilacibn sobre las suma- 
ci6n temporal y espacial del centro cardioinhibidor. Acta 
physiol, lat. amer., 1959, 9: 209-221. 
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and the electroencephalogram. Edited by John Stirling 
Meyer and Henri Gastaut. Charles C. Thomas, Springfield, 
1961, 617 pp. 
336. Soussen, G. and H. Chassaing. Quantitative 
evaluation of EEG changes during hypoxia, pp. 209-213 
in: Cerebral anoxia and the electroencephalogram. Edited 
by John Stirling Meyer and Henri Gastaut. Charles C. 
Thomas, Springfield, 1961, 617 pp. 
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Helv. physiol, acta, 1961, 19: 255-262. 
342. Walter, W. G. Discussion of the diagnostic value 
of the EEG manifestations provoked by hypoxia, pp. 402- 
406 in: Cerebral anoxia and the electroencephalogram. 
Edited by John Stirling Meyer and Henri Gastaut. Charles 
C. Thomas, Springfield, 1961, 617 pp. 
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Organization of central respiratory mechanisms in the 
brain stem of the cat: genesis of normal respiratory 
rhythmicity. Amer. J. Physiol., 1957, 190: 333-342. 
344. Weller, M. A. Asphyxia with nitrogen. Brit. med. 
J., 1959, 5121: 559. 
345. Wiersma, C. A. G. and J. G. Ramos. Oxygen 
uptake of crayfish cord and effect of anoxia on synaptic 
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Springfield, 1961, 617 pp. 
3. MUSCLE 
Stainsby, Cain and Otis (350) 1960, have 
shown that during progressive hypoxia, produced 
by rebreathing room air in a closed circuit, the 
oxygen consumption was constant and therefore 
independent of arterial oxygen tension until a 
tension of 60 mm. Hg was reached. Below this 
critical value the oxygen use paralleled the fall 
in arterial oxygen tension. 
347. Creese, R., N. W. Scholes and W. J. Whalen. 
Resting potentials of diaphragm muscle after prolonged 
anoxia. /. Physiol., Land., 1958, 140: 301-317. 
348. Fay, T. Effects of carbon dioxide (20%) and 
oxygen (80%) inhalations on movements and muscular 
hypertonus in athetoids. Trans. Amer. neurol. Ass., 1952, 
pp. 225-227. 
349. Langen, C. D. de. Hypoxaemia and myoglobin. 
Aeromed. Acta, 1957, 5: 355-358. 
350. Stainsby, W. N., S. M. Cain and A. B. Otis. 
Oxygen use by dog skeletal muscle during progressive hy- 
poxia. Fed. Proc., 1960, 19: 380. 
351. Vaughan, B. E. and N. Pace. Myoglobin con- 
tent of rats at sea level and chronically exposed to hy- 
poxia. Fed. Proc., 1955,14: 155. 
4. HEART AND CIRCULATION 
The diving environment holds many potential 
hazards for dangerous hypoxia. Cardiovascular 
responses are some of the most easily measured 
and can be very critical. A number of more 
general papers on cardiovascular responses to 
hypoxia may first be discussed. Johansen and 
Krog (402) 1959, have studied peripheral circula- 
tory responses to submergence asphyxia in the 
duck. The changes in peripheral blood flow 
were indicated by measuring the venous pressure 
rise in a branch of the femoral vein when the 
main venous return was occluded. Electrocardio- 
grams and arterial pressures were recorded 
simultaneously. As the animals dived there was 
an extreme bradycardia with only a small change 
in the arterial blood pressure. The slow drop in 
the arterial diastolic pressure during diving in- 
dicated a great reduction in the rate of emptying 
from the larger arteries. The peripheral blood 
flow, determined from the degree of venous re- 
turn, was likewise found to be reduced. The 
authors concluded that diving induces a com- 
pensatory shutdown of the circulation through 
the whole limb. This explains the animal’s 
ability to compensate for the extreme brady- 
cardia in the maintenance of high systemic 
arterial blood pressure, thus securing an ample 
circulation to the brain during asphyxia. Durfee 
and Sturkie (382) 1963, have pointed out that 
the initial responses of many animals to anoxia 
are transient vasoconstriction, hypertension and 
tachycardia. All of these are attributable to 
chemoreceptor stimulation and are of short dura- LOW OXYGEN PERCENTAGES—HEART AND CIRCULATION 
tion. These are followed by loss of vaso-motor 
control, vasodilatation and cardiac failure if 
severe anoxia is prolonged. These phenomena 
were studied by the authors in the domestic fowl 
by using the technique of artificial respiration 
by unidirectional airflow. Cyclic blood pressure 
changes observed in eupneic breathing were ob- 
literated by this procedure. Relative constant 
blood pressure and heart rate were maintained 
for long periods with humidified room air ad- 
ministered at ventilation rates above 350 cc./min. 
At lower rates (145 cc.-250 cc./min.) the animals 
responded by hypotension. With intact ennerva- 
tion tachycardia occurred concurrently. Both 
responses were reversed by increased ventilation 
rate and were repeatable. Similar changes in 
blood pressure occurred after bilateral vagotomy 
and after transection of the spinal cord. Results 
indicated to the authors that in the fowl the 
resting heart rate and reflex changes in heart 
rate are mediated by the vagus nerve. An initial 
hypertensive response to anoxia does not occur 
and the anoxic hypotension observed does not 
involve the central nervous system. Beard, Alex- 
ander and Howell {356) 1952, investigated the 
effects of breathing various oxygen deficient gas 
mixtures on heart rate, respiratory rate, arterial 
pressure and pulmonary arterial pressure in intact 
closed-chest narcotized dogs. Breathing mixtures 
of 8.5 percent oxygen in nitrogen for 30 minutes 
consistently produced increases in heart rate and 
systemic arterial pressure in a number of animals 
but did not significantly alter respiratory rate. 
Pulmonary arterial pressure remained essentially 
unaltered in spite of a slight and somewhat vari- 
able increase in cardiac output. Short periods 
of breathing mixtures containing approximately 
six percent oxygen consistently caused increases 
in heart rate, respiratory rate, systemic arterial 
pressure and pulmonary arterial pressure in four 
animals. Breathing oxygen free gas until apnea 
occurred produced the well-known pattern of 
changes in the systemic arterial pressure with 
some qualitatively different responses in the 
lesser circulation. Study of cardiovascular effects 
of low oxygen mixtures upon dogs has also been 
reported by Gorlin and Lewis (395) 1954. In 
these authors’ investigations, dogs were given 
mixtures containing 2.5-10 percent oxygen with 
arterial saturations ranging from 60 to below 20 
percent. With 60 percent arterial saturation 
there was an immediate systemic vasoconstriction 
and hypertension and with time, a gradually in- 
cremental pulmonary vasoconstruction. There 
were no changes in cardiac output. When the 
oxygen saturation was less than 60 percent, but 
greater than 40 percent, cardiac output and work 
done were increased. Systemic hypertension per- 
sisted, but vasodilatation occurred. With oxygen 
saturation below 40 percent cardiac work and 
cardiac output were greatly increased with in- 
creased diastolic filling. With severe hypoxia 
(saturations below 20 percent) this state could 
be maintained for varying but usually short 
periods. Since coronary blood flow could not 
supply the necessary oxygen, oxygen lack ac- 
cumulated, oxidative enzyme production eventu- 
ally decreased and cardiac contraction deterio- 
rated. A systemic hypertension was maintained. 
In studies of cardiovascular responses of fetal 
lambs in utero to hypoxia, Reynolds and Paul 
(429) 1958, have pointed out that bradycardia 
is a clinical sign of fetal distress. Experimental 
studies of these authors led to the conclusion that 
mild hypoxia may cause cardiac acceleration in 
fetal lambs. When the ewe was subjected to 13, 
10 and 6 percent oxygen in the inspired air for 
periods of 20 minutes, changes in systemic blood 
pressure and heart rate of the fetus were deter- 
mined. With 13 and 10 percent oxygen the 
fetal heart rate slowed, increased slightly or 
fluctuated. Diastolic pressure remained nearly 
constant but systolic pressure invariably in- 
creased, indicating increased cardiac output. On 
six percent oxygen the fetal heart rate slowed, 
blood pressure declined and the pulse pressure 
decreased, but not invariably so. When the fetal 
blood pressure fell, heart rate was always slowed. 
The results indicated to the authors that heart 
rate alone was not a reliable criterion of fetal 
distress. The oxygen tension associated with fall 
in blood pressure and usually heart rate was 10 
mm. Hg or less. Heart rate was affected when 
oxygen tensions were between 10 and 30 mm. 
Initial or early cardiac slowing could be inhibited 
by injection of atropine into the fetus. A further 
study on animals is that reported by Korner and 
Edwards (406) 1960, who found that mild de- 
grees of hypoxia produced an increase in ventila- 
tion in the rabbit without eliciting a detectable SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
circulatory response. The early circulatory effects 
consist of bradycardia, a rise in main arterial 
blood pressure and a fall in cardiac output, in- 
dicating a predominantly systemic vasoconstric- 
tion. The magnitude of the bradycardia and rise 
in arterial pressure were related to the fall in 
arterial saturation. Atropine or vagotomy re- 
duced or abolished the bradycardia, but greatly 
accentuated the rise in systemic blood pressure. 
Denervation of the carotid baroreceptors and 
chemoreceptors almost completely abolished the 
bradycardia and diminished the rise in systemic 
arterial blood pressure. 
For more comprehensive papers dealing with 
the effects of hypoxia upon cardiovascular func- 
tion, reference may be made to Daly and Scott 
(369) 1963; Fishman, McClement, Himmelstein 
and Cournand (388) 1952; and Russek (431) 
1962. 
Several papers on the effects of hypoxia on 
myocardial function may be discussed: the reader 
may wish to consult a review by Kardesch, Hogan- 
camp and Bing (404) 1958, dealing with the 
survival of excitability energy production and 
energy utilization of the heart under conditions 
of anoxia. Cardiac excitability is most vulnerable 
to hypoxia, energy production and energy utili- 
zation survive longer. Webb and Hollander 
(442) 1956, have studied depression of atrial 
metabolism in the rat as produced by anoxia. 
There was a reduction in contractility associated 
with changes in the electrical properties of cell 
membranes. The most marked result was a short- 
ening of action potentials due to more rapid 
repolarization rate. Changes in conduction rate 
were generally independent of potential changes 
but were related to increased latent periods in- 
duced by metabolic depression. All of these 
effects were mainly or completely reversible. In 
virtually intact animals with separately perfused 
carotid arteries, Cross, Rieben, Barron and Salis- 
bury (366) 1963, found that an arterial P0o be- 
low 40 mm. Hg (about 75 percent oxygen satura- 
tion) caused edema of the heart muscle. How- 
ever, the contractile strength and performance 
of isolated hearts were compromised severely 
when the arterial P0o had fallen below 15 mm. 
Hg (about 25 percent saturation). The acute 
circulatory crisis occurring when the arterial 
oxygen saturation fell below 80 percent was con- 
sidered not to be caused by impairment of the 
heart muscle itself but by reflexes from the 
carotid artery. Even when the oxygen saturation 
of systemic arterial blood had fallen as low as 
50 percent, this did not cause heart failure as long 
as the carotids were perfused with blood of 
normal oxygen. Severe heart failure occurred 
when the blood in the carotid arteries was moder- 
ately hypoxic (PQo below 50, saturation below 
80 percent) while the rest of the circulation was 
fully oxygenated. Studies on blood and cardiac 
muscle have been carried out by Moulder, Hager 
and Eichelberger (420) 1961, who rendered dogs 
under ether anesthesia anoxic by total occlusion 
of the vena cava for periods of 10 minutes. A 
recovery period of approximately 30 minutes in 
air was allowed immediately thereafter. Follow- 
ing the recovery period blood showed an increase 
of serum potassium concentration but no in- 
crease in potassium red cell concentration. In 
the heart muscle the phase volumes were not 
changed, indicating no edema or dehydration 
of the muscle. Potassium and magnesium con- 
centrations in the heart fibers were within normal 
limits, indicating that the architecture of the 
fibers had not changed and calcium concentra- 
tions were unmodified. Klein (405) 1961, found 
that embryonic chick myocardium anoxia had 
some, but small changes on cation movements 
in young embryos but the effects increased greatly 
at older ages. At different levels of cardiac work 
in the open-chest anesthetized dogs, Feinberg, 
Gerola and Katz (386) 1957, have examined 
the effect of increasing severity of hypoxemia on 
coronary flow and the myocardium. Coronary 
flow increased with increasing severity of hypo- 
xemia at the same level of cardiac work. Ar- 
terial oxygen saturation diminished at a greater 
rate than venous oxygen, hence the A-V oxygen 
difference decreased with hypoxemia. The A-V 
oxygen difference remained independent of car- 
diac work and rate throughout the entire range 
of arterial oxygen saturations studied. Thus, at 
any given arterial oxygen saturation coronary 
flow was found to be the principal variable in 
the calculation of oxygen consumption over a 
wide range of work and rate. Oxygen consump- 
tion at isowork levels remained relatively con- 
stant over a large range of diminished arterial 
oxygen saturation but declined slightly in the LOW OXYGEN PERCENTAGES—HEART AND CIRCULATION 
lower range. In the isolated rabbit heart Guz, 
Kurland and Freedberg (396) 1959, have studied 
the effects of acute changes in arterial oxygen 
content on coronary flow and myocardial oxygen 
consumption. Perfusion was performed with a 
60 cm. water pressure head using Ringer-Locke 
solution containing varying concentrations of 
fully saturated bovine hemoglobin in equili- 
brium with a 3 percent carbon dioxide balanced 
air mixture at atmospheric pressure. Myocardial 
oxygen consumption was estimated from coronary 
flow and A-V differences across the heart. Oxygen 
capacities of perfusing fluids varied from 16-2 
volumes percent, but were otherwise identical 
in pH, salt concentrations and viscosity. A shift 
from a high to a lower oxygen content fluid re- 
sulted in increased coronary flow; while the re- 
verse changes were followed by decreased flow. 
Myocardial oxygen consumption remained con- 
stant with an arterial oxygen content above 2 
volumes percent, but at this level fell reversibly 
by 15-30 percent. The authors concluded that 
changes in coronary resistance cannot be due to 
changes in arteriolar oxygen tension since this 
was atmospheric and constant throughout the 
experiment. Changes in oxygen tension at a more 
peripheral level in the vascular tree or the myo- 
cardium, with a reflex effect on the coronary 
resistance, or the accumulation of vasodilator 
metabolites were considered responsible for the 
changes observed in coronary flow. Increased 
coronary flow resulting from hypoxia may indeed 
be produced by release of adenosine from the 
myocardium under conditions of low myocardial 
PG., with the production of arterial dilation. 
Berne (358) 1961, has pointed out that adenosine 
is a potent coronary vasodilator which passes 
readily across cell membranes and is avidly in- 
corporated into ATP by the isolated heart. Ex- 
periments were carried out on isolated cats’ 
hearts perfused wtih Tyrode’s solution in the 
intact heart of the open-chest cat. Nucleotide 
derivatives present in perfusates or Coronary sinus 
plasma were adsorbed on charcoal, separated by 
column and paper chromatography and quan- 
titated enzymatically. Adenine nucleotides and 
adenosine were not found in perfusates or blood 
under control or experimental conditions, but 
significant amounts of inosine and hypoxanthine 
appeared in venous effluents during periods of 
myocardial hypoxia. Inosine and hypoxanthine 
are not vasodilators but are rapidly formed from 
adenosine in heart perfusates or blood. These 
findings led to the postulation that in hypoxia 
myocardial nucleotides give rise to adenosine 
which diffuses out of cardiac cells, induces vaso- 
dilatation, but is deaminated and split before 
separation from the perfusion of blood can be 
accomplished. 
Lemley and Meneely {410) 1952, have demon- 
strated that anoxia in vivo produces alterations 
in respiratory procesess of myocardial tissue as 
indicated by decreased oxygen consumption of 
tissue homogenates. These authors demonstrated 
that the oxygen uptake of homogenized myo- 
cardial tissues from rats subjected to anoxia was 
only one-half that of homogenates from normal 
animals. Oxygen consumption of homogenized 
myocardial tissue from anoxic rats could be re- 
stored to normal by supplementing with an 
aqueous extract of boiled hearts from normal 
rats. It was concluded therefore that the reduced 
oxygen consumption of myocardial tissue homo- 
genates from animals subjected to oxygen de- 
ficiency resulted from loss of inactivation of a 
heat stable rather than heat labile substance. It 
was apparently true that the decreased oxygen 
consumption of anoxic myocardial tissue was not 
due to destruction of the respiratory enzymes 
themselves, but rather to a deficit of factors es- 
sential for normal activity. Manometric estima- 
tion of lactic acid dehydrogenase gave no evi- 
dence of any difference in the activity of this 
enzyme in myocardial tissue of normal rats and 
those exposed to low oxygen tensions. A moder- 
ate reduction in both coenzyme I and cytochrome 
C was observed in the hearts of rats subjected to 
anoxia. As to the mechanism by which anoxia 
damages cardiac tissue, DeHaan and Field {371) 
1959, have suggested a hypothesis. It is suggested 
that lactic acid accumulation resulting from 
anoxia overcomes the buffer capacity of the sar- 
coplasm. The consequent increased intracellular 
acidity results in activation of proteolytic enzymes 
in the heart tissue and thus to destruction of 
apoenzyme protein and disruption of metabolic 
systems. To test this hypothesis and gain in- 
formation about the well-known resistance of 
infant tissue to hypoxia, DeHaan and Field sub- 
jected adult and infant rat heart muscle to de- SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
terminations of lactic acid production on anoxic 
buffer and proteolytic activity. Their results 
showed that a cathepsin is present in heart tissue 
which is active only at pH levels below 5 and is 
almost twice as active in adult heart as in infant 
heart. Lactic acid accumulates in both infant 
and adult anoxic hearts, but more rapidly in the 
adult heart, and in both is accompanied by in- 
tracellular proteolysis. The authors suggest that 
these findings are in accord with the hypothesis. 
Two papers concerning EKG changes follow- 
ing breathing of low oxygen mixtures may be 
cited: Busnengo {362) 1958, found a statistically 
verified increase in the QT interval in 50 healthy 
human subjects (average 22.8 years old) and 
subjected to 9.8 percent oxygen mixtures. Varma 
and Mellville {441) 1961, induced hypoxia 
in rabbits by inhalation of 10 percent oxygen 
and 90 percent nitrogen. Some of the rabbits 
were normal and the others were maintained 
on high fat cholesterol diets. During hypoxia 
greater ST-T depression ensued in the fat-fed 
animals as compared with the normal, although 
the duration of hypoxia necessary to produce the 
effect varied in both groups. In fat-fed rabbits 
ergometrine maleate induced only slight ST-T 
depression but when given after 5-10 minutes of 
hypoxia invariably resulted in marked ST-T de- 
pression. This effect appeared in 1-5 minutes 
and continued under hypoxia (30 minutes maxi- 
mum) and was readily reversed by placing the 
animal in room air or in oxygen but was not 
counteracted by glyceryltrinitrate. The slight 
ST-T depression produced by the ergometrine 
alone was readily overcome by similar doses of 
glyceryltrinitrate. Since hypoxia alone induces 
coronary dilatation, it seemed likely to the 
authors that ergometrine enhances myocardial 
anoxia by producing coronary constriction. - 
The effect of hypoxia upon the heart rate of 
the dog, with special reference to the contribu- 
tion of carotid body chemoreceptors, has been 
studied by Daly and Scott {367) 1959. The 
authors’ method permitted perfusion of the caro- 
tid bodies of anesthetized dogs with blood from 
the same animal or a donor animal. In spontane- 
ously breathing animals inhalation of seven per- 
cent oxygen in nitrogen almost invariably caused 
an increase in respiratory minute volume and an 
acceleration of the heart. If during the systemic 
hypoxia the carotid body perfusate was changed 
from hypoxic to oxygenated blood (obtained 
from a donor dog) further tachycardia occurred 
together with reduction in the respiratory minute 
volume. Restoration of hypoxic blood perfusion 
of the carotid bodies caused a slowing of the heart 
and the authors therefore concluded that the 
carotid bodies do not contribute to the produc- 
tion of the tachycardia of systemic hypoxia; on 
the contrary they antagonize it. Salisbury, Cross 
and Barron {432) 1963, have concluded that the 
acute circulatory crisis which supervenes when 
men or animals are suddenly exposed to arterial 
oxygen tensions below 45 mm. Hg is not repro- 
ducible unless blood having a P0o below 45 mm. 
Hg reaches the common carotid arteries. These 
studies of cardiovascular effects of hypoxia were 
carried out on slightly anesthetized dogs by 
methods which kept that arterial blood pH con- 
stant. In some studies isolated hearts were 
used. Artificial perfusion of the carotid artery, 
but not of other vascular territories with moder- 
ately hypoxic blood, caused a reflex bradycardia 
with simultaneous constriction of systemic arter- 
ies and veins and acute severe heart failure. The 
authors therefore conclude that hypoxia causes 
acute circulatory failure through reflex action. 
Changes of extracranial circulation during hy- 
poxia in young and older healthy men have been 
studied by Simonson {433) 1960. The author 
obtained impedance plethysmographic pulse trac- 
ings from the forehead before and in the tenth 
minute after breathing ten percent oxygen, 90 
percent nitrogen mixtures. Amplitude and in- 
terval changes were compared in 42 young 
healthy men of 18 to 30 years of age and in 58 
older men between 55 and 65 years of age with 
a drop of arterial oxygen saturation exceeding 
ten percent. There was no significant change of 
the peak amplitude and height of the cicrotic 
notch in the young men during hypoxia, in 
contrast to a highly significant increase in the 
older subjects. In both groups there was found a 
statistically highly significant acceleration of the 
heart rate and a lengthening of the relative peak 
time which was more pronounced in the older 
men. Greater changes of extracranial circulation 
in the older men during hypoxia, particularly in 
the amplitudes, may be interpreted as a loss 
of stability in the peripheral circulation during LOW OXYGEN PERCENTAGES—HEART AND CIRCULATION 
stress. For tables on heart rate and respiratory 
changes associated with reduced P0„, the mono- 
graph by Van Liere and Stickney (440) 1963, 
should be consulted. Van Liere, Northup and 
Baugh (439) 1962, in a study on rats, found that 
intermittent hypoxia resulted in a relatively 
greater degree of hypertrophy of the right 
ventricle than resulted from exercise. The 
authors suggested that this effect was probably 
related to pulmonary hypertension known to exist 
during hypoxic states. 
The regulation of cardiac output in hypoxia 
has been studied in dogs by Gomori, Kovach, 
Takacs, Foldi, Szabo, Nagy, Wiltner and Kallay 
(393) 1960. In this study cardiac output and 
total peripheral resistance were measured in 21 
dogs maintained on cortisone during hypoxia. 
Six adrenalectomized dogs were maintained on 
cortisone and desoxycorticosterone acetate during 
hypoxia. Twenty-two dogs with isolated cephalic 
hypoxia, and 6 dogs with isolated hypoxia of the 
trunk were studied. The studies showed that 
cardiac output is increased in arterial hypoxia, an 
increase not influenced by adrenalectomy. Cardiac 
output increase was induced by hypoxia of the 
trunk but not that of the head. The authors 
provide as the most probable explanation that 
hypoxia gives rise to local vasodilatation. It 
was not possible to demonstrate the existence of 
a regulatory mechanism of a neural or endocrine 
nature. 
The effects of hypoxia upon carotid body re- 
flexes have been studied by Neil (423) 1956, and 
others. Neil has described a technique whereby 
the carotid bodies can be supplied by carotid 
blood flow or by oxygenated Ringer-Locke solu- 
tion from a reservoir. In cats spontaneously 
breathing five percent oxygen in nitrogen, anoxic 
tachycardia develops. This tachycardia was not 
found to be affected if perfusion of Ringer- 
Locke solution replaces the carotid blood flow 
through the carotid bodies, although reflex 
hyperpnoea and hypotension result in these con- 
ditions. Restoration of the flow of anoxic blood 
through the carotid bodies after perfusing the 
glomus tissues with oxygenated Ringer-Locke in 
cats spontaneously breathing low oxygen mix- 
tures causes hyperpnea, hypertension and sub- 
sequent bradycardia. The author considered that 
the bradycardia is vagal in origin and appears 
to be secondary to post-perfusion hyperpnea. It 
is not seen following perfusion of oxygenated 
Ringer-Locke artificially ventilated with five 
percent oxygen in nitrogen mixtures. Neil con- 
cludes that the carotid chemoreceptor reflexes 
make no contribution to the tachycardia of sys- 
temic anoixa. According to Neil and Joels (424) 
1963, the local tissue tension of oxygen of the 
glomus cells must represent a balance between 
the oxygen flow to the tissue and the oxygen 
usage by the tissue. Therefore if oxygen usage 
is low in the glomus and oxygen in the blood is 
low, it may not signal the hypoxia. Systemic 
hypotension caused by hemorrhage was found to 
lead to an enormous discharge of chemoreceptor 
impulses—not even dispelled by administration 
of pure oxygen in the breathing mixture. Res- 
toration of blood pressure by transfusion abol- 
ished the chemoreceptor discharge. It is con- 
sidered possible by the author that the stagnant 
anoxia under these circumstances led to an ac- 
cumulation of metabolites causing excitation of 
chemosensory endings. The authors stress the 
fact that the chemoreceptors are particularly re- 
sponsive to a combination of tissue hypoxia plus 
hypercapnia and that variations in blood flow 
through the glomus are of potential importance 
in modifying the chemoreceptor respones to any 
gas mixture. The vigorous oxygen usage at the 
carotid body is masked by the fantastically high 
blood flow which the glomus ordinarily enjoys. 
Daly and Scott (368) 1962, have studied the 
contribution of the carotid baroreceptors and 
chemoreceptors in maintaining blood pressure 
during systemic hypoxia. In the anesthetized dog 
systemic hypoxia usually causes a rise of blood 
pressure and this response has been attributed to 
stimulation of chemoreceptors because when the 
test is repeated after cutting the carotid sinus 
and aortic nerves, a considerable fall in pressure 
occurs. However, this procedure also denervated 
the baroreceptors and this may therefore influ- 
ence the response. The authors devised a tech- 
nique for perfusion of the carotid sinuses and 
bodies which permitted a physiological denerva- 
tion of the baroreceptors and chemoreceptors in- 
dependent! yof each other. Dogs were anesthe- 
tized with either a mixture of morphine, chora- 
lose and urethane, or Nembutal, and both vagus SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
nerves were cut to denervate the aortic arch. 
With innervated carotid sinuses and bodies, in- 
halation of 7-12 percent oxygen in nitrogen 
caused a rise, a small fall or no change in blood 
pressure. After denervation of the carotid baro- 
receptors and chemoreceptors hypoxia caused an 
average fall in pressure of 43 percent. If, how- 
ever, only the chemoreceptors were denervated, 
with the carotid sinus baroreceptors remaining 
innervated, the fall of pressure was less than half 
this amount. When the baroreceptors were de- 
nervated the chemoreceptors being normally 
functional, systemic hypoxia caused either an in- 
crease of a decrease in blood pressure. These 
results indicated to the authors that the fall in 
blood pressure in response to systemic hypoxia 
after division of the sino-aortic nerve is in part 
the result of denervation of the baroreceptors. 
Nevertheless the chemoreceptors appear to play 
an important part in maintaining the blood 
pressure in hypoxia. In an attempt to quantitate 
chemoreceptors activity, Hornbein, Griffo and 
Roos (400) 1961, studied the relationship of 
chemoreceptor function to acute and chronic 
hypoxia on the basis of the magnitude of electri- 
cal activity of carotid chemoreceptors in response 
to changes in arterial PQo and (-f-) -P0„. At 
a Pa0-) of 40mm. Hg, changes in blood gas 
tenisons were not reflected in electrical activity 
of the chemoreceptors. Asphyxia elicited the 
maximum chemoreceptor response. When respi- 
ration was resumed nerve activity dropped to a 
low level for ten seconds, rose somewhat and then 
assumed a plateau. This was the transient re- 
sponse. The steady state response was as follows; 
with ventilation, pH and PCOo kept constant, 
chemoreceptor nerve activity was slight at a 
Pa0>) of 100 mm. Hg, increased rapidly with de- 
creasing Pac0„, and plateaued at a Pa0() of 30-40 
mm. Hg. Extremely low PaQo often decreased 
activity. When (H-f-) -PCOo was increased with 
hypoxia, chemoreceptor activity was potentiated. 
Chemoreceptor activity in the carotid body of the 
cat has been explored in isolated preparations by 
Eyzaguirre and Lewin (384) 1960. Action poten- 
tials were recorded from the Hering nerve which 
had been excised together with the sinus and 
carotid body and mounted in a flow chamber per- 
fused with 4 ml. per minute Ringer-Locke solu- 
tion at 37 °C., a pH of 7.4 and equilibrated with 
varying concentrations of oxygen in nitrogen 
(from 10-100 percent). The adventitia of the 
sinus had been removed to eliminate pressore- 
ceptor discharges. Chemoreceptor discharges 
were present in 100 percent oxygen and increased 
as oxygen was reduced. With oxygen reduction 
(50-20 percent) afferent frequency rose to a peak 
in several seconds followed by a slight decline. 
With a given p02 (e.g. or for example 50 per- 
cent) in the perfusion fluid, increases in tempera- 
ture above 38 °C. markedly increased chemore- 
ceptor discharge initially, followed by a decrease. 
In intact cats under gallamine and controlled 
ventilation progressive reduction in inhaled 
oxygen from 100 down to 10 percent increased 
chemoreceptor frequency. With constant oxygen 
inhalation of 6 percent carbon dioxide increased 
chemoreceptor impulses, and small changes in 
ventilation or blood pressure greatly changed 
chemoreceptor activity. 
A number of papers, now to be discussed, deal 
with the effects of hypoxia in animals and in 
man upon pulmonary circulation. Hiirlimann 
and Wiggers (401) 1953, examined the effects 
of progressive anoxia on the hemodynamic 
changes in the pulmonary circuit by the rhythmic 
positive pressure re-breather method on bar- 
bitalized dogs with open thoraxes. Calibrated 
optical manometers of adequate sensitivity and 
frequency were used for simultaneous recordings 
of pressures from the aorta, the pulmonary artery 
and the left atrium. When the air in the spirom- 
eter was reduced to ranges of 10-12 percent 
oxygen, the following changes occurred simul- 
taneously: there was increase in aortic and pul- 
monary pressure and pulse pressure. Configura- 
tion of the pressure pulses indicated augmented 
stroke volumes of both ventricles and the left 
atrial pressure was relatively unaffected. Two 
groups of supplementary experiments in which 
the blood flow through one entire lung or several 
lobes was recorded by the electromagnetic flow- 
meter revealed pulmonary blood flow to be in- 
creased concurrently with, but not prior to, 
elevation of pulmonary and arterial pressure 
when air mixtures were reduced to 10-12 percent 
oxygen. Changes in pulmonary arterial resist- 
ance, calculated both by using elevated pul- 
monary pressure and pressure equivalents to con- 
trol preceeding anoxia, indicated that while some LOW OXYGEN PERCENTAGES—HEART AND CIRCULATION 
variation occurs even in the same experiment, 
resistance is usually increased. The nature and 
the locus of the resistance and direct or indirect 
agents operative were not disclosed in the 
authors’ study. Consideration of all the data 
indicated to the authors that while increase in 
pulmonary arterial resistance may contribute to 
rise in pulmonary arterial pressure, increased 
output of the right ventricle was the major 
factor. Kuida, Lange, Brown and Hecht (407) 
1960, pointed out that the pulmonary vascular re- 
sponse to acute anoxia has been studied in several 
species with inconsistent results. The occurrence 
of spontaneous hypertension in calves grazing at 
high altitude provided a base for specifically 
examining the response in the bovine species. 
Using cardiac catheterization, dye dilution tech- 
niques and endotracheal intubation, measure- 
ments were made of pulmonary and carotid 
arterial pressures and oxygen saturation, as well 
as cardiac index, and calculated pulmonary vas- 
cular resistance before and after exposure to gas 
mixtures of 10-16 percent oxygen in air for 5-20 
minutes. Sixteen anoxic periods were produced 
in 13 unanesthetized normal calves with a fall 
in oxygen saturation from control levels of 87-91 
percent, averaging 33 percent ± 18. Four 
animals developed saturations less than 50 per- 
cent of the controls. Pulmonary arterial pressure 
inrceased in 14 of 15 instances, averaging 12 mm. 
Hg or ± 52 of controls. Cardiac index rose in 
eight and fell in three animals; the average 
change being -f-13 percent ±23. Pulmonary 
vascular resistance increased in ten and remained 
unchanged in two, with an average percentage 
increase over control data of -)-65 percent —77. 
This study indicates that in calves acute anoxia 
is generally associated with an increase in pul- 
monary vascular tone. By means of chronically 
implanted vinyl catheters Thilenius, Hoffer and 
Fitzgerald (437) 1961, recorded pressures in the 
aorta, the pulmonary artery and the left atrium, 
as well as the intrapleural space (by capsule), 
together with cardiac output by dye dilution tech- 
nique every two minutes. These studies were 
carried out in unanesthetized, unsedated, trained 
dogs for one hour during breathing of air and 
low oxygen mixtures (6-10 percent) via chronic 
tracheostomy. 
In nearly all of 35 experiments on six animals 
there were striking responses to hypoxia, consist- 
ing of a marked rise in pulmonary arterial 
pressure (up to 100 percent) in cardiac output 
(up to 80 percent) in pulmonary vascular re- 
sistance (up to 200 percent) and of a significant 
fall in left atrial pressure (up to 75 percent). 
These changes were not maintained throughout 
hypoxia. The pulmonary ventricular resistance 
usually returned towards normal first, followed 
by pulmonary arterial pressure, the cardiac out- 
put usually remaining elevated. The time 
sequence of these events varied in different ani- 
mals. Effects of the same magnitude, as in 
hypoxia, accompanied restlessness caused by 
stress, but fluctuated markedly, were of shorter 
duration, and could largely be eliminated by 
providing quiet surroundings and by avoiding 
prolonged experiments. The dilating action of 
anoxia on pulmonary vessels has been examined 
by Aviado, Cerletti, Alanis, Bulle and Schmidt 
(385) 1952. Dogs under morphine and chlora- 
lose, subjected to spontaneous inhalation of 5 or 
10 percent oxygen responded as follows: the 
pressure of the cannulated lobar artery increased 
by about 30 mm. of H20 with an arterial blood 
saturation of 60 percent. This pulmonary hyper- 
tension was caused chiefly by an anoxic rise in 
pulmonary flow. When the flow to the lung on 
one one side was kept constant by pumping the 
mixed venous blood from the right auricle to 
the pulmonary artery, the corresponding pul- 
monary arterial pressure decreased while the 
pressure of the other side supplied by its own 
heart increased during anoxia. An isolated per- 
fused lung showed vasodilatation when the 
oxygen content of either the ventilating air or 
the perfusing blood was reduced. The observed 
pulmonary hypertension in anoxic intact dogs 
was the combination of this local vasodilatation 
and of the increased pulmonary flow. The latter 
was elicited by the anoxic stimulation of carotid 
and aortic chemoreceptors and by the liberation 
of epinephrine. The net result of these responses 
was reflected in the radioactive measurement of 
erythrocytes tagged with P32 by means of a beta 
counter applied to the surface of the lung. This 
estimation of capillary blood volume in the lungs 
was observed to increase by about 10 percent 
during anoxia. All of these results in dogs were SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
found to be different from the reports that low 
oxygen content constricts the perfused pulmonary 
vessels of cats. Aviado, Cerletti, Alanis, Bulle 
and Schmidt {354) 1952, also commented on the 
rise in pulmonary arterial pressure observed in 
anesthetized dogs inhaling 5-10 percent oxygen 
and explained this by increased pulmonary flow 
through carotid and aortic chemoreflexes and 
epinephrine liberation. A total dilation is 
seen when the innervated lung is perfused with 
blood of low oxygen saturation or when venti- 
lated with low oxygen mixtures. In the dog 
estimations of the volume of the blood in the 
lungs (by P32) in animals breathing spontane- 
ously indicated that there was an increased 
amount of blood during anoxia. There was no 
evidence of any constrictor action of anoxia on 
the pulmonary vessels in this species. Gorlin and 
Lewis (394) 1952, and Lewis and Gorlin (411) 
1952 have reported on the effects of graded hy- 
poxemia on the pulmonary circulation of the dog. 
In their studies of severe hypoxemia they used 
dogs anesthetized with morphine-chloralose-ure- 
thane and subjected them to breathing mixtures 
containing 2.5-10 percent oxygen on several oc- 
casions. Arterial oxygen saturation varied from 
8-55 percent depending upon the inspired oxygen 
percentage. The mean pulmonary arterial and 
left atrial pressures were measured with indwell- 
ing catheters via the jugular vein and femoral 
artery respectively. Integrated cardiac output was 
measured by the Fick principle, using the Bene- 
dict-Roth method for oxygen consumption. Pul- 
monary vascular resistance was calculated. Obser- 
vations were made at intervals varying from 3.5 
minutes to 8 hours after induction of hypoxia. 
When the arterial oxygen saturation was above 
15 and less than 55 percent, the cardiac output 
increased from 40 to 300 percent above control 
values. Oxygen consumption remained un- 
changed. Mean pulmonary arterial pressure rose 
moderately while left arterial pressure remained 
the same or decreased. Pulmonary vascular resist- 
ance remained unchanged or actually decreased, 
regardless of the time duration of hypoxia. 
When arterial saturation was less than 15 percent 
left atrial pressure rose. In some observations 
cardiac output increased and in others remained 
the same or decreased. Pulmonary arterial pres- 
sure increased uniformity. No changes in pulmo- 
nary vascular resistance were observed. In these 
experiments arterial saturation was so low that 
tissue oxygen demands could be met only by in- 
crease in blood flow. Under these circumstances, 
although there was a wide variation in the de- 
gree and duration of the severe hypoxemia and 
in the cardiac response to hypoxemia, no altera- 
tions in pulmonary vascular resistance were 
demonstrable. Under conditions of moderate 
hypoxemia the authors studied dogs anesthetized 
also with morphine-chloralose-urethane anes- 
thesia. These animals were subjected to breath- 
ing mixtures containing 10 percent oxygen. The 
duration of hypoxia varied from 20 minutes to 8 
hours during which several sets of observations 
were made. Arterial oxygen saturation varied 
from 55-79 percent. Pulmonary arterial and left 
atrial pressures were recorded through indwelling 
catheters and the cardiac output was also meas- 
ured by the Fick principle. Pulmonary vascular 
resistance was calculated from the Poisseuille 
equation. The cardiac output did not vary signif- 
icantly fro mcontrol values regardless of the 
duration of hypoxemia. Oxygen consumption 
and arterio-venous oxygen differences did not 
change appreciably. Pulmonary arterial pressure 
rose somewhat and left atrial pressure fell so 
that the pulmonary pressure gradient increased. 
Pulmonary vascular resistance showed a statis- 
tically significant increase. The degree of increase 
varied directly with the duration of hypoxemia. 
A dog exposed to hypoxia for seven hours with 
a rise in pulmonary vascular resistance was then 
allowed to breathe room air for three hours and 
subsequent observations showed a fall in pulmo- 
nary vascular resistance. When the hypoxia is 
mild the authors’ experiments are similar to those 
of others who have observed pulmonary vasocon- 
striction, however, previous experiments of this 
group of authors have shown that when hypoxia 
is so severe that cardiac output must rise to main- 
tain tissue oxygen supply, the pulmonary vascular 
resistance does not rise. The former may be due 
to a local effect of hypoxia on the lungs, while 
hypoxia of the body as a whole appears to reverse 
the pulmonary vasoconstriction. Lewis, Gorlin 
and Houssay (412) 1953, found that moderate 
hypoxia produces an increase of pulmonary vascu- 
lar resistance with an unchanged cardiac output. 
Since this occurs in the isolated perfused lung LOW OXYGEN PERCENTAGES—HEART AND CIRCULATION 
and with unilateral as well as bilateral hypoxia, it 
seems to be due to the local action of low oxygen 
tensions. Severe hypoxia produced three types 
of response in spontaneously breathing dogs that 
hyperventilated during hypoxia: a) maintained 
oxygen consumption, increased cardiac output, 
unchanged left atrial pressure and unchanged 
pulmonary vascular resistance; b) maintained 
oxygen consumption, increased cardiac output 
and left atrial pressure and unchanged pulmonary 
vascular resistance; c) decreased oxygen con- 
sumption and cardiac output, increased left atrial 
pressure and unchanged or increased pulmonary 
vascular resistance. The influence of hyperven- 
tilation was investigated in a number of dogs 
with open chests, ventilated at a constant volume 
by a Starling “Ideal” pump. The pressure gradi- 
ent was measured from pulmonary arterial and 
left atrial catheters. Fick cardiac outputs were 
determined. During severe hypoxia, produced 
by breathing 5 percent oxygen, the oxygen con- 
sumption fell lower than in those with spontane- 
ous respiration, but three types of circulatory re- 
sponses were again seen: a) increased cardiac out- 
put, unchanged left atrial pressure and pulmo- 
nary vascular resistance; b) increased cardiac 
output and left atrial pressure, with unchanged 
pulmonary vascular resistance; c) decreased 
cardiac output, increased left atrial pressure, 
and a tendency to increased pulmonary vascular 
resistance in several experiments and a distinct 
rise in one experiment. This indicated to the 
authors that ventilation per se had no influence 
on the pattern of response at any given level of 
arterial oxygen saturation, including the pulmo- 
nary vascular resistance. 
The pulmonary effects of moderate and severe 
hypoxia in the dog were examined by Stroud 
and Conn ('436) 1954. In these experiments 
pentobarbital anesthetized dogs were used in a 
redetermination of the effects of hypoxia on the 
pulmonary vascular bed uisng a radioactive iso- 
tope dilution technique for measuring cardiac 
output instead of the Fick procedure. Experi- 
ments were divided into a control period, fol- 
lowed by 5-12 minutes during which 10 percent 
oxygen was breathed by the dogs, a 5-12 minute 
recovery period, and a 5-12 minute period with 
5 percent oxygen. With 10 percent oxygen 
(arterial oxygen saturation of 79 percent) a small 
mean increase in cardiac output was accom- 
panied by significant increase in pulmonary 
arterial pressure and resistance. With 5 percent 
oxygen (arterial oxygen saturation of 46 percent) 
there was a small increment in cardiac output 
with a small additional rise in pulmonary pres- 
sure and resistance. These “small rises” are prob- 
ably not at all significant according to the au- 
thors. In all dogs there was a small average 
increase in systemic arterial pressure with no 
change in systemic resistance. In addition to 
expected ventilatory responses, there were signif- 
icant increases in circulation time and ‘pulmo- 
nary’ blood volume. No arterial-venous shunting 
was evident from the isotope dilution curves 
which should reveal a bypass of 4 percent or more 
of the cardiac output. Nahas {421) 1956, con- 
ducted a study, the purpose of which was to 
investigate the influence of moderate hypoxia 
on the pulmonary circulation, in dogs after 
eliminating the ventilatory response to hypoxia 
and its secondary effects on circulation. After 
pentothal anesthesia, dogs were fitted with cathe- 
ters in the pulmonary artery and vein, the right 
atrium and the descending aorta. Respiratory 
arrest was induced by curare-like compounds and 
mechanical breathing instituted. Photokymo- 
graphic records of pressures and cardiac output 
determinations were made during artificial respi- 
ration and at the end of 90-second periods of 
‘apneic oxygenation’ and ‘apneic hypoxia’. ‘Ap- 
neic oxygenation’ was considered to be a period 
of respiratory arrest following denitrogenation 
of the animal and during which the trachea is 
connected to a reservoir containing 100 percent 
oxygen. ‘Apneic hypoxia’ was defined as a period 
of respiratory arrest following ventilation with 
room air. After 90 seconds of ‘apneic oxygena- 
tion’ mean pulmonary arterial and venous pres- 
sure and the pressure gradient between the pul- 
monary artery and the vein were significantly 
lowered. The mean femoral artery pressure was 
significantly increased. Cardiac output and cal- 
culated pulmonary and peripheral resistance 
were not changed. During ‘apneic hypoxia’ 
(with arterial oxygen saturation in the vicinity 
of 50 percent) mean pulmonary arterial, pul- 
monary venous, femoral arterial pressure and 
pressure gradient between the pulmonary artery 
and vein were significantly increased. Calculated SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
pulmonary and peripheral resistance rose signifi- 
cantly from 2.5 to 3.6 and from 45 to 54 mm. Hg 
respectively. These increases occurred in the 
presence of a significant fall in heart rate and in 
right atrial pressure, while cardiac output did 
not change significantly. Duke (378) 1954, found 
that inhalation of gas mixtures containing 5-10 
percent oxygen in nitrogen in cats caused a rise 
of left pulmonary arterial pressure in the living 
animal during perfusion of the left lung at con- 
stant volume inflow with blood from the right 
auricle. This response was not found to be de- 
pendent on changes in left auricular pressure, 
tidal air or systemic blood pressure. It was 
similar in duration and latency to that occurring 
in isolated lungs perfused at constant volume in- 
flow. Perfusion of isolated lungs with partially 
deoxygenated blood did not cause a rise of pul- 
monary arterial pressure if the lungs were respir- 
ing air. Ventilation of the lungs with nitrogen 
during perfusion with partially deoxygenated 
blood did cause a rise of pulmonary arterial 
pressure. Inhalation of nitrogen by isolated per- 
fused lungs caused a similar rise of inflow pres- 
sure, whether perfusion was made through the 
pulmonary artery or through the left auricle. 
Duke (379) 1957, found in isolated cats’ lungs 
perfused through the pulmonary artery with the 
animal’s own heparinized blood at constant 
volume inflow, that ventilation of the lungs with 
nitrogen instead of air produces a rise in pul- 
monary arterial pressure and a fall of left auricu- 
lar pressure. The pressor responses to nitrogen 
occurred in preparations made from animals in 
which the lungs were chronically denervated. 
There was no evidence of a circulating vasocon- 
strictor substance on perfusing the cat’s de- 
nervated hind limb with blood which has been 
partially deoxygenated in the lungs. Pulmonary 
pressor responses to hypoxia were found in iso- 
lated perfused dogs’ lungs and in anesthetized 
dogs with left lung perfusion. In the anesthe- 
tized cat with left lung perfusion the increase of 
left pulmonary arterial pressure in response to 
inhalation of 5 percent oxygen in nitrogen was 
not prevented by removal of both adrenal glands. 
In normal human subjects, Goldring, Turino, 
Cohen, Jameson and Fishman (392) 1960, meas- 
ured the concentrations of epinephrine and nor- 
epinephrine in the arterial and mixed venous 
blood during three experimental circumstances: 
1) breathing of 11 percent oxygen (acute hy- 
poxia) ; 2) the infusion of norepinephrine; and 
3) hypoxia plus infusion of norepinephrine. The 
measurements included cardiac output (by the 
direct Fick method), central blood volume (by 
dye dilution), and blood pressures (pulmonary 
and brachial artery as well as pulmonary wedge 
pressures). Results indicated: 1) the absence of 
abnormally high quantities of epinephrine or 
norepinephrine during acute hypoxia; 2) the 
need for a ten-fold increase in circulating epine- 
phrine or norepinephrine to duplicate the pul- 
monary arterial hypertension of acute hypoxia; 
and 3) unchanged wedge pressures during hy- 
poxia and increased wedge pressures during nore- 
pinephrine infusion. In other subjects injection 
of norepinephrine into the pulmonary artery 
during open thoracotomy showed that a rise in 
left atrial pressure anteceded the rise in pul- 
monary arterial pressure. The pulmonary pressor 
response to acute hypoxia in man was not found 
to be related to circulating levels of epinephrine 
and norepinephrine. Bergofsky, Lehr, Tuller, 
Rigatto and Fishman (357) 1961, found that 
neither intravenous injection of 0.4 molar sodium 
bicarbonate nor 0.3 molar tris-hydroxymethyl- 
aminomethane (300 ml. over 25 minutes) modi- 
fied the pulmonary arterial pressor response to 
hypoxia in man (12 percent oxygen) indicat- 
ing that neither extracellular or intracellular 
acidosis appeared to play a role in the pressor 
response. In anesthetized dogs breathing 5 per- 
cent oxygen and infused with lactic acid or hydro- 
chloric acid, there was a consistent rise in pul- 
monary arterial pressure during acute acidosis 
with no change in pulmonary blood flow or left 
ventricular blood pressure, suggesting pulmonary 
vasoconstriction. Increased pulmonary vascular 
resistance in relation to decreased blood pH was 
the same regardless of the method used to induce 
the acidosis, suggesting that the hydrogen ion 
rather than the associated anion is responsible 
for the pulmonary vascular response. In human 
subjects, Bishop, Harris and Segal (359) 1961, 
found that hypoxia caused a rise in pulmonary 
arterial pressure and an increase in cardiac out- 
put with no change in pulmonary wedge pressure. 
After producing postganglionic sympathetic 
blockade with guanethidine (10-27 mg. intraven- LOW OXYGEN PERCENTAGES—HEART AND CIRCULATION 
ously) hypoxia caused a greater average rise in 
puljnonary arterial pressure and a lesser increase 
in cardiac output and no change in pulmonary 
wedge pressure. These findings suggested to the 
authors that the effects of hypoxia on human 
pulmonary circulation are not mediated by the 
sympathetic nerves since the differences before 
and after post-ganglionic sympathetic blockade 
were slight. The experiments suggested that the 
sympathetic system plays no substantial role in 
governing the normal tone of the pulmonary 
vessels at rest. 
Peters and Roos {426) 1952, have investigated 
the effect of unilateral nitrogen breathing upon 
pulmonary blood flow in the dog. Blood flow 
through each lung was determined by the Fick 
principle both during bilateral oxygen breath- 
ing and during unilateral nitrogen breathing, the 
other lung receiving oxygen. Vascular resistance 
of each lung was calculated from mean pul- 
monary arterial pressure and blood flow. In all 
but a few animals there occurred a reduction of 
16-68 percent of the original fraction of total 
flow to the nitrogen lung. The maximal effect 
was already present after 25 minutes, and was 
promptly reversible on return to bilateral oxygen 
breathing. Resistance in the nitrogen lung was 
increased by factors of 1.3 to 4.5 while in the 
oxygen lung it remained essentially unchanged. 
Lanari-Zubiaur {408) 1957, and Lanari-Zubiaur 
and Hamilton (409) 1958, also in experiments 
on the dog, found no consistent flow change 
in the anoxic lung and concluded that the 
physiologic consequence of increased pulmo- 
nary resistance to flow due to anoxic breathing 
is of doubtful meaning in the dog. In human 
subjects, Himmelstein, Harris, Fritts and Cour- 
nand (399) 1958, administered 5 percent oxygen 
to one lung and found that there was a reduction 
in the fraction of total flow perfusing the hypoxic 
lung in 3 of 5 normal subjects. In the fourth the 
results were inconclusive, and in the fifth subject 
pulmonary hyperventilation developed with no 
change in the partition of flow. Fishman, Him- 
melstein and Cournand {387) 1955, found that 
a sharp reduction in the oxygen content of in- 
spired gas elicited pulmonary hypertension in 
man. In an attempt to analyze further the 
mechanisms underlying this pressor response they 
confined the hypoxic stimulus (8-12 percent 
oxygen) to one lung, while the other lung 
breathed a gas mixture enriched with 25-33 per- 
cent oxygen. The blood flow was measured by 
the Fick principle through both lungs as well as 
through the hyperoxic one. Flow through the 
hypoxic lung was obtained by difference. In 
seven subjects in whom the arterial blood 
oxyhemoglobin during unilateral hypoxia did 
not fall below 85 percent, the total minute ven- 
tilation and gas exchange for both lungs re- 
mained unchanged. During this period, regard- 
less of whether total blood flow stayed the same 
or increased slightly, the proportion of blood 
flow through each lung was unaltered. Since 
in these experiments the hypoxic stimulus was 
unilaterally applied to one lung and to its post- 
arteriolar vascular bed, failure to demonstrate 
any shift of blood from the hypoxic lung sug- 
gested that these pulmonary segments do not 
participate in the pressor response to acute 
hypoxia. In 1955 Cournand {364) concluded that 
the most likely cause of the increase in pul- 
monary arterial pressure, observed while breath- 
ing the hypoxic inspiratory mixture in man, 
was the association of an increased pulmonary 
blood flow together with some other hemo- 
dynamic factor related to severe arterial hy- 
poxemia (probably displacement of blood from 
the systemic to the pulmonary vascular bed). 
Doyle, Wilson and Warren {377) 1952, have 
shown differences in pulmonary vascular re- 
sponses to short term hypoxia in normal subjects 
and those with various cardiopulmonary abnor- 
malities. The normal group with oxygen satura 
tion about 75 percent showed considerable in- 
crease in pulmonary vascular resistance. The 
abnormal group with similar oxygen saturation 
showed smaller increases in pulmonary vascular 
resistance and little or no change in cardiac out- 
put. Pulmonary capillary pressure was unaltered 
in both groups. In contrast to the normal group, 
low oxygen caused severe dyspnea in the ab- 
normal group. There was no evidence of altera- 
tions of pulmonary blood volume during hypoxia 
in either group. Fritts, Harris, Clauss, Odell and 
Cournand {391) 1958, infused acetylcholine into 
the pulmonary artery of normal human subjects 
under normal and hypoxic conditions. This drug 
caused a fall in pulmonary arterial pressure 
which was more evident after hypoxia had pro- SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
duced pulmonary hypertension. The fall in pres- 
sure was not associated with a fall in cardiac 
output and there was no chagne in the pul- 
monary wedge pressure, heart rate, systemic blood 
pressure or central blood volume. It was con- 
cluded that acetylcholine causes pulmonary vaso- 
dilatation. Apparently the effect is enhanced in 
the presence of an increased vascular tone. 
The effect of hypoxia upon blood flow in vari- 
ous areas has been studied experimentally by a 
number of investigators. Rota and Rossanigo 
(430) 1958, found that in human subjects ex- 
posed to 7.7 percent oxygen there was an increase 
in flow index (average increase of 33 percent) 
as measured by rheographic recordings from the 
wrist and calf. Fairchild, Crawford and Guyton 
(385) 1959, studied the relation of blood flow 
through the hind limb of a dog to the gaseous 
content of the blood. In one series of dogs the 
oxygen saturation of the blood flowing through 
the leg was gradually changed by adding various 
amounts of venous blood to arterial blood. As 
the oxygen saturation decreased, the blood flow 
increased, slowly at first and then progressively 
more rapidly as the oxygen levels fell lower and 
lower. Even though the oxygen saturation in 
most experiments was decreased to 30 percent, 
the total oxygen transported to the tissues each 
minute decreased only to 75 percent of the con- 
trol value, showing that a definite compensatory 
mechanism exists with an efficiency of about 65 
percent, for preventing tissue hypoxemia. In an- 
other group of animals the oxygen saturation 
of the blood was maintained constant while the 
dogs were allowed to breathe 20 percent carbon 
dioxide for an hour. By checking the blood flow 
every 10 minutes it was found that there was no 
increase in blood flow, but rather in three of the 
animals a decrease to the extent of 35 percent of 
the control blood flow, and in the remainng two 
no change. These studies indicate that oxygen 
deficiency might well be one of the causes of 
reactive hyperemia but that excess carbon dioxide 
is probably not involved. 
As Carrier and Guyton (363) 1963, have 
pointed out, one of the most perplexing problems 
in the circulation field has been the mechanism 
by which blood flow is regulated in response to 
tissue metabolic needs. One thesis that has been 
advanced is that low oxygen levels in the tissues 
cause the arterioles to dilate, thus allowing more 
flow and a consequent increased nutritive supply 
to the area. To investigate this problem, the 
authors took isolated segments of very small 
arteries, 0.5-1.0 mm. in diameter and 1.0 cm. in 
length, from the dog and using various perfusion 
techniques found a direct correlation between 
oxygen level in the perfusion blood and resist- 
ance. For example, in a series of six vessels per- 
fuesd under constant pressure of 100 mm. Hg, 
they obtained a graded response to stepwise in- 
crease of p02 from 30 mm. Hg to 100 mm. Hg. 
In this series the individual vessels gave up to 
143.0 percent increase in resistance, the average 
response being 72.9 percent. Changes in re- 
sistance of this magnitude can maintain the sup- 
ply of oxygen to a tissue very nearly constant 
despite striking changes in oxygen supply. The 
authors therefore concluded that tissue oxygen 
pressure may well be the major stimulus for local 
autoregulation of blood flow in response to an 
area’s needs. Comparable results have been re- 
ported by Black and Roddie {360) 1958, in nor- 
mal human subjects who breathed 5-10 percent 
oxygen in nitrogen for 2-6 minutes. Forearm 
blood flow, as measured by venous occlusion 
plethysmography, was increased along with ven- 
tilation and heart rate. Studies by McGiff and 
Aviado (416) 1961, in dogs subjected to hypoxia 
(5 percent oxygen) indicate that the femoral 
bed’s resistance is reduced significantly more than 
the reduction in renal vascular resistance. These 
results suggest that the femoral bed is more re- 
active than the renal following baroreceptor or 
chemoreceptor induced changes. In contrast, the 
renal bed appeared to be more susceptible to 
hormonal stimuli. Hypoxia caused a greater in- 
crease in femoral resistance than in renal 
resistance. 
Dil, Litwin and Aviado (475) 1960, showed 
that vasoconstriction in the hind limb of the 
anesthetized dog occurred during inhalation of 
5 percent oxygen while vasodilatation occurred 
during reoxygenation. Both of the responses were 
eliminated by a transection of the cervical spinal 
cord. Denervation of chemoreceptors or com- 
bined adrenalectomy and blockade of sympa- 
thetic nerves by bretylium reduced the vasocon- 
strictor but not the vasodilator response. The 
responsible vasodilator nerves are partially LOW OXYGEN PERCENTAGES—HEART AND CIRCULATION 
352-359 
blocked by either hexamethonium or atropine, 
but are resistant to sympathetic blocking drugs. 
Human subjects breathing air, 11.5 and 7.5 per- 
cent oxygen in nitrogen, were shown by Eckstein 
and Horsley (383) 1960, to have insignificant 
changes in venous tone with 11.5 percent oxygen, 
but active venous constriction with the 7.5 per- 
cent oxygen mixture. This constriction was 
sufficient to displace small amounts of blood 
from the extremity. The change in venous tone 
could not be attributed to mild hyperventilation 
which occurred with low oxygen breathing. 
The influence of acute hypoxia on peripheral 
and central venous pressures have been studied 
by Nahas and Josse (422) 1954, in the non- 
narcotized dog trained to breathe 8 percent 
oxygen in nitrogen. Two series of experiments 
were carried out. In the first, pressures were 
measured in superior and inferior vena cavae 
through cardiac catheters. In addition intra- 
thoracic pressure was simultaneously recorded 
through an intrapleural cannula. In the second 
series of experiments, small vein and veinule 
pressures were measured in the dog’s foreleg. In 
both series, control measurements were recorded 
at one minute intervals with the animal breath- 
ing room air. After that control period the 
animal was switched to the lower oxygen mixture 
for ten minutes and measurements were taken at 
one minute intervals. The animal was then re- 
turned to room air and similar measurements 
taken during the recovery period at one minute 
intervals. Vena caval pressures were corrected 
with reference to the simultaneously recorded 
intrapleural pressures. During exposure to 8 per- 
cent oxygen there was no change in the effective 
pressures in the superior or inferior vena cavae. 
Under similar conditions there was a 2.3 mm. Hg 
and a 1.4 mm. Hg increase in the veinule and 
small vein pressure respectively in the dog’s fore- 
legs. The pressure gradient between the veinule 
and vein was similarly observed to rise during 
hypoxia. 
At critical levels of hypoxemia there is edema 
formation in perfused rat hind limbs. Di Pas- 
quale and Schiller (376) 1951, found in hind 
limbs perfused with blood of low colloidal con- 
tent that 5.5-9.4 volumes percent oxygen content 
of the perfusate were adequate in maintaining 
capillary function with a minimum rate of edema 
formation not varying appreciably with flow. 
Hind limbs perfused with 0.88-2.60 volumes 
percent oxygen exhibited augmented edema for- 
mation which increased with increased flow. The 
critical hypoxemia level affecting capillary per- 
meability is believed to lie between 2.6 and 5.5 
volumes percent oxygen content. Hendley and 
Schiller {398) 1954, perfused isolated rat hind 
legs with buffered Krebs-Ringer solution con- 
taining washed red cells and 0.33 percent gelatin. 
Edema formation with mild hypoxia (5-10 per- 
cent oxygen content) was slight, but with severe 
hypoxia (0-5 volumes percent) an elevated rate 
of edema formation in excess of predicted forma- 
tion from associated hemodynamic changes in- 
dicated increased capillary permeability. Distri- 
bution of perfused intravascular colloidal dye sug- 
gested decreased vascular resistance and increased 
permeability of capillaries to colloidal particles 
occurring in skeletal muscle vasculature during 
severe hypoxemia. 
For clinical reports of the action of hypoxia 
and recommendations for treatment, papers by 
Miles (419) 1957, and Francheteau (389) 1954, 
should be consulted. 
352. Amyes, E. W., D. V. Mahony and R. D. Good- 
man. Adams-Stokes syndrome and cerebral anoxia; occur- 
rence in a pregnant woman without previous history of 
heart disease. J. nerv. merit. Dis., 1953, 117: 334-340. 
353. Arborelius, M., Jr., G. Lundin, L. Svanberg 
and J. G. Defares. Influence of unilateral hypoxia on 
blood flow through the lungs in man in lateral position. 
/. appl. Physiol., I960, 15: 595-597. 
354. Aviado, D. M., Jr., A. Cerletti, J. Alanis, P. 
H. Bulle and C. F. Schmidt. Effects of anoxia on pres- 
sure, resistance and blood (P32) volume of pulmonary 
vessels. Amer. J. Physiol., 1952, 169: 460-470. 
355. Aviado, D. M., Jr., A. Cerletti, J. Alanis, 
P. H. Bulle and C. F. Schmidt. Dilating action of 
anoxia on pulmonary vessels. Fed. Proc., 1952, 11: 6. 
356. Beard, E. F., J. D, Alexander and T. W. 
Howell. Effects of various degrees of hypoxia on pul- 
monary and systemic hemodynamics in narcotized dogs. 
J. Aviat. Med., 1952, 23: 569-576; 625. 
357. Bergofsky, E. H., D. E. Lehr, M. A. Tuller, 
M. Rigatto and A. P. Fishman. The effects of acute 
alkalosis and acidosis on the pulmonary circulation Ann. 
N. Acad. Sci., 1961, 92: 627-631. 
358. Berne, R. M. Nucleotide degradation in the hy- 
poxic heart and its possible relation to regulation of coro- 
nary blood flow. Fed. Proc., 1961, 20: 101. 
359. Bishop, J. M., P. Harris and N. Segel. The 
influence of guanethidine on the response of the human 
circulation to hypoxia. J. Physiol., 1961, 156: 40P. 360-393 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
360. Black, J. E, and I. C. Roddie. The mechanism 
of the changes in forearm vascular resistance during 
hypoxia. J. Physiol., Lond., 1958,143: 226-235. 
361. Burchell, H. B., H. J. C. Swan and E. H. 
Wood. Demonstration of differential effects on pulmo- 
nary and systemic arterial pressure by variation in oxygen 
content of inspired air in patients with ductus arteriosus 
and pulmonary hypertension. Circulation, 1953, 8: 681- 
694. 
362. Busnengo, E. L’intervallo qt in soggetti sani 
durante ipossia provocata. Riv. Med. aero., 1958, 21: 305- 
319. 
363. Carrier, O., Jr. and A. C. Guyton. Role of tis- 
sue oxygen in local autoregulation of blood flow. Circula- 
tion, 1963, 28: 701. 
364. Cournand, A. The mysterious influence of uni- 
lateral pulmonary hypoxia upon the circulation in man. 
Acta cardiol., Brux., 1955, 10: 429-441. 
365. Cournand, A., A. Mitchell and A. P. Fishman. 
Applicability of direct Fick method to measurement of 
pulmonary blood flow during induced acute hypoxia. Fed. 
Proc., 1954, 13: 31. 
366. Cross, C. E., P. A. Rieben, C. I. Barron and 
P. F. Salisbury. Effects of arterial hypoxia on the heart 
and circulation: an integrative study. Amer. J. Physiol., 
1963, 205: 963-970. 
367. Daly, M. de B. and M. J. Scott. The effect of 
hypoxia on the heart rate of the dog with special reference 
to the contribution of the carotid body chemoreceptors. 
J. Physiol., 1959, 145: 440-446. 
368. Daly, M. de B. and M. J. Scott. The contribu- 
tion of the carotid baroreceptors and chemoreceptors to 
the maintenance of blood pressure during systemic hypoxia 
in vagotomized dogs. XXII Intern. Congr. physiol. Sci., 
Leiden, 1962, 2: Abstr. 173. 
369. Daly, M. de B. and M. J. Scott. The effects of 
changes in respiration on the cardiovascular responses to 
stimulation of the carotid body chemoreceptors. pp. 149- 
162 in: The regulation of human respiration. Edited by 
D. J. C. Cunningham and B. B. Lloyd. Blackwell Scientific 
Publications, Oxford, 1963, 591 pp. 
370. De Bersaques, J. Concerning the influence of 
different concentrations of oxygen in the cerebral ventricles 
on the respiratory and the vasomotor centers. Arch. int. 
Physiol., 1953, 61: 82-83. 
371. DeHaan, R. L. and J. Field. Mechanism of car- 
diac damage in anoxia. Amer. J. Physiol., 1959, 197: 449- 
453. 
372. Dejours, P. Control of respiration by arterial 
chemoreceptors. Ann. N.Y. Acad. Sci., 1963, 109: 682-695. 
373. Dejours, P., J. C. Mithoefer and A. Teillac. 
Essai de mise en evidence de chemorecepteurs veineux de 
ventilation. J. Physiol. Path, gen., 1955, 47: 160-163. 
374. Denny-Brown, D. and J. S. Meyer. The cere- 
bral collateral circulation. 2. Production of cerebral in- 
farction by ischemic anoxia and its reversibility in early 
stages. Neurology, 1957, 7: 567-579. 
375. Dil, A., J. Litwin and D. M. Aviado. Effects of 
anoxia on vascular resistance of hindlimb. Fed. Proc., 1960, 
19: 93. 
376. Di Pasquale, E. L. and A. A. Schiller. Effect 
of hypoxemia on edema formation in perfused isolated rat 
hind limb. Proc. Soc. exp. Biol., N.Y., 1951, 78: 567-571. 
377. Doyle, J. T., J. S. Wilson and J. V. Warren. 
The pulmonary vascular responses to short-term hypoxia 
in human subjects. Circulation, 1952, 5: 263-270. 
378. Duke, H. N. The site of action of anoxia on the 
pulmonary blood vessels of the cat. J. Physiol., 1954, 125: 
373-382. 
379. Duke, H. N. Observations on the effects of hy- 
poxia on the pulmonary vascular bed. J. Physiol., 1957, 
135: 45-51. 
380. Duke, H. N. and E. M. Killick. Pulmonary 
vasomotor responses of isolated perfused cat lungs to 
anoxia. J. Physiol., 1952,117: 303-316. 
381. Duke, H. N., J. R. Magalhaes and W. Rouse. 
Lung blood volume changes to hypoxia in isolated per- 
fused cats’ lungs. J. Physiol., 1961, 155: 37P-38P. 
382. Durfee, W. K. and P. D. Sturkie. Some cardio- 
vascualr responses to anoxia in the fowl. Fed. Proc., 1963, 
22: 182. 
383. Eckstein, J. W. and A. W. Horsley. Effects of 
hypoxia on peripheral venous tone in man. J. Lab. din. 
Med., 1960, 56: 847-853. 
384. Eyzaguirre, C. and J. Lewin. Chemoreceptor 
activity in the carotid body of cat. Physiologist, 1960, 3: 
54. 
385. Fairchild, H. M., D. G. Crawford and A. C. 
Guyton. Oxygen deficiency as a cause of reactive hype- 
remia. Fed. Proc., 1959,18: 43. 
386. Feinberg, H., A. Gerola and L. N. Katz. Effect 
of hypoxemia on coronary flow and cardiac oxygen con- 
sumption. Fed. Proc., 1957, 16: 36. 
387. Fishman, A. P., A. Himmelstein and A. Cour- 
nand. Pulmonary blood flow through each lung during 
acute unilateral hypoxia in man. Fed. Proc., 1955, 14: 48. 
388. Fishman, A. P., J. McClement, A. Himmel- 
stein and A. Cournand. Effects of acute anoxia on the 
circulation and respiration in patients with chronic pul- 
monary disease studied during the "steady state.” J. din. 
Invest., 1952, 31: 770-781. 
389. Francheteau, M. G. A propos d’un cas d’asphyxie 
mortelle en atmosphere constitute d’azote presque pur. 
C. R. Soc. Biol., Paris, 1954, 15: 381-383. 
390. Fritts, H. W., Jr., E. Braunwald, A. P. Fish- 
man and A. Cournand. Influence of induced hypoxia on 
central blood volume of normal man. Fed. Proc., 1956, 15: 
68. 
391. Fritts, H. W., Jr., P. Harris, R. H. Clauss, J. 
E. Odell and A. Cournand. The effect of acetylcholine 
on the human pulmonary circulation under normal and 
hypoxic conditions. J. din. Invest., 1958, 37: 99-110. 
392. Goldring, R. M., G. M. Turino, G. Cohen, 
A. G. Jameson and A. P. Fishman. Catecholamines in 
the pulmonary hypertension of acute hypoxia. Fed. Proc., 
1960, 19: 98. 
393. Gomori, P., A. G. B. Kovach, L. Takacs, M. 
Foldi, G. Szabo, Z. Nagy, W. Wiltner and K. Kallay. 
The regulation of cardiac output in hypoxia. Acuta med. 
Hung., 1960, 16: 93-98. LOW OXYGEN PERCENTAGES—HEART AND CIRCULATION 
394-429 
394. Gorlin, R. and B. M. Lewis. Effects of graded 
hypoxemia on the pulmonary circulation of the dog: 
severe hypoxemia. Fed. Proc., 1952, 11: 57. 
395. Gorlin, R. and B. M. Lewis. Circulatory adjust- 
ments to hypoxia in dogs. J. appl. Physiol, 1954, 7: ISO- 
185. 
396. Guz, A., G. S. Kurland and A. S. Freedberg. 
The relation of arterial 02 content to coronary flow and 
myocardial Oa consumption. Fed. Proc., 1959, 18: 62. 
397. Hall, P. W., III. Effects of anoxia on postarteri- 
olar pulmonary vascular resistance. Circ. Res., 1953, 1: 
238-241. 
398. Hendley, E. D. and A. A. Schiller. Change in 
capillary permeability during hypoxemic perfusion of rat 
hindlegs. Amer. J. Physiol, 1954, 179: 216-220. 
399. Himmelstein, A., P. Harris, H. W. Fritts, Jr. 
and A. Cournand. Effect of severe unilateral hypoxia on 
the partition of pulmonary blood flow in man. J. thorac. 
Surg., 1958. 36: 369-379. 
400. Hornbein, T. F., Z. J. Griffo and A. Roos. 
Quantitation of chemoreceptor activity: interrelation of 
hypoxia and hypercapnia. J. Neurophysiol, 1961, 24 : 561- 
568. 
401. Hiirlimann, A. and C. J. Wiggers. The effects 
of progressive general anoxia on the pulmonary circulation. 
Circ. Res., 1953, 1: 230-237. 
402. Johansen, K. and J. Krog. Peripheral circula- 
tory response to submersion asphyxia in the duck. Acta 
physiol, scand., 1959, 46: 194-200. 
403. Kampffmeyer, H. Kreislaufverhalten unter 
Sauerstoffmangelbelastung. Dtsch. Versuchanst. Luftf., 
Rept. 127, May 1960, 25 pp. 
404. Kardesch, M., C. E. Hogancamp and R. J. 
Bing. The survival of excitability, energy production and 
energy utilization of the heart. Circulation, 1958, 18: 935- 
945. 
405. Klein, R. L. Effects of ouabain, hypothermia and 
anoxia on cation fluexes in embryonic chick heart. Fed. 
Proc., 1961, 20: 128. 
406. Korner, P. I. and A. W. T. Edwards. The 
immediate effects of acute hypoxia on the heart rate, 
arterial pressure, cardiac output and ventilation of the 
unanaesthetized rabbit. Quart. J. exp. Physiol, 1960, 45: 
113-122. 
407. Kuida, H., R. L. Lange, A. M. Brown and 
H. H. Hecht. The effect of acute anoxia on pulmonary 
hemodynamics of the calf. Fed. Proc., 1960,19: 97. 
408. Lanari-Zubiaur, F. J. B. Effect of unilateral 
anoxia on pulmonary circulation. Fed. Proc., 1957, 16: 76. 
409. Lanari-Zubiaur, F. J. B. and W. F. Hamilton. 
Effect of unilateral anoxia on pulmonary circulation. Circ. 
Res., 1958, 6: 289-293. 
410. Lemley, J. M. and G. R. Meneely. Effects of 
anoxia on metabolism of myocardial tissue. Amer. J. 
Physiol, 1952, 169: 66-73. 
411. Lewis, B. M. and R. Gorlin. Effects of graded 
hypoxemia on the pulmonary circulation of the dog. II. 
Moderate hypoxemia. Fed. Proc., 1952, 11: 93. 
412. Lewis, B. M., R. Gorlin and H. E. J. Hous- 
say. Influence of ventilation on pulmonary vascular re- 
sponse to hypoxia. Fed. Proc., 1953, 12: 87. 
413. Loughead, W. M. and D. S. Kahn. Circumven- 
tion of anoxia during arrest of cerebral circulation for 
intracranial surgery. J. Neurosurg., 1955, 12: 226-239. 
414. Lucas, B. G. B. Some observations on anoxia. 
Anesthesiology, 1951, 12: 762-766. 
415. Madarasz, I., F. Obal and E. Csanda. On the 
mechanism of the hypoxia-induced augmentation of the 
intracranial pressure. XXII Inter. Congr. physiol. Sci., 
Leiden. 1962, 2: Abstr. 147. 
416. McGiff, J. C. and D. M. Aviado. Femoral and 
renal flow and resistance changes. Fed. Proc., 1961, 20: 109. 
417. Meyer, J. S. Studies of cerebral circulation in 
brain injury. IV. Ischemia and hypoxemia on the brain 
stem and respiratory center. EEG din. Neurophysiol., 1957, 
9: 83-100. 
418. Meyer, J. S. and J. Hunter. Effects of hypo- 
thermia on local blood flow and metabolism during cere- 
bral ischemia and hypoxia. J. Neurosurg., 1957, 14: 210- 
227. 
419. Miles, S. Unconsciousness in underwater swim- 
mers. Gt. Brit MRC, RNPRC, UPS. Kept. R.N.P. 57/901, 
U.P.S. 172, October 1957, 17 pp. 
420. Moulder, P. V., D. Hager and L. Eichelber- 
ger. Effect of anoxic arrest on water and electrolyte con- 
tent of blood and cardiac muscle. Fed. Proc., 1961, 20: 127. 
421. Nahas, G. G. Influence of acute hypoxia on pul- 
monary circulation of dogs during apnea. Fed. Proc., 1956, 
15: 134. 
422. Nahas, G. G. and J. W. Josse. Influence of acute 
hypoxia on peripheral and central venous pressures in the 
non-narcotized dog. Fed. Proc., 1954, 13: 103. 
423. Neil, E. Influence of the carotid chemoceptor re- 
flexes on the heart rate in systemic anoxia. Arch. int. 
Pharmacodyn., 1956, 105: 477-488. 
424. Neil, E. and N. Joels. The carotid glomus sen- 
sory mechanism, pp. 163-171 in: The regulation of human 
respiration. Edited by D. J. C. Cunningham and B. B. 
Lloyd, Blackwell Scientific Publications, Oxford, 1963, 
591 pp. 
425. Neugebauer, W. Hypoxamische Hirnschadigung 
im Einmanntorpedo. Arztl. Wschr., 1959, 14: 91-93. 
426. Peters, R. M. and A. Roos. Effect of unilateral 
nitrogen breathing upon pulmonary blood flow. Amer. J. 
Physiol, 1952, 171: 250-255. 
427. Rahn, H. and W. O. Fenn. Studies in respiratory 
physiology. Second series. Chemistry, mechanics, and circu- 
lation of the lung. Wright Air Development Center, Aero 
Medical Laboratory, Dayton, Ohio. WADC Tech. Kept. 
55-357, Nov. 1955, 438 pp. 
428. Record, R. G. and T. McKeown. The effect of 
oxygen deficiency on closure of the ductus arteriosus in the 
newborn guinea pig. Clin. Sci., 1955,14: 711-714. 
429. Reynolds, S. R. M. and W. M. Paul. Cardio- 
vascular responses of fetal lamb in utero to hypoxia. Fed. 
Proc., 1958, 17: 132. 430-445 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
430. Rota, P. and F. Rossanigo. Influenza dell’anos- 
sia an°ssica sul comportamento del reogramma degli arti. 
Riv. Med. aero., 1958, 21: 506-513. 
431. Russek, M. Histotoxic hypoxia. XXII Inter. 
Congr. Physiol. Sci., Leiden, 1962, Vol. I, Part I, pp. 87-92. 
432. Salisbury, P. F., C. E. Cross and C, I, Barron. 
Circulatory effects of arterial hypoxia. Aerospace Med., 
1963, 34: 935-938. 
433. Simonson, E. Changes of extracranial circulation 
during hypoxia in young and older healthy men. Fed. 
Proc., 1960,19: 92. 
434. Stewart, W, K. Acute anoxia. Proc. roy. Soc., 
1954,143: 5-8. 
435. Stone, D. J., A. Schwartz, W. Newman, J. A. 
Feltman and F. J. Lovelock. Precipitation by pulmo- 
nary infection of acute anoxia, cardiac failure and respira- 
tory acidosis in chronic pulmonary disease. Amer. J. Med., 
1953, 14: 14-22. 
436. Stroud, R. C. and H. L. Conn, Jr. Pulmonary 
effects of moderate and severe hypoxia in the dog. Amer. 
J. Physiol, 1954,179: 119-122. 
437. Thilenius, O. G., P. B. Hoffer and R. S. 
Fitzgerald. Response of the pulmonary vascular bed of 
unanesthetized resting dogs to hypoxia. Fed. Proc., 1961, 
20: 104. 
438. Turner, J., C. J. Lambertsen, S. G. Owen, 
H. Wendel, H. Chiodi and P. Linaweaver. Inadequacy 
of cerebral venous pOz as an index of mean brain tissue 
oxygen tension: Influence of changes in arterial p02 upon 
cerebral venous and calculated mean capillary oxygen 
tension at fixed reduced arterial pC02. Fed. Proc., 1958, 
17: 165. 
439. Van Liere, E. J., D. W. Northup and B. L. 
Baugh. Differences in cardiac hypertrophy in exercise and 
in hypoxia. XXII Inter. Congr. physiol. Sci., Leiden. 1962, 
2: Abstr. 346. 
440. Van Liere, E. J. and J. C. Stickney. Hypoxia. 
University of Chicago Press, Chicago, 1963, 381 pp. 
441. Varma, D. R. and K. I. Melville. Cardiovas- 
cular responses to ergometrine and hypoxia in normal and 
fat-fed rabbits. Fed. Proc., 1961, 20: 89. 
442. Webb, J. L. and P. B. Hollander. Metabolic 
aspects of the relationship between the contractility and 
membrane potentials of the rat atrium. Circ. Res., 1956, 
4: 618-626. 
443. Whalen, W. J. and J. Fangman. Effects of low 
p02 on isolated heart muscle. Fed. Proc., 1963, 22: 345. 
444. Witzleb, E. W, The excitation of chemorecep- 
tors by arterial hypoxia and hypercapnia, pp. 173-182 in: 
The regulation of human respiration. Edited by D. J. C. 
Cunningham and B. B. Lloyd, Blackwell Scientific Publi- 
cations, Oxford, 1963, 591 pp. 
445. Witzleb, E., H. Bartels, H. Budde and M. 
Mochizucki. Der Einfiuss des arteriellen 02-Drucks auf 
die chemoreceptorischen Aktionspotentiale im Carotis- 
sinusnerven. Pfliig. Arch. ges. Physiol, 1955, 261: 211-218. 
5. BLOOD 
It is well known that conditions of hypoxia, if 
severe enough, serve as a stimulus for erythro- 
poiesis. Short exposures may have no effect as 
demonstrated by Pannacciulli, Fumagalli and 
Mezzano (459) 1958. In studies of normal stu- 
dents, they observed that hypoxia (8.6-11.2 per- 
cent oxygen) at sea level for five minutes caused 
no immediate blood changes. There was some- 
times a moderate inconsistent reticulocytosis. 
Lambersten, Bunce, Drabkin and Schmidt {457) 
1952 examined the relationship of oxygen tension 
to hemoglobin oxygen saturation in the arterial 
blood of normal men. In their experiments the 
relationship of percentage hemoglobin saturation 
p02, pC02 and pH were determined in normal 
subjects by analysis of arterial blood collected 
during inhalation of gas mixtures from 21-4 
percent oxygen in nitrogen. The percent oxygen 
saturation was measured by both spectrophoto- 
metric and manometric methods in an attempt 
to evaluate apparent discrepancies between re- 
sults obtained by previous investigators using one 
or the other technique. No difference in dissocia- 
tion characteristics of oxyhemoglobin were de- 
tected in the subjects tested. Simultaneous meas- 
urements of percent oxygen saturation and p02 
indicated closer agreement with in vitro dissocia- 
tion curves of other workers. 
It is well known that infants have hemoglobin 
with a higher affinity for oxygen than that of the 
adult, and that hypoxia tolerances are greater 
in proportion to affinity. Barker {448) 1956 re- 
ported modifications of hemoglobin affinity and 
hypoxia tolerance in infant and adult rats fol- 
lowing exposure to low and high oxygen tension. 
High affinity hemoglobins with high tolerances 
were found in some adult rats and mice after 
exposure to low p02. Further studies indicated 
that high affinity hemoglobin appeared within 
24-72 hours in all adult rats exposed for two 
hours daily to a p02 of 50 mm. Hg, affinities often 
exceeding the mean for newborn rats if exposures 
were continued for a week. Exposures to a p02 
of 27 mm. of Hg for 10 minutes, or of 90 mm. of 
Hg for 20 hours, were less effective. Polycythemia 
does not necessarily accompany the shift. If high 
affinity hemoglobin, which normally occurs only 
in infants, is a consequence of intrauterine 
hypoxia, its production might be inhibited by 
high p02. In newborn rats exposed to 50 per- 
cent oxygen for 72-96 hours, the disappearance 
of high affinity hemoglobin and of hypoxia toler- LOW OXYGEN PERCENTAGES—BLOOD 
ance was greatly accelerated, and the infants were 
more anemic than controls. Although affinities 
did not increase on removal to air, they did on 
exposure to low p02. Since no high affinity 
hemoglobin was found during recovery from 
severe hemorrhage, its appearance was considered 
probably not related to a specific phase of erythro- 
cyte development. Splenectomized rats readily 
produce high affinity hemoglobin on exposure to 
low p02. No abnormalities attributable to the 
presence of high affinity hemoglobin were ob- 
served. In 1960, Kalff (455) determined hemoglo- 
bin values and erythrocyte counts in a group of 
50 pilots before and during exposure to hypoxia 
in a low-pressure chamber. A significant increase 
in the erythrocyte count and hemoglobin values 
over the initial values was noted in all subjects 
after three minutes exposure to anoxia. Measure- 
ments taken in the sixth minute showed a signifi- 
cant drop of these values from the initial level. A 
third measurement taken during the ninth 
minute of exposure to anoxia showed a tendency 
towards a slight increase in the hemoglobin and 
erythrocyte values. Some individuals showed 
more labile erythrocyte and hemoglobin values 
with wider fluctuation ranges than did others. 
For a consideration of hypoxia as a stimulus 
for erythropoiesis, papers by Grant and Root 
(453) 1952, and Root (461) 1954, should be con- 
sulted. Hypoxia is one of the commonest condi- 
tions associated with erythropoiesis and one of 
the most convenient means of experimenatlly pro- 
ducing erythroid stimulation. However, hypoxia 
does not act directly on the bone marrow accord- 
ing to Grant and Root. These authors consider 
that there is no convincing evidence that erythro- 
poiesis is controlled directly by the nervous sys- 
tem or by hormones of any single endocrine 
gland. Presumably lack of oxygen at some un- 
known region in the organism activates processes 
which release an erythroid stimulating agent. 
Effects of hypoxia on leucocyte formation have 
been studied by Altschul, MacFayden and White- 
head (447) 1957. In these authors’ experiments 
mice of the leukemia strain, AKR (Jax), were 
exposed to prenatal hypoxia by subjecting the 
mothers to a single period of five hours at at- 
mospheric pressure with oxygen percentages 
equivalent to conditions of 25,000 feet above sea 
level. This exposure was usually carried out dur- 
ing the 8-14 days of gestation. The offspring 
were studied for the appearance of leukemia. 
The offspring which had been subjected to this 
prenatal hypoxia revealed inhibition of leucocy- 
tosis. This inhibition was more pronounced and 
highly significant in males, but was not significant 
in females. It was concluded that prenatal 
hypoxia was the responsible factor in the inhibi- 
tion in the males. Hypoxia experienced during 
the seventh to tenth days of gestation was more 
effective than that undergone later, but the 
difference was not highly significant. 
A number of reports on the effects of hypoxia 
on plasma may now be considered. Battaglia, 
Meschia, Hellegers and Barron (449) 1958 found 
in experiments on adult rabbits, sheep, goats, 
lambs, and fetal sheep and goats that the osmotic 
pressure of the plasma invariably rose as a con- 
sequence of acute severe hypoxia. The findings 
of the authors were interpreted as suggesting that 
severe acute hypoxia causes a rise in intracellular 
osmotic pressure as a manifestation of a shift 
from aerobic to anaerobic metabolism. Intra- 
cellular rise in osmotic pressure would result 
in movement of water out of extracellular fluids 
and thus increase their effective electrolyte con- 
centration. Transcapillary passage of plasma 
proteins may occur in hypoxia, but Schiller and 
Wool (462) 1952 showed in intact rats that 
grades of hypoxemia corresponding to a 
p02 of 25 mm. Hg or an oxyhemoglobin satura- 
tion of 30 percent do not produce hemodynamic 
or permeability changes which significantly alter 
transcapillary passage of plasma proteins. The 
concentration of H ions, carbonic acid and bi- 
carbonate in the blood and blood plasma before 
and during and after acute hypoxia has been 
measured by Kunamann (456) 1960 in human 
subjects. Hypoxic hyperventilation after five to 
six minutes at an atmospheric pressure of 287 
mm. Hg was observed to produce a decrease 
in pC02, an increase in bicarbonate concentra- 
tion and an increase in the pH of the blood. 
During extended hypoxia the bicarbonate concen- 
tration and pH were decreased by the compensa- 
tory reaction of the kidneys in excreting bicarbo- 
nate ions while retaining hydrogen ions. Full 
recovery of the blood electrolyte balance was 
still incomplete one hour after return to normal 
atmospheric pressure. 446-465 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
Recently heparin has been recommended as 
an adjunctive agent in recompression treatment 
and as a prophylactic agent in decompression 
sickness as well as a drug in the specific treat- 
ment of decompression sickness. Its efficacy for 
these purposes is still under debate and the 
mechanism of action has not been delineated. 
For this reason the effects of heparin on the ac- 
tions of acute hypoxia on blood chemistry are 
of interest. Otey (458) 1953 points out that the 
anticoagulant effect of heparin has been thor- 
oughly investigated, but with the exception of 
its lipid clearing effect, little work has been done 
on its possible metabolic functions. Otey’s study 
was carried out to see what effect heparin may 
have on metabolism during hypoxia. In his 
studies anesthetized dogs were given heparin in 
doses of 5-10 mg./Kg. body weight. Following 
a control period of breathing room air, arterial 
oxygen tension was reduced to about 40 mm. Hg 
and held at this level for about two hours. Ar- 
terial blood samples were taken at ten minute 
intervals for analyses. Lactate and pyruvate con- 
centrations did not change significantly from 
control values throughout the duration of the 
hypoxia. In a control group of animals receiving 
no heparin lactate and pyruvate both rose 
initially with pyruvate leveling off while lactate 
continued to rise. In a group of heparinized 
animals, protamine sulfate was given to antago- 
nize the heparin while the hypoxia continued. In 
these animals, which had shown no increase in 
lactate or pyruvate prior to the administration 
of protamine, now showed the expected increase 
in lactate. Otey concluded from these experi- 
ments that heparin prevents either the produc- 
tion or release of lactate during hypoxia. 
446. Altland, P. D. Effect of hypoxia on turtle reticu- 
locyte formula. Fed. Proc., 1954, 13: 2. 
447. Altschul, R., D. J. MacFayden and W. F. 
Whitehead. Effect of prenatal hypoxia on spontaneous 
leukemia in mice. Cancer Res., 1957, 17: 222-226. 
448. Barker, J. N. Modifications of hemoglobin affin- 
ity and hypoxia tolerance in infant and adult rats follow- 
ing exposure to low and high 02 tensions and irradiation. 
Fed. Proc., 1956,15: 8. 
449. Battaglia, F. C., G. Meschia, A. Hellegers 
and D. H. Barron. The effects of acute hypoxia on 
osmotic pressure of the plasma. Quart. J. exp. Physiol, 
1958, 43: 197-208. 
450. Bramati, C. Influenza della splenectomia sulla 
poliglobulia da anossia anossica acuta. Riv. Med. aero., 
1958, 21: 499-505. 
451. Ernsting, J. Effect of acute hypoxia upon the 
oxygen content of the body in man. XXII Inter. Congr. 
physiol. Sci., Leiden. 1962, 2: Abstr. 344. 
452. Gibson, Q. H., F. Kreuzer, E. Meda and 
F. J. W. Roughton. The kinetics of human haemoglobin 
in solution and in the red cell at 37 C. J. Physiol., 1955, 
129: 65-89. 
453. Grant, W. C. and W. S. Root. Fundamental 
stimulus for erythropoiesis. Physiol. Rev., 1952, 32: 449- 
498. 
454. Hamburger, R. J. Haemoglobine electrophorese 
bij hypoxie. [Hemoglobin electrophoresis in hypoxia.] 
Aeromed. Acta, 1957, 5; 399-402. 
455. Kalff, G. Uber das Verhalten von Hamoglobin 
und Erythrozyten in der akuten Hypoxie. Dtsch. Versu- 
chanst. Luftf., Rept. 128, May 1960, 24 pp. 
456. Kunzmann, H. Effect of acute hypoxia on the 
electrolytic analysis of the blood. Btsch. Versuchanst. 
Luftf., Rept. 125. pp. 33-43, June 1960. 
457. Lambertsen, C. J., P. L. Bunce, D. L. Drab- 
kin and C. F. Schmidt. Relationship of oxygen tension 
to hemoglobin in oxygen saturation in the arterial blood 
of normal men. /. appl. Physiol., 1952, 4: 873-885. 
458. Otey, E. S. The effect of heparin on blood lac- 
tate and pyruvate during acute hypoxia. Fed. Proc., 1963, 
22: 635. 
459. Pannacciulli, I., G. Fumagalli and M. Mez- 
zano. Tasso, formula, maturazione reticolocitaria e rap- 
porto plasma/globuli in corso di ipossia acuta in soggetti 
normali. Riv. Med. aero., 1958, 21: 467-483. 
460. Riley, R. L., R. E. Dutton, Jr,, F, J. D. Fulei- 
han, S. Nath, H. H. Hurt, Jr., C. Yoshimoto, J. H. 
Sipple, S Permutt and B. Bromberger-Barnea. Regu- 
lation of respiration and blood gases. Ann. N.Y. Acad. 
Sci., 1963, 109: 829-851. 
461. Root, W. S. The stimulus for erythropoiesis. 
J. Mt Sinai Hasp., 1954, 20: 331-338. 
462. Schiller, A. A. and G. N. Wool. Disappearance 
rate of fluorescein conjugated plasma proteins from the 
circulation of hypoxic rats. Fed. Proc., 1952, 11: 139. 
463. Verel, D. and D. F. Kerridge. Mean corpus- 
cular hemoglobin concentration in anoxic lung disease. 
J. appl. Physiol, 1961, 16: 847-850. 
464. Weitzner, S. W., B. D. King and E. Ikezono. 
The rate of arterial oxygen desaturation during apnea in 
humans. Anesthesiology, 1959, 20: 624-627. 
465. Willard, P. W. and S. M. Horvath. Blood gas 
and plasma ion concentrations of asphyxiated hypothermic 
and normothermic rats. Amer. Heart J., 1960, 60: 244-250. 
6. CEREBROSPINAL FLUID 
Leusen and Demeester (466) 1960 have re- 
ported changes in the cerebrospinal fluid in dogs 
subjected to breathing ten percent oxygen at am- 
bient pressure. The pH of the cerebrospinal fluid 
paralleled the changes in blood pH during LOW OXYGEN PERCENTAGES—RESPIRATION 
466 
hypoxia and increased ventilation was also re- 
corded. The arterial pH under hypoxia was 7.49, 
cerebrospinal fluid pH was 7.44, the bicarbonate 
in plasma 19.5, cerebrospinal fluid bicarbonate 
23.0, PC02 in blood 23, and in cerebrospinal 
fluid 35. 
466. Leusen, I. and G. Demeester. Die chemische 
Reacktion der Cerebrospinalfliissigkeit im Sauerstoffman- 
gel. Pfliig. Arch. ges. Physiol., 1960, 270: 390-398. 
7. RESPIRATION 
In this section there has been included in the 
reference list a number of papers dealing with 
the complexities of respiratory physiology under 
conditions of hypoxia. Only a fraction of these 
are discussed in the text that follows. Respiratory 
patterns of divers subjected to hypoxia and car- 
bon dioxide have been studied by Miles {483) 
1957. In this report Miles conducted a survey of 
100 divers which indicated that a very wide varia- 
tion existed in respiratory responses when the 
divers were exposed to identical conditions. The 
subjects breathed from a balanced spirometer 
filled with air and a carbon dioxide absorbent. 
The air mixture breathed in these studies con- 
tained 10-11 percent oxygen. In general, no 
changes were seen in the first five minutes, but 
in the subsequent four or five minutes hypoxic 
effects began to appear. After a period of rest 
the procedure was repeated, except that carbon 
dioxide was allowed to accumulate (to levels of 
five or six percent). In a third and final series 
100 percent oxygen was used, but again carbon 
dioxide was allowed to accumulate. Breathing 
normal air the minute volume ranged from 7.6 
to 33.2 liters, with rates from 6-32 per minute. 
The tidal volume varied from 442 to 3259 cc. 
The responses were not considered extreme but 
were either slow and shallow or fast and deep. 
Thirty-two of the 100 subjects had somewhat 
irregular patterns, characteristically free of any 
rhythm. Periodic inspiratory spikes were seen in 
shallow breathers. In the first series (effects of 
hypoxia alone) 58 patients showed elevated 
minute volume, 39 a depressed minute volume, 
and three no change. Of the 39 showing a reduc- 
tion, 31 had a reduced tidal volume and nine a 
reduced rate, while nine showed no rate change 
at all. Thirteen revealed an elevation of rate. 
The remaining eight showed a reduction in rate 
along with the change in tidal volume. The 
variations in tidal volume were more significant 
than the rate variations. For the series in which 
carbon dioxide was allowed to accumulate with 
100 percent oxygen, three men showed a reduc- 
tion in ventilation and 15 an increase in their 
minute volume over 150 percent. When carbon 
dioxide was allowed to accumulate in air, as op- 
posed to 100 percent oxygen, there was an in- 
crease in minute volume from 0 to 150 percent. 
In oxygen, a greater proportion fell in the lower 
ranges of increase. The slow-deep breathers re- 
sponded less to carbon dioxide than the fast and 
shallow ones. The authors suggest that shallow 
breathers might be less efficient when using ap- 
paratus which introduced additional dead space. 
Shallow breathers probably retain more carbon 
dioxide. The shallow-fast breathers may have 
difficulty with increased dead space and increased 
resistance or increased gas density. The slow- 
deep breathers are probably the best subjects and 
are the best divers in this group. The hyper- 
ventilators are less acceptable as divers, adding 
to the hazards of diving. Lambersten, Wendel, 
Chiodi and Owen {486), 1957, have examined 
the respiratory effects of .08 and .8 atmospheres 
of inspired PG, at “constant” alveolar Pc09 of 
43 mm Hg. In these studies 8, 21 and 80 percent 
oxygen were administered at one atmosphere to 
six normal subjects maintained at an alveolar 
PC09 of 43 mm Hg. In the absence of altera- 
tions in arterial PCOo or pH, 8 percent oxygen 
produced a 26 percent increase, and 80 percent 
oxygen resulted in a 15 percent increase in respi- 
ratory minute volume above the control values 
obtained during 21 percent oxygen breathing. 
The respiratory stimulation associated with 80 
percent oxygen breathing was accompanied by a 
significant 1.6 mm Hg rise in cerebral venous 
PCOo, reflecting a central hypercapnia which 
may have produced the “oxygen” hyperpnea. 
Since neither cerebral circulation nor cerebral 
metabolism was altered by 80 percent oxygen, the 
internal jugular venous hypercapnia was due to 
diminished hemoglobin reduction. The hypoxic 
hyperventilation of eight percent oxygen breath- 
ing was associated with a five mm Hg fall in 
cerebral venous PCO(>, due to increased rate 
of brain blood flow. It was therefore considered 
possible that, in spite of a fixed arterial PCOo, SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
the chemoreflex respiratory response to hypoxia 
was, in part, counteracted by a fall in central 
stimulus level, brougth about by hypoxic cerebral 
vasodilatation. Hornbein and Roos (478) 1960, 
and Hornbein, Roos and Griffo (479) 1961, have 
studied the transient effect of sudden mild hy- 
poxia on respiration in cats. Recent studies of 
carotid body chemoreceptor activity in these ani- 
mals show that the activity of these organs in- 
creases greatly over a range of alveolar P09, 
considerably higher than the alveolar P09 
of 50-60 mm Hg which is known to produce an 
increase in ventilation in the steady state. In an 
attempt to explain this discrepancy between 
chemoreceptor activity and ventilation, the transi- 
ent ventilatory response to two breaths of a low 
oxygen mixture was observed and correlated with 
the alveolar P0>) during this brief hypoxic stimu- 
lus. A transient increase in ventilation could be 
detected at an alveolar P0<> of 93 mm Hg, that 
is, considerably higher than the highest PCo 
known to increase ventilation during the steady 
state. These results were interpreted as evidence 
of an increased chemoreceptor drive when alveo- 
lar oxygen tension was lowered only slightly be- 
low that existing at sea level. At relatively high 
alveolar oxygen tensions the effect of chemore- 
ceptor activity on ventilation is inhibited by 
other factors which only fully appear after several 
breaths. 
Honda, Natsui, Hasumura and Nakamura 
(477) 1963, examined threshold alveolar arterial 
PCo9 (PtCOo) for the respiratory system in acute 
hypoxia in anesthetized dogs by observing 
phrenic nerve discharges. The authors found 
that the lower the Pq2, the lower the Ptc09. The 
relationship between the Pa0o and the Pt0G9 
was curviliniar, Pt00o showing an abrupt fall 
in the range of Pa09 of 30-60 mm Hg. The 
hypoxic respiratory drive was extinguished by 
sufficiently lowering the alveolar PC09, showing 
that the respiratory drive continues to be attribut- 
able to Pco or cH even during intense hypoxia. 
It was inferred that a positive interaction be- 
tween P0o and PCOo or cH stimulus for ventila- 
tion exists when Pa0> falls below about 70 mm 
Hg. Since chlorpromazine has been reported to 
suppress chemoreceptor activity, Schopp (488) 
1958 investigated the action of chlorpromazine 
on the respiratory response to hypoxia. It was 
assumed that one might anticipate that stimuli 
which act at the chemoreceptor site should be 
less effective after the administration of chlor- 
promazine. Dogs were anesthetized with chlora- 
lose (70 mg/Kg body weight). Respiratory ac- 
tivity was recorded by allowing the expired air 
to pass through a gas meter. The respiratory 
response to nine percent oxygen in 91 percent 
nitrogen was determined in 16 animals. The 
response to nine percent oxygen was again de- 
termined in eight animals 30 minutes after in- 
travenous injection of chlorpromazine (5 mg/kg 
of body weight) and in six animals 30 minutes 
after a control injection of Ringer solution. After 
the injection of chlorpromazine, the increase in 
volume of expired air in response to hypoxia was 
about 2.5 liters greater than before injection, 
while after giving Ringer solution the response 
to hypoxia was similar to that observed before 
the injection. Thus a decrease in respiratory 
sensitivity to hypoxia which might be anticipated 
on the basis of the reported suppression of 
chemoreceptor activity after chlorpromazine, was 
not evident, but rather a greater respiratory re- 
sponse was observed. 
Daly, Lambertsen and Schweitzer (471) 1953 
have investigated central nervous control of 
bronchomotor tone in the dog. A technique of 
perfusing the brain through the common caro- 
tid or vertebral arteries with either blood from 
the left auricle or mixed venous blood from the 
right auricle is described. Changing the per- 
fusion from arterial to mixed venous blood 
caused bronchoconstriction. This response was 
potentiated by eserine and abolished by atropine, 
and also by section of the cervical vagosympa- 
thetic nerves. As the carotid sinus regions are 
denervated, the responses were considered central 
in origin. An analysis of the bronchoconstrictor 
effect of mixed venous blood has been made by 
changing the perfusion from arterial blood to 
blood equilibrated with various gas mixtures in 
the isolated perfused lungs of a second dog. 
Passing either anoxic and/or hypercapnic blood 
through the brain causes bronchoconstriction. 
Hypocapnic blood causes bronchodilatation, an 
effect which was considered to be due to a 
diminution of vagus tone. It was concluded that 
the normal carbon dioxide tension of the blood 
contributes to the maintenance of vagul broncho- 
motor tone. LOW OXYGEN PERCENTAGES—METABOLISM 
467-490 
467. Asmussen, E. and M. Nielsen. Alveolo-arterial 
gas exchange at rest and during work at different 02 
tensions. Acta physiol, scand., 1960, 50: 153-166. 
468. Boba, A., J. J. Cincotti, T. E. Piazza and 
C. M. Landmesser. The effects of apnea, endotracheal 
suction, and oxygen insufflation, alone and in combination, 
upon arterial oxygen saturation in anesthetized patients. 
J. Lab. din. Med., 1959, 53: 680-685. 
469. Branscomb, V. and G. W. Wright. Effects of 
controlled low oxygen breathing upon exchange of respira- 
tory gases in humans. Fed. Proc., 1952,11: 16. 
470. Christensen, E, H. Respiratory control in acute 
and prolonged hypoxia. Proc. roy. Soc., 1954, 143: 8-12. 
471. Daly, M. de B., C. J. Lambertsen and A. 
Schweitzer. The effects upon the bronchial musculature 
of altering the oxygen and carbon dioxide tensions of the 
blood perfusing the brain. /. Physiol., 1953, 119: 292-314. 
472. Defares, J. G. and J. M. Bogaard. Dynamic 
PAC02 and V response curves at contant PAC02 during 
hypoxia. XXII Inter. Congr. physiol. Sci., Leiden, 1962, 2: 
Abstr. 321. 
473. DeHaan, R. L. and J. Field. Anoxic endurance 
of cardiac and respiratory function in the adult and infant 
rat. Amer. J. Physiol., 1959, 197: 445^448. 
474. Donald, K. W. The definition and assessment of 
respiratory function. Brit. med. J., 1953, 1: 415^422. 
475. Donald, K. W. The definition and assessment of 
respiratory function. Brit. med. ]., 1953,1: 473^478. 
476. Filley, G. F., F. Gregoire and G. W. Wright. 
Alveolar and arterial oxygen tensions and the significance 
of the alveolar-arterial oxygen tension difference in normal 
men. J. din. Invest., 1954, 33: 517-529. 
477. Honda, Y., T. Natsui, N. Hasumura and K. 
Nakamura. Threshold PC02 for respiratory system in 
acute hypoxia of dogs. J. appl. Physiol., 1963,18: 1053-1056. 
478. Hornbein, T. F. and A. Roos. The transient 
effect of sudden mild hypoxia on respiration. Fed. Proc., 
1960, 19: 374. 
479. Hornbein, T. F., A. Roos and Z. J. Griffo. 
Transient effect of sudden mild hypoxia on respiration. 
J. appl. Physiol., 1961, 16: 11-14. 
480. Haab, P. and J. Piiper. Alveolar-arterial 02 
and CO, tension differences in dogs in hypoxia. XXII 
Inter. Congr. physiol., Sci., Leiden, 1962, 2: Abstr. 296. 
481. Kellogg, R. H. Effect of altitude on respiratory 
regulation. Ann. N.Y. Acad. Sci., 1963, 109: 815-826. 
482. Malette, W. G. and G. Eiseman. Cerebral 
anoxia resulting from hyperventilation; a dangerous para- 
dox. Aerospace Med., 1958, 29: 611-615. 
483. Miles, S. Respiratory patterns of 100 divers. 
Effects of hypoxia and carbon dioxide. Gt. Brit. MRC, 
RNPRC, UPS. R.N.P. 57/888, U.P.S. 164, April 1957, 17 pp. 
484. Milic-Emili, G. and J. M. Petit. Effets de la 
teneur en oxygene de Pair inspire sur les propri£t£s 
mecaniques des poumons chez 1’Homme normal. /. Physiol. 
Path, gen., 1960, 52: 175-177. 
485. Nielsen, M. and H. Smith. Studies on the regu- 
lation of respiration in acute hypoxia; with an appendix 
on respiratory control during prolonged hypoxia. Acta 
physiol, scand., 1952, 24: 293-313. 
486. Lambertsen, C. J., H. Wendel, H. Chiodi and 
S. G. Owen. Respiratory effects of .08 and .8 atmospheres 
of inspired p02 at a “constant” alveolar pCOs of 43 mm 
Hg. Fed. Proc., 1957, 16: 76. 
487. Saito, K., Y. Honda and N. Hasumura. Ventila- 
tory response to hypoxia at normal arterial pH and pC02 
in dogs. Jap. J. Physiol., 1960,10: 673-681. 
488. Schopp, R. T. Action of chlorpromazine on res- 
piratory response to hypoxia. Fed. Proc., 1958, 17: 144. 
489. Schopp, R. T. Influence of gas mixtures on a 
grouped type of periodic breathing. Fed. Proc., 1960, 19: 
373. 
8. ALIMENTARY TRACT 
In general, the effects of hypoxia is to reduce 
the activity of the gastrointestinal tract. This 
applies also to conditioned salivation as shown 
by Malmejac and Plane (490) 1952. These au- 
thors placed dogs in an atmosphere containing 
9-10 percent oxygen which resulted in a rapid 
diminution of conditioned salivation reflexes. 
Salivation was maintained if the oxygen was in- 
creased to 14 percent. In fact, at this level saliva- 
tion was often augmented. 
490. Malmejac, J. and P. Plane. Etude, a 1’aide du 
reflexe conditionnel salivaire chez le chien, de dysfonc- 
tionnements nerveux superieurs consecutifs k des agres- 
sions diverses: aspects techniques et physioliques. Bull. 
Acad. Nat. Med., Paris, 1952, 136: 24-28. 
9. METABOLISM 
Generally speaking, decrease of oxygen tension 
in the inspired air causes a decrease in oxygen 
consumption accompanied by a decrease in body 
temperature and an accumulation in the body of 
particles of incomplete oxidation. The literature 
indicates a considerable variation in the oxygen 
consumption rate of man and animals during 
hypoxia, and both increases and decreases have 
been found. Hypoxia also results in a mobiliza- 
tion of blood sugar with a drainage on glycogen 
stores. There may be a decrease of ketone bodies 
and total fats as well as lipoid phosphorus. Bile 
secretion may be at first accelerated and then de- 
creased; pancreatic excretion may also be de- 
creased. In human subjects there may be a 
reduction in daily urinary secretion of ascorbic 
acid due to increased utilization. There may 
also be a temporary increase in the excretion 
of sodium, potassium and fluoride. In prolonged 
mild hypoxic situations increase of 17-keto 
steroids may be decreased. There may also be a 
decrease in excretion of amino nitrogen. Hypoxia SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
may also result in increased secretion of 
epinephrine. 
The effects of hypoxia on brain metabolism 
may be serious and complicated. For a review of 
these effects, McFarland (570) 1952, may be con- 
sulted. This author concludes that sensory and 
mental impairment under experimental condi- 
tions of hypoxia may be attributed to diminished 
partial pressure of oxygen in the blood being 
delivered to nervous tissues; the changes are of 
cellular rather than of circulatory origin. Al- 
baum, Noell and Chinn (491) 1953, explored 
changes in metabolite concentrations of various 
portions of the rabbit brain during progressive 
stages of anoxia and correlated these with elec- 
trical measurements of function. Disappearance 
of function and the inexcitability of all meas- 
urable elements during anoxia were associated 
with a moderate decrease of ATP, phosphocrea- 
tine and glycogen. Disappearance of ATP was 
more rapid than that of phosphocreatine. Loss 
of spontaneous electrical activity during early 
stages of anoxia occurred before significant 
changes in chemical constituents could be de- 
tected. Urethane controls had a higher level 
of ATP than the unanesthetized animals. There 
was a significant decrease of ATP during all 
stages of anoxia. Different regions of the fore- 
brain showed no differences in ATP level nor in 
the depletion under anoxia. The level however 
was lower in the mesencephalon and the medulla 
and depletion occurred more slowly. In a study 
of metabolic processes in the brain at normal 
and reduced temperatures under anoxic and 
ischemic conditions, Thorn, Scholl, Pfleiderer 
and Mueldener (519) 1958, studied rabbits under 
conditions of ischemia and anoxia. Experiments 
were performed at normal and at lowered body 
temperatures (26°C.). Ischemia was induced by 
means of a cuff around the animal’s neck and 
anoxia was obtained by ventilation with a mix- 
ture of nitrogen and carbon dioxide. The brains 
were removed with a cooled spoon and frozen in 
liquid air. Deproteinized extracts served for the 
determination of ATP, ADP, fructosediphos- 
phate (FDP), dihydroxyacetone phosphate 
(DAP), pyruvic acid (BTS), lactic acid (MS), 
inorganic phosphate, alanine, glutamic acid and 
aspartic acid, which were partly estimated by 
optical enzymic methods. The shock of decere- 
bration momentarily affected the concentrations 
of inorganic phosphate, creatine phosphate 
(PKr), FDP, ATP and ADP. The concentration 
of inorganic phosphate was raised, and PKr and 
ATP lowered. The extent of this immediate 
change could be measured by comparison with 
the value obtained after freezing the whole head 
with the brain in situ. Similar changes were ob- 
tained under anoxic and ischemic conditions. 
The inorganic phosphate increased in ischemia 
and in anoxia. In anoxia and in ischemia the 
ADP concentration initially increased and de- 
creased later. Thorn and Heimann (515) 1958 
found that during anoxia ammonia concentra- 
tion in the brain increased. In a study of the 
tolerance to anoxia and development of cerebral 
succinic dehydrogenase and cytochrome oxidase 
activities in the rabbit, Cassin and Herron (498) 
1961, have reported that newborn rabbits tolerate 
30-35 minutes of anoxia, while adult rabbits 
withstand anoxia for only three to five minutes. 
In order to secure further information as to the 
mechanisms of resistance of the newborn animal 
to anoxia as compared with the adult, the authors 
studied changes in the cerebral succinic dehydro- 
genase and cytochrome oxidase activities in rab- 
bits varying in age from less than 24 hours to 
adulthood. It was found that succinic dehydro- 
genase and cytochrome oxidase activities were 
very low at birth, but gradually increased until 
the 15-18th post-natal day. It was found that 
between the age of 15 and 18 days there was a 
critical period in the development of these 
enzymes, and at this period adult levels of ac- 
tivity were reached. It was found that at this 
critical period in age the tolerance of the develop- 
ing rabbit to anoxia reached the adult level. 
This increase in oxidative enzyme activity is in 
agreement with the hypothesis that the metabo- 
lism of the mammal is transformed from a pre- 
dominantly anaerobic condition at birth to an 
aerobic condition with maturation. 
The effects of hypoxia on the myocardial 
metabolism of intact dogs have been reported 
by Hackel, Goodale and Kleinerman (505) 1954. 
In these studies the dogs were subjected to air 
mixtures containing ten percent, five percent and 
zero percent oxygen. It was found that coronary 
flow and myocardial oxygen extraction was 
significantly increased during oxygen lack. The LOW OXYGEN PERCENTAGES—METABOLISM 
result of this was that the total left ventricular 
oxygen consumption was maintained during the 
administration of 10% oxygen as well as 5% 
oxygen. With 10% oxygen there was little change 
in carbohydrate uptake by the myocardium. Ad- 
ministration of 5% oxygen resulted in increased 
arterial levels of lactate and pyruvate and 
significant decreases in arterial venous differences 
and coefficients of extraction of pyruvate, lactate 
and glucose. At the same time the total utiliza- 
tion of these substances was maintained. Com- 
plete oxygen deprivation resulted in negative 
arterial venous or arteriovenous differences for 
lactate, and greatly decreased values for pyruvate. 
Boring, Kammermeier and Byon (499) 1962, 
found that acute asphyxia resulted in a rapid 
dilation of the guinea pig’s heart in situ. A 
maximal cardiac dilatation was usually reached 
within one minute of asphyxia whereas cardiac 
arrest occurred after six to seven minutes. If 
normal respiration was then resumed, tone and 
contractility recovered completely within one 
minute, provided that the previous asphyxia had 
not endured longer than four minutes. Cardiac 
dilatation was accompanied by a corresponding 
breakdown of phosphocreatinine (1 /xM CP/gm 
in dilated hearts as contrasted with eight or nine 
fxM/g in the controls). During recovery phos- 
phocreatinine concentration was restored to nor- 
mal. A similar correlation between dilatation 
and phosphocreatinine breakdown was found 
after nitrogen or carbon monoxide respiration, 
and in hearts poisoned with cyanide and other 
substances such as 2, 4-dinitrophenol. There 
were relatively small changes in ATP during the 
initial phase of dilatation. Merrick and Ellis 
(512) 1952, and Merrick (511) 1954, have 
studied changes in cardiac glycogen in normal 
goldfish subjected to acute anoxia induced by 
bubbling pure nitrogen gas through the water in 
which the fish were swimming and maintaining 
the dissolved oxygen in the water at 0.58 ppm by 
keeping the water under nitrogen. It was found 
that displacement of dissolved oxygen by nitrogen 
caused no significant change in pH or salt balance 
in the well buffered tap water that was used. 
All of the control and revived fishes were carried 
in water of 7.4 ppm oxygen. It was found that 
the cardiac glycogen of the controls was 23.6 
mg/gm. of cardiac tissue. This is the highest 
normal value yet reported for any vertebrate. 
Acute distress developed in these fishes abruptly 
transferred to the low oxygen water in approxi- 
mately five hours. The end point for acute 
anoxia was set at 15 minutes after opercular move- 
ments ceased. It was found that in the anoxic 
series little or no change in cardiac glycogen oc- 
curred before the symptoms of acute anoxia ap- 
peared. However, with the onset of incoordina- 
tion and irregular opercular movements, cardiac 
glycogen fell rapidly to an average of 2.6 mg./gm. 
Cardiac glycogen did not return to normal in less 
than three hours or more in anoxic fishes revived 
in fresh water, although after six hours cardiac 
glycogen again approached the values for the 
controls. These anoxic and recovery experiments 
suggest that the high resistance of the goldfish to 
anoxia may be associated with a high glycogen 
content of the heart. It was concluded that com- 
plete removal of cardiac glycogen is not a pre- 
requisite to the failure of the respiratory and 
cardiovascular mechanisms during fulminating 
anoxia. These experiments considered collec- 
tively support the view that cardiac glycogen is 
an emergency standby utilized by the heart dur- 
ing periods of anoxic stress. With regard to fatty 
acid metabolism in the heart subjected to 
hypoxia, Evans and Jacobs {500) 1964, using the 
isolated rat heart, concluded that mild hypoxia 
impairs oxidations of fatty acid and increases 
formation of triglyceride and phospholipid. 
Severe hypoxia inhibits oxidation and triglyce- 
ride formation and favors accumulation of 
phospholipid and non-esterified fatty acid in 
heart muscle. 
Bassi and Bernelli-Zazzera (494) 1955, have 
studied the metabolism of vacuolated cells follow- 
ing hypoxia in adult albino rats. In these studies 
appreciable vacuolation of cells after hypoxia was 
present only in the liver. It appeared that the 
respiratory quotient significantly lowered in the 
vacuolated cells as compared with the controls. 
Oxygen uptake of octanoic-oxidase and succinic- 
oxidase activities remained unchanged. 
Since the autonomic nervous system and the 
adrenal glands participate in physiological ad- 
justments to many situations which disturb 
homeostasis, McElroy and Spitzer {509) 1961, 
performed studies to determine the response of 
plasma free fatty acid during hypoxia, a stress 491-513 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
which stimulates the sympatho-adrenal axis. 
These studies were carried out in fasting adult 
mongrel dogs of both sexes. Hypoxia resulted in 
an increase in blood sugar, the mean blood 
pressure, heart rate, femoral venous-arterial free 
fatty acid concentrations, respiratory minute 
volume, and tidal volumes. The hypoxia was 
produced by breathing eight percent oxygen in 
nitrogen for 15 minutes. The respiratory rate 
and minute volumes doubled over control levels 
although the tidal volume increased very little. 
The authors pointed out that recorded changes 
in these animals resemble qualitatively those 
observed after injection of epinephrine or during 
emergency response to stress. The changes were 
reproducible when the animals were rendered 
hypoxic a second time. Rises in free fatty acid 
and glucose levels closely follow circulatory com- 
pensatory responses. To determine the mechan- 
ism responsible for these results, similar experi- 
ments were performed on dogs with both adrenal 
glands occluded from the circulation. In these 
latter studies the blood sugar did not rise and 
the free fatty acid elevations were very slight. To 
differentiate changes in free fatty acid as being 
mediated through hormones secreted by the adre- 
nal medulla or adrenal cortex, a group of dogs 
were tested for hypoxic responses before and 
after bilateral sectioning of spleenic nerves. The 
changes observed in the intact animals were 
greatly reduced after spleenic sectioning. 
491. Albaum, H. G., W. K. Noell and H. I. Chinn. 
Chemical changes in rabbit brain during anoxia. Amer. J. 
Physiol, 1953,174: 408-412. 
492. Asvall, J. E. Transaminase activity after experi- 
mental hypoxia in rabbits. Scand. J. din. Lab. Invest., 1960, 
12: 239-246. 
493. Barach, A. L. and H. A. Bickerman. The effect 
of anoxia on tumor growth with special reference to 
Sarcoma 180 implanted in C57 mice. Cancer Res., 1954, 14: 
672-676. 
494. Bassi, M. and A. Bernelli-Zazzera. Prelimi- 
nary studies on the metabolism of vacuolated cells follow- 
ing hypoxia. Experientia, 1955, 11: 105-106. 
495. Beischer, D. E. Tissue metabolism under low 
and high oxygen tension, pp. 166-170 in: Man’s depend- 
ence on the earthly atmosphere. Edited by Karl E. 
Schaefer. The MacMillan Company, New York, 1962, 416 
pp. 
496. Brauer, R. W., G. F. Leony and R. J. Hollo- 
way. Oxygen uptake and anoxia of the liver. Fed. Proc., 
1961, 20: 286. 
497. Brodie, H. R. Heat production in the hypoxic 
new-born infant. /. Physiol., 1957,135: 9P-10P. 
498. Cassin, S. and C. S. Herron, Jr. Tolerance to 
anoxia and development of cerebral succinic dehydro- 
genase and cytochrome oxidase activities in the rabbit. 
Fed. Proc., 1961,20: 420. 
499. Doring, J., H. Kammermeier and K. Byon. 
Changes of cardiac tonus and high-energy phosphate con- 
centrations of the heart due to anoxia or metabolic inhibi- 
tors. XXII Inter. Congr. physiol. Sci., Leiden, 1962, 2: 
Abstr. 39. 
500. Evans, J. R. and M. H. Jacobs. Fatty acid 
metabolism in the hypoxic rat heart. Fed. Proc., 1964, 23: 
542. 
501. Genkin, A. M. and N. A. Udintsev. The effect 
of glutaminic acid on certain metabolic processes in anoxia 
and during physical work. Bull. exp. Biol. Med., 1959, 48: 
974-977. 
502. Gerlach, E. and R. H. Dreisbach. Formation 
of nucleosides, purines, and pyrimidines from free nu- 
cleotides in kidney and other tissues under ischemic or 
anoxic conditions. XXII Inter. Congr. physiol. Sci., Leiden, 
1962, 2: Abstr. 197. 
503. Goldblatt, H. and G. Cameron. Induced malig- 
nancy in cells from rat myocardium subjected to inter- 
mittent anaerobiosis during long propagation in vitro. J. 
exp. Med., 1953, 91: 525-552. 
504. Gott, V. L. The metabolic changes occurring in 
the canine heart during rigor associated with potassium 
citrate and anoxic arrest. Fed. Proc., 1961, 20: 127. 
505. Hackel, D. B., W. T. Goodale and J. Kleiner- 
man. Effects of hypoxia on the myocardial metabolism of 
intact dogs. Circ. Res., 1954, 2: 169-174. 
506. Khairallah, P. A. and W. F. H. M. Momma- 
erts. Nucleotide metabolism in cardiac activity. I. Meth- 
ods and initial observations. Circ. Res., 1953,1: 8-11. 
507. Kubicek, W. G., W. F. Geber and J. W. 
Geiger. Effects of fever and hypoxia in dogs. Fed. Proc., 
1955,14: 89. 
508. Leivestad, H., H. Anderson and P. F. Scho- 
lander. Physiological response to air exposure in the 
codfish. Science, 1957, 126: 505. 
509. McElroy, W. T., Jr. and J. J. Spitzer. Hypoxia 
as a stimulus for free fatty acid mobilization in dogs. 
appl. Physiol., 1961, 16: 760-762. 
510. McFarland, R. Anoxia, its effect on metabolism 
and physiologic activity of brain, pp. 335-355 in: The 
biology of mental health and disease. The twenty-seventh 
annual conference of the Milbank Memorial Fund. Paul 
B. Hoeber, Inc., 1952, 654 pp. 
511. Merrick, A. W. Cardiac glycogen following ful- 
minating anoxia. Amer. J. Physiol., 1954, 176: 83-85. 
512. Merrick, A. W. and M. M. Ellis. Cardiac 
glycogen in fishes during and following acute anoxia. 
Fed. Proc., 1952, 11: 106. 
513. Michael, G., S. Naegle, W. H. Danforth, F. B. 
Ballard and R. J. Bing. Metabolic changes in heart 
muscle during anoxia. Amer. J. Physiol., 1959, 197: 1147- 
1151. LOW OXYGEN PERCENTAGES—TEMPERATURE 
514-529 
514. Miller, J. A., Jr., R. Zakhary and F. S. Miller. 
Effects of hypothermia and asphyxia on cardiac glycogen 
in guinea pigs. Fed. Proc., 1964, 23: 310. 
515. Pichotka, J. and T. Luthardt. Uber die 
Abhangigkeit der 02-Aufnahme von der 02-Spannung der 
Einatmungsluft nach Versuchen am Meerschweinchen. 
Pfliig. Arch. ges. Physiol., 1959, 269: 417-427. 
516. Reed, W. A., R. T. Manning and L. T. Hop- 
kins, Jr. Effects of hypoxia and hyperthermia on hepatic 
tissue of the dog. Amer. J. Physiol., 1964, 206: 1304-1308. 
517. Reynafarje, B. and J. Green. Pyridine nucleo- 
tide-cytochrome c reductases in rats exposed to low oxygen 
tension. Proc. Soc. exp. Biol., N.Y., 1960, 103: 224-225. 
518. Thorn, W. and J. Heimann. The effects of 
anoxia, ischemia, asphyxia and reduced temperature on 
the ammonia level in the brain and other organs. J. 
Neurochem., 1958, 2: 166-177. 
519. Thorn, W., H. Scholl, G. Pfleiderer and B. 
Mueldener. Metabolic processes in the brain at normal 
and reduced temperatures and under anoxic and ischaemic 
conditions. J. Neurochem., 1958, 2: 150-165. 
520. Van Fossan, D. D., C. Biddulph and D. 
Criscuolo. Postmortem brain lactic acid as influenced by 
hypoxia and/or hypocapnia. Fed. Proc., 1957, 16: 131. 
10. ENDOCRINES 
It has been long known that hypoxia may elicit 
sympatho-adrenal responses. Gerst, Naaman, Ro- 
dil, Wolf and Root (525) 1961, have attempted 
to establish an arterial blood oxygen tension 
threshold at which a significant sympatho-adrenal 
response is initiated. In these studies anesthe- 
tized dogs with chronically denervated hearts, 
after a control period, were given gas mixtures 
containing low oxygen to breathe. Respiratory 
pattern, arterial blood pressure, electrocardio- 
gram and esophageal temperature were recorded 
continuously. Arterial blood samples were 
analyzed for carbon dioxide and oxygen content, 
oxygen capacity, hemoglobin concentration and 
pH. Arterial blood PGo was determined by refer- 
ence to an oxyhemoglobin dissociation curve for 
dog blood. There was no significant increase 
in the rate of the denervated heart of the spon- 
taneously breathing dog until the P0o fell to ap- 
proximately 55 mm Hg. Below this level there 
was a relatively sharp increase in heart rate 
over the control level: 11% at a Pa0o of 40 mm 
Hg, 35% at a Pa02 of 28 mm Hg. The accelera- 
tion was ascribed by the authors to release of 
catecholamines, although this was considered to 
require confirmation. Since the Pa09 at which 
an increase in heart rate occurs is within the 
physiological range, it was concluded that the 
sympatho-adrenal response probably serves as a 
compensatory mechanism in a stressing situation. 
The stressful effects of oxygen deficiency upon 
adrenal cortical functions have been pointed up 
by Aschan (525) 1953, in a study on white rats 
exposed to oxygen deficiency for two hours, result- 
ing in a significant reduction of ascorbic acid 
contents of the adrenal glands. 
521. Aschan, G. Oxygen deficiency and oxygen poison- 
ing as stress factors. Acta Soc. Med., Uppsala, 1953, 58: 
265-268. 
522. Bayliss, R. I. S. Factors influencing adrenocorti- 
cal activity in health and disease. Brit. med. J., 1955, 495- 
501. 
523. Gerst, E. C., Y. Naaman, D. Rodil, C. E. Wolf 
and W. S. Root. Hypoxia and sympatho-adrenal activity. 
Fed. Proc., 1961, 20: 422. 
524. Hale, H. B., K. I. Syndor and M. L. Sweat. 
Endocrine, cardiovascular, respiratory, and body tempera- 
ture changes in man exposed to hypoxia combined with 
heat. Fed. Proc., 1954,13: 65. 
525. Loomis, W. F. Reversible induction of sexual 
differentiation in Hydra. Science, 1954, 120: 145-146. 
526. Mcllroy, M. B., F. L. Eldridge and R. W. 
Stone. The mechanical properties of the lungs in anoxia, 
anemia and thyrotoxicosis. Clin. Sci., 1956,15: 353-360. 
527. Petukhov, M. I. Vliianie gipoksii i AKTG na 
sostoianie uglevodnogo rezerva tkanei belykh krys. [The 
effect of hypoxia and ACTH on the carbohydrate reserve 
in tissues of the white rat.] Bull. Biol. Med. exp. URSS, 
1960, 49: 57-60. Bull. exp. Biol. Med., 1960, 49: 257-259. 
528. Van Liere, E. J., G. B. McCarty and J. G. 
Matthews. Effect of hypoxia and anemic anoxia on 
uterus. Amer. J. Physiol., 1952,171: 245-249. 
529. Van Liere, E. J. and D. W. Northup. Effect 
of hypoxia and nitrous oxide on uterus of estrogenized 
dogs. Fed. Proc., 1958, 17: 167. 
11. TEMPERATURE 
Hypoxia acutely depresses the metabolic re- 
sponse to cold in newborn rabbits as reported by 
Blatteis (550) 1963. Experiments conducted to 
elucidate this mechanism revealed that the in- 
creased rate of oxygen consumption at 25° C. was 
initially depressed by 10 percent oxygen but re- 
verted towards pre-hypoxic levels during the next 
four hours, usually with vigorous shivering. Pre- 
vious exposure to hypoxia alone did not obviate 
the acute hypoxic depression of the metabolic re- 
sponse to cold. Neither did pre-exposure to cold 
alone unless shivering was already present. Bi- 
lateral section of the carotid sinus and/or vagus 
nerves had no effect on the thermogenic response 
to cold or its depression by hypoxia, but catecho- 
lamines caused some increase during cold and SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
hypoxia. These results suggest that the acute 
depressive reaction of hypoxia on the metabolic 
response to cold may be due to interference with 
some rate-limiting physiological process rather 
than a specific effect of hypoxia, as for instance, 
on the chemoreceptors. Bullard and Kollias 
(532) 1962, have studied the primary effects of 
hypoxia on the thermal regulatory mechanisms 
and the relation of hypoxic alteration of body 
temperature and hypoxic tolerance. They have 
also compared hypoxic and thermal responses in 
different mammalian species. The white rat at 
23° C. had the same depression of oxygen con- 
sumption with both hypoxia (Pq2 = 75 mm. Hg) 
and chlorpromazine treatment (25 mg./Kg body 
weight), while the cooling rate with chlorproma- 
zine treatment was three times greater than that 
with hypoxia. When white rats and ground 
squirrels (Citellus tridecemlineatus) were ex- 
posed to cold (10° C.) and hypoxia (Pq2 = 75 
mm. Hg) the ground squirrel showed less meta- 
bolic depression but greater body cooling. The 
ground squirrel had greater hypoxic tolerance 
even at higher temperatures, so this was not due 
to greater body cooling. Similar studies were 
done at White Mountains, California, at an 
altitude of 12,250 feet, with altitude adapted 
rats and native ground squirrels (Citellus latera- 
lis) . The hypoxia of C. lateralis was much 
greater than that of the altitude adapted rats 
and sea level rats and ground squirrels. The C. 
lateralis in hypoxia was able to maintain a higher 
body temperature, higher oxygen consumption, 
and a higher heart rate than the other species. 
The authors concluded that the high tolerance 
of the altitude squirrel is related to a greater 
capability for compensatory activity in hypoxia 
rather than greater tolerance to functional and 
thermal depression. 
In a study of approximately 20 cats, anesthe- 
tized with pentobarbital sodium adjusted so that 
shivering was absent or vigorous Hemingway and 
Birzis (353) 1955-56, subjected the cats to 
hypoxia by progressively decreasing the percent* 
age of oxygen in an inhaled nitrogen-oxygen 
mixture. It was found that decreasing the oxygen 
percentage between 21 and 13 percent had no 
effect on shivering. Between 13 and 8 percent 
shivering decreased until it was abolished and 
oxygen consumption rate decreased to the non- 
shivering value. With non-shivering decerebrate 
cats, as the inhaled oxygen was progressively de- 
creased, oxygen consumption rate did not change 
until the range of 6-3 percent oxygen was 
reached, after which gasping respiration and 
apnea supervened. 
Observations on small animals, such as rats, 
guinea pigs, as well as in man, indicate that 
mild degrees of hypoxia lower the physiological 
resistance to cold. This seems to be a character- 
istic of homothermic organisms and has been 
confirmed in the dog by Hemingway and Nahas 
(534) 1952. These investigators measured oxy- 
gen consumption rate, respiratory quotient, ven- 
tilation rate and rectal temperature in selected, 
trained dogs subjected to air, oxygen-nitrogen 
mixtures of 6-16 percent oxygen for one hour, 
and finally air. During the early part of the 
hypoxia interval there was a sharp rise in minute 
volume of respiration and respiratory quotient. 
Oxygen consumption rate at first fell to sub-nor- 
mal values and then slowly rose to approach 
normal basal values. In the third period, that 
is to say the post-hypoxic period, oxygen con- 
sumption rate was above normal. The rectal 
temperature fell during the hypoxic period but 
rose rapidly after air breathing was resumed. 
Lim and Luft (536) 1960, have investigated 
the effect of moderate hypoxia (tracheal P0l> 
= 65 mm. Hg) on thermoregulation under 
neutral (27.5° C. relative humidity of 30 per- 
cent) and hot (40.5° C. relative humidity 80 
percent) conditions over a period of two hours 
in healthy male subjects on different days with 
similar control periods of breathing air. It was 
found that neither the course of rectal and mean 
skin temperatures was significantly affected nor 
was the metabolic rate altered by the hypoxia 
imposed. The intensity of shivering estimated 
from oxygen consumption was the same (2.5 
times control level) in the cold with or without 
hypoxia. Weight loss due to perspiration was 
essentially equal whether breathing air or the 
hypoxic gas. Notable differences were observed 
in cardiorespiratory response to heat and cold 
during hypoxia. In the heart with hypoxia the 
heart rate increased in a synergistic rather than 
an additive fashion, and the diastolic pressure 
was much lower. In similar experiments, Bul- 
lard (331) 1961, found with human subjects LOW OXYGEN PERCENTAGES—KIDNEY 
530-539 
an increase in shivering activity and oxygen 
consumption 30 minutes after exposure to 5° C. 
during breathing of 10 percent oxygen. This 
increase in shivering and oxygen consumption 
usually subsided after 15 minutes. The recovery 
periods after hypoxia breathing were often char- 
acterized by greatly decreased shivering activity. 
The author found that both heart rate and pul- 
monary ventilation rates were higher in hypoxic 
cold exposed subjects than in hypoxic subjects in 
a room at 30° C. It was hypothesized that the 
shivering increase is a release phenomenon. 
The work of Miller, Miller and Farrar (557) 
1954 in guinea pigs subjected to asphyxia indi- 
cates that environmental cooling increases the 
tolerance of the animal to the asphyxial 
conditions. 
530. Blatteis, C. M. Studies on the oxygen consump- 
tion of newborn rabbits in cold and hypoxia. Fed. Proc., 
1963, 22: 684. 
531. Bullard, R. W. Effects of hypoxia on shivering in 
man. Aerospace Med., 1961,32: 1143-1147. 
532. Bullard, R. W. and J. Kollias. Effects of 
hyp xia on temperature regulation in small mammals. 
XXII Inter. Congr. physiol. Sci., Leiden, 1962, 2: Abstr. 
493. 
533. Hemingway, A. and L. Birzis. Effect of hypoxia 
on shivering. J. appl. Physiol., 1955-56, 8: 577-579. 
534. Hemingway, A. and G. G. Nahas. Effect of 
varying degrees of hypoxia on temperature regulation. 
Amer. J. Physiol, 1952, 170: 426-433. 
535. Hill, J. R. The relation between oxygen consump- 
tion, hypoxia and environmental temperature. J. Physiol, 
1958, 143: 64P. 
536. Lim, T. P. K. and U. C. Luft. Body tempera- 
ture regulation in hypoxia. Physiologist, 1960, 3: 105. 
537. Miller, J. A., Jr., F. S. Miller and C. B. 
Farrar. Factors in noenatal resistance to anoxia. II. Effects 
of elevated and reduced temperature upon survival and 
recovery by neonatal guinea pigs. Surgery, 1954, 36: 916- 
931. 
538. Pichotka, J. and T. Luthardt. Uber die 
Abhangigkeit der 02-Aufnahme von der C2-Spannung der 
Einatmungsluft nach Versuchen am Meerschweinchen. 
Pfliig. Arch. ges. Physiol, 1959, 269: 417^127. 
539. Pichotka, J. and P. Scholz. Das Verhalten von 
Oo-Aufnahme und Korpertemperatur im 02-Mangel bei 
Bedingungen, die kleine stabile Einstellung mehr ermog- 
lichen. Pfliig. Arch. ges. Physiol., 1959, 269: 428-438. 
12. KIDNEY 
The postnatal development of diuresis in re- 
sponse to hypoxia has been studied by Adolph 
and Hoy {540) 1955. Exposure to low oxygen 
mixtures in infant rats (P0 — 42-46 mm. Hg) 
induced within two minutes an anuria or marked 
oliguria, followed after 15-30 minutes by diuresis. 
The diuresis often persisted for 30-60 minutes 
after room air again surrounded the animals. 
At two days of age the diuresis was less pro- 
nounced than at five days of age, and the urinary 
chloride dilution was less. Hence this response, 
like some other urinary diuresis and clearances, 
developed postnatally. In adult animals an in- 
jection of epinephrine sometimes induced a 
diuresis similar to the diuresis of hypoxia, but no 
diuresis was found in infant rats of 2-9 days 
of age given epinephrine subcutaneously unless 
water was also administered. The postnatal de- 
velopment of hypoxic diuresis appeared to 
parallel that previously found for the water 
diuresis and the authors concluded that these 
two may share common factors. The interrela- 
tionships of renal blood flow and blood oxygen 
saturation during 8-11 percent oxygen breathing 
were investigated by Balint, Fekete, Gomori and 
Nagy {541) 1960. These studies were carried 
out in chloralosed dogs. Renal blood flow meas- 
ured directly by PAH clearance technique was 
seen to decrease during hypoxia at blood satura- 
tion levels below 50 percent. Blood oxygen satu- 
ration showed an inverse linear relation with 
renal resistance and a direct linear relationship 
with the renal fraction of total blood volume. A 
significant increase in minute volume was ob- 
served only when blood oxygen saturation fell 
below 50 percent. The response of the kidney 
to hypoxia created by a perfusion with venous 
blood obtained from the right ventricle was 
studied by Selkurt {546) 1953 in anesthetized 
dogs. A pump aided in supplying the blood with 
an adequate head of pressure. The advantage 
of the method was that it permitted a specific 
hypoxia to be imposed upon the kidney with 
minimal disturbance to the organism as a whole. 
Blood oxygen content in different experiments 
varied from 6.7-15.9 volumes percent during 
venous perfusion (average 10.7). The most 
consistent response was an increase in PAH 
clearance, in one instance as great as 92 percent, 
but averaging 22 percent. Renal vascular resist- 
ance showed a typical reduction during hypoxia. 
The nature of this hyperemia has not been 
clarified. Creatinine clearance characteristically 
decreased by an average of 10 percent. The net 540-546 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
effect therefore was a reduction in the filtration 
fraction. The usual response in the excretion of 
sodium, potassium and water, was an increase. 
Because excretion increased while filtration rate 
declined in several experiments, the conclusion 
was drawn that hypoxia had slightly impaired 
the tubular reabsorptive processes of these 
substances. 
Lowrance, Nickel, Smythe and Bradley (543) 
1956 have studied renal function in the harbor 
seal during the asphyxia of anoxia and during 
anoxic anoxia produced by inhalation of 10 per- 
cent oxygen in nitrogen. Both apnea and anoxia 
resulted in a diminution of glomerular filtration 
rate and renal plasma flow. Urine volume de- 
creased in these experiments and the total output 
of sodium and potassium was diminished. 
Urinary concentration of sodium tended to fall, 
whereas the urinary concentration of potassium 
usually remained unchanged. Tubular reabsorp- 
tion of water decreased relative to filtration. The 
influence of vagal activity, respiratory movements 
and cardiac rate and rhythm on renal function 
could be excluded. The authors came to the con- 
clusion from these experiments that apnea and 
anoxia have comparable effects on renal function 
in the seal. Selkurt (545) 1952 found that the 
creatinine/inulin clearance ratio remains close 
to one during hypoxia in anesthetized dogs with 
blood oxygen content as low as 5.5 volumes per- 
cent resulting from inhalation of an 8 percent 
oxygen mixture. Since the absolute clearance 
value did not increase it was concluded that 
the creatinine clearance remains an adequate 
measure of Igomerular filtration rate under these 
conditions. 
540. Adolph, E. F. and P. A. Hoy. Postnatal devel- 
opment of diuresis in response to hypoxia. Fed. Proc., 
1955,14: 2. 
541. Balint, P., A. Fekete, P. Gomori and Z. Nagy. 
Das Verhalten des Minutevolumens und der Nierendurch- 
blutung bei arterieller Hypoxie. Pfliig. Arch. ges. Physiol, 
1960, 271: 705-714. 
542. Bradley, S. E., G. H. Mudge and W. D. Blake. 
The renal excretion of sodum, potassium, and water by 
the harbor seal (Phoca Vitulina L.): Effect of apnea; 
sodium, potassium, and water loading; pitressin; and 
mercurial diuresis. J. cell comp. Physiol, 1954, 43: 1-22. 
543. Lowrence, P. B,, J. F. Nickel, C. McC. 
Smythe and S. E. Bradley. Comparison of the effect of 
anoxic anoxia and apnea on renal function in the harbor 
seal (Phoca Vitulina, L.). J. cell comp. Physiol, 1956, 48: 
35-49. 
544. Ramsay, A. G. Stop-flow analysis of the influence 
of pC02 on renal tubular transport of K and H. Amer. J. 
Physiol, 1964, 206: 1355-1360. 
545. Selkurt, E. E. Comparison of creatinine and 
inulin clearance in the dog during hypoxia. Proc. Soc. exp. 
Biol, N.Y., 1952, 81: 374-376. 
546. Selkurt, E. E. Influence of hypoxia on renal 
circulation and on excretion of electrolytes and water. 
Amer. J. Physiol, 1953, 172: 700-708. 
13. EFFECTS OF CARBON DIOXIDE ON 
HYPOXIA 
The interaction of hypoxia and hypercapnia 
at the carotid bodies in chemoreflex stimulation 
of breathing has been studied by Otey and Bern- 
thal (550) 1960. In this investigation arterial 
blood from one anesthetized dog (donor) was 
continuously circulated through the vascularly 
isolated carotid region of another dog (recipi- 
ent) . It was then returned to a vein of the doner. 
Breathing was continuously recorded by spirom- 
eter and end-tidal PCOo and P0l> were under 
control while being monitored by infra-red and 
paramagnetic analyzers respectively. Hyper- 
capnia in combination with normal end-tidal 
P09 in the donor evinced only slight increase 
in breathing by the recipient. When however 
hypercapnia of identical degree was superim- 
posed upon a pre-existing hypoxia of the donor, 
there occurred a significant increment in the 
hyperpnea of the recipient beyond that due to 
the carotid body hypoxemia alone. Thus com- 
bined, hypercapnia and hypoxia at the carotid 
bodies of the recipient produced a substantially 
greater increase in breathing, about 100 percent 
on the average, but sometimes as much as 350 
percent. This was more than would be predicted 
by merely adding the increase due to separately 
imposed hypoxia to the increase due to separately 
imposed hypercapnia. The authors concluded 
that the carotid chemoreceptors are the site of a 
positive interaction between these two agents, 
such that the stimulating action of one is en- 
hanced by the coexistence of the other. 
Cormack, Cunningham and Gee {547) 1957, 
have shown in human subjects that with higher 
levels of Pc0„ anoxia causes significantly greater 
responses in respiration, frequency, ventilation, 
etc. These authors’ results contradict the hypo- 
thesis that respiratory stimuli do not interact. 
Considerations of the effects of carbon dioxide 
upon hypoxic reactions raises the important LOW OXYGEN PERCENTAGES—ACCLIMATIZATION 
547-552 
question of the value of the administration of 
carbon dioxide under conditions in which arti- 
ficial respiration is indicated. If carbon dioxide 
is administered during artificial respiration, the 
Pco„ in the lungs and well-circulated organs 
may be raised to highly abnormal levels unless 
a considerable further increase of ventilation can 
be induced. Under first aid conditions the rescue 
worker never knows the initial levels of carbon 
dioxide in the body of the subject, nor the 
ventilatory volumes he is producing. The ad- 
ministration of carbon dioxide under these con- 
ditions is therefore uncontrolled and uncon- 
trollable, and in many cases is apt to cause a 
dangerous intensification of carbon dioxide ac- 
cumulation and intoxication. These points have 
been made by Donald and Paton (548) 1955. 
These authors emphasize the dangers of high con- 
centrations of carbon dioxide in the body. These 
dangers include depression of the central nervous 
system, especially the respiratory areas, vasomotor 
depression with peripheral vasodilatation, haz- 
ardous cardiac arrhythmias, and fall in body 
temperature. For these reasons the authors rec- 
ommend that in first aid practice carbon dioxide 
should not be administered with oxygen in the 
resuscitation of subjects requiring and receiving 
artificial respiration. 
547. Cormack, R. S., D. J. C. Cunningham and 
J. B, L. Gee. The effect of carbon dioxide on the 
respiratory response to want of oxygen in man. Quart. J. 
Physiol, 1957, 42: 303-319. 
548. Donald, K. W. and W. D. M. Paton. Gases 
administered in artificial respiration. With particular ref- 
erence to the use of carbon dioxide. Brit. med. J., 1955, 
1: 313-318. 
549. Kilmore, M. A. and H. F. Chase. Effects of 
hypercapnia and hypoxia during hypothermia. Fed. Proc., 
1960, 19: 179. 
550. Otey, E. S. and T. Bernthal. Interaction of 
hypoxia and hypercapnia at the carotid bodies in chemore- 
flex stimulation of breathing. Fed. Proc., 1960, 19: 373. 
551. Salzano, J. and F. G. Hall. The influence of 
Pa02 on respiratory threshold to PCOa at normal and re- 
duced body temperatures. Fed. Proc., 1964, 23: 311. 
14. ACCLIMATIZATION 
The mechanisms of acclimatization to hypoxia 
are not yet fully understood. Reference may be 
made to a review of the subject by Stickney and 
Van Liere (554) 1953. These authors have dis- 
cussed an integrated series of adaptation which 
characterized acclimatization to chronic exposure 
to low oxygen tension in the inspired air. These 
adaptations involve various organ systems and 
tissues of the body. Increased ventilation of the 
lungs elevates appreciably the oxygen tension 
in the alveoli while simultaneously reducing the 
carbon dioxide tension. The adaptation is com- 
plete when alkaline reserve has been reduced 
so that blood pH is brought within the normal 
range. At this point respiratory control is more 
or less completely based in the central nervous 
system respiratory areas and the chemoreceptors 
have little if any part in the picture. According 
to the authors the adrenal cortex may have a 
heightened activity in this state of acclimatiza- 
tion, but it is not apparent. Its chief role presum- 
ably has been discharged in the early adaptation 
of the acute phase of exposure while acid-base 
balance was being adjusted and while increased 
demands were being made on carbohydrate 
metabolism. While cardiac output may have 
been increased during the early adaptive phase, 
in the completely adjusted organism the output 
is not increased over the pre-exposure value, 
either at rest or in exercise. There may be a 
minimal amount of cardiac hypertrophy involv- 
ing mainly the right heart. The cause for this 
is not apparent. There is greatly increased vascu- 
larization of many tissues resulting in improved 
diffusion of oxygen nutrients and metabolites. 
The oxygen carrying capacity of the blood is 
greatly increased. There is no evidence that the 
resting metabolic rate is changed and growth 
and body weight remain normal. The question 
of increased muscle myoglobin content in the 
acclimatized state remains in doubt. Capacity 
for work in the acclimatized subject has been 
reported to be equal to that of the comparable 
sea level resident. Renal and gastrointestinal 
physiology remain normal. The authors also 
state that the finding of reduced scores in reaction 
time tests remains unchallenged. In an accli- 
matized person fertility and reproductive powers 
remain normal. 
552. Barbashova, Z. I. Specific and nonspecific lines 
of acclimatization to hypoxia, pp. 82-95 in: Problems of 
evolution of physiological functions. Translated from Rus- 
sian by S. Showshan. Academy of Sciences, USSR, Moscow- 
Leningrad, 1958. Republished by S. Monson, Jerusalem, 
1960, 162 pp. 553-567 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
cristae appeared broken and in some of the 
swollen mitochondria they had more or less dis- 
appeared. In the outer zone of the perikaryon, 
the granular and lamellar components of the 
endoplasmic reticulum were also disintegrated. 
These ultramicroscopic findings suggest the in- 
terpretation that severe acute hypoxia causes a 
rise of intracellular osmotic pressure due to an 
increasing concentration of osmotically active 
components. 
555. Becker, N. H. The cytochemistry of anoxic and 
anoxic-ischemic encephalopathy in rats. II. Alterations in 
neuronal mitochondria identified by diphosphopyridine 
and triphosphopyridine nucleotide diaphorases. Amer. J. 
Path., 1961, 38: 587. 
556. Becker, N. H. The cytochemistry of anoxic and 
anoxic-ischemic encephalopathy in rats. III. Alterations in 
the neuronal golgi apparatus identified by nucleoside 
diphosphatase activity. Amer. J. Path., 1962, 40: 243-252. 
557. Becker, N. H. and K. D. Barron. The cyto- 
chemistry of anoxic and anoxic-ischemic encephalopathy 
in rats. I. Alterations in neuronal lysosomes identified by 
acid phosphatase activity. Amer. J. Path., 1961, 38: 161- 
175. 
558. Brierley, J. B. Some neuropathological contri- 
butions to problems of hypoxia, pp. 164-171 in: Cerebral 
anoxia and the electroencephalogram. Edited by John 
Stirling Meyer and Henri Gastaut. Charles C. Thomas, 
Springfield, 1961, 617 pp. 
559. Courville, C. B. Case studies in cerebral anoxia. 
VIII. The relation of local impairment of the circulation 
to certain structural changes in the cerebral cortex. Bull. 
Los Angeles neurol. Soc., 1955, 20: 74-82. 
560. Dominguez, A. M., J. R. Halstead, L. R. 
Goldbaum, H. I. Chinn and F. W. Lovell. Metabolic 
aspects of post-mortem changes in hypoxia. Fed. Proc., 
1960, 19: 177. 
561. Duspiva, F. and F. H. Franken. Untersuchun- 
gen fiber den Stoffwechsel bei akuter Hypoxie, I. Beitr. 
path. Anat., 1957,118: 38-51. 
562. Duspiva, F. and H. Noltenius. Untersuchun- 
gen fiber den Stoffwechsel bei akuter Hypoxie, II. Beitr. 
path. Anat., 1957, 118: 52-66. 
563. Edstrom, R. F. S. and H. E. Essex. Swelling of 
the brain induced by anoxia. Neurology, 1956, 6: 118-124. 
564. Hager, H., W. Hirschberger and W. Scholtz. 
Electron microscopic changes in brain tissue of Syrian 
hamsters following acute hypoxia. Aerospace Med., 1960, 
31: 379-387. 
565. Ingalls, T. H., F. R. Avis, F. J. Curley and 
H. M. Temin. Genetic determinants of hypoxia-induced 
congenital anomalies. J. Hered., 1953, 44: 185-194. 
566. Kipshidze, N. N. The effect of oxygen deficiency 
on the development experimental atherosclerosis of the 
coronary arteries. Bull. exp. Biol. Med., 1959, 47: 447-453. 
567. Lawrence, M. and E. G. Wever. Effects of 
oxygen deprivation upon the structure of the organ of 
corti. Arch. Otolaryng., 1952, 55; 31-37. 
553. Gandel’sman, A. B., R. P. Gracheva and 
N. B. Prokopovich. Adaptatsiia cheloveka k gipoksemii 
pri myshechnoi deiatel’nosti. [The adaptation of man to 
hypoxemia during muscular activity.] Fiziol. Zh. S.S.S.R. 
Sechenov, 1960, 46: 851-859. 
554. Stickney, J. C. and E. J, Van Liere. Acclima- 
tization to low oxygen tension. Physiol. Rev., 1953, 33: 
13-34. 
15. PATHOLOGY 
Meyer (569) 1956, has reviewed neuropath- 
ological findings in the cases of six human beings 
who died from anesthesia. On histological ex- 
amination severe lesions were found in all cases 
in the cerebral cortex, Ammon’s horn and cere- 
bellar cortex. The white matter was affected in 
one case. The basal ganglia were damaged in 
most cases while the thalamus, reticular zone of 
the substantia nigra, the corpus Luysii and 
dentate nuclei involved in some cases. There 
were no definite changes seen in the hypothala- 
mus, red nucleus and the compact zone of the 
substantia nigra or the geniculate bodies and 
inferior olives. 
Comparing human cases with experimental 
data on cats, lesions the same as in human beings 
were found in these animals. 
Edstrom and Essex (563) 1956, in a study of 
dogs subjected to respiratory hypoxia found no 
noticeable swelling of the brain or increased 
intracranial pressure clearly attributable to cere- 
bral edema within several hours after the hypoxic 
period. 
Local anoxia of brain tissue induced by oil or 
starch emboli consistently caused very rapid 
swelling of the brain and increase in intracranial 
pressure in the absence of any obvious systemic 
hypodynamic change. 
In order to study the changes of nerve cells 
in the cerebral cortex following acute anoxia, 
Hager, Hirschberger and Scholz (564) 1960, ex- 
posed Syrian hamsters repeatedly to pure nitro- 
gen atmospheres and low atmospheric pressure. 
Another group of animals was treated with potas- 
sium cyanide. A special method of osmic acid 
fixation by perfusion was developed to avoid a 
postmortem autolytic breakdown of the ultra- 
structures. The changes in the submicroscopic 
structures regularly involved the cell body. The 
nucleus was generally better preserved. The 
mitochondria were swollen and the mitochondrial LOW OXYGEN TENSIONS—NERVOUS SYSTEM 
568-576 
568. Levine, S. Anoxic-ischemic encephalopathy in 
rats. Amer. J. Path., 1960, 36: 1-14. 
569. Meyer, A. Neuropathological aspects of anoxia. 
Proc. R. Soc. Med., 1956, 49: 619-622. 
570. Molbert, E. and D. Guerritore. Elektronen- 
mikroskopische. Untersuchungen am Leberparenchym bei 
akuter hypoxie. Beitr. path. Anat., 1957, 117: 32-49. 
571. Plum, F., J. B. Posner and R. F. Hain. Delayed 
neurological deterioration after anoxia. Arch, intern. Med., 
1962,110: 18-25. 
572. Richardson, J. C., R. A. Chambers and P. M. 
Heywood. Encephalopathies of anoxia and hypoglycemia. 
Arch. Neurol., 1959, 1: 178-190. 
573. Scholz, W. Selective neuronal necrosis and its 
topistic patterns in hypoxemia and oligemia. J. Neuropath., 
1953, 12: 249-261. 
574. Van Harreveld, A. Changes in volume of corti- 
cal neuronal elements during asphyxiation. Amer. J. Phys- 
iol., 1957,191: 233-242. 
575. Van Harreveld, A. Asphyxial volume changes 
of cortical cells and fibers. Fed. Proc., 1957, 16: 131. 
576. Ziilch, K. J. and R. C. Behrend. The pathogene- 
sis and topography of anoxia, hypoxia and ischemia of 
the brain in man. pp. 144-163 in: Cerebral anoxia and the 
electroencephalogram. Edited by John Stirling Meyer and 
Henri Gastaut. Charles C. Thomas, Springfield, 1961, 617 
pp. 
B. LOW OXYGEN TENSIONS DUE TO 
DECOMPRESSION 
1. NERVOUS SYSTEM 
General effects of decompression upon the 
nervous system have been summarized by Luft 
and Noell (586) 1955-56, and Grandjean (582) 
1954, and Donaldson, Carter, Billings and Hitch- 
cock (578) 1960. Luft and Noell examined cere- 
bral manifestations of hypoxia during and after 
exposure to a barometric pressure of 68-70 mm. 
Hg by rapid decompression while breathing 
oxygen in two human subjects in a series of tests 
ranging from 6-18 seconds duration. The fol- 
lowing rapid sequence of neurological events 
was observed: 1) a state of automatism which 
ensued 13-15 seconds after decompression and 
exposure of more than 16 seconds duration. The 
subjects behaved as if confused and incapable 
of proper interpretation of judgment. There 
was amnesia during this phase. The EEG 
changes during this time were slight and con- 
sisted mainly in the activation of normal rhy- 
thms. 2) There was then a phase of ‘arrest’ 
initiated by sudden loss of consciousness at about 
17-19 seconds. Almost all spontaneous move- 
ment ceased, the eyes became fixed and glaring, 
and this was followed shortly by conjugated up- 
ward rolling of the eyeballs. Posture was main- 
tained but respiration was arrested. The dura- 
tion of this phase did not exceed three seconds. 
The EEG lacked specific changes, but there was 
a continuous increase in slow wave activity. 3) 
There was then a phase of failing posture, begin- 
ning with a slow drooping of the head of the 
sitting subject seen 19-20 seconds after exposure 
for at least 12 seconds. The generalized weak- 
ness was intermittent and was interrupted by 
brisk, rhythmic muscular movements which 
temporarily counteracted falling. The EEG de- 
teriorated progressively, as evidenced by domi- 
nance of abnormally slow frequencies and tem- 
porary absence of brain activity. The authors 
established certain analogies between the ob- 
served phenomena and changes in consciousness 
during epileptic seizures. They considered that 
the pattern of anoxic failure depends upon the 
loss of normal function in major integrating sys- 
tems of cerebral activities. The net anoxic sur- 
vival time of the most sensitive of these systems 
appears to be 4-5 seconds, and of that which de- 
termines loss of comprehension (unconscious- 
ness) 7-8 seconds. These figures were compared 
with those obtained in other circumstances lead- 
ing to sudden impairment of brain oxygenation. 
Grandjean concluded that the central nervous 
system is stimulated by altitudes up to 3500 
meters and is then depressed at higher regions. 
This stimulation of nervous function may be 
the result of general emergency reactions of the 
autonomic nervous system which regulates adap- 
tation of the body to first degrees o£ oxygen lack. 
In Grandjean’s studies healthy human subjects 
were studied at low altitudes of 560 or 800 meters 
and then taken to an altitude of 3450 meters on 
the Jungfraujoch. They remained at altitude for 
two to three weeks. Thresholds of cutaneous 
sensitivity were lowered at altitude in most of 
the subjects. Thresholds of gustatory sensitivity 
to glucose, NaCl, tartaric acid, quinine, were 
lowered in all subjects examined at altitude. 
There was also increased visual sensitivity and 
lowering of the thresholds for the knee-jerk re- 
flex. Administration of pure oxygen rapidly 
raised the thresholds at altitude for cutaneous 
sensitivity and knee-jerk reflex. Carbon dioxide 
inhalation had no effect. At altitude there was SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
a decrease in the amplitude of equilibratory 
movements. The consensual light reflex of the 
pupil was shortened at altitude, as were reaction 
times to optic stimulation. 
The effect of altitude and oxygen upon primary 
taste perception has been examined by Finkel- 
stein and Pippitt (580) 1958. These authors 
studied the effects of breathing 100 percent oxy- 
gen at a simulated altitude of 25,000 feet upon 
the taste sensitivity of young male adults. The 
study was performed to determine whether taste 
perception levels, taste identification levels, 
or ability to identify tastes, are effected by alti- 
tude, or by breathing pure oxygen. Motivation 
for this study was derived from differences noted 
in food acceptability on the ground and on 
high altitude flight situations. No effects of alti- 
tude or breathing pure oxygen on primary taste 
sensations were found which could account for 
these differences. An inability to identify taste, 
both on the ground and at altitude, was ob- 
served. From the results of this study the authors 
conclude that taste test procedures should not 
include questions that assume a subject’s ability 
to identify the primary tastes, particularly of sour 
and bitter. 
In 1953 Tonndorf (588) carried out laboratory 
experiments on human subjects to determine the 
combined effect of noise and hypoxia upon audi- 
tory threshold. Hypoxia was found to enhance 
the effect of noise. 
Ernsting, Gedye and McHardy (579) 1961 
have observed EEG changes produced by brief 
periods of decompression at levels from 560-155 
mm. absolute pressure. Reference may also be 
made to a paper by Woolley (590) 1964 in which 
a report was given of rats chronically implanted 
with bipolar electrodes in the lateral olfactory 
tract for stimulation and in the prepyriform cor- 
tex for recording. Prepyriform (PPG) responses 
were evoked by single shock (4/sec.) stimulation 
of the lateral olfactory tract (LOT) and were 
averaged with a Mnemotron C.A.T. before, dur- 
ing and after two hours of exposure to simulated 
high altitudes. Averages of 150 responses were 
subject to spectral (amplitude vs. frequency) 
analysis with the aid of computers. In each of 
five rats control spectra were characterized by a 
dominant component with a peak amplitude be- 
tween 44 and 53 cycles per second. Other peaks 
were found at 1, 11, 19-25 and 65-100 cps. 
They usually had amplitudes less than half that 
of the dominant frequency. Exposure to 18,000 
feet altitude resulted in prompt decreases in the 
frequency and amplitude of the principal com- 
ponents of approximately 12 and 40 percent re- 
spectively. Similar changes were observed during 
exposure to 12,500 feet simulated altitude. Addi- 
tional studies showed that the latency between 
stimulus and the beginning of the evoked re- 
sponse was significantly prolonged at altitude. 
The data suggested that conduction rate may 
be decreased or synaptic transmission delayed 
during altitude exposure. 
Heim and Timiras {584) 1964 produced spinal 
cord convulsions in rats at sea level and in rats 
of the first generation (Fj) born at 12,470 feet. 
At 11 and 28 days of age rats of both groups were 
decapitated at the cervical region. The spinal 
cord was stimulated by a needle electrode in- 
serted into the cervical cord and the anode was 
attached to exposed tissue of the neck. Square- 
wave stimuli, supramaximal with respect to volt- 
age and duration, were obtained from a Grass 
stimulator at 100 pulses per second. Ten seconds 
after decapitation the cord was stimulated and 
the durations of hindlimb flexion and extension 
were recorded in both groups of rats. Mean 
values ± S.E. for the duration (seconds) of the 
tonic phases of convulsion in 11 day old controls 
and Fj rats were respectively: flexion ± 0.10 and 
1.30 ± 0.07, and extension 8.85 ± 0.30 and 11.15 
± 0.12; in 28 day old controls and p! rats; 
flexion 2.15 ± 0.15 and 1.48 ±0.1 and extension 
4.07 ± 0.5 and 6.60 ± 0.38. The shorter flexion 
and longer extension in both age groups of rats 
born at high altitudes indicated to the authors 
an increased activity of the spinal cord. It was 
suggested that hypoxia and/or hypercapnia oc- 
curring at high altitude affects spinal reflex ac- 
tivity and thereby influences the functional 
development of the central nervous system. In 
1963 Heim and Timiras (583) had carried out 
experiments on rats indicating that although 
brain maturation is delayed at altitude, greater 
convulsability is exhibited by rats developing at 
altitude than at sea level. 
That performance of human subjects at 20,000 
feet is inferior to performance at ground level 
was indicated by experiments of Lansberg (585) LOW OXYGEN TENSIONS—MUSCLE 
577-591 
1959. This investigator administered stereo- 
phonic discrimination tests to six experienced 
pilots under the following experimental condi- 
tions: 1) at ground level, 2) at 20,000 feet with- 
out oxygen, 3) at 20,000 feet with oxygen, and 
4) again at ground level. Signal tones of 750 
c.p.s. and 2,500 c.p.s. were presented over a set 
of headphones at a sound pressure level of 70 
decibels during one second, followed by a four 
second pause. A time delay line, which could be 
operated in 25 microsecond steps, dispatched 
a signal the right or left ear, or to both simultane- 
ously, and the subjects were asked to indicate 
on paper whether there was an impression of 
lateralization to the right side, to the left side, 
or no lateralization. The tabulated results 
showed considerable divergence between the in- 
dividuals and indicated, as has been said, that 
the performance at 20,000 feet was inferior to 
that at ground level. The author stated that 
further exploration of the effect of the time in- 
terval between tests at 20,000 feet and further 
eva’uations of individual susceptibility were 
warranted. 
Malmejac and Plane (557) 1952 have studied 
the influence of oxygen want on functional 
cortical fitness by analysis of salivary conditioned 
reflexes in dogs. For the details of this study the 
original paper should be consulted. 
577. Bonvallet, M., A. Hugelin and P. Dell. Sensi- 
bilite comparee du systeme reticule activateur ascendant et 
du centre respiratoire aux gas du sang et a 1’adrenaline. 
J. Physiol. Path, gen., 1955,17: 651-654. 
578. Donaldson, R. T., E. T. Carter, C. E. Bill- 
ings, Jr. and F. A. Hitchcock. Acute hypoxia during 
rapid decompression and emergency descent in a commer- 
cial jet aircraft. Aerospace Med., 1960, 31: 842-851. 
579. Ernsting, J., J. L. Gedye and G. J. R. 
McHardy. Further observations on brief profound 
anoxia. J. Physiol, 1961, 155: 3P-5P. 
580. Finkelstein, B. and R. G. Pippitt. Effect of 
altitude and oxygen upon primary taste perception. J. 
Aviat. Med., 1958, 29: 386-391. 
581. Fromm, G. H. An unusual case of hemianopia 
from cerebral anoxia at high altitude. Amer. J. Ophthal., 
1960, 50: 658-660. 
582. Grandjean, E. The effect of altitude upon various 
nervous functions. Proc. roy. Soc., 1954, 143: 12-13. 
583. Heim, L. M. and P. S. Timiras. Brain matura- 
tion at an altitude of 12,500 ft. Fed. Proc., 1963, 22: 684. 
584. Heim, L. M. and P. S. Timiras. Spinal cord 
convulsions in young rats during acclimatization to an 
altitude of 12,470 feet (3800 m). Fed. Proc., 1964, 23: 521. 
585. Lansberg, M. P. The influence of hypoxia upon 
the central decoding system. Aeromed. Acta, 1959, 7: 129- 
134. 
586. Luft, U. C. and W. K. Noell. Manifestations of 
brief instantaneous anoxia in man. J. appl. Physiol., 1955- 
56, 8: 444-454. 
587. Malmejac, J. and P. Plane. Influence of oxygen 
want on functional cortical fitness. J. Aviat. Med., 1952, 
23: 177-180; 193. 
588. Tonndorf, J. Combined effect of noise and hy- 
poxia upon the auditory threshold. USAF. School of Avia- 
tion Medicine. Randolph Field, Texas. Project 21-1203- 
001, Kept. 1, 1953, 10 pp. 
589. Williams, E. S. Sleep and wakefulness at high 
altitudes. Brit. med. J., 1959,1: 197-198. 
590. Woolley, D. E. Spectral analysis of evoked elec- 
trical responses of the prepyriform cortex during high 
altitude exposure. Fed. Proc., 1964, 23 : 521. 
2. MUSCLE 
The effects of 20,000 feet simulated altitude 
on myoglobin content of animals with and with- 
out exercise has been studied by Clark, Criscuolo 
and Coulson (59/) 1952. In one group of ex- 
periments heart, gastrocnemius and diaphragm 
muscles of hamsters were analyzed for myoglobin 
content after a continuous acclimatization period 
of six weeks without exercise to a simulated alti- 
tude of 20,000 feet. Myoglobin values in terms of 
mg./gm. of wet tissue were measured. In a sec- 
ond group the gastrocnemius was removed from 
one leg before acclimatization and from the other 
leg at the end of the exposure period. In an- 
other series rats were exposed to a simulated 
altitude of 20,000 feet for six weeks and exercised 
for 30 minutes each day on a treadmill. Control 
groups were kept at ground level and exercised 
on a treadmill for a similar period. The results 
showed approximately a 200 percent increase of 
myoglobin in heart muscle for animals exercised 
during acclimatization at 20,000 feet simulated 
altitude as contrasted with those exercised at 
ground level. There was a 50 percent increase 
of diaphragmatic and gastrocnemius muscle 
myoglobin in the exercised animals at altitude 
as contrasted with those at ground level. 
Vaughan and Pace (592) 1956 have also reported 
an increase of myoglobin in rats taken from 
sea level to high altitudes (12,500 feet). 
591. Clark, R. T., Jr., D. Criscuolo and C. K. 
Coulson. Effects of 20,000 ft. simulated altitude on myo- 
globin content of animals with and without exercise. 
Fed. Proc., 1952,11: 25. 592 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
592. Vaughan, B. E. and N. Pace. Changes in myo- 
globin content of the high altitude acclimatized rat. 
Amer. J. Physiol, 1956, 185: 549-556. 
3. HEART AND CIRCULATION 
Under progressive hypoxia there tends to be 
an acceleration of the heart with alteration in 
systolic blood pressure, the pressure being main- 
tained, then rising, and then gradually falling. 
The pulse pressure tends to remain unchanged 
or increases. Astrand and Astrand (599) 1958 
recorded heart rate on four subjects performing 
muscular work: at sea level, during a three week 
sojourn at 14,250 feet altitude, during reacclima- 
tization to sea level conditions, and during acute 
exposure in an altitude chamber. It was observed 
that an increase in oxygen supply during heavy 
work in these subjects promptly increased the 
heart rate well above the ceiling which had been 
established. This response was observed only in 
acclimatized subjects. After reacclimatization to 
sea level, when acute hypoxia in the altitude 
chamber was removed by switching to oxygen 
during work, the heart rate invariably decreased. 
The effect of hypoxic hypoxia and low baro- 
metric pressure on the human electrocardiogram 
(vector analysis) has been studied by Alifanov 
(593) 1961. These studies were carried out on 
healthy human subjects to simulated altitudes 
of 5000 meters while breathing either air or at 
an equivalent altitude of 10,000 meters while 
breathing oxygen. In subjects who did not tol- 
erate hypoxia well there was an indication of 
increased load on the right heart. When no ad- 
verse effects resulted, the shift of the cardiac 
vectors to the left was accompanied by signs of 
increased left ventricular activity. With deterio- 
ration of the subjects’ condition there was also an 
indication of increased load on the right heart, 
therefore an EKG indicating such an increased 
right heart load constitutes also an objective 
sign of deterioration of the physical condition. 
Several aspects of pulmonary circulation have 
been studied by Rotta ,Canepa, Hurtado, Velas- 
quez and Chavez (616) 1956 in healthy adult 
males living at sea level and in temporary and 
permanent residents at altitudes of 4,540 meters 
(14,900 feet) . A moderate, but significant degree 
of pulmonary hypertension has been found in 
men living at high altitudes. This condition be- 
ing accentuated in the permanent resident and 
most striking in the cases of chronic mountain 
sickness. The probable pathogenesis of this con- 
dition is discussed in the original paper. Pena- 
loza, Sime, Banchero, Gamboa, Cruz and Marti- 
corena (614) 1963, have also studied pulmonary 
hypertension in healthy men born at high alti- 
tudes and living in such localities. Mild hyper- 
tension and a moderate increase of pulmonary 
vascular resistance and high ventricular work 
were found in men living permanently at high 
altitude. Pulmonary wedge pressure, cardiac out- 
put and heart rate did not show significant differ- 
ences from similar data obtained at sea level. 
Changes occurring in pulmonary circulation in 
men at high altitudes were not quite comparable 
to changes described in temporary residents at 
high altitudes, nor with those experimentally ob- 
tained by acute hypoxia. Therefore, the effects 
of hypoxia upon the pulmonary circulation are 
related not only to the degree of hypoxia, but 
also seem to be related to the time of exposure 
to it. The augmented pulmonary vascular resist- 
ance in the high altitude dweller is related to 
the anatomic changes in the small pulmonary 
arteries and arterioles which have been described 
by other investigators. Functional factors such 
as vasoconstriction, hypervolemia and polycy- 
themia, do not play an important role in the 
mechanism of pulmonary hypertension at high 
altitudes. The role of pulmonary hypertension 
in the complex mechanism of acclimatization to 
life at high altitude is not well understood. Ap- 
parently pulmonary hypertension would not ac- 
complish a useful part in this mechanism. It is 
possible, however, that pulmonary hypertension 
in association with other factors, such as hyper- 
ventilation and an extensive capillary bed of 
the lungs, does play a part in improving the 
arterial oxygenation in men living permanently 
at high altitudes. Further studies on pulmonary 
circulation and pulmonary hypertension have 
been reported by Banchero, Sime, Penaloza, 
Cruz and Gamboa (602) 1963, and Sime, Ban- 
chero, Penaloza, Gamboa, Cruz and Marticorena 
(619) 1963. 
Associated with pulmonary hypertension, it 
has also been shown by electrocardiographic and 
vectorcardiographic observations that dwellers 
at high altitudes show moderate degrees of right LOW OXYGEN TENSIONS—HEART AND CIRCULATION 
ventricular hypertrophy (Penaloza, Gamboa, 
Dyer, Echevarria and Marticorena {612) 1960, 
Penaloza, Gamboa, Marticorena, Echevarria, 
Dyer and Gutierrez {613), 1961). Right ventric- 
ular hypertrophy was demonstrated, for ex- 
ample, by Rotta and Lopez {617) 1959, in adult 
natives or long-term residents of Morococha, 
Peru (14,900 feet above sea level). The EKG 
confirms the anatomic and radiographic finding 
previously obtained in normal individuals at 
high altitudes. The authors believe that the right 
ventricular hypertrophy was related to the pul- 
monary hypertension usually found in men at 
high altitudes. Studies of heart rates, at simu- 
lated altitude and at altitude, by Valdivia, Rud- 
zik and Richardson {622) 1963, demonstrated 
in guinea pigs the presence of right ventricular 
hypertrophy in animals submitted to experi- 
mental and natural altitudes above 12,000 feet. 
It was also demonstrated in six animal species 
(guinea pigs, rabbits, dogs, lambs, pigs and 
steers) by Hultgren, Marticorena and Miller 
(610) 1963. The study of formalin-fixed heart 
rates demonstrated a moderate hypertrophy of 
the right ventricle in animals living continuously 
at altitudes of 10,000 to 15,000 feet altitude. 
These authors related the hypertrophy to pul- 
monary hypertension. 
With regard to peripheral circulation and the 
effect of simulated altitude upon it, Sunahara 
and Girling {620) 1958, exposed normal human 
subjects to 225 mm. Hg absolute pressure (30,000 
feet simulated altitude). Forearm blood flow 
was not affected by the exposure whereas hand 
blood flow was reduced significantly in all 
subjects. There was no change in heart rate. 
Since arterial blood pressure did not change 
there must have been constriction in the hand 
vessels. The effect appeared to be immediate 
and to be independent of the time spent at the 
reduced barometric pressure. There was con- 
siderable variation in hand blood flow response 
to the post exposure period. In many subjects 
the hand blood flow remained reduced for a 
considerable period, while in others it returned 
immediately to control values. These studies 
indicate to the authors that reduced barometric 
pressure increases sympathetic activity of the 
skin and blood vessels in man. On the other 
hand, Turner, Lambertsen, Owen, Wendel and 
Chiodi {621) 1957, found in human subjects 
that inhalation of 8, 21 and 80 percent oxygen 
produced with 80 percent oxygen no change in 
brain circulation or cerebral vascular resistance 
from control levels obtained during 21 percent 
oxygen breathing. Inhalation of 8 percent oxy- 
gen decreased cerebral vascular resistance 29 
and increased brain blood flow 36 per- 
.nt, leaving cerebral oxygen consumption un- 
altered. The observed degree of cerebral vasodi- 
latation represented the action of low P02, un- 
modified by antagonistic effects of hypocapnea 
normally associated with hypoxia. 
In studies carried out on dogs exposed to simu- 
lated altitudes of 25,000 feet for six hours daily, 
five times a week, for 1-27 months, Altland and 
Highman {594) 1956, found marked vascular 
engorgement in the heart. Changes in cardiac 
valves in other regions attributable to high alti- 
tudes were similar, but less frequent and less 
severe than in similarly exposed rats. Nine dogs 
with hematocrits from 67-81 (exposed 5-8 
months) received bacteria (Staphylococcus au- 
reus) . Susceptibility to endocarditis under these 
experimental conditions was moderately in- 
creased in dogs exposed to simulated high 
altitudes. 
Exposure of animals to high altitudes appears 
to increase the incidence of cardiovascular ano- 
malies. Record and McKeown {615) 1955, found 
a high incidence of patent ductus arteriosus in 
guinea pigs examined 24-26 hours after birth. 
Baird {600) 1963, studied mice and rats at 
12,470 feet. Among 33 Swiss albino mice, 23 sea 
level controls had no cardiovascular anomalies. 
In contrast 4 of 10 mice born and maintained 
on the mountain had congenital cardiovascular 
malformations, including interarterial and in- 
terventricular septal defects, patent foramen 
ovale, and persistent ductus arteriosus. All had 
postnatal anomalies, including right cardiac 
hypertrophy, hypervascularity and extreme atrial 
dilatation. Among the 62 Long-Evans rats, 26 
sea level controls and 19 rats born at sea level, 
but transferred to the mountain, no congenital 
cardiovascular anomalies were seen. In contrast, 
5 out of 17 rats conceived on the mountain had 
cardiovascular malformations, including dextro- 
cardia with partial situs inversus, absent or ex- 
tremely elongated innominate arteries, and 593-613 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
anomalous duplication of the basilar artery. 
Postnatal anomalies, including right cardiac 
hypertrophy, myocardial hypervascularity and 
hematocrits ranging to 71, were found among rats 
that had been on the mountain for prolonged 
periods, whether they were born at sea level 
or at high altitude. There was a definite cor- 
relation between continuous moderate hypoxia 
and the occurrence of congenital cardiovascular 
malformations and of postnatal cardiovascular 
anomalies in mice and rats. Similar findings have 
been reported by Baird and Cook (601) 1964. 
Arias-Stella and Recavarren (692) 1962, 
studied 70 infants and children, born and living 
at sea level, and 59 similar subjects from high 
altitude (12,225-14,300 feet). The ratio of left 
and right ventricular weights (Hermann-Wilson 
Index) was measured in all of these subjects. It 
was shown that at sea level the Hermann-Wilson 
Index attained values corresponding to those 
characteristic of adults, beginning at the fourth 
month of life. In the high altitude group the 
ratio indicated a persistent right ventricular 
predominance. Normally present at birth, this 
ordinarily gives way in due course at sea level 
to left ventricular dominance. The apparent 
right ventricular hypertrophy in the high alti- 
tude group persisted from the fourth month of 
life up to the maximum age investigated (10 
years). It was also observed that the degree of 
right ventricular predominance at birth and up 
to age three months was greater in infants bom 
at high altitudes than at sea level. For further 
studies of cardiac anomalies in subjects bom at 
high altitudes, a paper by Alzamora, Rotta, Bat- 
tilana, Abugattas, Rubio, Bouroncle, Zapata, 
Santa-Maria, Binder, Subiria, Paredes, Pando 
and Graham (695) 1953, may be consulted. 
593. Alifanov, V. N. The effect of hypoxic hypoxia 
and low barometric pressure on the human electrocardio- 
gram. (Vector analysis). Bull. exp. Biol. Med., 1961, 50: 
1009-1012. 
594. Altland, P. D. and B. Highman. Effects of high 
altitude exposures on dogs and on their susceptibility to 
endocarditis. Fed. Proc., 1956, 15: 3. 
595. Alzamora, V., A. Rotta, G. Battilana, R. 
Abugattas, C. Rubio, J. Bouroncle, C. Zapata, E. 
Santa-Maria, T. Binder, R. Subiria, D. Paredes, B. 
Pando and G. G. Graham. On the possible influence of 
great altitudes on the determination of certain cardio- 
vascular anomalies: preliminary report. Pediatrics, 1953, 
12: 259-262. 
596. Arias-Stella, J. and S. Recavarren. Right 
ventricular hypertrophy in native children living at high 
altitude. Amer. J. Path., 1962, 41: 55-64. 
597. Arias-Stella, J. and M. Saldana. The terminal 
portion of the pulmonary arterial tree in people native to 
high altitudes. Circulation, 1963, 28: 915-925. 
598. Astrand, P. A study of chemoceptor activity in 
animals exposed to prolonged hypoxia. Acta physiol, 
scand., 1954, 30: 335-342. 
599. Astrand, P.—O. and I. Astrand. Heart rate 
during muscular work in man exposed to prolonged hy- 
poxia. Fed. Proc., 1958, 17: 6. 
600. Baird, B. Congenital and postnatal cardiovascu- 
lar anomalies in hypoxic mountain-bred rodents. Circula- 
tion, 1963, 28: 686. 
601. Baird, B. and S. F. Cook. Hypoxia and vascular 
responses of mountain deermice (Peromyscus). Fed. Proc., 
1964, 23: 522. 
602. Banchero, N., F. Sime, D. Penaloza, J. Cruz 
and R. Gamboa. Effects of exercise on the heart and 
pulmonary circulation of the high-altitude native. Circu- 
lation, 1963, 28: 686-687. 
603. Buckley, J. P., L. D. Edwards and W. A. 
Hiestand. Effect of discontinuous decompression on blood 
pressure in the rat. Amer. J. Physiol., 1953, 175: 93-95. 
604. Busnengo, E. Ipossia e circolo pulmonare. Riv. 
Med. aero., 1958, 21: 567-575. 
605. Campbell, F. W. The influence of a low atmos- 
pheric pressure on the development of the retinal vessels 
in the rat. Trans, ophthal. Soc. U.K., 1951, 71: 287-300. 
606. Dejours, P., F. Girard, Y. Labrousse and J. 
Raynaud. Stimulus oxygriie chemoreflexe de la ventilation 
<4 basse altitude (50 m) chez 1’Homme. II. Au cours de 
1’exercise musculaire. J. Physiol. Path, gen., 1957, 49: 120- 
124. 
607. Gilfillan, R. S., J. T. Hansen, R. H. Kellog, 
N. Pace and E. M. Cuthbertson. Physiologic study of 
the chemoreceptor mechanism in the dog at sea level and 
at high altitude (12,600 feet). Circulation, 1958, 18: 724. 
608. Hecht, H. H., H. Kuida, R. L. Lange, J. L. 
Thorne and A. M. Brown. Hemodynamics of altitude 
heart failure in calves. Fred. Proc., 1960, 19: 97. 
609. Houston, C. S. Acute pulmonary edema of high 
altitude. New Engl. J. Med., 1960, 263: 478-480. 
610. Hultgran, H. N., E. Marticorena and H. Mil- 
ler. Right ventricular hypertrophy in animals at high 
altitude. J. app. Physiol., 1963, 18: 913-918. 
611. Nahas, G. G. Effects of acute exposure to low 
oxygen tension on the circulation of vagotomized non- 
narcotized dogs. J. appl. Physiol., 1956, 9: 65-68. 
612. Penaloza, D., R. Gamboa, J. Dyer, M. Eche- 
varria and E. Marticorena. The influence of high alti- 
tudes on the electrical activity of the heart. I. Electro- 
cardiographic and vectorcardiographic observations in the 
newborn, infants, and children. Amer. Heart J., 1960, 59: 
111-128. 
613. Penaloza, D., R. Gamboa, E. Marticorena, 
M. Echevarria, J. Dyer and E. Gutierrez. The in- 
fluence of high altitudes on the electrical activity of the 
heart. Amer. Heart J., 1961, 61: 101-115. LOW OXYGEN TENSIONS—BLOOD 
614-623 
614. Penaloza, D., F. Sime, N. Banchero, R. Gam- 
boa, J. Cruz and E. Marticorena. Pulmonary hyper- 
tension in healthy men born and living at high altitudes. 
Artier. J. Card., 1963,11: 150-157. 
615. Record, R. G. and T. McKeown. The effect 
of reduced atmospheric pressure on closure of the ductus 
arteriosus in the guinea pig. Clin. Sci., 1955, 14: 255-228. 
616. Rotta, A., A. Canepa, A. Hurtado, T. Velas- 
quez and R. Chavez. Pulmonary circulation at sea level 
and at high altitudes. appl. Physiol., 1956, 9: 328-336. 
617. Rotta, A. and A. Lopez. Electrocardiographic 
patterns in man at high altitudes. Circulation, 1959, 19: 
719-728. 
618. Schumacher, K. Uber eine neue Methode zur 
Bestimmung der menschlichen Leistungsreserve mit Hilfe 
des Sauerstoffmangels. Dtsch. Versuchanst. Luftf., Rept. no. 
72, August 1958, 31 pp. 
619. Sime, F., N. Banchero, D. Penaloza, R. Gam- 
boa, J. Cruz and E. Marticorena. Pulmonary hyper- 
tension in children born and living at high altitudes. 
Amer. J. Card., 1963,11: 143-149. 
620. Sunahara, F. A. and F. Girling. Circulatory 
changes in the human forearm and hand at simulated 
altitude. Fed. Proc., 1958, 17: 158. 
621. Turner, J., C. J. Lambertsen, S. G. Owen, 
H. Wendel and H. Chiodi. Effects of .08 and .8 atmos- 
pheres of inspired p02 upon cerebral hemodynamics at a 
“constant” alveolar pC02 of 43 mm Hg. Fed. Proc., 1957, 
16: 130. 
622. Valdivia, E., J. R. Rudzik and L. D. Richard- 
son. Heart weights in experimental and natural high alti- 
tude. Circulation, 1963, 28: 820. 
623. Vavala, D. A. The blood transport of respiratory 
gases. The effects of altitude hypoxia and hyperventila- 
tion associated with positive pressure breathing. Milit. 
Med., 1955, 117: 513-520. 
4. BLOOD 
It is well established that, with wide varia- 
tions, exposure to reduced barometric pressure 
results in a polycythemic response. It appears 
that the response is directly proportional to the 
degree, duration, and continuity of the hypoxia, 
and that there is a limit beyond which the 
hypoxic stimulus will not cause a erythropoietic 
response. Extremely severe hypoxia may indeed 
cause a depression rather than further stimula- 
tion of the blood forming mechanisms. The 
immediate polycythemic response early in ex- 
posure to high altitude seems to be caused by 
release of stored blood, for example, from the 
spleen. Hyperactivity of the erythropoietic 
mechanism follows repeated or constant exposure 
to low pressures. 
It may be that subjects living at high altitudes 
may not show significant differences in blood 
values when compared and contrasted with per- 
sons living at low altitudes or at sea level. Such 
conclusions have been drawn by Sottano, Fer- 
nandez, Zangheri and Suarez (650) 1959. Blood 
values were determined in 30 men and 20 women 
between the ages of 18 and 27 living in Mendoza, 
Argentina (747 meters above sea level). The 
hemoglobin content was found in men to be 
15.67 gm/100 ml; in women 13.48 gm/100 ml. 
The average number of erythrocytes in men was 
5.449 million/mm3; and in women 4.697 mil- 
lion/mm.3 For men the hematocrit values were 
47.37 percent; and for women 43.17 percent. The 
average corpuscular hemoglobin content in men 
was 28.96 fifig., and in women 29.56 /x/xg. The 
average corpuscular volume in men was 87.56/x3, 
and in women 91.5 /x3. The average concentra 
tion of corpuscular hemoglobin in men was 33.08 
percent and in women 32.01 percent. The 
authors reviewed 34 references to previous work 
and concluded that no significant differences in 
blood values were found between their subjects 
and those living at lower levels or at sea level. 
The differences between the values for men and 
for women were not significant. In a study of 
polycythemia of high altitudes, Reynafarje, Lo- 
zano and Valdivieso (646) 1959, observed that 
the degree of reticular cytosis is closely related 
with changes in red cell iron turnover rate. 
There was an increase in human subjects ex- 
amined of intestinal iron absorption during the 
early period of exposure to an altitude of 14,900 
feet. After 48 hours of exposure this was esti- 
mated to be about three times higher than the 
absorption observed in subjects at sea level and 
in native residents at 14,900 feet. There was an 
increase of plasma and red cell iron turnover 
after two hours of arrival at 14,900 feet, indicat- 
ing that the increase in the production of red 
cells to compensate for hypoxia is a very early 
response. The highest increase in plasma and red 
cell iron turnover rate took place between 7-14 
days after exposure to high altitude. After six 
months of exposure there was still an elevated 
iron turnover rate. The native residents at 14,900 
feet showed a red cell iron turnover rate of 
approximately 30 percent higher than healthy 
subjects at sea level. A progressive decrease in 
the plasma and red cell iron turnover rate was 
observed in native residents of high altitudes SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
when brought down to sea level, reaching a 
maximum after two to five weeks, and indicat- 
ing a great degree of depression of red cell pro- 
duction. After that there was a gradual return 
to normal rates. Changes in the blood volume 
either during ascent or descent took place only 
after several weeks. The red cell mass variation 
occurring during the early periods of environ- 
mental change were compensated for by propor- 
tional changes in the plasma volume. The in- 
crease or decrease of the total blood volume after 
this period appeared to be due exclusively to red 
cell mass modification. Cytological studies of 
bone marrow carried out on subjects temporarily 
exposed or living permanently at high altitudes 
demonstrated a hyperplastic condition. The re- 
verse, or an inhibition of red cell production 
took place when high altitude polycythemic 
subjects were brought down to sea level. This 
constitutes cytologic counter-proof for the iron 
turnover studies. The life span of the red blood 
cells after descent from high altitudes to sea 
level fell within normal patterns. However, it 
was not possible to determine whether there was 
an increased destruction of red cells during the 
first week. If there is a greater destruction, this 
would appear to be of a small degree affecting 
only the older elements. Mazzella {641) 1958, 
decompressed rabbits to 267 mm Hg (800 meters 
equivalent) for one hour and then returned them 
to sea level. Blood was collected before flight, 
immediately afterward, and subsequently 15 
minutes, 30 minutes, 60 minutes and 120 minutes 
after flight. Hemoglobin, red blood corpuscles, 
platelets, white blood corpuscles, hematocrits, 
reticulocytes and mean corpuscular volume were 
found to be normal 15 minutes after return to 
sea level. There was some increase of hemoglo- 
bin, red blood count, hematocrit, platelets and 
reticulocytes. Similar findings were reported by 
Mazzella and Ghinozzi {642) 1958. 
Reynafarje {645) 1957 found a general but 
close relationship between the degree of polycy- 
themia and the level of altitude at which perma- 
nent residents live. These studies were carried 
out at Morococha, a mining town in the Andes, 
at an altitude of 4540 meters (14,900 feet), with 
a mean barometric pressure of 446 mm Hg. 
The native subjects showed a mean red cell 
count of 6,400,000 cells/mm3, and a hemoglobin 
of 20 grams/100 ml of blood. The hematocrit 
was about 60 percent. It was found that the size 
and shape of circulating erythrocytes and the 
hemoglobin content did not differ essentially 
from the values found at sea level. Generally 
the total blood volume and red blood count in- 
creased in ten subjects taken to 14,900 feet and 
observed during one year of continuous residence. 
The opposite effect was found on three natives 
taken to sea level and studied during four 
months. In these latter subjects the blood volume 
and red blood count dropped. In subjects taken 
up to 14,900 feet the reticulocyte count reached a 
peak on the sixth day of a two week stay and 
dropping back by the end of the 14-day period 
almost to normal. This author’s observations 
clearly showed that anoxic stimulus of high alti- 
tude environment causes an increase in red blood 
cell count in red blood cell precursors, but does 
not affect the granulocytes and the platelets. 
Hyperplasia of the erythropoietic tissue occurs 
at altitude and changing from high altitude to 
low altitude is characterized by an inhibition 
of the erythropoietic activity during the initial 
days of the new exposure. Working with rats, 
Contopoulos, Van Dyke, Simpson, Lawrence and 
Evans {629) 1954, found that suckling rats be- 
tween the age of 4-16 days did not respond to 
hypoxia (15,000 feet equivalent for six hours) 
with an increased erythropoiesis as judged by in- 
creased hematocrit, hemoglobin and red blood 
corpuscular volume. Colehour {628) 1960, has 
conducted a study of erythropoietic stimulating 
factor production in pubescent mice after a single 
exposure to hypoxia. Pubescent, pre-pubescent, 
and post-pubescent mice were exposed for six 
hours to a simulated altitude of 22,000 feet, after 
which cardiac punctures were made on the first, 
second, third or fourth day for hematocrit and 
reticulocyte determinations. Baseline values were 
determined using similar animals without ex- 
posure to hypoxia. It was shown that mice after 
puberty have a reticulocyte response greater than 
baseline when subjected to a single hypoxic ex- 
posure, but do not have this capacity before 
puberty. Furthermore, if the production of 
erythropoietic stimulating factor (ESF) is ac- 
cepted as the prerequisite to reticulocytosis 
it can be said that the endocrine changes at 
puberty are concomitant with the animals’ ability LOW OXYGEN TENSIONS—BLOOD 
to increase the production of ESF. These studies 
may be correlated with the observation that 
pre-pubescent animals exhibit an increased bind- 
ing capacity for oxygen by myoglobin. 
Using C 14 labelled glycine, Berlin, Reynafarje 
and Lawrence (625) 1954, found in Peruvians 
living at 12,000 feet that the red blood corpuscu- 
lar life span varied between 109 and 117 days 
(average 114), and paralleled that of men at 
sea level. Similar results were found in rats by 
Fryers and Berlin (634) 1952. In animals ac- 
climatized to high altitudes the life span of red 
blood cells was normal. Of the red cells produced 
during the initial phase of rapid erythropoiesis 
resulting from exposure of rats to simulated high 
altitude conditions, at least some showed a 
shorter than normal life span. Although not con- 
clusive, the authors’ evidence did not support the 
concept that increased destruction of red cells 
occurs on returning an altitude-acclimatized 
animal to sea level. 
In a study of hemoglobin content in residents 
at high altitude, Rathe (644) 1959, determined 
values in 25 normal persons between 5 and 20 
years of age, living at Mina Aguilar, Argentina 
(4515 meters altitude), and in Jujuy, Argentina 
(1270 meters altitude). No significant statistical 
differences were found in the hemoglobin content 
between the two groups. Dill (630) 1963, carried 
out a study during the summer of 1962 during 
the early phase of acclimatization to high altitude 
in six subjects who had participated in the previ- 
ous expedition to the Chilean Andes in 1935. 
The ages of these subjects at the 1962 study 
ranged from 58-71. Two of the subjects had also 
taken part in a high altitude study in 1929. In 
1935 the three on whom hemoglobin was de- 
termined beginning with their arrival at high 
altitude showed an immediate increase. A re- 
sponse in young men has been well established 
by other workers. In 1962 five of the six subjects 
exhibited a decrease in hemoglobin concentration 
during the first days. The greatest decrease was 
observed in the author who was the oldest subject. 
His hemoglobin was 88 percent of his sea level 
value after nine days at altitude and remained 
below his sea level value for another week. No 
observations were made on blood volume and 
hence the author could only speculate regarding 
the possible related responses. It seemed un- 
likely to the author that there was unusual de- 
struction of hemoglobin since none of the 
subjects engaged in strenuous exercise. Two 
hypotheses were advanced: 1) in this age range 
anoxia may slow up hematopoietic activity, or 
2) there may be an early increase in total plasma 
volume that outruns the early increase, if any, 
in total red cell volume. Metcalfe, Meschia, 
Hellegers, Prystowsky, Huckabee and Barron 
(643) 1959, studied 36 ewes that had been born 
and raised at high altitudes and bred on known 
dates at the Institute of Andean Biology at 15,000 
feet altitude. Samples of maternal arterial and 
uterine venous blood as well as fetal umbilical 
arterial and venous blood were taken anaero- 
bically with the mother under spinal anesthesia. 
The data so obtained, when compared with 
findings at sea level, suggested a pattern of com- 
pensations both maternal and fetal to the alveo- 
lar hypoxia of altitude. There was a higher 
hemoglobin concentration, in both fetal and ma- 
ternal blood, at high altitude. Despite this, the 
maternal arterial blood contained less oxygen 
due to its lower saturation. Uterine venous 
blood, however, contained more oxygen (at a 
slightly lower saturation) at high altitude than 
at sea level resulting in a decreased arteriovenous 
oxygen difference across the pregnant uterus, and 
a lower mean percentage saturation of maternal 
blood in the uterus. The umbilical venous blood, 
however, was as well saturated with oxygen by 
its passage through the uterus at high altitudes 
as at sea level. 
In a study of the effects of high altitude upon 
the protein composition of human blood, Smoli- 
chev (649) 1961, determined the protein com- 
position of the blood in 12 young healthy in- 
dividuals in Stalinabad (850 meters) and during 
their stay in the mountains of East Pamir (4200 
meters). During the first month of sojourn at 
high altitude the total concentration of protein 
was increased, while towards the end of the four- 
month period it dropped somewhat, but still 
remained above the initial level. The relative 
and absolute albumin content in the blood serum 
dropped immediately after the ascent and re- 
mained low for a month after descent from 4200 
meters to 850 meters. The figures for (alpha-1), 
B- and (gamma-) globulin rose immediately 
after ascent. During the four-month stay at alti- SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
tude, the (alpha-1) and gamma globulins went 
back to normal. During the first month after 
descent figures for alpha-1, beta and gamma 
globulins were higher than the initial levels. 
The alpha-1 globulin went up only after descent. 
The oncotic pressure of blood rose during the 
first month after ascent and then returned to 
normal at the expense of increased concentration 
of the globulin fraction, which compensates for 
the decreased albumin content in blood serum. 
Trapani and Bartel (653) 1958, investigated 
the effect of high altitude on the electrophoretic 
distribution of plasma proteins in the rabbit. 
Sea level samples were obtained at the California 
Institute of Technology (755 feet) and the high 
altitude samples were collected at the Barcroft 
Laboratory, White Mountain Research Station, 
California (12,470 feet). During the first week 
of acclimatization there was a decrease in the 
percentage of albumin and an increase in the 
alpha and beta globulins. However, after an 
additional 30-day period the albumin was in- 
creased, and the alpha and beta globulins were 
decreased in relation to the sea level values. The 
gamma globulin did not change significantly 
during the exposure period. Total protein con- 
centration increased approximately 30 percent 
after 37 days at altitude. Estimates of plasma 
volume based on the dilution of circulating anti- 
bodies give a value of approximately 30 percent 
less than plasma volumes measured in rabbits 
at sea level by the Evans Blue technique. The 
decrease in plasma volume and the increase in 
protein concentration indicate to the authors 
that the mass of circulating protein may not 
change, and in addition, the turnover rate did 
not appear to differ much from that in animals 
at sea level. 
Exposure to high altitude results in a decrease 
of plasma potassium. Sussman, Pratt, Smith 
and Ferguson (652) 1953, decompressed Long- 
Evans male rats to a simulated altitude of 25,000 
feet (282 mm Hg) and other rats to 30,000 feet 
(226 mm Hg) for 30 minutes and returned them 
to ground levels in 10-15 seconds. Controls were 
run with rats in the chamber at atmospheric con- 
ditions. Controls showed 6.23 mEq/liter; those 
at 25,000 feet showed 5.07 mEq/liter; and those 
at 30,000 feet showed 5.08 mEq/liter. The 
hematocrit was significantly elevated at 25,000 
and 30,000 feet with no apparent difference be- 
tween these two altitudes. Ferguson, Smith and 
Barry (632) 1956, subjected bilaterally adren- 
alectomized dogs maintained on cortisone or 
DCA, or in moderate adrenal insufficiency to a 
simulated altitude of 30,000 feet (225.6 mm Hg) 
for 90 minutes (three 30-minute periods). The 
plasma potassium concentration consistently 
showed a decrease by the end of the first 30- 
minute period and remained depressed for the 
duration of the decompression. This response 
was found to be statistically similar to that ob- 
served in intact dogs and indicated to the authors 
that, in this species, the hypokalemia of acute 
decompression stress is not mediated by the 
adrenal glands. As in intact dogs, the plasma 
sodium remained unchanged. In the adrenalec- 
tomized dogs, there was no increase in hematocrit. 
No eosinopenia was observed in intact dogs. 
Preliminary studies indicated that a respiratory 
alkalosis is associated with the plasma potassium 
changes occurring in dogs with decompression 
to 30,000 feet. Whether alkalosis is responsible 
for the potassium changes remains, according to 
the authors, to be determined. In subsequent 
reports Gold, Barry and Ferguson (635) 1959, 
(636) 1960, and (637) 1961, found that the 
potassium decrease at altitude in the dog in re- 
sponse to moderate altitude stress occurs without 
prior transient hyperkalemia, such as occurs 
in human subjects. It was also found that there 
was a temporal potassium-glucose relationship, 
the potassium decreasing and the glucose increas- 
ing simultaneously during exposure to altitude. 
It appears according to the authors that potas- 
sium ions leave the plasma and enter the tissue 
as a secondary response to alkalosis. 
Weiner (655) 1959, exposed both young and 
mature rabbits in a decompression chamber to a 
simulated altitude of 6000 meters (64 mm Hg) 
for 45 days, and then returned them to normal 
atmospheric pressure and observed them for an 
additional period of 42 days. At altitude the 
serum transaminase level fell from 6 units to 3.4 
units in 20 hours, and then rose to a value of 9.5 
to 33 units for the remainder of the experiment, 
including the stay at normal pressure. Similarly, 
the adult animals showed an initial decline fol- 
lowed by a sharp increase in transaminase. 
Hemoglobin levels increased at altitude in both LOW OXYGEN TENSIONS—BLOOD 
624-633 
the young and adult animals and decreased 
gradually at normal pressure. Lactic acid and 
pyruvic acid levels showed similar fluctuations, 
generally an initial rise followed by a decline 
and subsequent return to normal level. It ap- 
pears that transaminase activity, which reflects 
the level of protein metabolism, is independent 
of the synthesis of hemoglobin. The lactic acid 
and pyruvic acid levels indicate the level of 
carbohydrate metabolism. 
A study of the effect of decreased atmospheric 
pressure on blood volume of rats has been car- 
ried out by Fryers {633) 1952. The animals 
were exposed to an equivalent altitude of 15,000 
feet for 3 to 100 days. Fully acclimatized rats 
were studied at 8,000 feet, 15,000 feet and 20,000 
equivalent altitudes. A marked increase in total 
red cell volume and total hemoglobin was ob- 
served and it was reported that a steady state for 
hemoglobin and red cell volume at 15,000 feet 
was reached within ten days of lowering the 
barometric pressure. The total plasma volume 
was reduced to the same extent by exposure to 
altitudes of 15,000 feet and 20,000 feet. The 
rate of formation of new red cells was observed to 
be increased to 5.9 times normal during the de- 
velopment of acclimatization. 
Carter {626) 1955, and Carter and Clark 
{627) 1958, have examined the effect in dogs 
of carbonic anhydrase inhibition during hypoxia. 
Trained unanesthetized dogs were acutely ex- 
posed to a barometric pressure of 350 mm. Hg 
in a decompression chamber. Diamox, the car- 
bonic anhydrase inhibitor, was administered 
intravenously (100 mg/kg) before decompres- 
sion in one series of runs and after decompression 
in another series. Arterial blood samples were 
analyzed for P0o by the Riley technique. Alveo- 
lar PCOo was estimated from end-tidal gas sam- 
ples, while the arterial blood C02 content was 
determined by the method of Van Slyke. Venti- 
lation-gas exchange data were obtained on a 
recording spirometer. Decrease in arterial P0<? fol- 
lowing decompression was less in animals previ- 
ously given Diamox than in controls. The 
arterial P0„ rises when Diamox is given after 
steady state at altitude was obtained. Alveolar 
PCOo decreases more during ascent with Diamox 
than without Diamox. Alveolar PC09 decreases 
if Diamox is given after steady state at 350 mm. 
Hg pressure. Diamox treated dogs manifested a 
higher ventilation equivalent for carbon dioxide 
when at 350 mm. Hg than controls at the same 
altitude. Diamox treated dogs manifested greater 
decrease in arterial carbon dioxide content after 
ascent than did control dogs, while no differences 
in expired air R.Q. were noted when treated 
dogs were compared to controls. All initial ob- 
servations at altitude were made after at least 30 
minutes of exposure, and all ground level ob- 
servations represented the basal state. 
Other enzyme studies include a report by 
Marra {640) 1960, who found in rabbits decom- 
pressed at about 130 meters per minute to a 
simulated altitude of 6700 meters for five hours, 
an increase in blood aldolase and ciruloplasmin 
levels, with no change in blood transaminase 
level It was suggested by the author that modi- 
fications in blood enzymes are related to changes 
in the cellular permeability of muscles induced 
by hypoxic stress and its related metabolic 
changes. 
624. Astaldi, G., E. Bernardelli and G. Rebaudo. 
Research of the proliferation activity of erythroblasts at 
low atmospheric pressure. Experientia, 1952, 8: 117-119. 
625. Berlin, N. I., C. Reynafarje and J. H. Law- 
rence. Red cell life span in the polycythemia of high 
altitude. /. app. Physiol., 1954, 7: 271-272. 
626. Carter, E. T. Carbonic anhydrase inhibition 
during hypoxia. Fed. Proc., 1955, 14: 26. 
627. Carter, E. T. and R. T. Clark, Jr. Effects of 
carbonic anhydrase inhibition during acute hypoxia. J. 
nppl. Physiol, 1958, 13: 47-52. 
628. Colehour, J. K. Erythropoietic stimulating factor 
production in pubescent mice after a single exposure to 
hypoxia. Proc. Soc. exp. Biol., N.Y., 1960, 105: 673-675. 
629. Contopoulos, A. N., D. C. Van Dyke, M. E., 
Simpson, J. H. Lawrence and H. M. Evans. Failure 
of newborn rat to respond to hypoxia with increased ery- 
thropoiesis. Proc. Soc. exp. Biol., N.Y., 1954, 86: 713-715. 
630. Dill, D. B. Hemoglobin concentration at high 
altitude as related to age. Fed. Proc., 1963, 22: 455. 
631. Dunseath, W. J. R., F. P. Ferguson and D. 
C. Smith. Effects of moderate decompression stress upon 
plasma potassium and glucose in the adrenalectomized 
cat. Endocrinology, 1960, 66: 763-768. 
632. Ferguson, F. P., D. C. Smith and J. Q. Barry, 
The response of plasma potassium to acute decompression 
stress in adrenalectomized dogs. USAF, Randolph Field, 
Texas, School of aviation medicine. Project 57-14, Novem- 
ber 1956, 14 pp. 
633. Fryers, G. R. Effect of decreased atmospheric 
pressure on blood volume of rats. Amer. J. Physiol., 1952, 
171: 459-464. 634-656 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
634. Fryers, G. R. and N. I. Berlin. Mean red cell 
life of rats exposed to reduced barometric pressure. Amer. 
J. Physiol, 1952, 171: 465-170. 
635. Gold, A. J., J. Q. Barry and F. P. Ferguson. 
Early effects of moderate altitude stress on plasma potas- 
sium in the dog. Fed. Proc., 1959, 18: 54. 
636. Gold, A. J., J. Q. Barry and F. P. Ferguson. 
Early effect of moderate altitude stress on plasma potas- 
sium in the dog. J. appl. Physiol, 1960, 15: 37-39. 
637. Gold, A. J., J. Q. Barry and F. P. Ferguson. 
Relation of respiratory alkalosis to hypokalemia in anes- 
thetized dogs during altitude stress. J. appl. Physiol, 1961, 
16: 837-838. 
638. Hale, H. B. and J. E. Keator. Comparison of 
eosinophil responses in human subjects during flights in 
aircraft, decompression to 40,000 ft. and exposure to cold. 
Fed. Proc., 1952, 11: 63. 
639. Hall, F. G. Blood gas tensions in dogs following 
hyperventilation at altitude. Fed. Proc., 1954, 13: 66. 
640. Marra, V. Comportamento delle attivita transami- 
nasiche, aldolasiche e della ceruloplasmina in conigli 
sottoposti ad ipossia acuta. Riv. Med. aero., 1960, 23 : 500- 
507. 
641. Mazzella, G. Tempo di ritorno alia norma delle 
modificazioni indotte sulla crasi ematica dalla anossia 
acuta Riv. Med. aero., 1958, 21: 484—198. 
642. Mazzella, G. and G. P. Ghinozzi. Comporta- 
mento della temperatura rettale e variazioni ematiche e 
midollari ossee in conigli sottoposti a depressione baro- 
metrica in ambiente con diffenenti gradi di umidita’ rela- 
tiva. Riv. Med. aero., 1958, 21: 744-755. 
643. Metcalfe, J., G. Meschia, A. Hellegers, H. 
Prystowsky, W. Huckabee and D. Barron. Transfer 
of oxygen across the sheep placenta at high altitude. Fed. 
Proc., 1959, 18: 104. 
644. Rathe, G. Estudio de la hemoglobina de resi- 
dentes a 4515 m. sobre el nivel del mar. Rev. Soc. argent. 
Biol, 1959, 35: 275-278. 
645. Reynafarje, C. The influence of high altitude on 
erythropoietic activity. Brookhaven Symp. Biol, 1957, 10: 
132-146. 
646. Reynafarje, C., R. Lozano and J. Valdivieso. 
The polysythemia of high altitudes: Iron metabolism and 
related aspects. Blood, 1959, 14: 433-455. 
647. Riggs, A. The nature and significance of the 
Bohr effect in mammalian hemoglobins. J. gen. Physiol, 
1959-60, 43: 737-752. 
648. Severinghaus, J. W., R. A. Mitchell, B. W. 
Richardson and M. M. Singer. Respiratory control at 
high altitude suggesting active transport regulation of 
CSF pH. /. appl. Physiol, 1963, 18: 1155-1166. 
649. Smolichev, E. P. The effect of high altitude on 
the protein composition of human blood. Bull. exp. Biol. 
Med., 1961, 50: 1053-1055. 
650. Sottano, E. Y., F. O. Fernandez, E. O. Zang- 
heri and J. R. E. Suarez. Valores hematicos normales 
en sujetos jovenes residentes en Mendoza (747 m s.n.m.). 
Rev. Soc. argent. Biol, 1959, 35: 263-274. 
651. Stutman, L. J., F. H. Kriewaldt, V. Doerr and 
M. George. Effect of lipemia on arterial oxygen at high 
altitude. J. appl. Physiol., 1959, 14: 894-896. 
652. Sussman, K. E., A. J. Pratt, D. C. Smith and 
F. P. Ferguson. Effects of acute decompression stress 
upon plasma potassium and hematocrit in the rat. Bull. 
Univ. Md. Sch. Med., 1953, 38: 164-167. 
653. Trapani, I. L. and A. H. Bartel. Changes in 
circulating plasma proteins of rabbit blood under altitude 
stress. Fed. Proc., 1958, 17: 164. 
654. Villalonga, J. and W. Lins Filho. Tratamento 
da coqueluche pelo voo de altitude na Forca Aerea Brasi- 
leira Rev. tried. Aero., Rio de J., 1952, 4: 95-108. 
655. Weiner, K. Uber den Einfluss von langfristiger 
kontinuierlicher Hypoxie auf die Serum-GIutaminsaure- 
Oxalessigsaure-Transaminase. Dtsch. Versuchanst. Luftf., 
Kept. no. 101, September 1959, 27 pp. 
656. Wiinsche, O. and H. Hartmann. Zur Pathog- 
enese und Prophylaxe der Druckfallkrankheit des Hohen- 
fliegers. IV. Die Beeinflussung der intravasalen Gasblasen- 
bildung nach rascher Depression durch Anderung der 
Blutviscositat. Int. Z. angew. Physiol., 1960, 18: 456-459. 
5. RESPIRATION 
When one breathes ambient air at high alti- 
tudes a hypoxic stimulus causes a rapid increase 
in pulmonary ventilation. Pugh {678) 1957, 
{679) 1958, and Pugh, Gill, Lahiri, Milledge, 
Ward and West {680) 1964, have studied venti- 
lation under conditions of high mountain ex- 
ploration. Resting ventilation (BTPS) rose to 
13-22 liters per minute (mean 15.8 liters per 
minute) above 18,000 feet, compared with 5.5-9.8 
liters per minute (mean 7.3 liters per minute) 
at sea level. Ventilation at STPD was inde- 
pendent of altitude. Resistance hyperpnea on 
descending to lower altitude was not observed 
in the subjects studied and the reports of other 
members of the author’s party on Mt. Everest 
suggested that individual responses to change of 
altitude were highly variable. Hall {666) 1951, 
and {667) 1952, has pointed out that the full 
effect on pulmonary ventilation of the hypoxic 
stimulus is counteracted by a concomitant hypo- 
capnia. With the addition of carbon dioxide to 
the inspired air a more effective response to the 
hypoxic stimulus is manifested. The author con- 
cluded that while hypoxia and hypercapnia are 
separate stimulating factors and additive in their 
effects, the actual regulation of respiration at 
altitude appears to depend upon the manner of 
their interaction. Hornbein and Roos {670) 
1961, have reported that hypoxia of mild degree 
(PA0, above 60 mm. Hg) produces little or no LOW OXYGEN TENSIONS—RESPIRATION 
657-673 
ventilatory response in resting man during the 
steady state. How respiratory acclimatization to 
altitudes below 10,000-12,000 feet can take place 
in the absence of a detectable hypoxic chemore- 
ceptor drive has remained a mystery. It has been 
suggested that the mechanism initiating the 
process of acclimatization to mild hypoxia might 
differ basically from that at higher altitude 
where the ventilatory effect of chemoreceptor 
activity is apparent at rest. The possibility 
exists that the effectiveness of a hypoxic chemo- 
receptor drive might be enhanced by exercise. 
This was confirmed experimentally by the 
authors. These findings are confirmed by De- 
jours, Girard, Labrousse and Teillac (664) 1959, 
and Dejours, Labrousse, Raynaud, Girard and 
Teillac (665) 1958, in resting subjects. 
For studies on respiratory adaptations to pro- 
longed hypoxia, papers by Chiodi (660) 1956, 
(661) 1957, and (662) 1963, and by Astrand 
(658) 1954, should be consulted. The pulmonary 
ventilatory response to high altitude is higher 
in newcomers than in adapted residents. 
Studies by Kreuzer (671) 1960; by Kreuzer, 
Tenney, Andersen, Schreiner, Nye, Mithoefer, 
Valtin and Naitove (672) 1960; and Kreuzer, 
Tenney, Mithoefer and Remers (673) 1962, on 
alveolar-arterial oxygen gradient should be con- 
sulted. These authors find in dogs and in man 
that the alveolar arterial oxygen gradient with 
air at altitude is lower than with air at sea 
level, and also lower than with 11 percent oxygen 
at sea level. The effect at altitude may be due to 
an increase of pulmonary diffusing capacity at 
altitude. 
Of interest in connection with respiratory 
effects at high altitudes are studies during the 
past ten years or more on decompression treat- 
ment of whooping cough. The following authors 
may be consulted: Kriefer (674) 1953; Banks 
(659) 1955; Harnack (668) 1955; Verhoeven 
(683) 1957; and Heinonen and Karvonen (669) 
1958. These reports cover the treatment of sev- 
eral hundred patients in which it appears that 
the treatment is inadequate for acutely ill 
patients, and that it is not effective or even 
better in the milder than in the more severe 
cases. Subjects are taken to an equivalent alti- 
tude of about 12,000 feet and maintained for 30 
minutes to 45 minutes, three times a day, every 
other day. It does appear that the treatment may 
have value; with regard to the mechanism there 
are many questions. Possibly this treatment has 
an effect on the neurovegetative system as has 
been suggested by Verhoeven (683) 1957. 
657. Anderson, L. L., M. L. Dillcox, J. Silliman 
and S. G. Blount, Jr. The pulmonary physiology of 
normal individuals living at an altitude of one mile. J. 
din. Invest., 1953, 32: 490^196. 
658. Astrand, P. The respiratory activity in man ex- 
posed to prolonged hypoxia. Acta physiol., scand., 1954, 30: 
343^68. 
659. Banks, H. S. Decompression treatment of whoop- 
ing-cough. Brit. med. J., 1955, -: 1052-1055. 
660. Chiodi, H. Respiratory adaptations to chronic, 
high altitude hypoxia. Fed. Proc., 1956, 15: 35. 
661. Chiodi, H. Respiratory adaptations to chronic 
high altitude hypoxia. J. appl. Physiol., 1957,10: 81-87. 
662. Chiodi, H. Respiratory adaptation to high alti- 
tude. pp. 363-378 in: The regulation of human respiration. 
Edited by D. J. C. Cunningham and B. B. Lloyd, F. A. 
Davis Co., Philadelphia, 1963, 591 pp. 
663. Cotes, J. E. Ventilatory capacity at altitude and 
its relation to mask design. Proc. roy. Soc., 1954, 143: 32-39. 
664. Dejours, P., F. Girard, Y. Labrousse and A. 
Teillac. Etude de la regulation de la ventilation de repos 
chez 1’Homme en haute altitude. Rev. frang. din. biol., 
1959, 4: 115-127. 
665. Dejours, P., Y. Labrousse, J. Raynaud, F. 
Girard and A. Teillac. Stimulus oxyg£ne de la ventila- 
tion au repos et au cours de 1’exercise musculaire, a Basse 
altitude (50 M), chez I’Homme. Rev frang. din. biol., 1958, 
3: 105-123. 
666. Hall, F. G. Regulation of breathing in man at 
altitude. Proc. Soc. exp. Biol., N.Y., 1951, 78: 580-582. 
667. Hall, F. G. Regulation of breathing of man at 
altitude. Fed. Proc., 1952, 11: 63. 
668. Harnack, von, G. A. Die Beeinflussung des 
Keuchhustenverlaufes durch Hohenfliige. Dtsch. med. 
Wschr., 1955, 80: 958-961. 
669. Heinonen, A. O. and M. J. Karvonen. Hinkuy- 
skan hoito alipainekammiossa. [Treatment of pertussis in 
decompression chamber.] Duodecim, 1958, 74: 34-37. 
670. Hornbein, T. F. and A. Roos. Effect of mild 
hypoxia on ventilation during exercise. Fed. Proc., 1961, 
20: 430. 
671. Kreuzer, F. Alveolar-arterial oxygen gradient in 
dog at altitude. Fed. Proc., 1960, 19: 382. 
672. Kreuzer, F., S. M. Tenney, D. C. Andersen, 
B. F. Schreiner, R. E. Nye, J. C. Mithoefer, H. 
Valtin and A. Naitoye. Alveolar-arterial oxygen gradi- 
ent in the clog at altitude. J. appl. Physiol., 1960, 15: 796- 
800. 
673. Kreuzer, F., S. M. Tenney, J. C. Mithoefer 
and J. Remmers. Alveolar-arterial oxygen gradient 
(AaDOo) in Andean natives at high altitude. XXII Inter. 
Congr. physiol. Sci., Leiden. 1962, 2: Abstr. 673. 674-688 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
674. Krieger, K. Uber die Erfolge der Keuchhustenbe- 
handlung in der Klimakammer. Munch, med. Wschr., 1953, 
4: 148-150. 
675. Lambertsen, C. J. Anoxia, altitude, and acclima- 
tization. Anoxia, pp. 691-699 in: Medical physiology. 
Edited by P. Bard. C. V. Mosby Company, St. Louis, 1961, 
1339 pp. 
676. Lo Monaco, T. La vitesse inspiratoire dans 
1’anoxie anoxique comme methode d’exploration de la 
fonction respiratoire. pp. 19-30 in: Collected papers on 
aviation medicine. Butterworths Scientific Publications, 
London, 1955, 209 pp. 
677. Petty, T., W. Bartlett and J. L. Chapin. Effects 
of altitude acidosis, and alkalosis upon hypoxic threshold. 
Proc. Soc. exp. Biol, N.Y., 1955, 90: 664-666. 
678. Pugh, L. G. C. E. Resting ventilation and al- 
veolar air on Mount Everest: with remarks on the relation 
of barometric pressure to altitude in mountains. J. Physiol., 
1957,135: 590-610. 
679. Pugh, L. G. C. E. Muscular exercise on Mount 
Everest. /. Physiol, 1958, 141: 233-261. 
680. Pugh, L. G. C. E., M. B. Gill, S. Lahiri, J. W. 
Milledge, M. P. Ward and J. B. West. Muscular exer- 
cise at great altitudes. J. appl. Physiol, 1964, 19: 431-440. 
681. Reed, D. J. and R. H. Kellogg. Effect of sleep 
on hypoxic stimulation of breathing at sea level and alti- 
tude. J. appl. Physiol, 1960, 15: 1130-1134. 
682. Terman, J. W. The changes in alveolar and 
arterial gas tensions with altitude as related to age. Fed. 
Proc., 1963, 22: 455. 
683. Verhoeven, A. F. P. M. Kinkhoestbehandeling 
door onderdruk. Treatment of whooping cough with de- 
compression. Aeromed. Acta., 1957, 5: 211-238. 
684. Wayne, H. H. Clinical differentiation between 
hypoxia and hyperventilation. J. Aviat. Med., 1958, 29: 
307-315. 
685. West, J. B. Oxygen transfer by the lung at high 
altitude. XXII Inter. Congr. physiol. Sci., Leiden. 1962, 2: 
Abstr. 297. 
6. ALIMENTARY TRACT 
In general conditions of hypoxia decreased 
gastric motility can cause a delay in gastric empty- 
ing time in both animals and man. The gastroin- 
testinal tract has been stated to be relatively 
resistant to hypoxia, as contrasted for example 
with the central nervous system. The propulsive 
motility of the small intestine is known to be de- 
creased by hypoxia. The propulsive motility is 
significantly less in the unacclimatized than in 
the acclimatized animals. Gastric secretion tends 
to be diminished by hypoxia. According to Dan- 
hof and Steggerda (686) 1961, hyperventilation 
induced in human and animal subjects by simu- 
lated ascents to 15,000 feet altitude is accom- 
panied by a lowering of blood PC02 and a 
depression in gastric acid secretion presumably 
as a result of interference with the role of carbon 
dioxide intracellularly. Naitoye and Tenney 
(687) 1960, studied gastric acid secretion in two 
normal human subjects at sea level and after one 
and six days of continuous residence at high alti- 
tude (14,246 feet). An evaluation of the separ- 
ate and interacting effects of alveolar carbon 
dioxide and oxygen tensions on gastric acid 
secretion was made possibly by appropriate varia- 
tions in the inspired mixtures. Exposure to the 
hypoxia and hypocapnia of high altitude resulted 
in a man increase in free HC1 acid secretion to 
levels four times sea level controls. The same 
degree of hypocapnia at the higher P02 at sea 
level resulted in a net decrease. After six days at 
altitude there was a fall in secretory rate towards 
normal. Hypercapnia was uniformly associated 
with marked increases in secretory levels, being 
highest at altitude. The findings suggested to 
the authors that the level of gastric acid secretion 
was directly related to alveolar PC02 and that 
for any given PCOa, secretion was inversely re- 
lated to alveolar P02. 
686. Danhof, I. E. and F. R. Steggerda. Gastric acid 
secretory responses to distention at simulated altitude. 
Aerospace Med., 1961, 32: 520-523. 
687. Naitoye, A. and S. M. Tenney. Effects of al- 
veolar Oa and CO, on gastric secretion in man. Fed. Proc., 
1960, 19: 190. 
688. Steggerda, F. R., W. C. Clark and I. E. Dan- 
hof. Effects of altitude and diet on the C02 content of 
flatus in man. Fed. Proc., 1952, 11: 154. 
7. METABOLISM 
Cullumbine (690) 1952, has reported experi- 
ments in which male mice were exposed to a 
moderately low barometric pressure (460 mm. 
Hg) for a period of 48 hours. This exposure 
induced a preliminary involution of lymphoid 
tissue; increased weight, nitrogen and glycogen 
contents of the liver; reduced carcass fat and 
nitrogen; increased muscle glycogen; and reduced 
adrenal cholesterol content. Later there was a 
hypertrophy of the lymphoid tissue, reduced 
liver nitrogen and glycogen and a return of the 
carcass fat to near normal values. The carcass 
nitrogen continued to decrease, however, and 
the adrenal cholesterol remained at a low value. 
These responses were dependent on the presence 
of the pituitary gland and they were modified 
in various ways by removal of the adrenal 
glands, the thyroid and the testes. In order to ob- LOW OXYGEN TENSIONS—METABOLISM 
tain a better understanding of the process associ- 
ated with altitude acclimatizations, Green (693) 
1961, subjected white rats to a simulated alti- 
tude of 18,000 feet in a low pressure chamber for 
several months. Groups of animals were sacri- 
ficed at regular intervals and various tissues 
analyzed for biochemical changes. GOT and 
GPT were reduced in both the liver and kidneys 
of the hypoxic animal. Cytochrome C reductase 
activity was reduced initially in both the liver 
and the kidney, but was higher than the control 
values after two months exposure, coinciding 
with the acclimatization. Succinic dehydrogenase 
was erratic in response to decreased oxygen ten- 
sion, giving some insight into the contradictory 
results coming from different laboratories. Liver 
glycogen and blood glucose were consistently de- 
pressed in the hypoxic animals while heart gly- 
cogen was elevated during the early exposure, 
subsequently falling to a subnormal level. Heart- 
body ratios increased while other tissue ratios 
decreased. Total nucleotides were decreased in 
most tissues with heart and kidney being most 
resistant to change, respectively. It was con- 
cluded by the author that while many biochemi- 
cal reactions are affected by hypoxia, the kidney 
seems to be most dramatically affected by ac- 
climatization. 
Terzioglu and Aykut (699) 1954, determined 
basal metabolic rates in 12 subjects (20-30 years 
of age) at various times during a stay of 12 days 
at an altitude of 1.85 km. The basal metabolic 
rate of each subject was found to be raised on the 
fifth and sixth days and remained that way until 
returned to sea level. The mean RQ dropped 
from 0.92 to 0.84 at altitude. Respiratory minute 
volume increased also, but tended to return to 
normal while the subject was still at altitude. 
Picon-Reategui (698) 1961, determined basal 
metabolic rate and body composition in 17 
healthy adult male subjects living at an altitude 
of 14,900 feet above sea level. The BMR of high 
altitude residents fell within the limits considered 
normal for healthy adults at sea level. An in- 
crease in oxygen uptake in human beings at high 
altitude was observed by Grover (694) 1963. 
Multiple determinations of basal oxygen uptake 
were made on six individuals at both 5,200 feet 
and at 14,150 feet. The small but significant rise 
in oxygen uptake observed probably reflected, 
according to the author, the energy required to 
increase ventilation. All of the subjects had 
lived at altitude for one year. 
Growth rate may be reduced by long exposure 
to high altitude. Thus Valdivia, Richardson and 
Forbes (701) 1964, exposed pregnant guinea pigs 
to a simulated high altitude of 13,000 feet, the 
exposure starting between the 30th and 35th ges- 
tation days. Pregnant guinea pigs exposed to 
13,000 feet delivered litters of normal size. The 
time of delivery was between the 60th and 70th 
days of gestation. The average weight of nine 
newborn males exposed to high altitude was 
71 ± 4.8 gm. and for eight females was 73 ± 6,4 
gm. The animals born at simulated high alti- 
tudes continued to be exposed at 13,000 feet. As 
the exposure continued their body weights re- 
mained significantly lower when compared to 
sea level animals of similar ages. The average 
body weight for guinea pigs 16 weeks of age 
reared in the laboratories was 800 grams in con- 
trast with a weight of 600 grams for those reared 
in the low pressure chamber at a simulated high 
altitude of 13,000 feet. 
The lactic acid content in human venous blood 
during hypoxia at high altitude has been studied 
by Harboe (695) 1957. Lactic acid concentration 
increased with the degree and duration of hy- 
poxia. Apart from heights of 15,000 to approxi- 
mately 20,000 feet, where lactic acid concentra- 
tion increases simultaneously with increasing 
disability, such concentrations were poorly corre- 
lated with functional disability during hypoxia. 
Cain and Dunn (689) 1964, noted that blood 
lactic levels have been reported by some to be 
elevated during exposure to altitude and by oth- 
ers to be unaffected. After a three hour control 
period at ground level, unanesthetized dogs were 
exposed for eight hours at 21,000 feet simulated 
altitude (335 mm. Hg). Arterial lactic acid 
reached a peak value within the first two hours 
at altitude and gradually declined thereafter, and 
in most animals closely approached the control 
value during the eighth hour at altitude. Excess 
lactate changed in a similar manner. According 
to Lalli Venditti (697) 1959, there was an in- 
crease of lactic acid concentration in the brain 
of hypoxic rats which could be correlated with 
the duration of hypoxia and inversely correlated 
to the rate of ascent. 689-702 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
In studies of Fillios, Andrus and Naito {691) 
1961, it was found that rats made polycythemic 
by prolonged exposure to simulated high alti- 
tudes also had a marked degree of coronary in- 
volvement, but no apparent increase in en- 
docardial sudanophilia; whereas sea level cobalt 
polycythemia does not appear to favor an in- 
crease in coronary or endocardial sudanophilia. 
This suggests that polycythemia, per se, does not 
favor an increase in lipid deposition at these 
sites. These findings suggested to the authors 
that tissue hypoxia may account for the increase 
in coronary sudanophilia, while changes in en- 
docardial sudanophilia appear to be related 
more closely to the circulating cholesterol for 
all the groups. 
As to the effect of hypoxia upon succinic de- 
hydrogenase activity of the heart, liver and skele- 
tal muscles, Vacca {700) 1958, found in rats no 
noticeable changes at simulated altitudes of 8500- 
9000 meters (169-248 mm. Hg). 
Whitehorn, Ullrick, Krone and Brennan {702) 
1953, have reported on the influence of low 
oxygen tensions on the respiration of tissues of 
acclimatized rats. The purpose of the study was 
to determine whether tissues of acclimatized 
animals have increased ability to take and utilize 
oxygen at low tensions. Nine male albino rats 
were maintained at 18,000 feet simulated altitude 
for 10-15 weeks. Using a standard Warburg 
technique, respiratory rates of liver, ventricle, 
kidney and adrenal slices were compared to rates 
of tissues of five controls under concentrations 
of 100, 20 and 2 percent oxygen. It was found 
that the kidneys of acclimatized rats respired at 
a reduced rate under all three of the oxygen ten- 
sions, and that acclimatized adrenals showed 
higher than normal rates under all tensions. The 
respiration of liver and ventricle did not differ 
from control values. The acclimatized animals 
exhibited no changes in adrenal weight or total 
metabolism, but demonstrated cardiac hyper- 
trophy and increased hemoglobin. These results 
confirmed previous experiments indicating in- 
creased adrenal and decreased kidney respiration 
in acclimatization. There is no indication that 
acclimatized tissues are better able to take up 
oxygen at low tensions than are tissues from un- 
acclimatized animals. 
689. Cain, S. M. and J. E. Dunn II. Transient ar- 
terial lactic acid changes in unanesthetized dogs at 21,000 
feet. Amer. J. Physiol., 1964, 206: 1437-1440. 
690. Cullumbine, H. Changes in composition of tissues 
of mice after exposure to low pressure. Amer. J. Physiol., 
1952, 169: 515-524. 
691. Fillios, L. C., S. B. Andrus and C. Naito. 
Coronary lipid deposition during chronic anemia or high 
altitude exposure. J. appl. Physiol., 1961, 16: 103-106. 
692. Gray, G. W. Life at high altitudes. Sci. Amer., 
1955, 193: 59-68. 
693. Green, J. A. Some biochemical changes in re- 
sponse to hypoxia. Fed. Proc., 1961, 20: 210. 
694. Grover, R. F. Basal oxygen uptake of man at 
high altitude. J. appl. Physiol., 1963, 18: 909-912. 
695. Harboe, M. Lactic acid content in human venous 
blood during hypoxia at high altitude. Acta physiol, scand., 
1957, 40: 248-253. 
696. Jewell, H. A. Blood sugar levels and hypoxia. 
Fed. Proc., 1952, 11: 78. 
697. Lalli, G. and G. Venditti. Comportamento 
dell’acido lattice cerebrale nel ratto ucciso mediante anos- 
sia anossica in rapporto alia velocity de decompressione 
barometrica. Riv. Med. aero., 1959, 22: 69-76. 
698. Picon-Reategui, E. Basal metabolic rate and 
body composition at high altitudes. J. appl. Physiol., 1961, 
16: 431-434. 
699. Terzioglu, M. and R. Aykut. Variations in 
basal metabolic rate at 1.85 km altitude. J. appl. Physiol., 
1954, 7; 329-332. 
700. Vacca, C. Comportamento dell’attivita’ succinico- 
deidrogenasica e succinico-ossidasica nei ratti in condizioni 
di ipossia. Riv. Med. aero., 1958, 21: 715-724. 
701. Valdivia, E., L. D. Richardson and S. Forbes. 
Guinea pig growth during exposure to simulated high 
altitude. Fed. Proc., 1964, 23: 522. 
702. Whitehorn, W. V., W. C. Ullrick, J. G. Krone 
and B. B. Brennan. Influence of low oxygen tensions on 
respiration of tissues of acclimatized rats. Fed. Proc., 1953, 
12: 154. 
8. ENDOCRINES 
Timiras, Batts, Hollinger, Karler, Krum and 
Pace (712) 1956, have studied endocrine re- 
sponses during adaptation to moderately high 
altitude in rats. The weight and morphology of 
the adrenal glands, hypophysis, pancreas, testes 
and thyroid were investigated in these animals 
(P animals) exposed for various periods of time 
at the 12,500 foot level at the White Mountain 
Research Station, and in rats of the second gen- 
eration born at the station (F2 animals). These 
animals were compared with rats remaining in 
the parent colony on the Berkeley campus (sea 
level controls). Comparable conditions of food, 
caging and temperature were maintained. The P 
animals were born at sea level and maintained LOW OXYGEN TENSIONS—ENDOCRINES 
at these levels for about ten weeks before trans- 
fer to White Mountain one and three days and 
two months before sacrifice. After one to three 
days of exposure, adrenal cortical activity was 
stimulated as indicated by 1) a 40-50 percent 
increase in adrenal weight, 2) a loss of adrenal 
ascorbic acid (after one day’s exposure), and 3) 
a 60-80 percent decrease in the weight of the 
thymus, spleen and lymph nodes. No change in 
weight could be observed in the hypophysis, 
testes and thyroid. The preputial glands were 
significantly enlarged after three days exposure. 
After two months’ exposure, the P animals ex- 
hibited a significant enlargement of the hypoph- 
ysis and thyroid as well as of the adrenal, even 
when other criteria (such as growth, reproduc- 
tion, blood hemoglobin and hematocrit) indi- 
cated adaptation to the new situation. Testes 
and preputial glands remained unchanged. On 
the other hand, in the F2 animals born at high 
altitude, endocrine weights appeared to be simi- 
lar to those of sea level controls. 
Kline (708) 1952, has stated that exposure of 
cats to moderate and severe anoxia indicates in- 
volvement of the adrenal gland with an antago- 
nistic action of medullary and cortical divisions. 
At 28,000 feet for 90 minutes the adrenal cortex 
exercises dominant control, as evidenced by de- 
creases in plasma potassium concentration of 18 
percent in normal cats, 19 percent in nephrecto- 
mized animals, and 14 percent in splanchnecto- 
mized cats. It is suggested that a 51 percen tin- 
crease in urinary potassium and an 88 percent 
increase in volume indicate the action of cortin. 
When animals were acutely adrenalectomized, or 
adrenalectomized and nephrectomized, there was 
no decrease in plasma potassium with exposure to 
28,000 feet. It was believed that increases of 58 
percent and 69 percent in the plasma potassium 
concentration of normal and nephrectomized cats 
exposed to 40,000 feet were under the influence 
of the adrenal medulla, since similar increases 
were observed with the injection of adrenaline. 
When adrenalectomized and splanchnectomized 
cats were exposed to 40,000 feet the plasma potas- 
sium increased only 18 percent and 11 percent 
respectively. Pratt, Smith and Ferguson (711) 
1955, found in 41 unanesthetized Wistar rats de- 
compressed to simulated altitudes of 25,000, 28,- 
000, 30,000 and 35,000 feet for 30 minutes, that 
there was a significant reduction in plasma po- 
tassium concentration from the average value of 
6.35 mEq/liter in 18 ground level control rats. 
In 20 unanesthetized, chronically adrenalecto- 
mized rats, maintained on 1 percent NaCl, there 
was no change in the plasma potassium con- 
centration after decompression to a simulated 
altitude of 30,000 feet for 30 minutes. Injection 
of adrenaline (0.02 mg./100 gm.) into 14 adren- 
alectomized rats reduced the plasma potassium 
concentration by approximately the same amount 
as does moderate decompression in the intact rat. 
When either seven intact or two adrenalecto- 
mized rats were subjected to 40,000 feet (to the 
point of respiratory collapse), there was a sig- 
nificant increase in the plasma potassium con- 
centration. Similar results were reported in 
dogs by Ferguson, Smith and Barry (707) 1957, 
and Barry, Ferguson, Gold and Smith (704) 
1961. In the latter study the authors concluded 
that adrenal involvement appears to be a factor in 
the hypokalemia observed in restrained intact 
dogs subjected to simulated high altitude while 
in unrestrained dogs respiratory alkalosis seems 
to be solely responsible. 
Urinary excretion rates of epinephrine and 
norepinephrine were measured in six men by 
Pace, Griswold and Grunbaum (710) 1964. 
After three days in Berkeley (100 meters) , the 
subjects were taken to the Barcroft Laboratory of 
the White Mountain Research Station (3800 
meters) where measurements were made for 24 
days. Little change occurred in the epinephrine 
excretion rate, other than the expected diurnal 
variation. In contrast, norepinephrine excretion 
rate increased steadily, starting the second day at 
Barcroft, to twice that at sea level by the end 
of the 14 day sojourn (58.9 ug./24 hrs. compared 
with a mean sea level value of 30.8 ug./24 hrs.). 
Although the bulk of the increase occurred dur- 
ing the day, an increase was also noted in the 
overnight period. Mean resting heart rate rose 
from 69/minute at sea level to 92/minute by the 
second day at altitude, and then gradually fell to 
87/minute by the 14th day. Neither norepine- 
phrine excretion rate nor heart rate had returned 
to the original sea level value by the fourth day 
after the altitude sojourn. These data are in- 
terpreted by the authors as evidence for a sub- 
stantial and continuing response of the sym- 703-712 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
pathetic nervous system during at least the first 
14 days at altitude. They also indicate some 
measure of functional adaptation to increased 
norepinephrine. 
The effects of hypoxia on fertility have been 
studied by Baird and Cook {703) 1961, who ex- 
posed Swiss albino rats continuously or discon- 
tinuously to simulated altitudes up to 25,000 
feet or to 12 percent oxygen in nitrogen at sea 
level. All control matings were found to be 
fertile. Of 30 matings during continuous ex- 
posure to 14,200 or 18,000 feet, all were fertile. 
Of 36 matings during discontinuous exposure (6 
hours/day) to 20,000 or to 25,000 feet, all re- 
sulted in impregnation. Of 28 matings during 
continuous exposure to 12 percent oxygen, only 
one gave negative results. In these mice aberrant 
reproductivity was manifested by gestational ab- 
normalities, fetal and maternal deaths, congenital 
anomalies and cannibalism. Under the experi- 
mental conditions studied, fertility per se was 
adequate for the propagation of the species. 
703. Baird, B. and S. F. Cook. Hypoxia and fertility 
in adapted mice. Fed. Proc., 1961, 20: 210. 
704. Barry, J. Q., F. P. Ferguson, A. J. Gold and 
D. C. Smith. Relation of respiratory alkalosis and adrenal 
activity to hypokalemia in restrained and unrestrained 
dogs subjected to simulated high altitude. Fed. Proc., 1961, 
20: 210. 
705. Bruner, H., D. Jovy and K. E. Klein. Hypoxia 
as a stressor. Aerospace Med., 1961, 32: 1009-1018. 
706. DeBias, D. A. and K. E. Paschkis. Survival of 
adrenal-ectoraized animals exposed to low barometric 
pressure. Fed. Proc., 1960, 19: 154. 
707. Ferguson, F. P., D. C. Smith and J. Q. Barry. 
Hypokalemia in adrenalectomized dogs during acute de- 
compression stress. Endocrinology, 1957, 60: 761-767. 
708. Kline, R. F. Role of adrenal glands in the plasma 
and urinary electrolyte changes during moderate and 
severe anoxia. Fed. Proc., 1952,11: 84. 
709. Mefferd, R. B., Jr. Catecholamines in high alti- 
tude stress — a correlational analysis. Fed. Proc., 1963, 22: 
684. 
710. Pace, N., R. L. Griswold and B. W. Grun- 
baum. Increase in urinary norepinephrine excretion dur- 
ing 14 days sojourn at 3,800 meters elevation. Fed. Proc., 
1964, 23: 521. 
711. Pratt, A. J., D. C. Smith and F. P. Ferguson, 
Role of the adrenal gland in the response of plasma potas- 
sium of the rat to moderate and severe hypoxia. Endocri- 
nology, 1955, 57: 450^55. 
712. Timiras, P. S., A. A. Batts, G. W. Hollinger, 
R. Karler, A. A. Krum and N. Pace. Endocrine re- 
sponses during adaptation to moderately high altitude. 
Fed. Proc., 1956,15: 187. 
9. TEMPERATURE 
Decompression to simulated 18,000 (380 mm. 
Hg) in a cool environment has been shown by 
Brown, Vawter and Marbarger {713) 1952, to 
produce significant changes in heart rate, systolic 
and diastolic blood pressure as compared to re- 
sponses elicited during exposure to a cool en- 
vironment uncomplicated by anoxia. Skin and 
rectal temperatures in these subjects were not 
significantly different during exposure to hy- 
poxia in a cool environment, than those observed 
during exposure to the same environment in the 
presence of adequate oxygen. The response in 
human beings to exposure to a cool environment 
does not appear to be significantly altered by a 
reduced partial pressure of oxygen in the in- 
spired air. Hale {714) 1953, in a series of ob- 
servations on men exposed to hypoxia at high 
environmental temperatures, studied changes in 
circulation, respiration, body temperature and 
adrenal cortical function in male subjects during 
standardized exposures to low barometric pres- 
sure under two different conditions of tempera- 
ture (80° and 120° F.). In preliminary tests, the 
elevation in heart rate resulting from 15 minutes 
exposure to 18,000 feet simulated altitude was 
slightly greater in 12 out of 19 subjects when they 
were in the overheated state. In the remaining 
seven, heart rate changes were elevated, but not 
to the degree seen when the temperature was in 
the comfort range. The elevation in heart rate 
due to the heat factor was apparent both before 
and after the hypoxia phase, but a truly ‘additive’ 
effect was not seen during hypoxia. Results from 
tests on a second group of subjects breathing a 
ten percent oxygen in nitrogen mixture show 
that time is an important element because there 
was a tendency for heart rates to decrease slightly 
after 15 minutes exposure to hypoxia at 80° F., 
but at higher temperatures heart rates either 
continued to climb throughout the exposure 
period or suddenly dropped to subnormal levels. 
For a study of effects of thermal conditioning 
on metabolic response of rats to altitude, a paper 
by Mefferd and Hale {716) 1958, should be con- 
sulted. Hale and Mefferd {715) 1958, have also 
examined metabolic responses to thermal stresses 
of altitude acclimatized rats. LOW OXYGEN TENSIONS—KIDNEY 
713-716 
713. Brown, A. L., Jr., G. F. Vawter and J. P, 
Marbarger. Temperature changes in human subjects dur- 
ing exposure to lowered oxygen tension in a cool environ- 
ment. J. Aviat. Med., 1952, 23: 456-463. 
714. Hale, H. B. Observations on men exposed to 
hypoxia at different environmental temperatures. Fed. 
Proc., 1953,12: 59. 
715. Hale, H. B. and R. B. Mefferd, Jr. Studies on 
cross-adaptation; metabolic responses to thermal stressors 
of altitude-acclimated rats. USAF. Randolph AFB, Texas. 
School of Aviation Medicine. Kept. no. 58-108, September 
1958, 6 pp. 
716. Mefferd, R. B., Jr. and H. B. Hale. Studies on 
cross-adaptation; effects of thermal conditioning on me- 
tabolic responses of rats to altitude. USAF. Randolph AFB, 
Texas. School of Aviation Medicine, Kept. no. 58-107, 
September 1958, 5 pp. 
10. KIDNEY 
Renal function in men acclimatized to high 
altitude has been studied by Becker, Schilling and 
Harvey (717) 1957. These authors conducted 
their studies at the Andean Institute of Biology, 
Morococha, Peru (15,000 feet) on natives who 
for generations had been living at high altitude. 
These acclimatized persons represent a climato- 
physiological variety of the human race, different 
from sea level dwellers. The mean data on all 
subjects showed an 11 percent decrease in filtra- 
tion rate, a 52 percent decrease in effective renal 
plasma flow, and an 89 percent increase in filtra- 
tion fraction, with a 44 percent increase in 
hematocrit as compared to normal sea level 
values taken from the literature. In a study of 20 
normal Peruvian men and women, natives at an 
altitude of 12,240 feet above sea level, Narvaes 
and Markley (722) 1957, found that plasma, 
sodium, and chloride were increased, plasma bi- 
carbonate decreased and plasma potassium re- 
mained unchanged, as compared with corre- 
sponding values at sea level. In 18 natives of high 
altitude undergoing elective surgery for abdomi- 
nal conditions, the postoperative response to sur- 
gical stress as measured by hematocrit, plasma 
and urinary electrolytes, as well as water and ion 
balance studies, were quite similar to the altera- 
tions reported at sea level in Peru and in other 
countries. All patients concerned withstood ma- 
jor abdominal surgery well and were discharged 
from the hospital symptomatically improved. 
A number of studies have been carried out on 
the effects of hypoxia (decompression) on renal 
function in dogs. Marshall, Hanna and Specht 
(721) 1952, found that intermittent exposure of 
dogs to progressively lowered barometric pressure 
approximately doubled the relative viscosity of 
the systemic blood when measured in capillary 
tubes. Effective renal plasma flow (PAH) rose 
slightly in three of the four dogs and changed 
little in the fourth. Since the plasma fraction of 
the blood was decreased (high hematocrit value) 
the calculated whole blood flow through the 
kidneys was approximately doubled. This was 
accomplished by vasodilatation which predomi- 
nated in the afferent arterioles, as shown by a 
greater increase in glomerular filtration (cre- 
atinine) , than in effective renal blood flow, so 
that the filtration fraction rose. Indirect evidence 
seemed to the authors to indicate that the 
changes depend solely on blood viscosity and not 
on renal tissue changes after adaptation has be- 
come adequate. This evidence consists of low 
early values for maximal tubular transfer of 
PAH which revert to normal as exposures are 
continued, statistically insignificant effects of alti- 
tude on PAH excretion at different saturation 
plasma levels, and simultaneous regression to- 
ward control levels of both circulatory and renal 
changes before the termination of exposures. Fer- 
guson and Smith (718) 1953, and (719) 1953, 
studied the effects of hypoxia produced by de- 
compression to a simulated altitude of 30,000 for 
90 minutes in the case of unanesthetized dogs. 
Controls were subjected to all experimental 
manipulations except actual decompression. Par- 
ticular attention was given to alterations in 
plasma electrolytes and renal function. Plasma 
potassium concentration consistently decreased 
(average about 19 percent) during the first 30 
minutes of decompression, and remained at the 
low level throughout the rest of the period. 
Plasma sodium remained unchanged. Hematoc- 
rit values increased (average 5 percent) during 
the first 30 minutes and remained elevated 
throughout the rest of the decompression period. 
The significance of this effect was heightened by 
the fact that in the controls, hematocrit values 
decreased progressively with blood sampling. The 
eosinophil count showed a downward trend dur- 
ing decompression although the effect was not 
marked, however, blood samples taken 90 min- 
utes after the animals had been returned to 
atmospheric pressure showed a significant de- 717-725 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
crease in eosinophiles. In the kidney, glomerular 
filtration rate showed no significant change dur- 
ing decompression, but urine flow decreased 
markedly in most experiments (average 44 per- 
cent) , indicating an increased tubular reabsorp- 
tion of water. Effects on sodium excretion were 
inconsistent, an increase being noted in about 
half of the experiments, a decrease, or no change, 
in the remainder. The data did not indicate 
to the authors that increased sodium excretion, 
when observed, was due to actual depression of 
tubular reabsorption of sodium. Potassium ex- 
cretion consistently increased (average 30 per- 
cent) during decompression. Since this effect 
occurred simultaneously with decreased potas- 
sium filtration, it indicated to the authors a 
decreased tubular reabsorption and/or increased 
tubular secretion of potassium during decompres- 
sion. Subsequent works by Ferguson and Smith 
(720) 1956, demonstrated that exposure of un- 
anesthetized dogs to severe hypoxia (45,000- 
60,000 feet) until the onset of respiratory ar- 
rest, consistently produced a marked rise in 
plasma K concentration. In an attempt to de- 
termine whether the adrenal glands were es- 
sential for these responses, the experiments were 
repeated on bilaterally adrenalectomized dogs 
maintained on cortisone or DCA. In 17 experi- 
ments upon cortisone-maintained dogs, plasma K 
concentration decreased by an average of 19.7 
percent during a 90 minute exposure to 30,000 
feet. In 16 experiments on DCA-maintained dogs 
it decreased by an average of 15.5 percent under 
the same conditions. Urinary excretion of K 
increased during hypoxia in both series of experi- 
ments. Exposure of cortisone-maintained dogs to 
severe hypoxia resulted in an increase in plasma 
K concentration similar to that observed in in- 
tact animals under comparable conditions. These 
results appeared to the authors to support the 
conclusion that in dogs the presence of the 
adrenal gland was not essential for the changes in 
plasma and urinary K observed during acute 
decompression stress. 
Effects of reducing atmospheric pressure on 
body water content have been studied by Pic6n- 
Reategui, Fryers, Berlin and Lawrence (725) 
1953, and by Siri, Reynafarje, Berlin and Law- 
rence (724) 1954, and Waterlow and Bunje 
(725) 1958. In the studies of the first group of 
authors, on rats, water and weight loss were both 
maximal within the first week of exposure to a 
simulated altitude of 15,000 feet. Loss of water 
accounts for 94 percent of the reduction in weight 
observed during the first six days of exposure of 
rats to reduced atmospheric pressure at this 
level. 
717. Becker, E. L., J. A. Schilling and R. B. Har- 
vey. Renal function in man acclimatized to high altitude. 
J. appl. Physiol, 1957, 10: 79-80. 
718. Ferguson, F. P. and D. C. Smith. Effects of 
acute decompression stress upon plasma electrolytes and 
renal function in dogs. Amer. J. Physiol, 1953, 173: 503- 
510. 
719. Ferguson, F. P. and D. C. Smith. Effects of 
severe hypoxia upon plasma electrolytes and renal function 
in dogs. Fed. Proc., 1953, 12: 42. 
720. Ferguson, F. P. and D. C. Smith. Effects of 
acute decompression stress upon plasma and urinary 
potassium in adrenalectomized dogs. Fed. Proc., 1956, 13: 
62. 
721. Marshall, L. H., C. H. Hanna and H. Specht. 
Renal function in the dog during increased blood viscosity 
produced by simulated altitude exposure. Amer. J. Physiol, 
1952,171: 499-506. 
722. Narvaes, E. and K. Markley. Postoperative 
water and electrolyte changes in natives of high altitudes. 
J. appl. Physiol, 1957, 10: 383-387. 
723. Picon-Reategui, E., G. R. Fryers, N. I. Berlin 
and J. H. Lawrence. Effect of reducing the atmospheric 
pressure on body water content of rats. Amer. J. Physiol, 
1953,172: 33-36. 
724. Siri, W. E., C. Reynafarje, N. I. Berlin and 
J. H. Lawrence. Body water at sea level and at altitude. 
J. appl. Physiol, 1954, 7; 333-334. 
725. Waterlow, J. C. and H. W. Bunje. Electrolyte 
changes during acclimatization to high altitude: observa- 
tions made on the British Expedition to the Colombian 
Andes, January, 1957. USAF, Randolph Air Force Base, 
Texas. School of Aviation Medicine. Kept. no. 58-79, 
August, 1958, 15 pp. 
11. TOLERANCE 
For general papers on tolerance the reader is 
referred to reports by Balke (726) 1963, Balke 
and Wells (727) 1958, Darling (757) 1959, and 
Parsons (740) 1958. Pugh has reported that 
above 23,000 feet without oxygen there occurs 
paralysis, loss of vision and euphoria preceding 
loss of consciousness. Prolonged exposure (two 
hours) at this level is fatal. Mood changes are 
similar to alcohol intoxication. Memory and in- 
telligence are affected between 12,000 and 18,000 
feet. The auditory system is less sensitive to LOW OXYGEN TENSIONS—TOLERANCE 
hypoxia than is the visual system. The accepted 
limit of arterial oxygen saturation for normal 
mental function is 85 percent (10,000 feet breath- 
ing air, or 33,000 feet breathing oxygen). For 
consciousness it is 55-60 percent (five to seven 
minutes at 25,000 feet or two minutes at 30,000 
feet). Chronic exposure to altitudes between 
20.000 and 23,000 result in insomnia, anorexia 
and weakness. Mental work is slow but efficient. 
Above 25,000 feet there is impairment of judg- 
ment and insight and of ability to initiate 
thought or action, although once a task is begun 
it is usually completed. Use of oxygen above 
20.000 feet prevents symptoms. Full recovery 
from fatigue at extreme altitude takes days or 
weeks after descent. There is apparently little 
aftereffect of chronic exposure, but occasionally 
persistent impairment of memory may be a 
symptom. Ilk, Seguin, Bhatia and Stevenson 
(736) 1961, have used cessation of abdominal 
contractions in unanesthetized rats decompressed 
to 40,000 feet, as the end point for tolerance with 
survival to decompression hypoxia. Using this 
end point it was found that tolerance to altitude 
was decreased by acute exposure to severe heat 
or repeated restraint before decompression, and 
was increased by acute exposure to heat and then 
cold. Altitude tolerance was not affected by 
prior intermittent exposure to severe cold, but 
was reduced by intermittent exposure to severe 
heat or by decompression in a relatively dry 
environment. A pentobarbital anesthesia in- 
hibited gasping and abdominal contractions and 
appeared to reduce altitude tolerance. 
Young adult male and female Sprague-Dawley 
rats were exposed by Bartlett and Altland (728) 
1959, to a simulated altitude of 33,500 feet, both 
with and without restraint. The exposure was 
begun immediately upon the restraint of the 
experimental animals. The restrained animals 
died significantly sooner than did the nonre- 
strained controls. Bartlett and Phillips (729) 
1960, in a study of restraint adaptation and alti- 
tude tolerance in the rats used 64 adult, male, 
albino, Wistar rats, divided equally into two 
groups. Members of one group were subjected to 
the stress of light restraint for one week to pro- 
duce adaptation to this stress. The other group 
was not restrained and served as controls. For 
altitude tolerance studies both groups were fur- 
ther divided into restrained and nonrestrained 
animals which were simultaneously exposed to 
an altitude of 33,500 feet. Both the restrained 
and nonrestrained animals showed significantly 
longer survival times than the corresponding non- 
adapted rats. Restraint adaptation, however, did 
not prevent the earlier deaths of the restrained 
as compared to the nonrestrained animals. 
A paper by Sobel, Sideman and Arce (746) 
1960, serves as an example of a study of effects 
of hormone on tolerance. These authors found 
a mortality of 37 percent in guinea pigs decom- 
pressed to a simulated altitude of 25,000 feet for 
six hours. Morphine sulfate in doses of 2.5 mg. 
or 5 mg./100 gm. of body weight, increased the 
mortality to 50 and 70 percent respectively. Prior 
treatment with cortisone for three days reduced 
the mortality to 22 and 29 percent respectively. 
Multiple injections with ACTH reduced mor- 
tality to 19 percent. 
The anoretic responses to radiation and their 
effect upon altitude tolerance have been reported 
by Newsom and Kimeldorf {739) 1956. Food 
consumption of rats, rabbits, mice, guinea pigs 
and hamsters was measured for three days follow- 
ing an approximately mid-lethal dose of x-irradi- 
ation to assess the degree of postirradiation 
anorexia. Seventy-two hours after irradiation 
these animals, as well as ad libitum fed and food 
deprived (72 hours) nonirradiated animals, were 
exposed to an altitude tolerance test. The mor- 
tality produced was used as the criterion of alti- 
tude tolerance. The altitude exposure selected 
for these species was sufficient to produce a mor- 
tality response of 50 percent or greater in non- 
irradiated animals during four hours of ex- 
posure. Irradiated rabbits and rats exhibited a 
severe decrease in food consumption which per- 
sisted for the three days of observation. Irradiated 
rabbits had an increased altitude tolerance simi- 
lar to that previously observed by the authors in 
the rat. When nonirradiated rabbits were de- 
prived of food for 72 hours prior to altitude ex- 
posure, the altitude tolerance was similar to that 
of the irradiated animal. While the food con- 
sumption was lower during the three days follow- 
ing irradiation in mice, the effect was much 
smaller than that observed for rats and rabbits. 
Guinea pigs and hamsters exhibited only a slight 
decrease in food consumption with recovery oc- 726-739 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
curring after 24 hours. The mice, guinea pigs 
and hamsters did not exhibit an increase in alti- 
tude tolerance three days after irradiation. How- 
ever, when nonirradiated mice and guinea pigs 
were food deprived, the altitude tolerance was 
significantly increased. These observations pro- 
vide further evidence that the post-irradiation in- 
crease in altitude tolerance is dependent upon the 
post-irradiation anorexia. The character of the 
diet affects tolerance to altitude hypoxia as shown 
in the mouse by Hershgold and Riley {734) 1959. 
It has previously been shown that mice with 
alimentary lipemia had a diminished survival 
time at altitude compared with controls fed 
isocaloric amounts of starch. These results were 
believed by the authors to provide evidence of a 
relative hypoxia associated with lipemia. In the 
authors’ study 230 mice were brought to a sim- 
ulated altitude of 33,000 feet and showed sur- 
vival times distributed into three groups depend- 
ing on the food given them four hours prior 
to exposure. Animals which were fasting (20 
hours previously), or which had been fed coco- 
nut, olive or corn oils had survival times of about 
56 ± 20 seconds. Those given a normal diet, or 
one with added olive oil or protein survived an 
average of 110 ± 49 seconds. Mice fed a starch- 
sucrose, or sucrose solution isocaloric with the 
lipids, lived about 320 ±162 seconds. The differ- 
ences were found to be statistically significant 
(p. < .01). These studies show a salutory in- 
fluence of carbohydrates on oxygen utilization at 
altitude. This effect was present when carbohy- 
drate was given alone, or with either fat or the 
normal diet. Fat added to a normal diet failed to 
decrease resistance. Since there was no difference 
in tolerance between the fat-fed mice and the 
fasting mice, it was felt by the authors that lipids 
are not themselves detrimental, but rather are 
unable to provide the protection conferred by 
carbohydrates. 
In both man (Dill, Robinson, Balke and New- 
ton {732) 1964) and in animals (rats) (Flucki- 
ger and Verzar {733) 1955), tolerance to altitude 
hypoxia decreases with age. A species difference 
may also be discerned as shown by Cook and 
Leon {730) 1960. These authors showed that 
squirrel monkeys had a lower tolerance than 
C-57 mice. 
Tolerance to acute hypoxia in man has been 
shown by Velasquez {747) 1959, to be higher in 
subjects born and living at high altitudes, than 
at sea level. Native residents living at an altitude 
of 14,900 feet were suddenly exposed to simulated 
higher altitudes ranging from 30,000-40,000 feet 
in a low pressure chamber. The ‘time of con- 
sciousness’ and the ceiling breathing air were 
determined. Comparing the results with those 
given by other investigators using sea level resi- 
dents the author concluded that a man born and 
residing at an altitude of 14,900 feet has a defi- 
nitely greater tolerance to acute hypoxia than a 
man born and living at sea level. 
726. Balke, B. Human tolerances, pp. 149-171 in: 
Physiology of man in space. Edited by J. H. U. Brown, 
Academic Press Inc., New York, 1963, 348 pp. 
727. Balke, B. and J. G. Wells. Ceiling altitude 
tolerance following physical training and acclimatization. 
J. Aviat. Med., 1958, 29: 40-47. 
728. Bartlett, R. G., Jr. and P. D. Altland. Effect of 
restraint on altitude tolerance in the rat. J. appl. Physiol., 
1959,14: 395-396. 
729. Bartlett, R. G., Jr. and N. E. Phillips. Re- 
straint adaptation and altitude tolerance in the rat. J. 
appl. Physiol, 1960, 15: 921-924. 
730. Cook, S. F. and H. A. Leon. Survival of C-57 
mice and squirrel monkeys in high and low pressures of 
oxygen. USAF. Holloman Air Force Base, New Mexico. 
Air Force Missile Development Center. Project 6892, Kept, 
no. AFMDC-TR-60-21, October 1960, 34 pp. 
731. Darling, R. C. High altitude sickness, pp. 480- 
483 in: A textbook of medicine. Edited by R. L. Cecil and 
R. F. Loeb, W. B. Saunders Co., Philadelphia, 1959, 1665 
pp. 
732. Dill, D. B., S. Robinson, B. Balke and J. L. 
Newton. Work tolerance: age and altitude. J. appl. 
Physiol, 1964, 19: 483-488. 
733. Fluckiger, E, and F. Verzar. Lack of adapta- 
tion to low oxygen pressure in aged animals. /. Geront., 
1955, 10: 306-311. 
734. Hershgold, E. J. and M. B. Riley. Diet in- 
duced variations in tolerance to altitude hypoxia in the 
mouse. Fed. Proc., 1959, 18: 68. 
735. Hock, R. J. Translocation in altitude and en- 
durance running of deer mice. Fed. Proc., 1964, 23: 522. 
736. Ilk, S. G., J. J. Seguin, B. Bhatia and J. A. F. 
Stevenson. A criterion to assess the effect of various 
factors on altitude tolerance. Fed. Proc., 1961, 20: 211. 
737. Luft, U. C. Altitude sickness, pp. 120-142 in; 
Aerospace medicine. Edited by H. G. Armstrong, Williams 
and Wilkens Co., Baltimore, 1961, 633 pp. 
738. Matthews, B. Limiting factors at high altitude. 
Proc. roy Soc., 1954, 143: 1-4. 
739. Newsome, B. D. and D. J. Kimeldorf. Anoretic 
responses to radiation and their effect upon altitude toler- 
ance. Fed. Proc., 1956, 15: 136. LOW OXYGEN TENSIONS—ACCLIMATIZATION 
740-760 
740. Parsons, V. A brief review of aviator’s decom- 
pression sickness and the high altitude selection test. J. R. 
nav. med. Serv., 1958, 44: 2-13. 
741. Pugh, L. G. C. E. The effect of acute and chronic 
exposure to low oxygen supply on consciousness, pp. 106- 
116 in: Environmental effects on consciousness. Edited by 
Karl E. Schaefer. The MacMillan Company, New York, 
1962, 146 pp. 
742. Reed, D. J. and R. H. Kellogg. Effect of sleep 
on hypoxic stimulation of breathing at sea level and alti- 
tude. J. appl. Physiol, 1960,15: 1130-1134. 
743. Scano, A. Alcuni effetti dell’intemperanza e del 
riposo insufficiente sulla resistenza alia depressione baro- 
metrica. Riv. Med. aero., 1958, 21: 63-67. 
744. Schilling, J. A., R. B. Harvey, E. L. Becker, 
T. Velasquez, G. Wells and B. Balke. Work perform- 
ance at altitude after adaptation in man and dog. J. appl. 
Physiol, 1955-56, 8: 381-387. 
745. Shephard, R. J. Physiological changes and psy- 
chomotor performance during acute hypoxia. J. appl. 
Physiol, 1956, 9: 343-351. 
746. Sobel, H., M. Sideman and R. Arce. Effect of 
cortisone on survival of morphine treated guinea pigs un- 
der decompression hypoxia. Proc. Soc. exp. Biol, N.Y., 
1960, 104: 31-32. 
747. Velasquez, T. Tolerance to acute anoxia in high 
altitude natives. J. appl. Physiol, 1959, 14: 357-362. 
12. ACCLIMATIZATION 
The functional adaptations underlying ac- 
climatization are highly complex and involve 
changes in cardiovascular and respiratory sys- 
tems, as well as alterations in neurological, hema- 
tological and other functions. For general studies 
of acclimatization the reader is referred to papers 
by Clark, Bancroft and Hale (751) 1960; Hur- 
tado (755) 1960; Hurtado (756) 1963; Hurtado 
and Clark (757) 1960; Hurtado, Velasquez, 
Reynafarje, Lozano, Chavez, Salazar, Reynafarje, 
Sanchez and Munoz (758) 1956; Lalli (762) 
1958; Lambertsen (763) 1961; Lambertsen (764) 
1961; Lawrence, Huff, Siri, Wasserman and Hen- 
nessy (765) 1952; Specht (772) 1958; and Ward 
(779) 1954. Studies of tissue changes accompany- 
ing acclimatization to low atmospheric oxygen 
have been carried out by Duckworth (752) 1961; 
Tappan, Potter, Reynafarje and Hurtado (733) 
1956; Tappan and Reynafarje (774) 1956; Tap- 
pan and Reynafarje (775) 1957; Tappan, Reyna- 
farje, Potter and Hurtado (776) 1957; and Ull- 
rick, Whitehorn, Brennan and Krone (777) 1956. 
For studies on brain metabolism during accli- 
matization at high altitude a paper by Albaum 
and Chinn (748) 1953, may be consulted. Sever- 
inghaus, Mitchell, Richardson and Singer (770) 
1963, have made measurements of CSF pH in 
human subjects during acclimatization. Excre- 
tion of urinary steroids at sea level and high 
altitude have been studied by San Martin, Prato 
and Fernandez (769) 1956; and acclimatization 
and deacclimatization changes in bone marrow 
volume and cellularity have been studied by 
Gong (753) 1963. For a paper on the effects of 
altitude acclimatization on work capacity, a re- 
port of Balke, Wells and Ellis (749) 1956, should 
be consulted. 
748. Albaum, H. G. and H. I. Chinn. Brain metabo- 
lism during acclimatization to high altitude. Amer. J. 
Physiol, 1953,174: 141-145. 
749. Balke, B., J. G. Wells and J. P. Ellis. Effects 
of altitude acclimatization on work capacity. Fed. Proc., 
1956,15: 7. 
750. Bourdillon, T. D. The use of oxygen apparatus 
by acclimatized men. Proc. roy. Soc., 1954,145: 24-32. 
751. Clark, R. T., R. W. Bancroft and H. B. Hale. 
Aviation medicine, pp. 43-48 in: Medical physics. O. Glas- 
ser, Editor. Year Book Press, Chicago, 1960, 754 pp. 
752. Duckworth, M. W. Tissue changes accompany- 
ing acclimatization to low atmospheric oxygen in the rat. 
J. Physiol, 1961,156: 603-610. 
753. Gong, J. K. Acclimatization and deacclimatiza- 
tion changes in marrow volume and cellularity in dogs. 
Fed. Proc., 1963, 22: 684. 
754. Gray, E. LeB. Appetite and acclimatization to 
high altitude. Milit. Med., 1955,117: 427-431. 
755. Hurtado, A. Some clinical aspects of life at high 
altitude. Ann. intern. Med., 1960, 55: 247-258. 
756. Hurtado, A. Natural acclimatization to high 
altitudes, pp. 71-82 in: The regulation of human respira- 
tion. Edited by D. J. C. Cunningham and B. B. Lloyd. 
Blackwell Scientific Publications, Oxford, 1963, 591 pp. 
757. Hurtado, A. and R. J. Clark. Parameters of 
human adaptation to altitude, pp. 352-369 in: Physics and 
medicine of the atmosphere and space. Edited by O. O. 
Benson and H. Strughold. John Wiley and Sons, New 
York, 1960, 645 pp. 
758. Hurtado, A., T. Velasquez, C. Reynafarje, 
R. Lozano, R. Chavez, H. A. Salazar, B. Reynafarje, 
C. Sanchez and J. Munoz. Mechanisms of natural ac- 
climatization. Studies on the native resident of Morococha, 
Peru at an altitude of 14,900 feet. USAF, Randolph AFB, 
Texas. School of Aviation Medicine. Kept. no. 56-1, March 
1956, 62 pp. 
759. Kellogg, R. H., N. Pace, E. R. Archibald and 
B. E. Vaughan. Respiratory response to inspired COz 
during acclimatization to altitude. Fed. Proc., 1956, 15: 
108. 
760. Kellogg, R. H., N. Pace, E. R. Archibald and 
B. E. Vaughan. Respiratory response to inspired C02 
during acclimatization to an altitude of 12,470 feet. J. 
appl. Physiol, 1957, 11: 65-71. 761-786 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
761. Kellogg, R. H., B. E. Vaughan and D. W. 
Badger. Respiratory responses to acute changes in 02 and 
C02 during acclimatization to high altitude. Fed. Proc., 
1957,16: 70. 
762. Lallx, G. 1 meccanismi chimici tissulari nell* 
acclimatazione alle quote elevate. Riv. Med. aero., 1958, 
21: 119-136. 
763. Lambertsen, C. J. Anoxia, altitude, and ac- 
climatization. Altitude and aviation, pp. 699-705 in: Medi- 
cal physiology. Edited by P. Bard. C. V. Mosby Company, 
St. Louis, 1961, 1339 pp. 
764. Lambertsen, C. J. Anoxia, altitude, and acclima- 
tization. Acclimatization, pp. 705-709 in: Medical physiol- 
ogy. Edited by P. Bard. C. V. Mosby Company, St. Louis, 
1961, 1339 pp. 
765. Lawrence, J. H., R. L. Huff, W. Siri, L. R. 
Wasserman and T. G. Hennessy. A physiological study 
in the Peruvian Andes. Acta med. scand., 1952, 142: 117- 
131. 
766. Michel, C. C. and J. S. Milledge. Respiratory 
regulation in man during acclimatization to high altitude. 
J. Physiol, 1963, 168: 631-643. 
767. Push, L. G. C. E. The effects of oxygen on ac- 
climatized men at high altitude. Proc. roy. Soc., 1954, 143: 
14-17. 
768. Riley, R. L., A. B. Otis and C. S. Houston. 
Respiratory features of acclimatization to altitude, pp. 
143-157 in: Handbook of respiratory physiology. Edited 
by W. M. Boothby. USAF, Randolph AFB, Texas, School 
of Aviation Medicine, September 1954, 189 pp. 
769. San Martin, M., Y. Prato and L. Fernandez. 
Mechanisms of natural acclimatization; excretion of uri- 
nary steroids at sea level and at high altitudes. USAF, 
Randolph AFB, Texas. School of Aviation Medicine. 
Kept. no. 55-100, August 1956, 2 pp. 
770. Severinghaus, J. W., R. A. Mitchell, B. Rich- 
ardson and M. M. Singer. CSF pH in man during ac- 
climatization to high altitude. Fed. Proc., 1963, 22: 223. 
771. Skrypin, V. A. Znachenie ugol’noi kisloty pri 
kislorodnom golodanii organizma. The significance of car- 
bon dioxide in anoxia. Vo.-med. Zh., 1960, 1: 65-71. Milit. 
med. J., 1960, 1: 104-113. 
772. Specht, H. Effects of maintained low atmospheric 
pressure, pp. 611-619 in: Industrial hygiene and toxicology. 
Volume I. Edited by F. A. Patty, Interscience Publishers, 
Inc., New York, 1958, 830 pp. 
773. Tappan, D. V., V. R. Potter, B. Reynafarje 
and A. Hurtado. Mechanisms of natural acclimatization; 
tissue enzyme studies and metabolic constituents in alti- 
tude adaptation. USAF, Randolph AFB, Texas. School of 
Aviation Medicine, Kept. no. 55-98, October 1956, 13 pp. 
774. Tappan, D. V. and B. Reynafarje. Mechanisms 
of natural acclimatization; tissue pigment studies in alti- 
tude adaptation. USAF, Randolph AFB, Texas. School of 
Aviation Medicine, Kept. no. 56-97, October 1956, 8 pp. 
775. Tappan, D. V. and B. Reynafarje. Tissue pig- 
ment manifestations of adaptation to high altitudes. 
Amer. J. Physiol., 1957, 190: 99-103. 
776. Tappan, D. V., B. Reynafarje, V. R. Potter 
and A. Hurtado. Alterations in enzymes and metabolites 
resulting from adaptation to low oxygen tensions. Amer. 
J. Physiol, 1957, 190: 93-98. 
777. Ullrick, W. C., W. V. Whitehorn, B. B. 
Brennan and J. G. Krone. Tissue respiration of rats 
acclimatized to low barometric pressure. J. appl. Physiol, 
1956, 9: 49-52. 
778. Valdivia, E. Mechanisms of natural acclimatiza- 
tion; capillary studies at high altitudes. USAF, Randolph 
AFB, School of Aviation Medicine, Kept. no. 55-101, June 
1956, 6 pp. 
779. Ward, M. High altitude deterioration. Proc. roy. 
Soc., 1954, 143: 40-42. 
13. PATHOLOGY 
The extent and severity of pathological lesions 
in both man and animals attributable to high 
altitude hypoxia depend upon the duration of 
exposure, the severity of hypoxia and the repeti- 
tive character of the exposure. There is an or- 
gan and system specificity, the central nervous 
system being most susceptible. The following 
references represent a small selection of the litera- 
ture on this subject: Hurtado (782) 1955; Metz 
(784) 1951; Brooks and Reeves (781) 1960; Tal- 
bott (783) 1960; Altland and Highman (780) 
1960; Valdivia (786) 1961; and Innes and Saund- 
ers (783) 1962. 
780. Altland, P. D. and B. Highman. Effects of high 
altitude on cholesterol-fed rabbits: Production of severe 
pulmonary atherosclerosis with calcification. Arch. Path., 
1960, 70: 349-357. 
781. Brooks, R. A. and J. L. Reeves. Influence of 
intermittent exposure to simulated altitude on organ 
histology in rats. USAF. Brooks AFB, Texas. School of 
Aviation Medicine. Kept. no. 60-81, September 1960, 8 pp. 
782. Hurtado, A. Pathological aspects of life at high 
altitude. Milit. Med., 1955,117: 272-284. 
783. Innes, J. R. M. and L. Z. Saunders. Experi- 
mental lesions produced by anoxia (decompression cham- 
ber) and by carbon monoxide, pp. 78-80 in: Comparative 
neuropathology. Academic Press, New York, 1962, 839 pp. 
784. Metz, B. Comparative experimental studies of 
the effects of simulated high altitudes on five vertebrates. 
J. Aviat. Med., 1951, 22: 132-136. 
785. Talbot, J. H. Altitude: pathologic effects, pp. 14- 
16 in: Medical physics. Vol. III. O. Glasser, Editor. Year 
Book Publishers, Chicago, 1960, 754 pp. 
786. Valdivia, E. Histochemical demonstration of 
tissue adaptation to chronic hypoxia. Fed. Proc., 1961, 20: 
209. PHYSIOLOGICAL EFFECTS OF HIGH CARBON DIOXIDE—GENERAL STUDIES 
787-801 
IV. PHYSIOLOGICAL EFFECTS OF 
HIGH CARBON DIOXIDE CONTENT 
IN ENVIRONMENTAL AIR 
A. GENERAL STUDIES 
Although the acute and sub-acute effects of 
increased carbon dioxide content in the respired 
air has been thoroughly investigated in man as 
well as animals, nevertheless there are still in- 
adequacies in our comprehension of the action 
of high concentrations of carbon dioxide over 
prolonged time periods. Our lack of this knowl- 
edge is no longer as critical so far as submarine 
operations are concerned. This is primarily be- 
cause the modem nuclear boats are equipped 
with scrubber systems which hold the carbon 
dioxide concentrations within limits that are 
tolerable for even extended operations. In hard 
hat diving the ventilation is adequate, or more 
than adequate, to obviate carbon dioxide prob- 
lems. But in the design of SCUBA equipment 
in which technical progress is constantly being 
made, the question of carbon dioxide accumula- 
tion must always be considered as a design and 
physiological problem. Moreover, in pressure 
chamber operations one has always to be con- 
stantly on guard against intolerable levels of 
carbon dioxide. For example, the chamber must 
be adequately ventilated, and/or the chamber 
atmosphere continuously scrubbed. 
The papers listed in the present section pro- 
vide an overall view of the carbon dioxide prob- 
lem as a whole. Special mention may be made 
of the National Research Council Committee 
report on Underwater Physiology (800) 1956, 
pointing out that in general carbon dioxide in- 
halation produces respiratory stimulation, cere- 
bral dilatation, and headache, and if the carbon 
dioxide concentration is above ten percent at sea 
level, there is confusion leading to unconscious- 
ness. Concentrations of 20-30 percent result in 
myoclonic twitchings and convulsions. Cerebral 
blood flow increases when the carbon dioxide is 
above two percent. Increase of carbon dioxide 
tension to levels above 50 mm. Hg will decrease 
oxygen tolerance. White (801) 1954, has also 
dealt in general with the acute toxicity of carbon 
dioxide. This paper is useful as a review of 
older reports. Major difficulty may be expected 
to be encountered when the inhaled carbon diox- 
ide ranges from four to seven percent, that is to 
say when the physiological equivalent of inhaled 
pC02 approaches the alveolar pC02. Uncon- 
sciousness has been reported in 3 out of 31 sub- 
jects when 10.4 percent carbon dioxide was used 
and 2 out of 41 human subjects with 7.6 percent 
carbon dioxide. 
787. Altman, P, L., J. F. Gibson, Jr. and C. C. 
Wang. Handbook of respiration. Edited by D. S. Dittrner 
and R. M. Grebe. W. B. Saunders Co., Philadelphia, 1958, 
403 pp. 
788. Alvis, H. J. Man, submarines and carbon dioxide. 
Arch, industr. Hyg., 1952, 5; 344-346. 
789. Goddard, D. R. The biological role of carbon 
dioxide. Anesthesiology, 1960, 21: 587-596. 
790. Lambertsen, C. J. Neurological control of respi- 
ration. pp. 613-632 in: Medical physiology. Edited by P. 
Bard. C. V. Mosby Company, St. Louis, 1961, 1339 pp. 
791. Lambertsen, C. J. Harmful effects of oxygen, 
nitrogen, carbon dioxide, and carbon monoxide. Carbon 
dioxide, pp. 714-716 in: Medical physiology. Edited by P. 
Bard. C. V. Mosby Company, St. Louis, 1961, 1339 pp. 
792. Manfredi, F., H. O. Sieker, A. P. Spoto and 
H. A. Saltzman. Severe carbon dioxide intoxication. 
Treatment with organic buffer (trihydroxymethylaminome- 
thane). J. Amer. med. Ass., 1960, 173: 999-1003. 
793. McConnell, W. J. Silo filler’s disease, pp. 489 
in: A textbook of medicine. Edited by R. L. Cecil and R. 
F. Loeb. W. B. Saunders Co., Philadelphia, 1959, 1665 pp. 
794. Miles, S. Carbon dioxide and other gases, pp. 
140-147 in: Underwater medicine. J. B. Lippincott Co., 
Philadelphia, 1962, 328 pp. 
795. Neugebauer, W. Todliche Kohlendioxydver- 
giftung. Arch. Toxikol., 1960, 18: 269-271. 
796. Perkins, J. F., Jr. Respiration. Annu. Rev. 
Physiol, 1960, 22: 245-282. 
797. Schaefer, K. E. The role of carbon dioxide in 
the physiology of human diving, pp. 131-141 in: Proceed- 
ings of the nuderwater physiology symposium. U.S. NRC, 
Publication 377, 1955, 153 pp. 
798. Schaefer, K. E., E. R. Cornish and S. E. 
Stuntz. Effect of increased alveolar carbon dioxide ten- 
sions on various physiological functions. Fed. Proc., 1952, 
11: 138. 
799. Troisi, F. M. Delayed death caused by gassing 
in a silo containing green forage. Brit. J. industr. Med., 
1957, 14: 56-58. 
800. U.S. NRC. Carbon dioxide, pp. 8-10 in: Status of 
research in underwater physiology. U.S. NRC-CUW, Rept. 
468, March 1956, 24 pp. 
801. White, C. S. The significance of high concentra- 
tions of carbon dioxide in aviation medicine, pp. 159-189 
in: Handbook of respiratory physiology. Edited by W. M. 
Boothby. USAF. Randolph AFB, Texas. School of Aviation 
Medicine. September 1954, 189 pp. SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
activity increased in amplitude forming regular 
three to five cps waves of 75 microvolts and per- 
sisted for one to two minutes after changing to 
air. Carbonic anhydrase activity and sodium 
content fell significantly in the hypothalamic re- 
gion and increased with slight fall in potassium 
in cortical areas in guinea pigs exposed to 15 
percent carbon dioxide for seven days. Histo- 
pathologically, according to the author, carbon 
dioxide is a specific rather than an anoxic agent. 
For studies on the physiological action of car- 
bon dioxide on the cortex and hypothalamus, 
papers by Gellhorn (824) 1953, and (823) 1952, 
should be studied. This author has found that 
the inhalation of 10 percent carbon dioxide 
reduces the responsiveness of specific sensory pro- 
jection areas to optic and acoustic stimuli, while 
increasing reactivity of the hypothalamic cortical 
system. Gellhorn and French (826) 1953 have 
also found that carbon dioxide inhaled for brief 
periods in concentrations varying from 10-35 
percent increases the frequency of topically in- 
duced cortical strychnine spikes in the normal 
cortex, but reduces it if the cortex is isolated 
from underlying structures by surgical under- 
cutting. This result appears to be due, according 
to the author, to the fact that carbon dioxide 
exerts an excitatory effect on the hypothalamus 
and through increased hypothalmic-cortical dis- 
charges indirectly upon the cortex and in addi- 
tion has a direct inhibitory action on the cortical 
gray matter of the brain. Carbon dioxide pro- 
duces an inhibitory action on the “isolated” 
cortex since the hypothalmic-cortical influence 
is eliminated. Nearly complete sectioning of the 
inter-hemispheral transmission systems does not 
alter the action of carbon dioxide on cortical 
spikes. According to Gyarfas and Pollock (829) 
1952, inhalation of 30 percent carbon dioxide 
and 70 percent oxygen results in an increase in 
the frequency and a decrease of the amplitude of 
cortical electrical discharges. This effect pro- 
ceeds until the cortical activity becomes isoelec- 
tric, although fast bursts still appear. The sub- 
cortical structures studied showed less respon- 
siveness to carbon dioxide than the cerebral 
cortex. There was some decrease in the am- 
plitude and some increase in the frequency. 
However, the tendency to resemble cortical ac- 
tivity was strongest in the caudate nucleus and 
B. NERVOUS SYSTEM 
For a general paper on the effects of carbon 
dioxide on nervous system function, the reader 
is referred to Schaefer (860) 1962. Acute ex- 
posure to carbon dioxide in human subjects 
for 15 minutes (7.5 percent proving minimum 
for generalized symptoms) results in various 
combinations of dyspnea and headaches, vertigo, 
sweating and numbness, over-activity of limbs, 
increased motor activity and restlessness, visual 
and color distortions, loss of balance and mental 
disorientation. Exposure of human subjects 
for three to six days in three percent carbon 
dioxide results during the first 24 hours in gen- 
eral excitation associated with a drive for in- 
creased activity as well as euphoria. During 
the second day there is a feeling comparable to 
a hangover, together with dullness and volatile 
changes of mood. During the second and third 
day memory and attentiveness are decreased and 
during the following day a restless sleep. A 
slight improvement occurs after the third day. 
Equivalent effects are seen in guinea pigs sub- 
jected to three percent carbon dioxide and more 
striking effects in animals breathing 12 percent 
carbon dioxide. Performance tests in man re- 
veal an increased error production. Nerve ex- 
citation time chronaxie and the rheobase were 
decreased during the first day and a half and in- 
creased to twice their original value from the 
third day on. The biphasic response corres- 
ponded to a period of uncompensated respiratory 
acidosis followed by a period of compensation. 
Carbon dioxide accumulation during prolonged 
submerged operations in submarines showed 
similar effects with adaptation after two weeks 
except for abberations in thinking processes and 
altered mental alertness. Subjects with normally 
slow respiratory rates and large tidal volumes 
exhibited increased tolerance to hypercapnia as 
well as to hypoxia. The mechanism of carbon 
dioxide action was examined in eight waking 
monkeys exposed to 10-30 percent carbon diox- 
ide. Spontaneous electrical activity in the cor- 
tex after ten minutes exposure to carbon dioxide 
showed a decrease in amplitude of background 
activity and reduction of high voltage bursts. 
In the hypothalamus, within five minutes of 
exposure the three to five cycles per second (cps) PHYSIOLOGICAL EFFECTS OF HIGH CARBON DIOXIDE—NERVOUS SYSTEM 
less in the globus pallidus where an autonomous 
reaction could be discerned. The thalamus, 
hypothalamus and the mesencephalic structures 
studied exhibited an increasingly independent 
reaction to carbon dioxide. Electrical activity 
recorded from the thalamus, hypothalamus, the 
pallidum and mesencephalic structures was con- 
sidered to be either release phenomena or idio- 
pathic discharge. On return to room air all 
changes disappeared promptly regardless of the 
duration of carbon dioxide administration. 
Schaefer and Carey (862) 1953 and (863) 1954 
and Schaefer, Cornish, Stuntz, Lukas, Brewer 
and Carey (864) 1952, have examined experi- 
mentally in human subjects the effects of ex- 
posure to various carbon dioxide concentrations 
upon flicker fusion frequency and alpha block- 
ing time. Exposure of subjects to 1.5, 3.4, 5.4 and 
7.5 percent carbon dioxide concentrations over 
periods of 20 minutes with 10 minutes allowed 
for dark adaptation was carried out. During 
this time a steady state in respiration was usually 
reached as indicated in respiratory minute vol- 
ume and alveolar carbon dioxide. The results 
indicated that concentrations of five percent 
carbon dioxide and higher produced a significant 
drop in flicker fusion frequency, a decreased 
qualitative blocking effect, and an increased 
alpha blocking time. Schaefer and Barton (861) 
1956, studied carbonic anhydrase activity and K 
and Na content in hypothalamic and cortical 
areas of guinea pigs exposed to 15 percent carbon 
dioxide in 21 percent oxygen over periods up 
to seven days. Carbonic anhydrase activity of 
the cortex increased while that of the hypothala- 
mus decreased after seven days exposure. In the 
cortex the Na level was maintained while the K 
content declined slightly. In the hypothalamus 
the Na sodium content fell significantly parallel- 
ing the decrease in carbonic anhydrase activity 
in the reticular substance and later the hy- 
pothalamus showed bursts of three per second 
waves of 200-300 microvolts. These bursts were 
rather discreetly localized and only from time 
to time spread to more superficial structures. 
The threshold of electrical stimulation of the hy- 
pothalamus and the reticular formation decreased 
under 10, 15 and 30 percent carbon dioxide. 
Thresholds in other areas of the brain showed 
variable changes. According to Woodbury, Rol- 
lins, Gardner, Hirschi, Hogan, Rallison, Tan- 
ner and Brodie (878) 1958, inhalation of rela- 
tively low concentrations of carbon dioxide (5- 
20 percent) decreases brain excitability. Inhala- 
tions of high concentrations of carbon dioxide 
(40 percent or higher) greatly decreases brain 
excitability and causes anesthesia. Abrupt re- 
moval of rats from high (anesthestic) concen- 
trations of carbon dioxide results in spontaneous 
clonic seizure within 30 seconds to one minute 
after withdrawal. The seizures last ,for one to 
two minutes. Inhalation of 50 percent carbon 
dioxide decreased brain intracellular Na and K 
concentration and resulted in striking cellular 
acidosis. Thirty seconds after abrupt withdrawal 
of rats from 50 percent carbon dioxide, but prior 
to the onset of seizures, concentrations of Na in 
brain cells increased and the concentrations of K 
decreased. Sicker and Wilson (865) 1960 de- 
signed a study in human subjects to investigate 
the relationship of serum K levels in hypoxia and 
hypercapnia to changes in the EEG. It was found 
that acute hypoxia was associated with a sig- 
nificant increase in serum K, and an inconsistent 
change in the EEG (electroencephalographic) in 
this area. The K level was found only slightly 
lowered. The K/Na potassium-sodium ratios 
changed in opposite directions showing an in- 
crease in the hypothalamic area and a decrease 
in the cortex. 
Carey, Schaefer and Delgado (818) 1955, work- 
ing with monkeys have examined experimentally 
the effects of various carbon dioxide concentra- 
tions on electrical activity and excitability of 
the brain in the waking animal. In a series of 
monkeys multilead electrodes were permanently 
implanted for periods of one to three months to 
study the action of 5, 10, 15 and 30 percent 
concentrations of carbon dioxide in the air. 
The authors examined the motor cortex, the oc- 
cipital cortex, as well as areas in the thalamus, 
hypothalamus and reticular substance. The pat- 
tern of the spontaneous electrical activity of each 
of the areas of the brain recorded on different 
days was rather constant throughout all the ob- 
servation periods on air. After 10 minutes of 
exposure to 10, 15 or 30 percent carbon dioxide 
there was generalized slowing down and decrease 
in amplitude in monopolar recording of all the 
areas with the exception of the hypothalamus SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
which appeared to be less affected. With 10 and 
15 percent carbon dioxide bipolar recordings of 
the hypothalamus and the reticular substance 
revealed increased occurrence of runs of five to 
seven cps of higher amplitude. This phenomenon 
was also observed when the animals were ex- 
posed to five percent. With 30 percent carbon 
dioxide there was an initial period of increased 
number of five to seven cps followed by a gradual 
disappearance of this activity. In some animals 
after 18 minutes of exposure to 15 percent carbon 
dioxide pattern. When subjects breathed 10 per- 
cent oxygen, 2.5 percent carbon dioxide and 
nitrogen mixtures, the electroencephalographic 
EEG pattern remained unaltered. Particularly 
because the arterial oxygen saturation did not 
fall to levels observed when carbon dioxide was 
not used in the mixture. With comparable levels 
of arterial oxygen saturation produced by breath- 
ing 7.5 percent oxygen, 2.5 percent carbon 
dioxide and nitrogen, the electroencephalo- 
graphic EEG alterations of hypoxia were noted. 
The authors concluded that carbon dioxide ap- 
parently exerts a protective effect by stimulat- 
ing respiration and preventing as severe hypoxia 
as observed when it is not used. Holmberg 
(831) 1954, conducted an evaluation of the effect 
of carbon dioxide on convulsions induced by 
electric shock treatment. The author studied 
the effects of administration of a mixture con- 
taining 6.6 percent carbon dioxide, 15.8 percent 
oxygen and 77.6 percent nitrogen for two minutes 
immediately preceding the shock. Ten percent 
carbon dioxide significantly prolonged the dura- 
tion of the tonic phase of the convulsive seizure, 
but the duration of the clonic phase was not 
changed appreciably, nor was the peak intensity 
of the convulsion. During the latter part of the 
seizure corresponding to the clonic phase, the 
intensity of the convulsion was increased signifi- 
cantly. There was also an increase in the total 
amount of muscular energy developed during 
the seizure as a whole. The most striking effect 
was a very constant and highly significant in- 
crease in. the frequency of the clonic jerks. The 
gas mixture did not affect the degree of post 
convulsive unrest. It was assumed by the authors 
that the effect of carbon dioxide administration 
was to increase cerebral circulation and oxygena- 
tion. The particularly pronounced effect on the 
frequency of the clonic jerks may possibly indi- 
cate that subcortical structures were more 
strongly influenced. A direct effect on the muscu- 
lature was considered to play an unimportant 
role. Confirmatory results were given in sup- 
plementary experiments with inhalation of a 
carbon dioxide-oxygen mixture, and with hyper- 
ventilation with hair. Dahlberg-Parron (819) 
1951, studied the effect of hypercapnia on elec- 
trically induced convulsions in rabbits. The 
animals were unanesthetized and uncurarized 
and were studied by recording electromyo- 
graphically the activity of the gastrocnemius 
muscles. Hypercapnia was produced by pre- 
treatment for 5 minutes with 12 percent carbon 
dioxide in oxygen. Hypercapnia was found to 
prolong the flexion stage that introduces the 
tonic phase. The subsequent extension stage 
was shortened as well as the total tonic phase. 
Conversely the succeeding clonic phase was pro- 
longed. Also a clonic phase was produced in 
animals which normally had none. In a study 
of factors influencing the development of carbon 
dioxide withdrawal seizures, Carey and Schaefer 
(812) 1959, exposed rats to carbon dioxide con- 
centrations of 30 and 50 percent in oxygen for 
various periods of time. The authors found no 
consistent seizure activity after withdrawal from 
exposure to 30 percent carbon dioxide for one 
hour. However, after five hours exposure to 30 
percent carbon dioxide transition to air produced 
seizures in most animals. After exposure to 50 
percent carbon dioxide for ten minutes with- 
drawal seizures occurred within one minute in 95 
percent of the animals. Exposure to 50 percent 
carbon dioxide for one hour eliminated the 
seizure activity. The development of seizures 
was found to be related to: (1) a drop in blood 
carbon dioxide tension exceeding 100 mm. Hg 
and resultant decreases in brain tissue carbon 
dioxide content, (2) a fall in plasma calcium 
to approximately 2 mEq/L, and (3) significant 
changes in the extra and intracellular H20 and 
Na content. 
In studies of excised rat sciatic nerve Carpen- 
ter (814) 1961, and (815) 1963, has found that 
exposure to carbon dioxide (0 to 40 mm. Hg) 
caused a reduction in spontaneous repetitive ac- 
tivity as the pC02 increased. The increased 
spontaneous activity in low carbon dioxide was PHYSIOLOGICAL EFFECTS OF HIGH CARBON DIOXIDE—NERVOUS SYSTEM 
thought to be due to the increase in pH and 
consequent loss of calcium ions. The addition 
of carbon dioxide prevents this loss. Therman 
{872) 1962, has found that nerve fibers are 
more susceptible to temporary lack of carbon 
dioxide (less than five percent) than to brief 
periods of anoxia. Moderately increased carbon 
dioxide tension leads to an increase of the slow 
electronic component (recovery process) of the 
membrane potential (L fraction) and is more 
pronounced in small nerve fibers. Carbon dioxide 
increases the threshold of stimulation, decreases 
the speed of nerve impulse conduction, increases 
duration and height of the action potential, in- 
creases the ability of nerve fibers to endure 
prolonged stimulation and delays the onset of 
anoxic depolarization. Carbon dioxide also re- 
duces the endplate potential while pure oxygen 
restores it. The L fraction produced by carbon 
dioxide requires inherent metabolic mechanisms 
as opposed to similar effects of an anodal cur- 
rent which requires a source of nergy. Carbon 
dioxide similarly increases the L fraction in the 
sympathetic ganglion. Reduction of the external 
pH in the absence of carbon dioxide does not 
mimic carbon dioxide responses. The author 
concluded that carbon dioxide acts by partici- 
pating in reacting derived from oxidative metab- 
olism. It was believed that the central nervous 
system effect of carbon dioxide on the L frac- 
tion and thus on the threshold of excitability. 
A rapid decrease of carbon dioxide tension tends 
to produce “spontaneous” discharge of nerve im- 
pulses. The effects of end-tidal carbon dioxide 
levels have been studied by Gill {827) 1963, in 
single phrenic motor neurones in decerebrate 
cats ventilated to maintain complete oxygen 
saturation. As carbon dioxide levels were raised 
to threshold activity became irregular. Above 
threshold, intensity of unit discharge generally 
tended to increase (more rapidly at first) and 
often reaching a plateau. As end-tidal carbon 
dioxide was reduced, activity continued to show 
clear discharge and silent phases, becoming ir- 
regular near threshold. The threshold on de- 
creasing the carbon dioxide level was lower than 
the threshold on increasing carbon dioxide. 
For further studies on the effects of carbon 
dioxide inhalation on respiratory regulation, 
papers by Ngai and Wang {849) 1953, Tang 
{871) 1959, Cohen {818) 1959, and Rosenstein 
and Borison {859) 1963, should be consulted. 
Frederickson and Schenk {822) 1959, have 
found that asphyxia of a neuromuscular prepara- 
tion in a cat (tibialis anticus-sciatic nerve prep- 
aration) causes an increase in the maximal 
twitch height, and augmented initial response to 
D-tubocurarine, and a reversal of a D-tubocura- 
rine block. Increased carbon dioxide decreases 
the maximal twitch height in most experiments 
and this decreased twitch due to hypercarbia is 
transiently returned to normal by epinephrine. 
Hypercarbia produces an increased sensitivity of 
the preparation to D-tubocurarine, but has no 
effect on the course of a D-tubocurarine block. 
Bartels and Witzleb {804) 1956, have found 
that the action potential in the carotid sinus 
nerve of cats is reduced by increasing carbon 
dioxide inhalation from 3.2-12.7 percent. For 
other studies on the effects of carbon dioxide on 
chemosensitivity, papers by Heymans and Neil 
{830) 1958, Joels and Neil {833) 1961, Loes- 
chcke, Mitchell, Katsaros, Perkins and Konig 
{839) 1963, Mitchell, Loeschcke, Severinghaus, 
Richardson and Massion {844) 1963, and 
Mitchell, Massion, Carman and Severinghaus 
{845) 1960, should be studied. 
Young, Sealy, Harris and Botwin {879) 1951, 
have found that hypercapnia caused by breath- 
ing 20 percent oxygen mixtures enhances the 
effect of vagal stimulation on the heart in adult 
mongrel dogs. Campbell {811) 1955, in dogs also 
found that hypercapnia augmented cardiac in- 
hibition during vagal stimulation. 
The effect of varying rates of concentration in- 
crease upon the analgesic potency of various 
concentrations of carbon dioxide in rats has 
been recorded by McQuarrie {840) 1961. 
The rats were subjected to carbon dioxide for 
periods of five minutes, one hour, five hours and 
24 hours, during which time the concentration 
of carbon dioxide was increased linearly to either 
5, 10 or 16 percent. The method is believed to be 
reliable at low carbon dioxide levels (not much 
over 16 percent) because anesthesia is ap- 
proached. The rats had a demonstrable and 
statistically significant analgesic effect due to 
exposure to carbon dioxide in all groups except 
the one to a five percent carbon dioxide concen- 
tration in 24 hours. At all three concentrations SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
when the rate of concentration rise was both pro- 
longed (beyond one hour in the five and ten 
percent groups, and to 24 hours in the 16 per- 
cent group) there was a significant attentua- 
tion of the analgesic effect of carbon dioxide. The 
author concluded that an animal is able to toler- 
ate higher concentrations of carbon dioxide 
acutely if the rate of concentration rise is pro- 
longed, even though the rate of concentration in- 
crease and progressive prolongation of exposure 
time could not be critically differentiated. 
The effects of changes in carbon dioxide upon 
sense organs is exemplified by a study reported 
by Wing, Harris, Stover and Brouillette (876) 
1952. Cochlear microphonics were recorded by 
means of an electrode placed in the round win- 
dow in the ear of anesthetized cats breathing 
different mixtures of oxygen in nitrogen through 
a resuscitator. Simultaneous electrocardiographic 
(EKG) changes were made and changes were 
studied and a few observations made concerning 
the effects of administered carbon dioxide upon 
microphonics. Cochlear microphonics were re- 
versibly reduced by carbon dioxide between 5.2 
percent and 25 percent in oxygen. 
According to Kollias and Bullard (835) 1963, 
carbon dioxide (6 percent in air) was proven to 
be the most effective of several procedures studied 
in increasing the heat tolerance of the white 
rat. Control rats restrained at 34°C. had a mean 
survival time of 154 minutes, while those breath- 
ing 6 percent carbon dioxide in air survived the 
entire exposure time of 240 minutes (100 per- 
cent survival). Rats breathing carbon dioxide 
also showed a decreased rate of body temperature 
increase. Survival was also enhanced by 6 per- 
cent carbon dioxide in unrestrained rats at 40°C. 
When the gas or air mixture was saturated with 
water vapor to prevent evaporative heat loss, the 
control rats survived a mean of 17 minutes longer 
than the carbon dioxide rats. This observation 
and direct measurement indicated to the authors 
that carbon dioxide protected by increasing evap- 
oration probably from the respiratory tract 
rather than by the prevention of respiratory alka- 
losis. A similar finding has been reported by 
Bacharach, Snyder and Templeton (803) 1961. 
In dogs a 30 minute period of circulatory arrest 
was begun when the esophageal temperature 
reached 10-15°C. During cooling and rewarm- 
ing, perfusion was maintained at 2 L/m2/min. 
One series of 15 dogs was ventilated with 100 
percent oxygen, and a second series of 15 with 
5 percent carbon dioxide in oxygen, both at 20 
cpm with a constant flow of gas at 7 L/minute. 
In adults with 100 percent oxygen the brain 
(left cerebral hemisphere) temperature lagged 
2-4° behind esophageal temperature during cool- 
ing. After the 30 minute period of arrest the 
brain temperature had drifted up 4-6° and the 
esophageal temperature up 3-5°. In the dogs 
with 5 percent carbon dioxide the brain tempera- 
ture became 1-3° lower than the esophageal near 
the end of the cooling phase. After arrest the 
brain had drifted up 3-5°C. 
In human subjects exposed to an ambient 
temperature of 5°C. for 75 minute periods breath- 
ing of 2.5 percent carbon dioxide was shown by 
Bullard and Crise (808) 1961, to inhibit shiver- 
ing. After carbon dioxide inhalation shivering 
and metabolic rate were greatly increased. When 
6 percent carbon dioxide was inhaled for 30 
minutes the inhibition was overcome and shiver- 
ing and metabolic activity approached high levels. 
Increased respiratory heat loss associated with 
carbon dioxide breathing may be one factor, ac- 
cording to the authors, causing breakthrough of 
the inhibition. Bullard and Crise (807) 1959, 
also found that all subjects breathing 10 percent 
oxygen and 4 out of 6 subjects breathing 12 per- 
cent oxygen showed marked augmentation of 
shivering activity. In these experiments return 
to normal air resulted in a depression of 
shivering. 
The effects of carbon dioxide on behaviour 
has been reported by Goldberg, Peck, Chappell 
and Lipinski (828) 1962, and by Weinstein 
(875) 1963. The former authors gave electric 
shock to rats trained to press a bar for a food re- 
ward. The effect of the shock was the formation 
of a conditioned suppression. An experimental 
group of rats was then given carbon dioxide to 
the point of coma. On recovery these rats began 
to bar-press again at a significantly shorter time 
than the control group who had not received 
the carbon dioxide. It was felt that the situation 
was analogous to the human situation where 
anxiety is reduced by inhalation of carbon 
dioxide. Weinstein’s report is that of experi- 
ments performed to determine the effectiveness PHYSIOLOGICAL EFFECTS OF HIGH CARBON DIOXIDE—NERVOUS SYSTEM 
802-816 
of carbon dioxide as a reinforcer in conditioning 
procedures. Pigeons were placed in an apparatus 
permitting either the investigator or the experi- 
menter to produce stepwise changes in inspired 
gas concentration. In avoidance conditioning, 
the effect of increase in the magnitude of the 
change in carbon dioxide concentration upon the 
time elapsing between the onset of the concentra- 
tion and the operant response was determined. 
This latent period decreased as the magnitude of 
the concentration change increased. It also de- 
creased as the interval between presentations of 
carbon dioxide decreased. Anoxia did not elicit 
operant responses directed toward relieving the 
anoxic state. If the anoxia was not relieved by 
the investigator the pigeon soon expired. When 
inspired carbon dioxide was progressively in- 
creased the pigeons operant response rate in- 
creased adequately to maintain a constant toler- 
able level of inspired carbon dioxide. Ingested 
NaHCOs increased the operant response rate. 
The relation between carbon dioxide inhalation 
and drug and other chemical substances has 
been reported by Brassfield and Sealby (805) 
1961; Normann (851) 1956; Payne (852) 1960; 
and Woodbury and Karler (877) 1960. 
Since inhalation of carbon dioxide does pro- 
duce predictable effects upon the central nervous 
system, it may be hypothesized that it may be 
used as a therapeutic modality in the therapy of 
psychiatric conditions. The literature in this 
field is large and selected papers only are given 
in this section. The reader should consult re- 
ports by Weaver, Peterson and Anderson (874) 
1951; Moriarty (846) 1952; Meduna (841) 1953; 
LaVerne and Herman (836) 1953; Smith (867) 
1953; Silver (866) 1953; Moriarty (847) 1954; 
Brick (806) 1956; and Meduna (842) 1958. For 
a discussion of the possible physiological basis 
of carbon dioxide therapy and of the psychoneu- 
rosis a paper by Gellhorn (825) 1953, should be 
examined. Also, a paper by Fay on 20 percent 
carbon dioxide inhalation in muscular rigidity 
(821) 1953, may also be read. A special group 
of papers on carbon dioxide therapy for stutter- 
ing has been included. These reports are by 
Arthurs, Cappon, Douglass and Quarrington 
(802) 1954; Kent (834) 1961; and Smith (868) 
1953. In connection with carbon dioxide therapy 
it should be pointed out that Stephens (869) 
1951 has reported cellular changes in the central 
nervous system resulting from carbon dioxide ad- 
ministration in animals. Therefore caution in 
repeated use of carbon dioxide as a therapeutic 
procedure is warrented. 
802. Arthurs, R. G. S., D. Cappon, E. Douglass 
and B. Quarrington. Carbon dioxide therapy with stut- 
terers. Dis. new. Syst., 1954, 15: 123-126. 
803. Bacharach, B., H. M. Snyder and J. Y. Tem- 
pleton, III. Effect of inhaling carbon dioxide on brain 
during hypothermia. Surg. Forum, 1961, 12: 186-187. 
804. Bartels, H. and E. Witzleb. Der Einfluss des 
arteriellen CO, — Druckes auf die chemoreceptorischen 
Aktionspotentiale im Carotissinusnerven. Pflilg. Arch. ges. 
Physiol, 1956, 262: 466-472. 
805. Brassfield, C. F. and R. L. Sealby. Respiratory 
effects of carbon dioxide administration and vagal block 
after injection of gamma-aminobutyric acid. Fed. Proc., 
1961, 20: 431. 
806. Brick, H. Carbon dioxide therapy in private 
practice and in the Virginia State Penitentiary. (A study of 
101 patients). Tri-St. med. J., 1956, 3: 14-17. 
807. Bullard, R. W. and J. R. Crise. The effects of 
carbon dioxide and hypoxia on shivering. Fed. Proc., 1959, 
18: 20. 
808. Bullard, R. W. and J. R. Crise. Effects of car- 
bon dioxide on cold-exposed human subjects. J. appl. 
Physiol, 1961, 16: 633-638. 
809. Burr, H. S. and R. B. Livingston. Effect of 
hypoxia and hypercapnia on standing potential of man. 
Fed. Proc., 1952,11: 21. 
810. Busse, E. W., T. M. Parry, E. S. Goldensohn, 
R. W. Whitehead and W. B. Draper, Alteration of 
cerebral function in man produced by diffusion respira- 
tion and prolonged inhalation of carbon dioxide. Dis. 
new. Syst., 1952, 13: 35-41. 
811. Campbell, G. S. Cardiac arrest: further studies 
on the effect of pH changes on vagal inhibitation of the 
heart. Surgery, 1955, 38: 615-634. 
812. Carey, C. R. and K. E. Schaefer. Factors in- 
fluencing the development of carbon dioxide withdrawal 
seizures. Fed. Proc., 1959, 18: 23. 
813. Carey, C. R., K. E. Schaefer and J. M. R. 
Delgado. Influence of various C02 concentrations on 
electrical activity and excitability of the brain in the wak- 
ing monkey. Fed. Proc., 1955, 14: 25. 
814. Carpenter, F. G. Alterations in the stability of 
mammalian A fibers produced by N,0 and by C02. Amer. 
J. Physiol, 1961, 200: 187-191. 
815. Carpenter, F. G. The stabilizing action of car- 
bon dioxide on peripheral nerve fibers and on the neurons 
of the medullary reticular formation in the rat. Ann. 
N.Y. Acad. Sci., 1963, 109: 48(M93. 
816. Chalazonitis, N. Effects of changes in Pr(>2 and 
P02 on rhythmic potentials from giant neurons. Ann. N.Y. 
Acad. Sci., 1963, 109: 451-479. 817-852 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
817. Chapin, J. L., A. B. Otis and H. Rahn. Changes 
in the sensitivity of the respiratory center in man after 
prolonged exposure to 3% COs. pp. 250-254 in: Studies in 
respiratory physiology. Second series. Chemistry, mechan- 
ics, and circulation of the lung. Edited by H. Rahn and 
W. O. Fenn. Wright Air Development Center, Aero 
Medical Laboratory, Dayton, Ohio. WADC Tech. Kept. 
55-357, November 1955, 438 pp. 
818. Cohen, M. I. Effects of carbon dioxide on dis- 
charge patterns of respiratory neurons. Fed. Proc., 1959, 
18: 28. 
819. Dahlberg-Parron, R. The effect of hypercapnia 
and hypoxia on electrically induced convulsions in rabbits. 
Acta physiol, scand., 1951, 23: 55-63. 
820. Downing, S. E., J. P. Remensnyder and J. H. 
Mitchell. Cardiovascular response to carotid body stimu- 
lation. Fed. Proc., 1961,20: 132. 
821. Fay, T. Twenty per cent carbon dioxide inhala- 
tion in muscular rigidity: indications and contraindica- 
tions. J. Amer. med. Ass., 1953, 152: 1623-1626. 
822. Frederickson, E. L. and E. A. Schenk. Re- 
sponse of neuromuscular junction preparations to changes 
in oxygen and CQ2. Fed. Proc., 1959, 18: 463. 
823. Gellhorn, E. Studies on the action of carbon 
dioxide on cortex and hypothalamus. EEG din. Neuro- 
physiol., 1952, 4: 117. 
811. Gellhorn, E. On the physiological action of car- 
bon dioxide on cortex and hypothalamus. EEG din. Neuro- 
physiol., 1953, 5: 401-513. 
825. Gellhorn, E. The physiological basis of the 
carbon dioxide therapy of psychoneuroses. J. ment. Sci., 
1953, 99: 357-373. 
826. Gellhorn, E. and L. A. French. Carbon dioxide 
and cortical spike frequency. Arch. int. Pharmacodyn., 
1953, 93: 427-433. 
827. Gill, P. K. The effects of end-tital C02 on the 
discharge of individual phrenic motoneurones. /. Physiol., 
1963, 239-257. 
828. Goldberg, H. D., R. E. Peck, M. N. Chappell 
and C. E. Lipinski. Effect of carbon dioxide on anxious 
behaviour in the rat. J. Neuropsychiat., 1962, 3: 390-392. 
829. Gyarfas, K. and G. H. Pollock. The subcortical 
effects of carbon dioxide in the cat. Arch. int. Pharma- 
codyn., 1952, 90: 233-240. 
830. Heymans, C. and E. Neil. The chemoreceptors. 
pp. 114-199 in: Reflexogenic areas of the cardiovascular 
system. J. A. Churchill Ltd., 1958, 271 pp. 
831. Holmberg, G. The effect of carbon dioxide on 
convulsions induced by electric shock treatment. Acta 
psychiat. neurol. scand., 1954, 29: 99-111. 
832. Hurtado, A. Effect of carbon dioxide on the respi- 
ratory center. J. Amer. med. Ass., 1956, 160: 315. 
833. Joels, N. and E. Neil. The influence of anoxia 
and hypercapnia, separately and in combination, on 
chemoreceptor impulse discharge. J. Physiol., 1961, 155: 
45P-46P. 
834. Kent, L. R. Carbon dioxide therapy as a medical 
treatment for stuttering. J. Speech Dis., 1961,26: 268-271. 
835. Kollias, J. and R. W. Bullard. Effects of carbon 
dioxide on heat tolerance of the white rat. Fed. Proc., 1963, 
22: 175. 
836. LaVerne, A. A. and M. Herman. Carbon diox- 
ide inhalation therapy. Dis. nerv. Syst., 1953, 14: 209-212. 
837. Liljestrand, A. Respiratory reactions elicited 
from medulla oblongata of the cat. Acta physiol, scand., 
1952, Suppl. 106, 29: 321-393. 
838. Loeschcke, H. H. Uber den Einfluss von C02 
auf die Bestandspotentiale der Hirnhdute. Pflug. Arch, 
ges. Physiol., 1956, 262: 532-536. 
839. Loeschcke, H. H., R. A. Mitchell, B. Katsa- 
ros, J. F. Perkins, Jr. and A. Konig. Interaction of 
intracranial chemosensitivity with peripheral afferents to 
the respiratory centers. Ann. N.Y. Acad. Sci., 1963, 109: 
651-660. 
840. McQuarrie, D. G. and S. N. Stein. The effect 
of varying rates of concentration increase upon the anal- 
gesic potency of various concentrations of C02 in rats. 
U.S. Navy. NMRI. Project MR 005.14-3001.01, Kept. no. 1, 
2 July 1961, 7 pp. 
841. Meduna, L. J. A modification of carbon dioxide 
treatment using nitrous oxide. Dis. nerv. Syst., 1953, 14: 
102-107. 
842. Meduna, L. J. Technique and theory, pp. 3-99 
in: Carbon dioxide therapy. C. C. Thomas, Springfield, 111. 
1958, 275 pp. 
843. Miller, A., R. A. Bader and M. E. Bader. The 
neurological syndrome due to marked hypercapnia, with 
papilledema. Amer. J. Med., 1962, 33: 309-318. 
844. Mitchell, R. A., H. H. Loeschcke, J. W. 
Severinghaus, B. W. Richardson and W. H. Mas- 
sion. Regions of respiratory chemosensitivity on the sur- 
face of the medulla. Ann. N.Y. Acad. Sci., 1963, 109: 661- 
681. 
845. Mitchell, R. A., W. Massion, C. T. Carman 
and J. W. Severinghaus. 4th ventricle respiratory 
chemosensitivity and the area postrema. Fed. Proc., 1960, 
19: 374. 
846. Moriarty, J. D. Carbon dioxide inhalation ther- 
apy of neuroses. J. din. exp. Psychopath., 1952, 13: 181-194. 
847. Moriarty, J. D. Evaluation of carbon dioxide 
inhalation therapy. Amer. J. Psychiat., 1954, 110: 765-769. 
848. Morrice, J. K. W. Slow wave production in the 
EEC, with reference to hypernea, carbon dioxide and 
autonomic balance. EEG din. Neurophysiol., 1956, 8: 49- 
72. 
849. Ngai, S. H. and S. C. Wang. Respiratory char- 
acteristics of pontile and medullary cats: Responses to C02 
inhalation. Fed. Proc., 1953, 12: 103. 
850. Nixon, C. W. Differential effect of breathing 
selected gases upon temporary auditory-threshold shift. 
Aerospace Med., 1961,32: 947-952. 
851. Normann, N. Succinylcholine paralysis, artificial 
respiration and carbon dioxide causing prolonged central 
respiratory depression. Fed. Proc., 1956, 15: 138. 
852. Payne, J. P. Further studies of the influence of 
carbon dioxide on neuromuscular blocking agents in the 
cat. Brit. J. Anaesth., 1960, 32: 202-205. PHYSIOLOGICAL EFFECTS OF HIGH CARBON DIOXIDE—HEART AND CIRCULATION853-879 
853. Peters, R. M. Bronchospasm due to increased 
carbon dioxide in inspired air; a vagal reflex. Amer. Col. 
Surg., Clin. Cong., 1954, 40: 702-707. 
854. Plum, F. and H. W. Brown. Hypoxic-hyper- 
capnic interaction in subjects with bilateral cerebral 
dysfunction. J. appl. Physiol., 1963, 18: 1139-1145. 
855. Potes, J. and C. E. Wells. The electroencephalo- 
gram during administration of 100% oxygen and of 5% 
carbon dioxide in patients with cerebral infarction. 
Neurology, 1961,11: 738-741. 
856. Rickels, K., C. J. Lambertsen and J. H. 
Ewing. Effectiveness of anti-convulsive drugs in prevent- 
ing generalized convulsions produced in monkeys by in- 
halation of 30% COa in 02. Fed. Proc., 1959,18: 437. 
857. Riedstra, J. W. Role of bulbar respiratory cen- 
tre and of peripheral chemoceptors in the regulation of 
ventilation. XXII Inter. Congr. physiol. Sci., Leiden. 1962, 
2: Abstr. 315. 
858. Robin, E. D., R. D. Whaley, C. H. Crump and 
D. M. Travis. Alveolar gas concentrations and respira- 
tory center sensitivity to C02 during natural sleep. Fed. 
Proc., 1957,16: 107. 
859. Rosenstein, R. and H. L. Borison. Actions of 
carbon dioxide and sodium salicylate on central control of 
respiration in cats. J. Pharmacol, 1963, 139: 361-367. 
860. Schaefer, K. E. Effects of carbon dioxide on 
consciousness, pp. 96-105 in; Environmental effects on 
consciousness. Edited by Karl E. Schaefer. MacMillan 
Company, New York, 1962, 146 pp. 
861. Schaefer, K. E. and B. Barton. C02 effects on 
carbonic anhydrase activity and electrolytes of hypothala- 
mus and cortex. Fed. Proc., 1956,15: 162. 
862. Schaefer, K. E. and C. Carey. Effect of in- 
creased C02 concentrations on flicker fusion frequency and 
alpha blocking time. Fed. Proc., 1953,12: 125. 
863. Schaefer, K. E. and C. R. Carey. Influence of 
exposure to various carbon dioxide concentrations on 
flicker fusion frequency and alpha blocking. U.S. Navy. 
Submarine base, New London, Conn. Medical research 
laboratory. Project NM 002 015.11, Kept. no. 2, 27 August 
1954. 
864. Schaefer, K. E., E. R. Cornish, Jr., S. E. 
Stuntz, C. A. Lukas, H. E. Brewer and C. R. Carey. 
Effect of inhalation of various carbon dioxide concentra- 
tions on the inhibitory effect of light stimuli on alpha 
waves and muscle potential output of the forehead. U.S. 
Navy. Submarine base. New London, Conn. Medical re- 
search laboratory. Project NM 002 015.03.07, 17 March 
1952, 21 pp. 
865. Sieker, H. O. and W. P. Wilson. Electroen- 
cephalographic and biochemical changes in acute hypoxia 
and hypercapnia. Arch. Neurol, 1960, 3: 704-710. 
866. Silver, G. A. Carbon dioxide therapy. Psychiat. 
Quart., 1953, 27: 52-58. 
867. Smith, J. A. An evaluation of the results of 
treatment of 33 patients with carbon dioxide inhalations. 
Amer. J. Psychiat., 1953, 109: 626. 
868. Smith, A. M. Treatment of stutterers with car- 
bon dioxide. Bis. new. Syst., 1953, 14: 243-244. 
869. Stephens, W. M. The central nervous system 
changes resulting from increased concentrations of carbon 
dioxide. J. Neuropath, din. Neurol., 1951, 1: 88-97. 
870. Swanson, A. G., L. S. Stavney and F, Plum. 
Effects of blood pH and carbon dioxide on cerebral elec- 
trical activity. Neurology, 1958, 8: 787-792. 
871. Tang, P. C. Nervous regulation of respiration. 
Fed. Proc., 1959,18: 156. 
872. Therman, P. O. Neurophysiological effects of 
carbon dioxide, pp. 31-40 in: Environmental effects on con- 
sciousness. Edited by K. E. Schaefer. MacMillan Company, 
New York, 1962, 146 pp. 
873. Waltz, J. M., J. E. von Weiss and J. Stevens. 
The effect of C02 inhalation on the electroencephalogram 
of patients with cerebral infraction. EEG din. Neuro- 
physiol., 1957, 9: 527-530. 
874. Weaver, O. M., D. B. Peterson and W. H. 
Anderson. Carbon dioxide therapy of pxychoneuroses. 
Bis. new. Syst., 1951,12: 355-361. 
875. Weinstein, S. A. 02 and C02 as reinforcers in 
conditioning. Fed. Proc., 1963, 22: 222. 
876. Wing, K. G., J. D. Harris, A. D. Stover and 
J. H. Brouillette. Effects of changes in arterial carbon 
dioxide upon cochlear microphonics. U.S. Navy. Submarine 
Base, New London, Conn. Medical research laboratory. 
Project NM 003 041.27.03, 28 February 1952, 37 pp. 
877. Woodbury, D. M. and R. Karier. The role of 
carbon dioxide in the nervous system. Anesthesiology, 1960, 
21: 686-703. 
878. Woodbury, D. M., L. T. Rollins, M. D. Gard- 
ner, W. L. Hirschi, J. R. Hogan, M. L. Rallison, 
G. S. Tanner and D. A. Brodie. Effects of carbon 
dioxide on brain excitability and electrolytes. Amer. J. 
Physiol, 1958, 192: 79-90. 
879. Young, W. G., Jr., W. C. Sealy, J. Harris 
and A. Botwin. The effects of hypercapnia and hypoxia 
on the response of the heart to vagal stimulation. Surg. 
Gynec. Obstet., 1951, 93: 51-55. 
C. HEART AND CIRCULATION 
Several general papers on the effects of carbon 
dioxide on the heart and circulation may be 
discussed first. Price {928) 1960, stated that in 
the isolated heart increased Pc02 reduces the 
contractile force and rate of contraction in vari- 
ous mammalian species. The ability of carbon 
dioxide to reduce pH is believed to be a primary 
factor. With few exceptions the effect of carbon 
dioxide is relaxation of peripheral blood vessels. 
It is not clear whether pH or PCOo is the more 
important. Capillaries and veins may be most 
affected. Aortic and carotid body chemorecep- 
tors are very sensitive to carbon dioxide which 
also affects the posterior hypothalamus, the 
mesenphalic reticular substance, and respiratory 
and vasomotor control areas further caudally. As SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
Pco>> increases, acidosis reduces body responses 
(roughly 50 percent at 30 percent carbon 
dioxide). Cardiac output is increased in normal 
men breathing carbon dioxide while lying 
supine. Vascular resistance is reduced as PCOo 
increases. Arterial hypertension is almost in- 
variable during carbon dioxide inhalation, but 
is relatively minor. Systolic and diastolic blood 
pressure and heart rate are increased in healthy 
males. The most reliable circulatory indication 
of hypercarbia in anesthetized subjects is cardiac 
arrhythmia. Posthypercapnic hypotension oc- 
curs. Various arrhythmias, especially ventricular 
arrhythmias, can occur both during hypercarbia 
and during its correction, due probably to in- 
creased sympathetic nervous system activity. 
Heath and Brown (907) 1954, have reported on 
fall in arterial blood pressure, cardiac arrhyth- 
mias, and in some instances, ventricular fibrilla- 
tion and death, following return to air breathing 
after inhalation of carbon dioxide for two to four 
hours in dogs. It has also been shown that an 
increase in circulating blood volume occurs dur- 
ing hypercapnia and persists during the period 
of most severe hypotension following return to 
air breathing. In order to determine the relative 
role of reduction in cardiac output and peri- 
pheral resistance in this hypotension, 30 percent 
carbon dioxide in oxygen was administered from 
an open system to pentothal anesthetized dogs. 
Cardiac output was determined by the direct 
Fick method, before, five minutes after, and two 
hours after the carbon dioxide breathing. The 
central arterial pressure was recorded continu- 
ously during the blood sampling by means of a 
strain gauge connected to a catheter and inserted 
through the carotid artery into the aorta. 
Within five minutes after returning the dogs to 
air breathing, the mean arterial pressure usually 
fell to approximately one-half the control level. 
These data indicate that a reduction in cardiac 
output accounts for this hypotension with no 
significant change in peripheral resistance at this 
time. When the fall in blood pressure was pre- 
vented by intravenous administration of nor- 
epinephrine, cardiac output fell to the same ex- 
tent as before and the blood pressure was 
maintained entirely by an increase in peripheral 
resistance. Sechzer, Egbert, Linde, Cooper, 
Dripps, and Price (985) 1960, gave carbon 
dioxide in oxygen ranging from 7-14 percent for 
periods of 10-20 minutes to human male volun- 
teers. It was found that respiratory minute 
volume, arterial pressure, heart rate, and plasma 
concentrations of epinephrine, norepinephrine 
and 17-OH corticosteroids were increased in 
every subject during hypercarbia. Abnormal 
cardiac rhythms were infrequently observed. Fol- 
lowing substitution of oxygen for the carbon 
dioxide-oxygen mixture, the altered measure- 
ments returned to normal over a period of 
roughly ten minutes. Neither marked hypoten- 
sion nor cardiac arrhythmia was observed after 
correction of hypercarbia. A further study of 
carbon dioxide inhalation upon the circulation 
is that by Hille, Hild, Melchelke and Barth 
(908) 1961. In this investigation changes in 
muscle and skin circulation and arterial blood 
pressure were recorded in 12 healthy human 
subjects during unrestricted breathing of 7 per- 
cent carbon dioxide and during hyperventilation 
with approximately similar volumes of air, or 4 
and 7 percent carbon dioxide-oxygen mixtures. 
Hyperventilation with air as well as carbon 
dioxide breathing resulted in a vasoconstriction 
of skin blood vessels. The actions of both factors 
were additive. Hyperventilation increased circu- 
lation in underwarm muscles, carbon dioxide 
breathing lowered this increased circulation. 
Tachycardia due to hyperventilation was lessened 
by carbon dioxide. The blood pressure fell 
during hyperventilation with air while during 
carbon dioxide breathing it was regularly in- 
creased. The authors concluded that circulatory 
changes brought about by carbon dioxide 
breathing and those effected by hyperventilation 
as a result of carbon dioxide breathing are in- 
dependent of one another. Circulatory reactions 
to hyperventilation with air are not considered 
a result of hypocapnia. The authors believe they 
are probably caused by stimulation of the 
sympathetic nervous system and release of 
adrenaline. 
Breathing carbon dioxide mixtures tends to 
decrease cardiac contractile force. This has been 
demonstrated in acute experiments by Boniface 
and Brown (884) 1953, using a modified Cushny 
myocardiograph to measure the effect of carbon 
dioxide mixtures on the contractile force of a 
representative segment of the right ventricle. PHYSIOLOGICAL EFFECTS OF HIGH CARBON DIOXIDE—HEART AND CIRCULATION 
With reduction in contractile force there was 
also a decrease in the amplitude of systolic ex- 
cursion. Pronounced cardiac dilatation also oc- 
curred. The extent and rapidity of these changes 
were roughly proportional to the concentration 
of carbon dioxide in the respired gases. Carbon 
dioxide differed from the common and typical 
cardiac depressants in that the heart sometimes 
regained its original contractile force during con- 
tinuous administration of carbon dioxide and 
again when the gas was withdrawn a characteristic 
and marked ‘rebound’ effect sometimes appeared. 
In isolated rabbit auricles, Vaughan-Williams 
(942) 1955, found that carbon dioxide had a 
specific effect upon conduction velocity. The 
higher the carbon dioxide concentration, the 
faster the velocity of conduction. At a constant 
carbon dioxide concentration the conduction 
velocity was to some extent increased by alkali 
and decreased by acids. Monroe, French and 
Whittenberger (922) 1960, found that moderate 
elevations of PCOo (61-75 mm. Hg) did not con- 
sistently depress myocardial contractility in mon- 
grel dogs as determined by standard ventricular 
function curves. With an altered preparation in 
which the heart rate and left atrial pressure were 
held constant, a PCOo of 60-75 mm. Hg was ac- 
companied by an average reduction in stroke 
work to 73.6 percent of control value, while hypo- 
capnia with an alveolar PCOo of 6-13 mm. Hg 
was unaccompanied by any consistent reduction 
in stroke work. 
The tolerance of the dog heart to carbon 
dioxide has been studied by Brown and Miller 
(886) 1952 and (887) 1952. When the carbon 
dioxide concentration in the inhaled air was 
gradually increased over a period of 60-90 
minutes, most dogs reached levels above 90 per- 
cent before the blood pressure fell to zero and 
cardiac arrest followed. The average pH of the 
last arterial blood sample drawn was 6.41. A 
gradual slowing of heart rate and a slight in- 
crease in P-R interval regularly accompanied the 
increasing carbon dioxide tension. Respiratory 
arrest usually appeared when the carbon dioxide 
concentration reached 60-65 percent and arti- 
ficial respiration was required above this con- 
centration. Blood pressure usually started to fall 
when the carbon dioxide concentration reached 
50-70 percent, and cardiac arrest followed a 
severe fall in blood pressure. For other studies 
on cardiac tolerance to carbon dioxide papers by 
Biicherl and Kloos (888) 1960, and Clowes, Hop- 
kins, and Simeone (890) 1955, may be consulted. 
Sealy, Young and Harris (943) 1954, have 
suggested hypercapnia is a factor in the patho- 
genesis of cardiac arrest. The critical period for 
the heart is the posthypercapnic period. Posthy- 
percapnic ventricular fibrillation can be pre- 
vented by intravenous injection of 20 percent 
glucose and 3 percent sodium chloride when 
warning electrocardiographic changes develop. 
Brown (885) 1955, suggests that the elevated 
plasma potassium is not sufficient to produce 
the severe cardiac effects following hyper- 
capnia, but that a rapid decrease in arterial 
Pco-) and hydrogen ion concentration in the 
presence of the sub-lethal potassium concen- 
tration may produce cardiac arrest or ventricular 
fibrillation. Young, Sealy, and Harris (945) 
1954, studied the effects of acute prolonged 
hypercapnia on electrolyte metabolism and on 
electrocardiograms in dogs and rats. When 
breathing 30-45 percent carbon dioxide these 
animals showed a progressive rise in plasma 
potassium concentration. In the immediate post- 
hypercapneic period there was an additional 
sharp increase in the plasma potassium level. 
At the same time serious electrocardiographic 
disturbances frequently appeared and terminated 
in ventricular fibrillation or cardiac arrest. The 
authors advance the hypothesis that the rise in 
plasma potassium concentration is the primary 
cause of the electrocardiographic abnormalities, 
although secondary and less specific factors may 
play roles. Hypertonic glucose and saline solu- 
tion have been found effective in reversing the 
electrocardiographic changes if given sufficiently 
early. These results have implications in human 
cardiac arrest occurring during surgery. Cardiac 
arrhythmias and ventricular fibrillation result- 
ing from rapid reversal of hypercarbia have been 
studied by Andrews, Adrian and Gordon (880) 
1957, and Gordon, Andrews, Adrian and Beattie 
(902) 1957. Cardiac arrhythmias and ventricular 
fibrillation have been reported following rapid 
reversal of hypercarbia in animals, and this 
process has been implicated also in human cases 
of ventricular fibrillation occurring during or 
immediately after surgery. In the study by An- SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
drews, Adrian and Gordon, nembutalized dogs 
rebreathed into a bag for periods of 90 minutes. 
The dogs were then rapidly hyperventilated with 
room air. EKGs and carotid artery blood pres- 
sure were recorded continuously; serial arterial 
plasma pH, carbon dioxide content, and potas- 
sium were measured as often as every minute 
during periods of rapid change. The plasma 
potassium reached peaks of 50 percent above the 
control levels within ten minutes after the onset 
of rebreathing. It then fell gradually to values 
slightly above the control and remained there 
until the carbon dioxide was blown off, at which 
time it reached a second peak more rapidly 
and higher than the first. The height of the 
second peak correlated with the speed of carbon 
dioxide elimination. The EKG was essentially 
unchanged until the carbon dioxide was removed 
when ominous arrhythmias developed in 50 per- 
cent of the dogs and ventricular fibrillation in 
20 percent. The severe arrhythmias occurred in 
dogs having the most rapid removal of carbon 
dioxide. The Pco., reached levels of over 300 
mm. Hg, but could be brought to subnormal 
levels with two to three minutes by hyperventila- 
tion. This gradual accumulation of endogenous 
carbon dioxide and its subsequent rapid removal 
results in changes similar to those described after 
breathing 30-40 percent COa for two to four 
hours, or with sudden reversal of hypercarbia 
during and immediately following surgery. In 
the paper by Gordon, Andrews, Adrian and 
Beattie, the anesthetized dogs rebreathed con- 
tinuously from a large rubber bag for 90 minutes, 
into which oxygen was replaced as needed, and 
then were hyperventilated with air for one 
minute. A second series of dogs was given 0.05 
mg. of epinephrine per kilogram body weight 
intravenously at the beginning of a rapid re- 
versal of hypercarbia. In the first series during 
carbon dioxide retention the arterial Pco>) rose 
gradually from 38 to 247 mm. Hg at 90 minutes; 
the pH fell from 7.42 to 6.82, and the plasma 
potassium K had a transient rise (within the 
first two minutes) and gradually returned to 
normal. With hyperventilation the PCOo dropped 
to a subnormal level of 25 mm. Hg while the 
pH made an alkolotic swing to 7.5 within two 
to three minutes and persisted, and the potas- 
sium K rose from 4.6 to 5.7 mEq/1 at four 
minutes, returning to normal within five minutes. 
Initially during rebreathing all dogs showed 
sinus tachycardia, tachypnea, and rising blood 
pressure; but after one hour they exhibited 
progressive slowing of pulse and respiration and 
decrease in blood pressure. During hyperventila- 
tion, cardiac arrhythmias, A-V dissociation, ven- 
tricular extrasystoles and tachycardia occurred 
in all dogs. There was a brief pulse acceleration 
and systolic blood pressure rise followed in most 
cases by a relative bradycardia and hypotension. 
The results of the second series were the same 
except that the plasma potassium K almost 
doubled within two minutes after the onset of 
hyperventilation and EKG changes were more 
severe. Posthypercapneic bradycardia and hypo- 
tension were prevented. 
Of the physiological factors important in the 
regulation of cardiac output, blood PCOo has 
been investigated relatively little. Richardson, 
Wasserman, Dingledine and Patterson (930) 
1959, reported striking changes in hemodynamics 
associated with hypercapnia induced by breath- 
ing 7 percent carbon dioxide for seven minutes in 
16 experiments in 10 normal human volunteers. 
In additional experiments subjects performed 
maximal voluntary hyperventilation with a 
variable inspired carbon dioxide concentration 
adjusted to maintain constancy of end-tidal PCOo. 
During voluntary hyperventilation with alveolar 
PCOo maintained at control levels, the average 
respiratory minute volume of the group in- 
creased from 13 to 33 liters, and the average 
cardiac index remained constant at 3.6 
L/min/m2. During breathing of 7 percent carbon 
dioxide there was an increase in respiratory 
minute volume from 9 to 45 liters, in Pc0„ from 
42 to 58 mm. Hg, and in cardiac index from 
2.9 to 4.2 L/min/m2 (p<0.001). Mean arterial 
pressure rose from 89 to 105 mm. Hg (p = 0.001) 
during 7 percent carbon dioxide breathing but 
rose only 3.5 mm. Hg (p = 0.1) during vigorous 
breathing without change in PCOo. The reported 
results demonstrated to the authors that the 
large alterations in circulatory dynamics associ- 
ated with induced hypercapnia are the results of 
changes in blood PCOo and not of the vigorous 
respiratory movements. The thorax apparently 
does not act as a blood pump during hyperventi- 
lation. In dogs, Li, Kao, McCoy and Harmel PHYSIOLOGICAL EFFECTS OF HIGH CARBON DIOXIDE—HEART AND CIRCULATION 
(916) 1961, found no significant change in car- 
diac output in hypercapnia. 
Feinberg, Gerola and Katz (898) 1958, and 
(899) 1960, studied the effects of changes in 
blood carbon dioxide level on coronary flow 
and myocardial oxygen consumption. The 
effect of hypo- and hypercapnia induced by 
changing the respiratory gas mixture on coronary 
flow and myocardial oxygen consumption was 
observed at constant cardiac output and over a 
broad range of pressure loads in open-chested 
anesthetized dogs. The correlation of cardiac 
effort (as indexed by the product of heart rate 
and mean aortic blood pressure) with myocardial 
oxygen consumption was not altered by increas- 
ing or decreasing the arterial carbon dioxide 
content. Coronary blood flow was observed to 
be increased relative to the cardiac effort during 
hypercapnia but not during hypocapnia. The 
coronary arteriovenous oxygen differences and 
the percentage of oxygen extracted decreased dur- 
ing hypercapnia ‘pari passu’ with the increase 
in venous oxygen content. 
Several studies of the effects of carbon dioxide 
on peripheral circulation have been carried out. 
McArdle, Roddie, Shepherd and Whelan (920) 
1957, examined the effect of inhalation of 30 
percent carbon dioxide for one to two minutes 
on the cardiovascular system in men undergoing 
carbon dioxide treatment for stammering. There 
was increased activity of respiratory muscles due 
to increase in depth and, to a lesser extent, rate 
of respiration. Consciousness was dulled and 
sweating perfuse. Blood flow through the nor- 
mal forearm and calf showed a transient in- 
crease followed by a decided fall (on occasion 
almost ceasing). Peak flow after carbon dioxide 
was two to five times greater than the control. 
Since there was an associated increase in arterial 
blood pressure (i.e. 125/75 to 205/110) during 
carbon dioxide inhalation, the decrease in flow 
was due to intense vasoconstriction, probably 
deep to the skin because oxygen saturation in 
superficial venous blood did not fall. There 
was a slight decrease in blood flow through the 
forearm despite the increased blood pressure, 
when in one case the nerves of the forearm were 
blocked with local anesthesia, suggesting that 
nervous vasoconstriction cannot completely ac- 
count for the marked decrease in muscle flow. 
Changes in hand blood flow were equivocal. 
McArdle and Rodide (919) 1958, administered 
30 percent carbon dioxide for one to two minutes 
to young women following minor gynaecological 
surgery and after general anesthesia. This pro- 
cedure led to hyperpnea, eliminating volatile 
anesthetics and therefore causing rapid return 
to consciousness. The conscious patients ex- 
hibited 120/75 to 210/100 mm. Hg rise in 
arterial blood pressure accompanied by slowing 
of the heart. Forearm blood flow after transient 
increase was greatly reduced to almost zero. If 
the forearm was nerve-blocked, a similar fall did 
not occur, implicating vasomotor nerves in vaso- 
constriction. In the normal forearm, on cessation 
of carbon dioxide inhalation, there was a transi- 
ent vasodilitation. With anesthesia the re- 
sponses were modified; arterial blood pressure 
was only slightly increased, heart rate increased 
slightly with little or no change in blood flow 
and no transient vasodilitation initially. Transi- 
ent vasodilitation did occur on cessation of 
carbon dioxide inhalation, however. The respira- 
tory response was depressed, but arterial pH 
was comparable to that in a conscious subject. 
Evidence indicates to the authors that alterations 
in response during anesthesia were due to gen- 
eral depression of reflex activity. Local injec- 
tion of carbon dioxide into the skin, or im- 
mersion of the hand in water saturated whh 
carbon dioxide have been found by Diji and 
Greenfield (894) 1958, and (895) 1960, and Diji 
(893) 1959, to exert local vasodilator action. 
For further studies on peripheral vasodilitation 
following carbon dioxide inhalation in man, 
papers by Black and Roddie (882) 1958; and 
Blair, Glover, McArdle and Roddie (883) 1960, 
may be consulted. 
Carbon dioxide inhalation has been shown to 
increase cerebral blood flow. This cerebral blood 
flow response to carbon dioxide is greatly reduced 
in cerebral vascular disease. Patterson, Heyman, 
Battey and Ferguson (925) 1955, have reported 
that the vasodilator response of normal cerebral 
vessels to rapid increase in arteial PCOo appears 
to be a threshold type of phenomenon. In a 
group of 28 subjects a mean increase in arterial 
PC09 of less than 4.5 mm. Hg was without vascu- 
lar effect, whereas increases greater than this 
value produced progressive vasodilatation. In- 880-897 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
halation of 3.5 percent carbon dioxide produced 
a ten percent mean increase in cerebral blood 
flow. For other studies of the effects of carbon 
dioxide inhalation on cerebral circulation papers 
by Hafkenschiel and Friedland (904) 1952; 
Novack, Shenkin, Bortin, Goluboff and Soffee 
(924) 1953; Schieve and Wilson (932) 1953; 
Wilson, Odom and Schieve (944) 1953; Hansen, 
Sultzer, Freygang and Sokoloff (906) 1953; Soko- 
loff (937) 1960; Lambertsen, Semple, Smyth and 
Gelfand (915) 1961; and Rapela, Machowicz and 
Freeman (929) 1963, should be consulted. 
According to Stroud and Rahn (940) 1953, 
and Fishman, Fritts and Cournand (900) 1960, 
inhalation of carbon dioxide did not produce 
pulmonary vasoconstriction. On the other hand 
Stroud (939) 1962, stated that high carbon 
dioxide, and more strongly and definitely, low 
oxygen caused resistance to blood flow through 
the lungs due to vasoconstriction. The vaso- 
motor response to changes in gas tensions is 
stated to be neurogenic with both thoracic sym- 
pathetic outflow and the vagus nerves implicated. 
Epstein, Wheeler, Frumin, Habif, Papper, 
and Bradley (897) 1961, found that estimated 
hepatic flow, splanchnic blood volume, calcu- 
lated splanchnic vascular resistance and mean 
arterial pressure, did not change significantly or 
consistently during light general anesthesia with 
thiropental and nitrous oxide, maintained by 
mechanically controller artificial respiration fol- 
lowing neuromuscular blockade with succinylcho- 
line. Hypercapnia (PaCOf) 56 mm. Hg on the 
average) under these circumstances resulted in 
statistically significant increment in mean calcu- 
lated splanchnic vascular resistance. The esti- 
mated hepatic blood flow was decreased, re- 
mained unchanged, or rose, depending upon 
the behavior of arterial blood pressure. The 
average value for circulatory splanchnic volume 
also decreased significantly. These changes were 
ascribed by the authors to a combination of 
arteriolar and venous constriction. Sulphobro- 
mophthalin clearance and extraction by the liver, 
although unaffected by anesthesia, decreased 
significantly during hypercapnia. 
880. Andrews, P. W., F. E. Adrian and A. S. 
Gordon. Hyperpotassemia, cardiac arrhythmias and ven- 
tricular fibrillation resulting from rapid reversal of hyper- 
carbia. Fed. Proc., 1957,16: 3. 
881. Bernthal, T., E. Otey and B. Metz. Effects of 
altered C02 tension upon hypoxic initiation and central 
mediation of carotid chemoreflex respiratory drive. XXII 
Inter. Congr. physiol. Sci., Leiden. 1962, 2: Abstr. 317. 
882. Black, J. E. and I. C. Roddie. The role of C02 
in the changes in forearm vascular resistance with anoxia. 
J. Physiol., 1958, 140: 39P-10P. 
883. Blair, D. A., W. E. Glover, L. McArdle and 
I. C. Roddie. The mechanism of the peripheral vasodila- 
tion following carbon dioxide inhalation in man. Clin. 
Sci., 1960, 19: 407-423. 
884. Boniface, K. J. and J. M. Brown. Effect of 
carbon dioxide excess on contractile force of heart, in 
situ. Amer. J. Physiol., 1953, 172: 752-756. 
885. Brown, E. B., Jr. Role of hyperkalemia in pro- 
duction of ventricular fibrillation following hypercapnia. 
Proc. Soc. exp. Biol., N.Y., 1955, 90: 319-323. 
886. Brown, E. B., Jr. and F. Miller. Tolerance of 
the dog heart to carbon dioxide. Amer. J. Physiol., 1952, 
170: 550-554. 
887. Brown, E. B., Jr. and F. A. Miller. Carbon 
dioxide tolerance of the dog heart. Fed. Proc., 1952,11: 18. 
888. Bucherl, E. S. and K. Kldos. Anatomische 
Befunde, Elektrolythaushalt und Gasspannungen im Blut 
vor, wahrend und nach experimenteller Beatmung mit 
extrem hohen Kohlensaurekonzentrationen bei Hunden. 
Verh. dtsch. Ges. Path., 1960, 44: 251-256. 
889. Buckley, J. J., F. H. Van Bergen, A. B. 
Dobkin, E. B. Brown, Jr., F. A. Miller and R. L. 
Varco. Postanesthetic hypotension following cyclopro- 
pane: its relationship to hypercapnia. Anesthesiology, 
1953, 14: 226-237. 
890. Clowes, G. H. A., Jr., A. L. Hopkins and F. 
A. Simeone. A comparison of the physiological effects of 
hypercapnia and hypoxia in the production of cardiac ar- 
rest. Ann. Surg., 1955, 142: 446-460. 
891. Cropp, G. and J. H. Comroe, Jr. The role of 
carbon dioxide tension in pulmonary artery blood in the 
control of respiration. Physiologist, 1960, 3: 43. 
892. Diamond, J. and A. Howe. Chemoreceptor 
activity in the aortic bodies of the cat. J. Physiol., 1956, 
134: 319-326. 
893. Diji, A. Local vasodilator action of carbon di- 
oxide on blood vessels of the hand. J. appl. Physiol., 1959, 
14: 414-416. 
894. Diji, A. and A. D. M. Greenfield. The local 
effect of carbon dioxide on the blood vessels of the human 
skin. J. Physiol., 1958, 140: 42P. 
895. Diji, A. and A. D. M. Greenfield, The local 
effect of carbon dioxide on human blood vessels. Amer. 
Heart J., 1960, 60: 907-914. 
896. Dzierzynski, M., M. Kalinowski and G. 
Straburzynski. Uber das Verhalten des peripheren 
Kreislaufs im Greisenalter unter dem Einfluss der Kohlen- 
sauregasbader. Arch. phys. Ther., 1961, 13: 227-233. 
897. Epstein, R. M., H. O. Wheeler, M. J. Frumin, 
D. V. Habif, E. M. Papper and S. E. Bradley. The 
effect of hypercapnia on estimated hepatic blood flow, 
circulating splanchnic blood volume, and hepatic sulfo- 
bromophthalein clearance during general anesthesia in 
man. J. din. Invest., 1961, 40: 592-598. PHYSIOLOGICAL EFFECTS OF HIGH CARBON DIOXIDE—HEART AND CIRCULATION898-931 
898. Feinberg, H., A. Gerola and L. N. Katz. 
Coronary flow and myocardial oxygen consumption in 
hypercapnia. Fed. Proc., 1958, 17: 45. 
899. Feinberg, H., A. Gerola and L. N. Katz. 
Effect of changes in blood C02 level on coronary flow and 
myocardial 02 consumption. Amer. J. Physiol., 1960, 199: 
349-354. 
900. Fishman, A. P., H. W. Fritts, Jr. and A. 
Cournand. Effects of breathing carbon dioxide upon the 
pulmonary circulation. Circulation, 1960, 22: 220-225. 
901. Forssander, C. A. Alveolar air changes follow- 
ing inhalation of carbon dioxide during exercise, and cal- 
culation of cardiac output. J. appl. Physiol., 1955-56, 8: 
509-512. 
902. Gordon, A. S., P. W. Andrews, F. E. Adrian 
and E. J. Beattie, Jr. Cardiac arrhythmias and ventricu- 
lar fibrillation resulting from rapid reversal of hyper- 
carbia. Surg. Forum, 1957, 8: 306-310. 
903. Gotoh, F., Y. Tazaki and J. S. Meyer. Trans- 
port of gases through brain and their extravascular motor 
action. Exp. Neurol., 1961, 4: 48-58. 
904. Hafkenschiel, J. H. and C. K. Friedland. 
Physiology of the cerebral circulation in essential hyperten- 
sion: the effects of inhalation of 5% carbon dioxide oxy- 
gen mixtures on cerebral hemodynamics and oxygen me- 
tabolism. J. Pharmacol., 1952, 106: 391. 
905. Hall, F. G., J. Salzano and F. Zechman, Jr. 
The effects of venous infusion of gaseous carbon dioxide 
into dogs. J. Aviat. Med., 1958, 29: 544-548. 
906. Hansen, D. B., M. R. Sultzer, W. H. Frey- 
gang and L. Sokoloff. Effects of low 02 and high C02 
concentrations in inspired air on local cerebral circulation. 
Fed. Proc., 1957, 16: 54. 
907. Heath, C. and E. B. Brown, Jr. Hemodynamic 
changes following 30% carbon dioxide breathing in dogs. 
Fed. Proc., 1954,13: 68. 
908. Hille, H., R. Hild, K. Melchelke and C. 
Barth. Uber die Wirkung von C02-Inhalation und Hyper- 
ventilation auf den Kreislauf des Menschen. Z. Kreisl 
Forsch., 1961, 50: 255-263. 
909. Honig, C. R. and S. M. Tenney. Determinants 
of the circulatory response to hypoxia and hypercapnia. 
Amer. Heart ]., 1957, 53: 687-698. 
910. Horan, L. G., R. L. Andreae and H. F. Yoffee. 
The effect of intracavitary carbon dioxide on surface po- 
tentials in the intact canine chest. Amer. Heart J., 1961, 
61: 504-514. 
911. Joels, N. and E. Neil. The excitation mechan- 
ism of the carotid body. Brit. med. Bull., 1963,19: 21-24. 
912. Joels, N. and M. Samueloff. Metabolic acidosis 
in diffusion respiration. J. Physiol., 1956, 133: 347-372. 
913. Johnston, R. F. The syndrome of carbon dioxide 
intoxication: its etiology, diagnosis and treatment. Univ. 
Mich. med. Bull, 1959, 25: 280-292. 
914. Jordan, E. C., B. Mehlman and G. G. Nahas. 
The buffering of C02 by T.H.A.M. during hypercapnia. 
Effects on the circulation. Fed. Proc., 1959, 18: 78. 
915. Lambertsen, C. J., S. J. G. Semple, M. G. 
Smyth and R. Gelfand. H and pC02 as chemical factors 
in respiratory and cerebral circulatory control. J. appl. 
Physiol, 1961,16: 473-484. 
916. Li, W. K., F. F. Kao, G. McCoy and M. H. 
Harmel. Hypo-hypercapnia and cardiac output. Fed. 
Proc., 1961, 20: 132. 
917. Lovejoy, F. W., Jr., P. N. G. Yu, R. E. Nye, 
Jr., H. A. Joos and J. H. Simpson. Pulmonary hyper- 
tension. III. Physiologic studies in three cases of carbon 
dioxide narcosis treated by artificial respiration. Amer. J. 
Med., 1954,16: 4-11. 
918. Lurie, A. A., R. E. Jones, H. W. Linde, M, L. 
Price, R. D. Dripps and H. L. Price. Cyclopropane 
anesthesia. I. Cardiac rate and rhythm during steady levels 
of cyclopropane anesthesia at normal and elevated end- 
expiratory carbon dioxide tensions. Anesthesiology, 1958, 
19: 457-472. 
919. McArdle, L. and I. C. Roddie. Vascular re- 
sponses to carbon dioxide during anaesthesia in man. 
Brit. J. Anaesth., 1958, 30: 358-366. 
920. McArdle, L., I. C. Roddie, J. T. Shepherd 
and R. F. Whelan, The effect of inhalation of 30% 
carbon dioxide on the peripheral circulation of the human 
subject. Brit. J. Pharmacol., 1957, 12: 293-296. 
921. Miller, F. A., E. B. Brown, J. J. Buckley, 
F. H. Van Bergen and R. L. Varco. Respiratory 
acidosis: its relationship to cardiac function and other 
physiologic mechanisms. Surgery, 1952, 32: 171-183. 
922. Monroe, R. G., G. French and J. L. Whitten- 
berger. Effects of hypocapnia and hypercapnia on myo- 
cardial contractility. Amer. J. Physiol., 1960, 199: 1121- 
1124. 
923. Nahas, G. G. and H. M. Cavert. Cardiac de- 
pressor effects of CO, in the intact dog and heart lung 
preparation. Fed. Proc., 1957, 16: 92. 
924. Novack, P., H. A. Shenkin, L. Bortin, B. 
Goluboff and A. M. Soffe. The effects of carbon dioxide 
inhalation upon the cerebral blood flow and cerebral oxy- 
gen consumption in vascular disease. J. din. Invest., 1953, 
32: 696-702. 
925. Patterson, J. L., Jr., A. Heyman, L. L. Bat- 
tey and R. W. Ferguson. Threshold of response of the 
cerebral vessels of man to increase in blood carbon dioxide. 
J. din. Invest., 1955, 34: 1857-1864. 
926. Phillips, J. H., Jr., G. E. Burch and R. Hel- 
linger. The use of carbon dioxide in the diagnosis of 
pericardial disease. Amer. Heart J., 1961, 61: 748-755. 
927. Power, G., R. W. Hyde, W. H. Lawson, Jr. 
and R. E. Forster. Measurement of pulmonary capillary 
volume with carbon dioxide. Fed. Proc., 1961, 20: 424. 
928. Price, H. Effects of carbon dioxide on the cardio- 
vascular system. Anesthesiology, 1960, 21: 652-663. 
929. Rapela, C. E., P. P. Machowicz and G. Free- 
man. Effect of CO, on autoregulation of cerebral blood 
flow. Fed. Proc., 1963, 22: 344. 
930. Richardson, D. W., A. J. Wasserman, W. S. 
Dingledine and J. L. Patterson, Jr. Role of hypercap- 
nia in the control of cardiac output. Fed. Proc., 1959, 18: 
127. 
931. Richardson, D. W., A. J. Wasserman and 
J. L. Patterson, Jr. General and regional circulatory 
responses to change in blood pH and carbon dioxide ten- 
sion. J. din. Invest., 1961, 40: 31-43. 932-945 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
932. Schieve, J. E. and W. P. Wilson. The influence 
of age, anesthesia and cerebral arteriosclerosis on cerebral 
vascular activity to C02. Amer. J. Med., 1953, 15: 171-174. 
933. Schieve, J. F. and W. P. Wilson. The changes 
in cerebral vascular resistance of man in experimental 
alkalosis and acidosis. J. din. Invest., 1953, 32: 33-38. 
934. Sealy, W. C., W. G. Young, Jr. and J. S. 
Harris. Studies on cardiac arrest: the relationship of 
hypercapnia to ventricular fibrillation. J. thorac. Surg., 
1954, 28: 447-462. 
935. Sechzer, P. H., L. D. Egbert, H. W. Linde, 
D. Y. Cooper, R. D. Dripps and H. L. Price. Effect of 
C02 inhalation on arterial pressure, ECG and plasma cate- 
cholamines and 17-OH corticosteroids in normal man. J. 
appl. Physiol., 1960, 15: 454-458. 
936. Shephard, R. J. The carbon dioxide balance- 
sheets of the body; their determination in normal subjects 
and in cases of congenital heart disease. J. Physiol., 1955, 
129: 142-158. 
937. Sokoloff, L. The effects of carbon dioxide on the 
cerebral circulation. Anesthesiology, 1960, 21: 664-673. 
938. Stewart, B. D., R. W. Virtue and H. Swan. 
Cardiac arrest and ventricular fibrillation. Experimental 
study in dogs with acute hypoxia and hypercapnia and 
in dogs with chronic hypoxia. Arch. Surg., 1953, 66: 703- 
713. 
939. Stroud, R. C. Pulmonary circulatory effects of 
carbon dioxide and oxygen, pp. 228-233 in: Man’s de- 
pendence on the earthly atmosphere. Edited by K. E. 
Schaefer. The MacMillan Company, New York, 1962, 416 
pp. 
940. Stroud, R. C. and H. Rahn. Effect of 02 and C02 
tensions upon the resistance of pulmonary blood vessels. 
Amer. J. Physiol, 1953, 172: 211-220. 
941. Trethwie, E. R. and M. M. Hodgkinson. The 
influence of carbon dioxide and pH on the electrocardio- 
gram of the isolated perfused heart. Quart. J. exp. 
Physiol, 1955, 40: 1-11. 
942. Vaughan Williams, E. M. The individual ef- 
fects of CC2, bicarbonate and pH on the electrical and 
mechanical activity of isolated rabbit auricles. J. Physiol, 
1955, 129: 90-110. 
943. Viles, P. H., J. L. Ankeney and L. M. Cox. 
The effect of 2 per cent carbon dioxide on pH and pC02 
during extracorporeal circulation. /. thorac. cardiov. Surg., 
1960, 39: 619-623. 
944. Wilson, W. P., G. L. Odom and J. F. Schieve. 
The effect of carbon dioxide on cerebral blood flow, spinal 
fluid pressure and brain volume during pentothal sodium 
anesthesia. Curr. Res. Anesth., 1953, 32: 268-273. 
945. Young, G. W., Jr., W. C. Sealy and J. S. 
Harris. The role of intracellular and extracellular elec- 
trolytes in the cardiac arrhythmias produced by prolonged 
hypercapnia. Surgery, 1954, 36: 636-649. 
D. BLOOD 
The disturbances in plasma volume, thiocyan- 
ate space and cellular components of the blood 
during diffusion respiration and during inhala- 
tion of oxygen or mixtures of 20 or 40 percent 
carbon dioxide in oxygen have been investigated 
in the dog by Arends, Rayburn, Draper and 
Whitehead {947) 1952. Severe hypercarbia, 
whether brought by diffusion respiration or by in- 
halation of carbon dioxide in oxygen, results in 
a striking increase in plasma volume, an irregular 
increase in thiocyanate space and substantial in- 
creases in the red cell count, red cell volume and 
oxygen capacity of venous blood. There is no 
change in either the white or differential count. 
In a general review paper on carbon dioxide and 
respiration in acid-base homeostasis, Lambert- 
sen (958) 1960, discusses the respiratory re- 
sponse to concentrations of carbon dioxide from 
0 to 6 percent. The response of respiratory 
neurons to deviations in local environment plays 
the dominant role in the total process responsi- 
ble for acid-base and oxygen homeostasis. In re- 
sponding to local changes the respiratory neurons 
cause alterations in the acid-base composition 
of arterial blood and other fluids which modify 
the local environment of many other cells. Only 
the small fraction of these cells showing intrinsic 
reactivity to acid-base change are capable of 
responding and therefore acute active homeo- 
static regulation of the internal environment is 
restricted to these reactive cells. These cells, 
including central respiratory neurons, vascular 
smooth muscle cells and chemoreceptor glomus 
cells, exist Jn their most stable states at entirely 
different acid-base levels and provide independ- 
ent sensing components in the fluctuating 
dynamic interaction of factors concerned with 
acute adjustment of the acid-base composition by 
the total respiratory control mechanism. 
Hypoxemia in the presence of severe hyper- 
capnia is commonly assumed to be due to the 
Bohr effect. In order to determine the influence 
of this effect, MacArthur and Brown (961) 1958, 
have determined oxygen dissociation curves on 
dog’s blood at carbon dioxide tensions of ap- 
proximately 40, 200, 350 and 430 mm. Hg. 
Blood pH was determined on some of the samples 
after equilibration with the proper gas mixture. 
The curves indicate that hemoglobin is approxi- 
mately 90 percent saturated at an oxygen tension 
of 175 mm. Hg and a carbon dioxide tension of 
430 mm. Hg (pH 6.55). With a carbon dioxide 
tension of 340 mm. Hg (pH 6.65) blood was PHYSIOLOGICAL EFFECTS OF HIGH CARBON DIOXIDE—BLOOD 
saturated 95 percent at an oxygen tension of 150 
mm. Hg. It seems unlikely that displacement of 
the oxygen hemoglobin dissociation curve due 
to high carbon dioxide tension is responsible 
for an appreciable degree of oxygen unsatura- 
tion as long as (at sea level) 25-30 percent of 
the alveolar gas is oxygen. The Bohr effect 
(Margaria {962) 1962) refers to the increased 
acidic properties of hemoglobin as a consequence 
of oxygenation. The effect of varying carbon 
dioxide tensions on the oxyhemoglobin dissocia- 
tion curves under hypothermic conditions have 
been studied by Callaghan, Lister, Patton and 
Swan (952) 1961. Experiments were designed 
to investigate the effects of different carbon 
dioxide tensions on the oxygen dissociation curve 
of blood at various temperature levels using a 
rotating disc oxygenator as a tonometer. Varia- 
tions in hematocrit were shown to be inept in 
construction of curves obtained. Rising carbon 
dioxide tension moves the dissociation curve to 
the right, and flattens it in shape at all tempera- 
tures studied; and raising carbon dioxide tension 
opposes the effect of simultaneous fall in tempera- 
ture. In a study of tissue carbon dioxide dis- 
sociation curves Schaefer and Carey (971) 1959, 
exposed guinea pigs and rats to carbon dioxide 
concentrations of 15 percent, carbon dioxide in 
air, and 30 and 50 percent carbon dioxide in 
oxygen, for various time intervals. Carbon 
dioxide content, pH, and electrolytes of blood 
and tissues were determined and time curves es- 
tablished. Carbon dioxide dissociation curves of 
individual organs showed significant differences; 
slopes ranked in the order of blood, heart, kid- 
ney, liver, hypothalamus, cortex, and muscle, 
and are influenced by: individual differences in 
electrolyte exchange, blood content, and carbonic 
anhydrase activity. The time required to reach 
a steady state in tissue carbon dioxide concen- 
tration varied with the slope of the carbon 
dioxide dissociation curve being longest for 
blood and shortest for muscle. Periods between 
onset of exposure to carbon dioxide and the 
attainment of a steady state in carbon dioxide 
content of all organs increased with decreasing 
carbon dioxide concentrations and appeared to 
be related to a reduced speed of the processes in- 
volved in the compensation of acidosis. The 
effect of carbon dioxide inhalation is to lower 
the pH, as has been shown by Platts and Greaves 
(968) 1957. In these authors’ studies acute 
respiratory acidosis was induced in four normal 
persons by inhalation of seven percent carbon 
dioxide in air. Acute respiratory acidosis pro- 
duced a greater reduction in the pH of both 
plasma and red cells than does chronic respira- 
tory acidosis. The pH in the red cells in chronic 
respiratory acidosis is almost normal. In acute 
respiratory acidosis, CL passes from the plasma 
to the red cells so that the concentration of the 
CL in the cells rises. In chronic respiratory acido- 
sis the concentration of CL in the red cells is 
normal although the plasma CL is very low. 
Chloride is lost from the blood. The patients 
studied in this experiment were several emphy- 
sematous and showed low concentrations of 
hemoglobin in their red cells. This may increase 
the efficiency with which the red cell contents 
are buffered in this condition. The anoxia of 
patients with chronic respiratory acidosis does 
not account for the changes in the composition 
of their blood. In a study of the influence of 
Diamox on posthypercapnic sequelae, Brown 
and Hayden (951) 1956, found that the rate 
of rise of arterial blood pH paralleled the rate 
of rise of blood pH after hypercapnia was de- 
termined during the first 10 minutes after switch- 
ing from 30 percent carbon dioxide to oxygen, 
with and without administration of Diamox. 
With Diamox (50 mg/kg), the rate of rise of 
pH was significantly slower than it was in the 
control run. The nature of the carbon dioxide 
titration curve in the normal dog has been 
studied by Cohen, Brackett and Schwartz (953) 
1964. In these studies unanesthetized dogs were 
used in a chamber with different carbon dioxide 
levels. Each dog was exposed abruptly to the 
carbon dioxide and then held there for six hours 
(8, 12 and 18 percent carbon dioxide). Blood 
samples were drawn at one, two, four and six 
hours. No dog was exposed twice. Their data 
demonstrated that increasing degrees of hyper- 
capnia induced a curvilinear rise in extracellular 
HCO;?- and the HCO.s~ fell as the Pco., rose. 
On the other hand, changes in Pro„ induced 
linear changes in H+ concentration over the 
entire range of carbon dioxide tensions studied. 
These studies suggest that whole body titration 
with carbon dioxide may provide a useful means SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
for detecting experimentally induced changes 
in whole body buffer characteristics. 
Balance studies have been conducted in dogs 
by Schwartz, Hays, Polak and Haynie {972) 1961, 
during recovery from chronic respiratory acidosis 
induced by high carbon dioxide atmospheres. 
Four animals received high salt diets and four 
others low salt diets during periods of exposure 
to carbon dioxide, and each group was main- 
tained on the same diet throughout the recovery 
period. At the end of the carbon dioxide ad- 
ministration plasma HC03~ ranged from 35-39 
mEq/L), and plasma CL rose simultaneously 
was depressed. After being returned to room 
air the high-salt dogs showed prompt reduction 
in plasma HC03- to a normal range (21-24 
mEq/L), and plasma cL rose simultaneously 
to a normal level. In contrast, low-salt dogs had 
significantly smaller reductions in plasma HC03~ 
to values of approximately 27-30 mEq/L, and 
became mildly alkalotic. Plasma CL showed little 
or no change. The fall in plasma HC03" in both 
groups usually took place without loss of HC03~ 
into the urine. During the subsequent six days, 
low-salt dogs stabilized plasma HC03~ levels in 
a range consistently above normal. Plasma Cl- in 
these animals remained grossly subnormal. Per- 
sistent elevation of plasma HC03~ in low-salt 
animals produced an elevated rate of H+ secre- 
tion which persisted, despite normal plasma Pc0-) 
Potassium deficiency did not appear to be factor 
in the difference observed between the low and 
high-salt groups. When salt was added to the 
diet of low-salt dogs, plasma HC03~ fell to nor- 
mal and there was a reciprocal rise of plasma CL. 
Reduction in HC03~ was achieved without uri- 
nary HC03~ loss, but was associated with marked 
suppression of acid excretion. Two additional 
studies of animals given diets low in Na+, but 
containing moderate amounts of CL, demon- 
strated that the acid-base distribution and hypo- 
chloremia' could be corrected solely by provision 
of CL. 
Plasma K+ is increased by inhalation of carbon 
dioxide. In a study of mongrel dogs anesthetized 
with Pentothal, Brown {950) 1955, administered 
30 percent carbon dioxide in oxygen for two 
hours, followed by 40 percent carbon dioxide in 
oxygen for two hours, and then returned to air. 
Potassium determinations were carried out on a 
protein-free filtrate of plasma with a flame photo- 
meter. The mean plasma K+ increased during 
the carbon dioxide breathing as follows; controls 
3.9; 15 minutes, 4.1; 30 minutes, 4.2; 1 hour, 4.8; 
2 hours, 5.6; 3 hours, 5.8; 4 hours, 6.1. Following 
return to air the mean values for 12 dogs were 
6.7 after 5 minutes, 5.6 after 30 minutes and 4.7 
after one hour. All values are expressed in 
mEq/L. The gradual rise over the first two hours 
of high carbon dioxide breathing with the level 
remaining high over the next two hours is in 
contrast to the rapid rise during the first 15 
minutes, with subsequent return toward normal 
which has been reported previously in cats. The 
additional rise within the first five minutes after 
return to air breathing was a regular finding in 
the dog. This is qualitatively similar to changes 
reported in cats breathing comparable mixtures. 
The effects of carbon dioxide on relative red 
cell volume has been reported by Jackson and 
Nutt {955) 1954. The effect of a range of carbon 
dioxide tensions from 5-700 mm. Hg in room 
air on relative red cell volume, as measured by the 
Meyerstein hematocrit, was studied in the ox, 
sheep, rabbits and in human subjects. Red cells 
of all species investigated swelled with increas- 
ing carbon dioxide tensions up to seven percent 
of the cell volume in room air, in ox and sheep, 
up to 13 percent and up to 9 percent in human 
blood. Over the limits of the physiological range, 
that is to say from 40-60 ml. of carbon dioxide 
per 100 ml. of blood, there was no significant 
change in relative red cell volume. A second 
series of experiments was performed exposing 
sheep, rabbit and human bloods to approxi- 
mately 100 percent carbon dioxide, oxygen and 
nitrogen. The high carbon dioxide mixture alone 
caused a significant change in relative cell 
volume. Therefore the red cell swelling ob- 
served throughout this work may be assumed to 
be due to carbon dioxide itself and not to changes 
in the state of oxygenation of the particular 
blood sample. A third series of experiments, in 
which the effect of carbon dioxide saturation was 
studied for times from 5-60 minutes, showed no 
significant increase in the degree of swelling of 
the cells up to 40 minutes equilibration, and only 
a slight increase thereafter. In a study of blood 
sugar and absolute eosinophile response in the 
rat exposed to 30 percent carbon dioxide in PHYSIOLOGICAL EFFECTS OF HIGH CARBON DIOXIDE—BLOOD 
946-967 
air and in oxygen, King, Mego, Williams and 
Schaefer (957) 1953, exposed highly inbred 
animals of the Wistar-Hisaw strain (70 ±10 days 
of age) to 30 percent carbon dioxide in air and 
30 percent in oxygen in a plastic chamber over 
a period of one hour and allowed recovery in 
air in the same chamber for three hours. Blood 
samples were taken from the tail vein prior to 
exposure, during exposure, at intervals of 10, 30 
and 60 minutes, and 3 hours after exposure. 
Determinations were made of total blood sugar, 
absolute eosinophile counts, differential counts, 
hemoglobin, carbon dioxide and oxygen content. 
The results indicated that during exposure to 
carbon dioxide, both in air and in oxygen, there 
was a marked rise in blood sugar but no signifi- 
cant change in the eosinophile count. The white 
blood count increased and the hemoglobin de- 
creased slightly. There was a significant drop in 
eosinophiles and lymphocytes during the re- 
covery period while the blood sugar returned 
to normal. These responses were essentially the 
same in exposure to carbon dioxide in air and 
in oxygen, although the oxygen content of the 
blood of the animals exposed to carbon dioxide 
in air dropped to hypoxic levels, while in those 
animals that were exposed to carbon dioxide in 
oxygen, the oxygen content of the blood re- 
mained practically normal. These results indi- 
cated that under high carbon dioxide glycogenic 
effects were produced independently of any 
changes in absolute eosinophiles. 
946. Alexander, J. K., J. R. West, J. A. Wood and 
D. W. Richards. Analysis of the respiratory response to 
carbon dioxide inhalation in varying clinical states of 
hypercapnia, anoxia, and acid-base derangement. J. din. 
Invest., 1955, 34: 511-532. 
947. Arends, R. L., C. J. Rayburn, W. B. Draper 
and R. W. Whitehead. Effect of diffusion respiration 
and of inhalation of high concentrations of CO, on plasma 
volume, thiocyanate space, blood cells and 02 capacity. 
Amer. J. Physiol, 1952, 171: 507-512. 
948. Blank, M. The permeability of monolayers (about 
38 A thick) to CO, and Oa. Fed. Proc., 1961, 20: 424. 
949. Brown, E. A. The effect of carbon dioxide on 
human red cells in vitro. J. cell. comp. Physiol, 1957, 50: 
167-168. 
950. Brown, E. B. Plasma potassium changes pro- 
duced by inhalation of 30% and 40% carbon dioxide in 
the dog. Fed. Proc., 1955, 14: 21. 
951. Brown, E. B., Jr. and R. Hayden. Influence of 
Diamox on posthypercapnic sequelae. Fed. Proc., 1956, 
15: 25. 
952. Callaghan, P. B., J. Lister, B. C. Patton and 
H. Swan. Effect of varying carbon dioxide tensions on the 
oxyhemoglobin dissocation curves under hypothermic con- 
ditions. Ann. Surg., 1961, 154: 903-910. 
953. Cohen, J. J., N. C. Brackett, Jr. and W. B. 
Schwartz, The nature of the carbon dioxide titration 
curve in the normal dog. J. din. Invest., 1964, 43: 777-786. 
954. Freeman, F. H. and W. O. Fenn. Changes in 
carbon dioxide stores of rats due to atmospheres low in 
oxygen or high in carbon dioxide. Amer. J. Physiol., 1953, 
174 : 422-430. 
955. Jackson, D. M. and M. E. Nutt. The effect of 
carbon dioxide on relative red cell volume. J. Physiol., 
1954, 123: 367-376. 
956. Katsaros, B., H. H. Loeschcke, D. Lerche, 
H. Schonthal and N. Hahn. Wirkung der Bicarbonat- 
Alkalose auf die Lungenbeliiftung beim Menschen. Bestim- 
mung der Teilwirkungen von pH ad COa-Druck auf die 
Ventilation und Veagleich mit den Ergebnissen bei Aci- 
dose. Pfliig. Arch. ges. Physiol., 1960, 271: 732-747. 
957. King, C. T. G., J. L. Mego, E. E. Williams 
and K. E. Schaefer. Blood sugar and absolute eosino- 
phile response in the rat to 30% carbon dioxide in air and 
in oxygen. Fed. Proc., 1953, 12: 76. 
958. Lambertsen, C. J. Carbon dioxide and respira- 
tion in acid-base homeostasis. Anesthesiology, 1960, 21: 
642-651. 
959. Lloyd, B. B. The chemical stimulus to breath- 
ing. Brit. med. Bull., 1963,19: 10-14. 
960. Loeschcke, H. H. Homoiostase des arteriellen 
COo-Drucks und Anpassung der Lungenventilation an den 
Stof fwechsel als Leistungen eines Regelsystems. Klin. 
Wschr., 1960, 38: 366-376. 
961. MacArthur, J. D. and E. B. Brown, Jr. High 
C03 and blood 02 saturation. Fed. Proc., 1958, 17: 101. 
962. Margaria, R. Recent research on oxygen-carbon 
dioxide transport in blood, pp. 277-290 in: Man’s depend- 
ence on the earthly atmosphere. Edited by K. E. Schaefer. 
The MacMillan Company, New York, 1962, 416 pp. 
963. Matell, G. Time-courses of changes in ventilation 
and arterial gas tensions in man induced by moderate 
exercise. Acta physiol, scand., 1963, 58: Suppl. 206, 53 pp. 
964. Meyer, J. S. and A. G. Waltz. Arterial oxygen 
saturation and alveolar carbon dioxide during electroen- 
cephalography. pp. 329-342 in: Cerebral anoxia and the 
electroencephalogram. Edited by J. S. Meyer and H. 
Gastaut. Charles C. Thomas, Springfield, 1961, 617 pp. 
965. Nahas, G. G. and E. C. Jordan. Neutralization 
of the acute effects of hypercapnic acidosis by T.H.A.M. 
Aerospace Med., 1960, 31: 61-68. 
966. Nahas, G. G., E. C. Jordan and J. C. Ligou. 
Effects of a “CO, buffer” on hypercapnia of apneic oxy- 
genation. Amer. J. Physiol., 1959, 197: 1308-1316. 
967. Ngai, S. H. Pulmonary ventilation studies on 
pontile and medullary cats: changes in 02 consumption in 
arterial blood pH, CO, tension and O, saturation, and in 
response to C02 and cyanide. Amer. J. Physiol., 1957, 190: 
356-360. 968-973 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
968. Platts, M. M. and M. S. Greaves. The com- 
position of the blood in respiratory acidosis. Clin. Sci., 
1957,16: 695-708. 
969. Refsum, H. E. Arterial blood gases in respiratory 
insufficiency. Acta chir. scand., 1960, 253: 175-181. 
970. Schaefer, K. E. A concept of triple tolerance 
limits based on chronic carbon dioxide toxicity studies. 
Aerospace Med., 1961, 32: 197-204. 
971. Schaefer, K. E. and C. R. Carey. Tissue car- 
bon dioxide dissociation curves and electrolyte exchange 
in various organs. Fed. Proc., 1959,18: 137. 
972. Schwartz, W. B., R. M. Hays, A. Polak and 
G. D. Haynie. Effects of chronic hypercapnia on elec- 
trolyte and acid-base equilibrium. II. Recovery, with spe- 
cial reference to the influence of chloride intake. J. din. 
Invest., 1961, 40: 1238-1249. 
973. Woldring, S. and G. Owens. Lung volume, ar- 
terial PCo2 and respiratory activity. Fed. Proc., 1964, 23: 
259. 
E. CEREBROSPINAL FLUID 
According to Leusen (982) 1963, in acute 
acidosis produced in dogs by breathing carbon 
dioxide the cerebral spinal fluid changes rapidly 
follow those of the blood, while changes pro- 
duced by ammonium chloride, lactic acid or 
hydrochloric acid, were not followed by the same 
CSF changes. Small, Weitzner and Nahas (984) 
1958, have reported changes in the CSF pressures 
measured in the cisterna magna during apneic 
oxygenation in dogs. The CSF pressure rose an 
average of 88 percent within the first two minutes 
of apnea, from an average control value of 12.3 
cm. H20 of water. The average peak increase 
(375 percent) occurred at an average time of 8.5 
minutes, although the total period of apneic 
oxygenation averaged 17.6 minutes. Because the 
increased carbon dioxide appeared to be respon- 
sible for this rise, five of the seven dogs were 
ventilated with 5-25 percent carbon dioxide 
in oxygen after arterial, venous, and CSF pres- 
sures had returned to control values. This re- 
sulted in consistent similar rises in CSF pressure, 
again without parallel increases in arterial pres- 
sure. Venous pressure changes tended to parallel 
CSF pressure changes, but the degree of response 
was usually much less than that of the cerebro- 
spinal fluid, and in some cases was absent. The 
initial rises in CSF pressure was interpreted as 
being due to cerebral vasodilatation. The later 
changes may be related to CSF production and 
absorption, and arterial and venous pressure. 
These studies have been reported in more detail 
by Small, Weitzner and Nahas (985) 1960. The 
effect of carbon dioxide inhalation on the blood- 
brain barrier has been examined by Clemedson, 
Hartelius and Holmberg (975) 1956, in experi- 
ments performed on rabbits to various concen- 
trations (10, 15, 20 and 30 percent) of carbon 
dioxide in oxygen in a gas chamber. Exposure 
times varied from 2-60 minutes. Ten minutes 
before exposure a trypan blue solution was in- 
jected intravenously. Ten minutes after the ex- 
posure the animals were killed and their vessels 
washed out with normal saline followed by a 20 
percent formalin solution for fixation. On serial 
frozen sections the whole brains were examined 
for blue stainings and hemorrhages. Thirty per- 
cent carbon dioxide for two minutes scarcely 
caused any obvious changes; but after three 
minutes of exposure more consistent effects were 
seen. After 4, 5 and 10 minutes exposure the 
changes were more pronounced, consisting 
of well-defined multiple stainings as well as 
hemorrhages. After 15 minutes or more the 
changes often were maximal. Some of these 
brains were almost totally blue, and there were 
rich hemorrhages in the brain substance and the 
meninges. In animals exposed to lower concentra- 
tions of carbon dioxide the changes were propor- 
tionally less pronounced and occurred only after 
somewhat longer exposure. However, with as 
little as 10 percent carbon dioxide and 15 minutes 
exposure clear changes were seen. The damage 
to the walls of the blood vessels obviously was 
reversible within a short time, which was shown 
by the fact that when trypan blue was injected 
a few minutes after the gas exposure, the stain- 
ings were only slight and the hemorrhages were 
unstained. The authors raised the question 
whether or not the cause of the barrier damage 
was a vigorous dilatation of the thin-walled ves- 
sels or possibly a direct toxic effect on the en- 
dothelial membranes. The results indicate to the 
authors that hypercapnia is a factor that should 
not be disregarded as a cause of cerebral damage, 
for example, in asphyxia, where the component 
of anoxia sometimes seems to have been over- 
emphasized. These studies are more fully de- 
scribed by Clemedson, Hartelius and Holmberg 
(976) in 1958, in which not only rabbits were 
studied, but also guinea pigs and cats. Guinea 
pigs showed similar changes to those in rabbits. PHYSIOLOGICAL EFFECTS OF HIGH CARBON DIOXIDE—RESPIRATION 
974-985 
The capillaries in the cats seemed to be more 
resistant, but changes of the same kind only less 
pronounced were nevertheless observed. It is 
possible, according to the authors, that carbon 
dioxide is a physiologic regulator of permeability 
of the brain capillaries, as well as being a means 
of enhancing the penetration of pharmacological 
agents to the brain. Lending, Slobody and 
Mestern (981) 1961, have also examined the 
effect of hypercapnia on the blood cerebral spinal 
fluid barrier. The effect was evaluated in puppies 
and adult dogs by measuring the rate of passage 
of radioactive iodinated human serum albumin 
from plasma into the cerebrospinal fluid and by 
determining the plasma and cerebrospinal fluid 
glutamic oxalacetic transaminase and lactic acid 
dehydrogenase activities. In the puppies there 
was an increase in the blood brain transmission, 
but in adult dogs hypercapnia did not result in 
comparable findings. 
The dynamics of change in respiration and 
arterial blood and cerebrospinal fluid acid base 
parameters during administration and with- 
drawal of carbon dioxide have been studied by 
Lambertsen, Wollman and Gelfand (980) 1961. 
Following both administration and withdrawal of 
7 percent carbon dioxide in anesthetized dogs, 
respiratory minute volume changed more slowly 
than arterial pH and P00„ but more rapidly than 
cerebrospinal fluid pH and PCOo. On adminis- 
tration of 7 percent carbon dioxide blood pH 
fell 0.131, while the cerebrospinal pH fell 0.117, 
and the respiratory minute volume rose 15.6 
L/min. in 30 minutes. The changes were expo- 
nential, with approximate half times of less than 
one minute for arterial pH, two minutes for 
respiratory minute volume, and five and a half 
minutes for cerebrospinal fluid pH. On with- 
drawal of carbon dioxide, changes were similar 
in magnitude but more rapid. Arterial pH rose 
0.143, cerebrospinal fluid pH rose 0.135 and 
respiratory minute volume fell 13.8 L/min. in 30 
minutes. Approximately half times were less than 
one half minute for arterial pH, one minute for 
respiratory minute volume and five minutes for 
cerebrospinal fluid pH. An overshoot of 0.026 
in arterial pH was maximal at three minutes and 
compensated at five minutes. The differences 
between rates of change betwen arterial pH, 
CSF pH and respiratory minute volume, indi- 
cated to the authors that the changing stimulus 
to respiration during carbon dioxide inhalation 
cannot be accounted for by pH or Pcc,2 changes 
in either arterial blood or cerebrospinal fluid 
alone. 
974. Alexander, S. C., R. Gelfand and C. J. Lam- 
bertsen. The pK’ of carbonic acid in cerebrospinal fluid. 
biol. Chem., 1961, 236: 592-596. 
975. Clemedson, C.-J., H. Hartelius and G. Holm- 
berg. Effect of carbon dioxide inhalation on the blood- 
brain barrier. Nature, Land., 1956,178: 915. 
976. Clemedson, C.-J., H. Hartelius and G. Holm- 
berg. The influence of carbon dioxide inhalation on the 
cerebral vascular permeability to trypan blue (“the 
blood-brain barrier”). Acta path, microbiol. scand., 1958, 
42: 137-149. 
977. Goldberg, M. A., C. F. Barlow and L. J. Roth. 
The effects of carbon dioxide on the entry and accumu- 
lation of drugs in the central nervous system. J. Phar- 
macol, 1961,131: 308-318. 
978. Hassam, D., G. G. Nahas, M. H. Holmdahl 
and W. M. Manger. Buffering of carbon dioxide with 
sodium carbonate during apneic oxygenation (A.O.). Fed. 
Proc., 1961, 20: 424. 
979. Heisey, S. R., D. Held and V. Fend. The 
role of cerebrospinal fluid (CSF) in respiratory response to 
COo in unanesthetized goats. Fed. Proc., 1964, 23: 258. 
980. Lambertsen, C. J., H. Wollman and R. Gel- 
fand. The dynamics of change in respiration and arterial 
blood and CSF acid base parameters during administra- 
tion and withdrawal of COa. Fed. Proc., 1961, 20: 430. 
981. Lending, M., L. B. Slobody and J. Mestern. 
Effect of hyperoxia, hypercapnia, and hypoxia on blood- 
cerebrospinal fluid barrier. Amer. J. Physiol, 1961, 200: 
959-962. 
982. Leusen, I. Aspects of the chemosensitivity of the 
respiratory centres, pp. 207-222 in: The regulation of hu- 
man respiration. Edited by D. J. C. Cunningham and 
B. B. Lloyd, Blackwell Scientific Publications, Oxford, 1963, 
591 pp. 
983. Loeschcke, H. H. Beziehungen zwischen C02 
und Atmung. Anaesthesist, 1960, 9: 38-46. 
984. Small, H. S., S. W. Weitzner and G. G. 
Nahas. Spinal fluid pressure changes during apneic 
oxygenation and carbon dioxide administration. Fed. 
Proc., 1958, 17: 150. 
985. Small, H. S., S. W. Weitzner and G. G. Na- 
has. Cerebrospinal Audi pressures during hypercapnia 
and hypoxia in dogs. Amer. J. Physiol, 1960, 198: 704— 
708. 
F. RESPIRATION 
Acute studies generally indicate an increase 
in respiratory activity from breathing high carbon 
dioxide mixtures. A level of PCOo is reached at 
which ventilatory depression occurs. For general SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
studies of the effects of carbon dioxide excess 
papers by Astrom {991) 1952, and Asmussen 
{989) 1963, should be consulted. 
Froeb {1023) 1960, has conducted a study to 
compare the ventilatory response of SCUBA div- 
ers and nondivers to carbon dioxide inhalation 
under ambient conditions, at rest and during 
light exercise. Although there was some tendency 
for the SCUBA divers to have a slightly lower 
ventilatory response at rest, there was not a clear- 
cut difference. It appears that the response to 
carbon dioxide had no relation to the time spent 
in diving. Tank instructors, who hold their 
breath during dives, demonstrated an increased 
tolerance of carbon dioxide (Bond and Schaefer 
(996) 1962). There are individual differences 
in sensitivity to carbon dioxide. Schaefer {1065) 
1954, has examined these group differences in 
carbon dioxide response of human subjects. The 
carbon dioxide response was studied in 70 per- 
sons, using concentrations of 1.5, 3.3, 5.4 and 7.5 
percent carbon dioxide. These studies permitted 
a differentiation of a low and a high ventilation 
group on the basis of a quantitative difference 
in ventilatory response to 5.4 and 7.5 percent 
carbon dioxide. Subjects of these two groups 
also differed in their normal respiratory pattern 
in air. The low ventilation group showed larger 
tidal volume, smaller respiratory rate and higher 
alveolar carbon dioxide. The high ventilation 
group exhibited smaller tidal volume, higher 
respiratory rate and lower alveolar carbon 
dioxide. The low ventilation group also showed 
during exposure to 7 percent carbon dioxide a 
lower pulse rate increase, a lower blood sugar 
increase and a lesser eosinopenia. Schaefer 
{1066) 1958, also reported that subjects with a 
high sensitivity to carbon dioxide were found to 
have a high sensitivity to low oxygen, and vice 
versa. The differences in the ventilatory response 
to carbon dioxide appears to be correlated with 
differences in the adrenal sympathetic response 
to carbon dioxide. The respiratory response to 
carbon dioxide is discussed by Schaefer as a pos- 
sible physiological selection test for underwater 
swimmers. Lanphier {1040) 1956, has noted that 
certain divers tend to develop high carbon 
dioxide levels during work while breathing nitro- 
gen-oxygen mixtures at depth. This tendency 
is believed to be related to respiratory sensitivity 
to carbon dioxide, and the latter might thus 
form the basis of practical personnel selection 
tests. 
Chapters by Lambertsen {1035) 154, and 
{1036) 1963, should be consulted for authorita- 
tive discussions on the factors in the stimulation 
of respiration by carbon dioxide. The respira- 
tory minute volume reaches a peak in man be- 
tween 16 and 20 percent carbon dioxide. 
Lambertsen {1036) 1963, concludes that there 
are not two qualitative types of respiratory stimu- 
lation (pH and carbon dioxide), but that there 
is only one carbon dioxide induced stimulus, 
namely a change in hydrogen ion concentration 
which is altered at different rates at two different 
sites and is responsible for the carbon dioxide re- 
spiratory response at rest. A change in the 
hydrogen ion concentration of arterial blood, 
while it certainly alters the environment of the 
peripheral chemoreceptors, can conceivably also 
affect the level of central acid-base stimulus. 
Also, Loeschcke, Koepchen and Gertz {1048) 
1958, have concluded that hydrogen ions and not 
carbon dioxide contribute to driving lung venti- 
lation. In these authors’ studies the fourth ven- 
tricle and adjacent areas of the brain in cats 
were perfused with isotonic bicarbonate buffers 
equilibrated with carbon dioxide. Carbon 
dioxide tension and pH of the perfusion fluids 
were varied separately. Respiratory volumes were 
recorded. Loeschcke and Mitchell {1049) 1963, 
stated that when the PCOo is increased in the 
cerebrospinal fluid perfusate the ventilation is in- 
creased, but when the pH is kept constant the 
ventilation is diminished. Apparently in the 
opinion of the authors the stimulation is due to 
an acid shift inside the cell. A review of the 
effects of arterial carbon dioxide and hydrogen 
ion concentrations, as independent additive res- 
piratory stimuli, has been provided by Perkins 
{1056) 1963. 
In studies by Dejours, Labrousse, Raynoud 
and Flandrois {1015) 1958, men breathed gas 
mixtures with 6.9 percent carbon dioxide to pro- 
duce a hypercapnia. The response to the carbon 
dioxide was more intense when the subjects had 
been made hypocapnic prior to breathing carbon 
dioxide. Schaefer, Cornish, Lukas and Carey 
{1069) 1952, carried out studies in which 38 
male subjects, after resting for 30 minutes, PHYSIOLOGICAL EFFECTS OF HIGH CARBON DIOXIDE—RESPIRATION 
breathed gas mixtures containing 3.3, 5.4 and 7.5 
percent carbon dioxide for 15 minutes, followed 
by 15 minutes breathing air. Respiratory and 
circulatory responses were used to compile a 
carbon dioxide toxicity chart. The increase in 
respiratory minute volume during exposure to 3 
and 5 percent carbon dioxide was produced by 
increased tidal volume only. With 7 percent car- 
bon dioxide the respiratory rate was unchanged, 
and at 5 percent there was a small (4 percent) 
increase, and at 7 percent there was a 24 percent 
increase. Alveolar carbon dioxide and oxygen 
tensions were continuously measured and in 
most subjects plateaued within 10 minutes of 
7.5 percent carbon dioxide inhalation. After 
transition to air, alveolar Pco>) dropped signifi- 
cantly below the initial level in eight subjects 
and was considered an after-effect of central ex- 
citation. The effect was greater after 5 percent, 
suggesting that 7 percent has a narcotic effect, 
commensurate with the direct stimulatory effect 
on the respiratory center, A group of trained 
instructors at the escape training tank, who had 
previously shown significantly lower respiratory 
responses to low oxygen than a group of labora- 
tory personnel, also showed a significantly lower 
respiratory response to the carbon dioxide mix- 
tures, suggesting that the differences in response 
to carbon dioxide and low oxygen are based on 
different sensitivity of the chemoreceptors. How- 
ever, adaptation to low oxygen and high carbon 
dioxide, with a resulting change in the centro- 
genic drive of breathing, might take place. Tests 
of ventilatory response to high carbon dioxide 
as well as low oxygen, were considered as a physi- 
ological selection device for underwater swim- 
mers. Norins, Schroeder, Grodins, Gray and 
Jones (1054) 1953, have pointed out that there 
is considerable evidence in the literature in- 
dicating that ventilation is a positive linear 
function of arterial PC0(> during the steady state 
of carbon dioxide inhalation in man. There is 
other evidence however, indicating that this 
relationship does not hold in the transient states 
following either the initiation or termination 
of carbon dioxide inhalation. Various qualita- 
tive explanations of this transient association 
between ventilation and arterial PCOl, have been 
suggested, but none have been adequately ex- 
plored according to the authors. In their analysis 
they investigated the implications of a hypothesis 
assigning the effective controlling carbon dioxide 
concentration to tissues rather than to arterial 
blood. That very high concentrations of carbon 
dioxide are actually depressant to respiration 
in the human being has been confirmed by the 
studies of Stroud, Ewing and Mack (1073) 1953. 
These authors studied the effects of inhalation 
of 30 percent carbon dioxide in oxygen on 
alveolar PCO(>, the respiratory minute volume, 
respiratory rate and tidal volume, in a young 
female psychiatric patient. The average result 
of eight exposures for 2-2.75 minutes were as 
follows: The Pc0„ rose rapidly from 35 to 205 
mm. Hg within a minute, and remained almost 
constant during carbon dioxide inhalation. The 
respiratory rate curve followed the PaCOo closely 
increasing from 15 to 35. The respiratory minute 
volume rose more slowly from 11 to 36 liters 
in 1.25 minutes, and then fell steadily to 29 
liters at 2 minutes. The tidal volume changes 
parallelled those of respiratory minute volume, 
with values of 0.85, 1.0 and 0.80 liters, respec- 
tively. Unconsciousness occurred within one 
minute. Following the abrupt return to air 
breathing, the PCOl) fell to 43 mm. Hg within one 
minute, and then to 39 mm. Hg in 4.5 minutes. 
Respiratory minute volume rose from 20 to 30 
liters in 1.25 minutes after withdrawal of carbon 
dioxide, and then declined to 16 liters in 4.5 
minutes. The corresponding values for respira- 
tory rate were 28, 30 and 18. Those for tidal 
volume were 0.70, 0.90 and 0.90 liters. Convul- 
sive phenomena occurred or were accentuated 
during the most rapid change in PC09. Conscious- 
ness was regained after about three minutes of 
air breathing. Chapin (1001) 1954, and (1002) 
1955, has studied the ventilatory response of un- 
restrained and unanesthetized hamsters to carbon 
dioxide. The chamber containing these animals 
was ventilated with 3-35 percent carbon dioxide 
and 20 percent oxygen in nitrogen at the rate of 
five liters per minute for 20-30 minutes (a time 
calculated to achieve a steady state) . Each ex- 
periment was preceded by a 20 to 30 minute 
control run. The resting respiratory rate showed 
an inverse ratio with body weight and a direct 
ratio with tidal volume and minute volume. 
Breathing carbon dioxide increased the rate more 
than the tidal volume. The peak ventilation oc- SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
curred when the inspired gas mixture contained 
20 percent carbon dioxide in 20 percent oxygen 
and 60 percent nitrogen, and at this level there 
was an approximately 6.6 fold increase in the 
ventilatory ratio. 
In a review of reflex control of airway calibre, 
Widdicombe {1079) 1962, has drawn attention 
to the finding that in animals breathing high 
carbon dioxide mixtures results in bronchial 
spasm, and that this effect depends upon the 
intact vagus nerve. This bronchial constriction 
has been reported also by Daly, Lambertsen and 
Schweitzer {1011) 1952; by Peters {1037) 1955; 
and by Whittenberger {1078) 1962. 
According to Forster {1021) 1962, the diffu- 
sion capacity of the lungs is increased 24.5 per- 
cent in dogs breathing 7.5 percent carbon dioxide 
for 5-10 minutes. Increased breathing resistance 
favors carbon dioxide retention and therefore 
decreases sensitivity to carbon dioxide (Lanphier 
{1041) 1958). In Lanphier’s studies it was found 
that subjects breathing nitrogen-oxygen revealed 
absent or minimal carbon dioxide retention. The 
degree to which subjects retained carbon dioxide 
varies and there is a relationship between this 
tendency and their ventilatory response to carbon 
dioxide. The author favors abandoning nitro- 
gen-oxygen mixtures in favor of helium-oxygen 
mixtures for mixed-gas SCUBA diving. These 
results have been verified by Eldridge and Davis 
{1020) 1959. With increasing resistance these 
authors found that the PCC9 and work, rose in 
parallel, whereas ventilation remained constant 
or even decreased. In the presence of a constant 
carbon dioxide stimulus, increasing airway re- 
sistance caused a progressive decrease in the 
ventilatory response to carbon dioxide. The 
maximum breathing capacity was not in itself 
the limiting factor in the ventilatory response 
to carbon dioxide. It was concluded that the 
mechanical abnormalities of the respiratory ap- 
paratus are important factors in reducing the 
ventilatory response to carbon dioxide, and that 
work of breathing is a more satisfactory index 
of respiratory stimulation than ventilation. Since 
patients with obstructive emphysema have non- 
elastic resistance values in the same range as 
those used in this study, it was concluded that the 
low ventilatory response to carbon dioxide in 
these patients can in large part be explained by 
the mechanical abnormalities. For further con- 
sideration of the effect of respiratory tract ob- 
struction upon the ventilatory response to in- 
haled carbon dioxide, a report by Samet, Fierer 
and Bernstein {1064) 1960, should be consulted. 
The linear part of the carbon dioxide response 
curve has been shown to be an inverse function 
of alveolar oxygen pressure. This has been 
confirmed by Lloyd, Jukes and Cunningham 
{1046) 1958. This has likewise been demon- 
strated by Lambertsen, Hall, Wollman and 
Goodman {1037) 1963, using two atmospheres 
of oxygen and 0.2 atmospheres of oxygen. The 
authors pose an important question: does high 
oxygen deactivate chemically the peripheral 
arterial chemoreceptors, even blocking the stim- 
ulatory influences of increased PCOo. It may be 
that anoxia and increased carbon dioxide effect 
the same sensors. 
There are age differences in carbon dioxide 
sensitivity. Cross, Hooper and Oppe {1009) 
1953, and Avery, Chernick, Dutton and Permutt 
(992) 1963, have shown that infants are more 
sensitive to carbon dioxide than adults. On the 
other hand, Bour and Blimet {997) 1961, found 
that healthy aged subjects showed a normal sen- 
sitivity to carbon dioxide, as compared with 
healthy young adults, but that there was a de- 
crease in the respiratory sensitivity to carbon 
dioxide in patients with respiratory insufficiency. 
In general, hypothermia diminishes the respira- 
tory response of increased carbon dioxide and 
hyperthermia increases the response. Pertinent 
reports have been given by Cunningham and 
O’Riordan {1010) 1957; by Salzano and Hall 
{1063) I960; by Albers {986) 1961; and by Kil- 
more and Chase {1034) 1962. 
Patients with obstructive emphysema reveal a 
diminished ventilatory response to carbon diox- 
ide. For papers dealing with this subject the 
reader should consult the following: Prime and 
Westlake {1038) 1954; Alexander, West, Wood 
and Richards {988) 1955; Cherniack and Snidal 
{1003) 1956; Fritts, Fishman and Cournand 
{1022) 1957; Richards, Fritts and Davis {1061) 
1958; and Brodovsky, MacDonnell and Cherniack 
{999) 1960. PHYSIOLOGICAL EFFECTS OF HIGH CARBON DIOXIDE—RESPIRATION 
986-1015 
986. Alberts, C. Der Mechanismus der Varmehechelns 
bein Hund. III. Die C02 Empfindlichkeit des Atemzen- 
trums wahrend des Varmehechelns. Pflilg. Arch. ges. Phys- 
iol, 1961, 274: 166-183. 
987. Alexander, J. K., H. F. Spalter and J. R. 
West. Modification of the respiratory response to carbon 
dioxide by salicylate. J. din. Invest., 1955, 34: 533-537. 
988. Alexander, J. K., J. R. West, J. A. Wood and 
D. W. Richards. Analysis of the respiratory response to 
carbon dioxide inhalation in varying clinical states of 
hypercapnia, anoxia and acid-base derangement. J. din. 
Invest., 1955, 34: 511-532. 
989. Asmussen, E. The regulation of respiration, pp. 
59-70 in: The regulation of human respiration. Edited 
by D. J. C. Cunningham and B. B. Lloyd. Blackwell 
Scientific Publications, Oxford, 1963, 591 pp. 
990. Asmussen, E. and M. Nielsen. Ventilatory 
response to COa during work at normal and at low oxygen 
tensions. Acta physiol, scand., 1957, 39: 27-35. 
991. Astrom, A. On the action of combined carbon 
dioxide excess and oxygen deficiency in the regulation of 
breathing. Acta physiol, scand., 1952, 27: suppl. 98, 61 pp. 
992. Avery, M. E., V. Chernick, R. E. Dutton and 
S. Permutt. Ventilatory response to inspired carbon 
dioxide in infants and adults. J. app. Physiol, 1963, 18: 
895-903. 
993. Bedell, G. N. and R. S. Rosenberg. An evalua- 
tion of the respiratory response to breathing 7.5% C02 in 
air as a test of respiratory center depression. Fed. Proc., 
1960,19: 379. 
994. Bellville, J. W., W. S. Howland, J. C. Seed 
and R. W. Houde. The effect of sleep on the respiratory 
response to carbon dioxide. Anesthesiology, 1959, 20: 
628-634. 
995. Bellville, J. W. and J. C. Seed. Respiratory 
carbon dioxide response curve computer. It gives more 
complete alveolar ventilation-Pco<> response curves than 
could formerly be obtained. Science, 1959, 130: 1079-1083. 
996. Bond, G. and K. E. Schaefer. Carbon dioxide 
exchange during skindiving, pp. 335-336 in: Man’s depend- 
ence on the earthly atmosphere. Edited by K. E. Schaefer. 
The MacMillan Company, New York, 1962, 416 pp. 
997. Bour, H. and T. Blimet. Etude comparative de 
la sensibilite respiratoire au C02 des sujets ages et des 
insuffisants respiratoires chroniques. Path, biol, 1961, 9: 
1473-1476. 
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in various acute and chronic acid-base disturbances with 
special reference to the chemical control of ventilation, 
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Edited by D. J. C. Cunningham and B. B. Lloyd, Black- 
well Scientific Publications, Oxford, 1963, 591 pp. 
999. Brodovsky, D., J. A. MacDonnell and R. M. 
Cherniack. The respiratory response to carbon dioxide 
in health and in emphysema. J. din. Invest., 1960, 39: 724- 
729. 
1000. Biicherl, E. S. Saure-, Basen-, und Elektrolyt- 
stoffwechsel, Kreislauf und Ventilation wahrend “Kohlen- 
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Physiol, 1954, 179: 140-148. 
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in: Studies in respiratory physiology. Second series. Chem- 
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C02. J. din. Invest., 1956, 35: 1286-1290. 
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the functional respiratory dead space in normal men. Fed. 
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Cournand. Factors contributing to the diminished ventila- 
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sema. Fed. Proc., 1957,16: 41. 
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Variation in respiratory response to C02 at different con- 
stant levels of blood pH. Fed. Proc., 1964, 23: 259. 
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The respiratory threshold for carbon dioxide in anes- 
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1030. Hickam, J. B., H. O. Sieker, W. W. Pryor 
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591 pp. 
1037. Lambertsen, C. J., P. Hall, H. Wollman and 
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P0o and PCq2 upon respiration in man. Ann. N.Y. Acad. 
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1038. Lambertsen, C. J., M. G. Smyth, S. J. G. 
Semple and R. Gelfand. Respiratory effects in normal 
men of blood pH change at “constant” arterial and inter- 
nal jugular venous pC02. Fed. Proc., 1958, 17: 92. 
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“transients” in normal volunteers. Anesthesiology, 1957, 
18: 807-830. 
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respiration. Amer. J. Physiol., 1954, 176: 39-44. 
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1044. Linde, L. M., D. H. Simmons and N. Lewis. 
Pulmonary hemodynamics in respiratory acidosis in dogs. 
Amer. J. Physiol., 1963, 205: 1008-1012. 
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R. C. Powell. Effects of C02 breathing on pulmonary 
hemodynamics. Fed. Proc., 1961, 20: 106. 
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Cunningham. The relation between alveolar oxygen 
pressure and the respiratory response to carbon dioxide in 
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1047. Loeschcke, H. H., B, Katsaros and D. 
Lerche. Differenziering der Wirkungen von COs-Druck 
und Wasserstoffionenkonzentration im Blut auf die At- 
mung beim Menschen. Pfliig. Arch. ges. Physiol., 1960, 
270: 461-466. 
1048. Loeschcke, H. H., H. P. Koepchen and K. 
H. Gertz. Uber den Einfluss von Wasserstoffionenkon- 
zentration und CC2-Druck im Liquor cerebrospinalis auf 
die Atmung. Pftiig. Arch. ges. Physiol., 1958, 266: 569-585. 
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erties and localization of intracranial chemosensitivity. 
pp. 243-256 in: The regulation of human respiration. 
Edited by D. J. C. Cunningham and B. B. Lloyd, Black- 
well Scientific Publications, Oxford, 1963, 591 pp. 
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holm, D. Hudson, W. M. Boothby and C. S. White. 
Human tolerance to acute exposure to carbon dioxide. 
Respiratory response to oxygen and 4.1 and 6.2 percent 
carbon dioxide in air and oxygen at a ground level of 
5,000 feet. USAF, Randolph Field, Texas. School of avia- 
tion medicine. Project 21-1402-0001, Kept. no. 3, July 
1954, 14 pp. 
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H. Van Bergen and R. L. Varco. Respiratory acidosis: 
its relationship to cardiac function and other physiologic 
mechanisms. Surgery, 1952, 32: 171-183. 
1052. Mitchell, R. A. and C. R. Bainton. Respira- 
tory response to elevated C02, hypoxia, and metabolic 
acidosis in awake dogs. Fed. Proc., 1964, 23: 259. 
1053. Mithoefer, J. C. and H. Kazemi. Gas exchange 
during rebreathing. Ann. N.Y. Acad. Sci., 1963, 109: 743- 
753. 
1054. Morins, A. L., K. R. Schroeder, F. S. Gro- 
dins, J. S. Gray and R. W. Jones. Transient respiratory 
response to CC2 inhalation. Fed. Proc., 1953, 12: 104. 
1055. Palecek, F. The assessment of the respiratory 
response to CC2 in rabbits. XXII Inter. Congr. physiol. Sci., 
Leiden. 1962, 2: Abstr. 319. 
1056. Perkins, J. F., Jr. Arterial CC2 and hydrogen 
ion as independent, additive respiratory stimuli: Support 
for one part of the Gray multiple factor theory, pp. 303- 
317 in: The regulation of human respiration. Edited by 
D. J. C. Cunningham and B. B. Lloyd. F. A. Davis Co., 
Philadelphia, 1963, 591 pp. 
1057. Peters, R. M. Relationship between per cent of 
carbon dioxide in inspired air and degree of bronchocon- 
striction. Ann. Surg., 1955, 142: 461-468. 
1058. Prime, F, J, and E. K. Westlake. The respira- 
tory response to CC2 in emphysema. Clin. Sci., 1954, 13: 
321-332. 
1059. Reed, D. J. and R. H. Kellogg. Changes in 
respiratory response to C02 during natural sleep at sea 
level and at altitude. J. appl. Physiol., 1958, 13: 325-330. 
1060. Reed, D. J. and R. H. Kellogg. Effect of 
sleep on CO, stimulation of breathing in acute and chronic 
hypoxia. J. appl. Physiol., 1960, 15: 1135-1138. 
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Davis. Observations on the control of respiration in 
emphysema: The effects of oxygen on ventilatory response 
to C02 inhalation. Trans. Ass. Amer. Phycns., 1958, 71: 
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drogen ion concentration of arterial blood in rabbits and 
dogs. Jap. J. Physiol., I960,10: 634-645. 
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mia on ventilatory response to carbon dioxide inhalation 
and carbon dioxide infusion in dogs. J. appl. Physiol., 1960, 
15: 397-401. 
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effect of respiratory tract obstruction upon the ventilatory 
response to inhaled C02. Fed. Proc., 1960, 19: 376. 
1065. Schaefer, K. E. Group differences in carbon 
dioxide response of human subjects. Fed. Proc., 1954, 13: 
128. 
1066. Schaefer, K. E. Respiratory pattern and respira- 
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London, Conn. Medical research laboratory. Project NM 
24 01 20. 01, Kept. no. 1, 1958. 
1067. Schaefer, K. E. Respiratory adaptation to 
chronic hypercapnia. Ann. N.Y. Acad. Sci., 1963, 109: 772- 
780. 
1068. Schaefer, K. E. Effect of prolonged diving train- 
ing. pp. 271-278 in: Second symposium on underwater 
physiology. Edited by C. J. Lambertsen and L. J. Green- 
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N.R.C. Publication 1181, 296 pp. 
1069. Schaefer, K. E., E. R. Cornish, Jr., C. A. 
Lukas and C. R. Carey. Respiration and circulation dur- 
ing and after inhalation of various concentrations of car- 
bon dioxide. U.S. Navy. Submarine Base, New London, 
Conn. Medical Research Laboratory. Project NM 002 015. 
03.06, 6 March 1952, 20 pp. 
1070. Schopp, R. T. Couplet periodic breathing re- 
sponse to high carbon dioxide and high and low oxygen. 
Science, I960, 132: 957-958. 
1071. Shephard, R. J. Some effects of carbon dioxide 
on foreign gas uptake. J. appl. Physiol., 1959, 14: 333-338. 
1072. Sicker, H. O. and J. B. Hickham. Carbon di- 
oxide intoxication: the clinical syndrome, its etiology and 
management with particular reference to the use of me- 
chanical respirators. Medicine, 1956, 35: 389-423. 
1073. Stroud, M. W., Ill, J. H, Ewing and C. L. 
Mack. Respiratory changes induced in the unanesthetized 
human by the inhalation of 30 per cent carbon dioxide. 
Fed. Proc., 1953,12: 140. 
1074. Stroud, R. C. and K. E. Schaefer. Some lung 
volume factors related to the measurement of respiratory 
sensitivity to C02. Fed. Proc., 1959, 18: 153. 
1075. Van Liew, H. D. Subcutaneous tissue pC2 and 
pCOo of rats in a high CC2 atmosphere. Aerospace Med., 
1963, 34: 499-500. 
1076. Visser, B. F. Pulmonary diffusion of carbon 
dioxide. Phys. Med. Biol., Land., 1960, 5: 155-166. 
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and N. P. V. Lundgren. Human tolerance to acute ex- 
posure to carbon dioxide. Report No. 1: Six per cent 
carbon dioxide in air and in oxygen. J. Aviat. Med., 1952, 
23: 439-455. 1078-1080 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
1078. Whittenberger, J. L. Effects of atmospheric 
factors on the mechanics of breathing, pp. 257-261 in: 
Man’s dependence on the earthly atmosphere. Edited by 
K. E. Schaefer. The MacMillan Company, New York, 1962, 
416 pp. 
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I, Part I, pp. 115-120. 
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Homeostasis of carbon dioxide during intravenous infu- 
sion of carbon dioxide. J. appl. Physiol., 1960, 15: 807-818. 
G. METABOLISM 
For a general review of the subject of tissue 
buffering the reader is referred to a paper on 
carbon dioxide and intracellular homeostasis by 
Fenn {1084) 1961. Johnson and Schaefer {1088) 
1955, have reported a study of plasma, whole 
blood, liver and muscle electrolytes during car- 
bon dioxide retention and recovery. During ex- 
posure of guinea pigs to 15 percent carbon diox- 
ide, three phases of electrolyte changes are ob- 
served. An initial 24 hour period of hemocon- 
centration and uncompensated respiratory acid- 
osis is succeeded by a transient hemodilution 
during the next two days. As indicated by rising 
blood pH, the acidosis becomes compensated 
after 24 hours of exposure. Hematocrit values re- 
turn to normal during the fourth and seventh day 
of exposure. Both plasma and whole blood water 
content reflect this pattern. These changes are 
accompanied by an initial sharp rise in carbon 
dioxide tension in whole blood, with a continued 
more gradual rise throughout exposure. Tissue 
water remains relatively constant during these 
shifts in concentration of extracellular fluid. 
During the period of acute uncompensated acid- 
osis there is a pronounced fall in blood potassium 
concentration, while sodium in whole blood and 
plasma rises slightly. Simultaneously, sodium 
concentration of liver and striated muscle in- 
creases but returns to normal during the period 
of compensated acidosis. Blood chloride shows 
little change during the acute phase, but de- 
creases during the period of compensation. Tis- 
sue phosphorus increases sharply during the first 
24 hours under carbon dioxide and remains high 
during the phase of compensation while blood 
and plasma phosphorus decreases. During re- 
covery periods up to 12 days after exposure, cer- 
tain of the tissue electrolytes return towards nor- 
mal only gradually. Liver and muscle phosphorus 
remained below control values. In acidosis pro- 
duced by administering 6 percent carbon dioxide 
to dogs, Robin {1099) 1963, reported a change 
of 0.35 pH units in extracellular water ac- 
companied by an 0.23 pH unit change in intra- 
cellular water. The bicarbonate ion showed cor- 
responding changes in both compartments. Elkin- 
ton, Singer, Barker and Clark {1083) 1955, have 
reported studies in man of the effects of acute 
experimental respiratory alkalosis and acidosis on 
ionic transfers in total body fluids. Ionic trans- 
fers between the extracellular fluid (assumed to 
be 20 percent of body weight with changes esti- 
mated on the basis of the chloride space) and 
the intracellular fluid were calculated in normal 
subjects during and after acute respiratory al- 
kalosis produced by hyperventilation. In another 
group of human subjects the same transfers were 
calculated during and after respiratory acidosis 
produced by carbon dioxide inhalation. Direct 
calculations were made of sodium and potassium 
transfers, as well as indirect calculations of in- 
tracellular hydrogen on the basis of changes in 
bicarbonate and other buffer anions in the ex- 
tracellular fluid and red cells. In respiratory 
alkalosis the authors found that hydrogen left 
the cells and sodium entered the cells. In respira- 
tory acidosis, hydrogen tended to enter, and sod- 
ium to leave the cells; but these mean changes 
were not quite significant at the five level. In 
both types of experiments the sums of hydrogen 
transfer in one direction, and of sodium in the 
other, were highly significant. The ratio of 
hydrogen transfer to sodium transfer in the op- 
posite direction was approximately two to one 
under these conditions. A one to one transfer 
of anion with that of hydrogen not exchanged 
for sodium appeared to be involved. In both 
types of experiments the changes in cell potas- 
sium were much smaller in magnitude, or were 
negligible, for the short duration of the stimuli. 
The authors concluded that in acute respiratory 
acid-base disturbances a large part of the im- 
mediate buffering of the extracellular fluid is 
achieved by exchanges of hydrogen for sodium 
across the cell boundaries in body tissues. 
Thompson and Brown (1105) 1957, and 
{1106) 1960, have studied the tissue carbon diox- 
ide concentrations in hypercapnic rats. As part 
of an investigation of the chemical changes in PHYSIOLOGICAL EFFECTS OF HIGH CARBON DIOXIDE—METABOLISM 
tissues resulting from hypercapnia post-mortem, 
tissue carbon dioxide concentrations were meas- 
ured in the rat following exposure of the live 
animal to high concentrations of carbon dioxide. 
The tissue was rapidly frozen in liquid nitrogen, 
ground and transferred to 1.0 N sodium hydrox- 
ide. It was then digested at 60° C. and the carbon 
dioxide determined by a modified Van Slyke 
technique. Control values in the skeletal 
muscle averaged 13.2 mM. of carbon dioxide/Kg 
wet tissue. Following exposure to 30 percent 
carbon dioxide in 70 percent oxygen for one 
hour the skeletal muscle carbon dioxide con- 
centration averaged 29.2. Serial changes in tissue 
carbon dioxide content during acute respiratory 
acidosis have been investigated by Nichols 
(1096) 1958. Male albino rats were exposed to 
24 percent carbon dioxide in air for periods 
ranging from one half to 24 hours, and the pH 
and carbon dioxide of blood and tissues com- 
pared with control rats. A profound respiratory 
acidosis with high plasma carbon dioxide and a 
plasma pH of 6.92 appeared after one half hour 
of exposure, followed after 7-15 hours by a 
further slow rise in plasma carbon dioxide and a 
rising pH which reached 7.10 after 48 hours. The 
total carbon dioxide content of muscle and brain 
rose rapidly but reached a plateau after five 
hours. The rate of rise, and the absolute level of 
tissues carbon dioxide was higher in the brain 
than in muscle. In contrast to other tissues, the 
bone carbon dioxide content remained fixed 
or declined slightly, even after 48 hours of ex- 
posure. The author concluded that soft tissues 
rather than bone form the site of storage of 
carbon dioxide under conditions of these ex- 
periments. In the experiments of Levitin, Jock- 
ers and Epstein (1093) 1958, female rats were 
subjected to 8 percent carbon dioxide for 24 
hours and compared with controls kept in room 
air. Immediately after removal from the carbon 
dioxide chamber the animals were sacrificed by 
exsanguination and specimens of liver, bone and 
muscle obtained for analysis. Exposure to carbon 
dioxide caused elevation of plasma carbon diox- 
ide content and a decrease in plasma chloride. 
The plasma sodium remained unchanged and 
plasma potassium was slightly but significantly 
elevated. There were no differences between the 
experimental and control groups in water and 
fat content of liver, bone and muscle. Experi- 
mental and control groups were not differentiated 
in terms of sodium content of liver, bone or 
muscle. There was no difference in calcium. 
Muscle potassium of rats in carbon dioxide 
chamber decreased significantly while bone potas- 
sium remained similar to control values. These 
results differ from those of previous workers, 
possibly because the short durtion of the present 
experiments avoided certain metabolic effects 
which complicate long-term studies of experi- 
mental respiratory acidosis. The data suggest to 
the authors that potassium proteinate of muscle 
is capable of buffering carbonic acid as well as 
strong acids, but that combinations of sodium 
with carbonate in bone, although capable of 
buffering metabolic acidosis, cannot serve as an 
effective buffer for carbonic acid. 
Katzman, Villee and Beecher (1089) 1953, 
have found that when bicarbonate concentration 
was kept constant rat and dog tissues incubated at 
10, 15 and 20 percent carbon dioxide production 
of lactic acid was less than when duplicate tis- 
sues were incubated at five percent carbon diox- 
ide. This change in lactic acid production is 
reversed if the Krebs cycle is inhibited by malon- 
ate or arsenite. If the pH is kept constant at 
7.4, rat and dog tissues incubated at 10, 15 and 20 
percent carbon dioxide produce more lactic acid 
than to duplicate tissues incubated at five percent 
carbon dioxide. At a pH 6.8-7.1 this effect is 
diminished or absent. Human tissue, like rat and 
dog tissue, shows an increased production of 
lactic acid in an iso-pH system as the carbon 
dioxide concentration is increased, and a de- 
creased production of lactic acid in an isobicar- 
bonate system at carbon dioxide concentrations 
of 15 and 20 percent. The serum calcium re- 
sponse was cyclic, rising from 10.02 mg. percent 
to 11.06 mg. percent after the second day, 
falling to 9.84 in the third day, rising to 11.20 
on the fifth and 11.55 on the sixth, and began 
decreasing on the seventh day. The values 
between the seventh and fifteenth days were not 
measured but on the last day of this period the 
calcium was 10.30 mg. percent. Serum inorganic 
phosphate changes inversely parallel to calcium 
changes through the sixth day when a fall in 
phosphate becomes precipitous to 5.1 mg. per- 
cent (control value 9.85 mg. percent). The au- SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
thors suggest that the second and sixth day 
peaks were accounted for by parathyroid stimu- 
lation. 
The hyperglycemic response to carbon dioxide 
has been reported by King, Williams and 
Schaefer (1092) 1954. These authors made total 
blood sugar determinations from the tail vein 
blood of normal, adrenalectomized and hypo- 
physectomized rats of the Wistar-Hisaw strain 
(70 ± 10 days of age). These determinations 
were carried out before exposure, during ex- 
posure at intervals of 10, 30 and 60 minutes, and 
one hour after exposure to 30 percent carbon 
dioxide in air and in oxygen. In the normal rats 
the blood sugar increased 60 percent over the 
normal after one hour exposure to 30 percent 
carbon dioxide in air, and increased 30 percent 
after one hour exposure to 30 percent carbon 
dioxide in oxygen. The blood sugars returned 
to normal one hour after exposure. Neither 
adrenalectomy nor hypophysectomy muscle com- 
position in respiratory acidosis a paper by Cooke, 
Coughlin and Segar (1081) 1952, may be con- 
sulted. Male albino rats were exposed to an 
atmosphere: a) containing 11 percent carbon 
dioxide for two weeks, and b) containing 13 
percent carbon dioxide for three weeks. Oxygen 
concentrations did not fall below 17 percent. 
Temperature was maintained at 23°C. and 
relative humidity at 80 percent. Rats were re- 
moved from the chamber for 20 minutes every 
third day for cleaning, etc. After periods of 
exposure animals were anesthetized with ether 
within one to three minutes after removal from 
the chamber. Bicarbonate, pH and carbonic acid 
were not determined. Changes in serum were 
characteristic of chronic respiratory acidosis as 
follows: high serum bicarbonate (41 mM/1) and 
low serum chloride (85 mM/1). Muscle potas- 
sium content was at an upper limit of normal, 
namely 48 mM/100 gms. of fat-free solids. In- 
tracellular sodium was somewhat reduced, 
namely 2.2 mM/100 gms. of fat-free solids. These 
results are in striking contrast to those of meta- 
bolic acidosis in which serum bicarbonate is high 
and serum chloride low. Rises in serum calcium 
have been shown by Stanmeyer, King, Scofield 
and Colby (1104) 1962, to result from exposure 
to carbon dioxide. Histological examination of 
the dentin of the incisor tooth of rats exposed to 
15 percent carbon dioxide and 21 percent oxy- 
gen for 1-15 days (plus 7 days with 7 days re- 
covery, and 14 days with 14 days recovery) 
showed an accentuation of the incremental cal- 
cification pattern and vascular inclusions. The 
dentin matrix was formed at the same rate as 
in control animals. The experimental animals 
tended to lose weight and those allowed to re- 
cover showed a weight gain during the recovery 
completely eliminated the hyperglycemic re- 
sponse to 30 percent carbon dioxide in air or in 
oxygen. As in the normal animal, the response 
was less under 30 percent carbon dioxide in oxy- 
gen than in air. These results correlate with the 
findings of previous workers. King (1091) 1957, 
exposed normal and adrenalectomized mature 
male rats of the Wistar-Hisaw strain to an at- 
mosphere of 30 percent carbon dioxide in oxygen 
for periods up to five hours. Epinephrine hydro- 
chloride was injected subcutaneously just prior 
to exposure at a dose level of 0.02 mg./100 gm. of 
body weight. Liver, muscle glycogen and blood 
sugar determinations were carried out one, two, 
three, four and five hours after injection. In the 
normal rats narcotized with carbon dioxide, 
epinephrine effects neither the muscle glycogen 
stores nor the carbon dioxide-evoked hypergly- 
cemia, but prevents the cyclic reaccumulation of 
liver glycogen observed under conditions of 
carbon dioxide narcosis alone. In the adren- 
alectomized rats epinephrine does not change the 
lowering of liver glycogen produced by high 
concentrations of carbon dioxide but reverses 
the previously observed hypoglycemia to hyper- 
glycemia at the apparent further expense of 
glycogen stores in the muscle which are prac- 
tically depleted. These studies indicated to the 
author that epinephrine inhibits the reaccum- 
ulation of liver glycogen which occurs in rats un- 
der conditions of carbon dioxide narcosis. 
Regarding the effect of exposure of carbon 
dioxide on oxygen consumption, Killion and 
Schaefer (1090) 1953, studied cellular oxidation 
in liver tissue slices of guinea pigs and rats ex- 
posed to 1.5 percent carbon dioxide for periods 
from 1 to 41 days. No significant changes in 
oxidation were found, as measured by the 
oxygen consumption of liver tissue slices. Simi- 
lar studies have been conducted by Stamm PHYSIOLOGICAL EFFECTS OF HIGH CARBON DIOXIDE—METABOLISM 
1081-1109 
{1103) 1960, who investigated in vitro influence 
of carbon dioxide on the metabolism of lung and 
liver tissues. At carbon dioxide concentrations 
of 2.5-13 percent, the oxygen uptake of lung 
tissue remained practically the same, whereas 
that of the liver was reduced. The effect on liver 
slices was greatest in the 13 percent carbon diox- 
ide and least in the 2.5 percent carbon dioxide. 
Significantly, with a carbon dioxide concentra- 
tion of 13 percent a considerable reduction of 
liver metabolism occurred. With the lower car- 
bon dioxide concentration of 2.5 percent the 
metabolism was likewise reduced, but less than in 
the case of the 13 percent concentration. 
1081. Cooke, R. E., F. R. Coughlin, Jr. and W. E. 
Segar. Muscle composition in respiratory acidosis. J. din. 
Invest., 1952, 31: 1006-1010. 
1082. Day, S. B., W. O. Griffin, Jr., A. Castaneda, 
D. M. Nicoloff, R. C. Doberneck and N. H. Stone. 
Potentiating influence of apnea, hypoxia, and hypercap- 
nia on bile-induced hemorrhagic pancreatic neurosis. 
Surg. Gynec. Obstet., 1960, 111: 304-308. 
1083. Elkinton, J. R., R. B. Singer, E. S. Barker 
and J. K. Clark. Effects in man of acute experimental 
respiratory alkalosis and acidosis on ionic transfers in the 
total body fluids. J. din. Invest., 1955, 34: 1671-1690. 
1084. Fenn, W. O. Carbon dioxide and intracellular 
homeostasis. Ann. N.Y. Acad. Sci., 1961, 92: 547-558. 
1085. Furlong, N. B. and M. J. Schwarz. Environ- 
mentally induced changes in cerebral oxygen availability. 
Fed. Proc., 1957,16: 42. 
1086. Giebisch, G., L. Berger and R. F. Pitts. The 
extrarenal response to acute acid-base disturbances of 
respiratory origin. J. din. Invest., 1955, 34: 231-245. 
1087. Hastings, A. B. and E. B. Dowdle. Effect of 
C02 tension on synthesis of liver glycogen in vitro. Trans. 
Ass. Amer. Phycns., 1960, 73 : 240-246. 
1088. Johnson, B. B. and K. E. Schaefer. Tissue 
acid-base balance during C02 retention. Fed. Proc., 1955, 
14: 80. 
1089. Katzman, R., C. A. Villee and H. K. 
Beecher. Effect of increased carbon dioxide concentra- 
tions on fixed acid production in vitro. Amer. J. Physiol., 
1953,172: 317-323. 
1090. Killion, P. J. and K. E. Schaefer. Effect of 
prolonged exposure to carbon dioxide upon oxygen con- 
sumption of liver tissue and barbiturate detoxication time 
in guinea pigs and rats. U.S. Navy. Submarine base. New 
London, Conn. Medical research laboratory. Project NM 
002 015.11, Kept. no.. 1, 25 November 1953. 
1091. King, C. T. G. Effect of epinephrine on carbo- 
hydrate metabolism of C02 narcotized rats. Fed. Proc., 
1957,16: 72. 
1092. King, C. T. G., E. E. Williams and K. E. 
Schaefer. Hyperglycemic response to 30% carbon dioxide 
in air and in oxygen. Fed. Proc., 1954,13: 79. 
1093. Levitin, H., C. R. Jockers and F. H. Ep- 
stein. The response of tissue electrolytes to respiratory 
acidosis. Clin. Res., 1958, 6: 259-260. 
1094. Loeschcke, H. H. and K. H. Gertz. Einfluss 
des 02-Druckes in der Einatmungsluft auf die Atemtatig- 
heit des Menschen, gepriift unter Konstanthaltung des al- 
veolaren C02-Druckes. Pfliig. Arch. ges. Physiol., 1958, 267: 
460-477. 
1095. Malette, W. G., J. B. Fitzgerald and B. 
Eiseman. Hypercapnia—a means of increasing oxygen 
availability during hypothermic perfusion. Surg. Forum, 
1961,72; 184-186. 
1096. Nichols, G., Jr. Serial changes in tissue carbon 
dioxide content during acute respiratory acidosis. J. din. 
Invest., 1958, 37: 1111-1122. 
1097. Piiper, J. Oxygen exchange of subcutaneous gas 
cavities in rats. Amer. J. Physiol., 1963, 205: 1005-1007. 
1098. Rahn, H. The gas stores of the body, with par- 
ticular reference to carbon dioxide, pp. 297-304 in: Man’s 
dependence on the earthly atmosphere. Edited by K. E. 
Schaefer. The MacMillan Company, New York, 1962, 416 
pp. 
1099. Robin, E. D. Intra- and subcellular aspects of 
the chemical control of ventilation, pp. 223-233 in: The 
regulation of human respiration. Edited by D. J. C. Cun- 
ningham and B. B. Lloyd. Blackwell Scientific Publications, 
Oxford, 1963, 591 pp. 
1100. Sears, D. F. and R. M. Eisenberg. A model 
representing a physiological role of C02 at the cell mem- 
brane. J. gen. Physiol., 1961, 44: 869-887. 
1101. Shephard, R. J. The immediate metabolic effects 
of breathing carbon dioxide mixtures. J. Physiol., 1955, 
129: 393^07. 
1102. Singer, R. B., J. R. Elkinton, E. S. Barker 
and J. K. Clark. Transfers of cellular cations during 
acute respiratory alkalosis and acidosis experimentally 
produced in man. /. din. Invest., 1953, 32: 604. 
1103. Stamm, W. Der Einfluss der Kohlensaure auf 
den Stoffwechsel von Lungen- und Lebergewebe. Med. 
Exp., 1960, 3: 279-283. 
1104. Stanmeyer, W. R., C. T. G. King, H. Sco- 
field and R. Colby. The effect of prolonged exposure to 
carbondioxide on clasification. pp. 157-165 in: Man’s 
dependence on the earthly atmosphere. Edited by K. E. 
Schaefer. The MacMillan Company, 1962, 416 pp. 
1105. Thompson, A. M. and E. B. Brown, Jr. 
Tissue C02 concentrations in the hypercapnic rat. Fed. 
Proc., 1957, 16: 128. 
1106. Thompson, A. M. and E. B. Brown, Jr. 
Tissue carbon dioxide concentrations in rats during acute 
respiratory acidosis. J. appl. Physiol., 1960,15: 49-52. 
1107. Travis, D. M., S. N. Chaudhuri and S. P. 
Martin. Mitochondrial respiratory responses to hydrogen 
ion and carbon dioxide. Fed. Proc., 1963, 22: 634. 
1108. Van Liew, H. D. 02 and C02 exchanges in sub- 
cutaneous gas pockets. Fed. Proc., 1959, 18: 163. 
1109. Anon. Carbon dioxide retention. N.Y. St. J. Med., 
1960, 3459-3460. SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
H. ENDOCRINES 
It appears from a paper by Tenney (1123) 
1960, that critical concentrations of carbon diox- 
ide are essential for optimum synthesis of acetyl- 
choline. This action is apparently specific. Car- 
bon dioxide also enhances the excitability of 
sympathetic fibers to electrical stimulation. 
Higher concentrations of carbon dioxide initiate 
release of catecholamines from the renal me- 
dulla. Studies by the author lead to the conclu- 
sion that the sympathetico-adrenal response to 
carbon dioxide is determined solely by an H+ 
effect. There is a direct relation between the 
carbon dioxide concentration of the blood and 
hydrochloric acid secretion by the stomach. Car- 
bon dioxide also invariably increases the salivary 
flow in the dog. 
According to Johnson and Bean (1114) 1955, 
carbon dioxide augments pulmonary damage 
produced by oxygen under high pressure. Sym- 
pathetic blockage prevents this augmentation, 
as well as damage by high pressure oxygen it- 
self. This augmentation by carbon dioxide, that 
of pulmonary effects of oxygen under high pres- 
sure itself, is in large measure mediated through 
the sympathetics and adrenals and possibly the 
hypothalamus. King, Williams, Mego and 
Schaefer (1116) 1954, exposed normal and hy- 
pophysectomized rats to 1.5 percent carbon diox- 
ide for 42 days. Both groups of animals revealed 
a notable eosinopenia and lymphopenia, cor- 
related with a drop in adrenal cholesterol and 
ascorbic acid. The blood sugar was maintained 
at a normal level, apparently at the expense of 
liver and muscle glycogen stores. During this 
period of exposure to carbon dioxide adrenal 
cortical activity was increased and had not re- 
turned to pre-stimulation levels when the animals 
were sacrificed at intervals during a ten day 
recovery period in normal air. Results of the 
blood and adrenal studies indicated to the au- 
thors that prolonged exposure to 1.5 percent 
carbon dioxide causes a stress on the pituitary- 
adrenal system which is not reversed during a ten 
day recovery period. Similar results have been 
reported by King (1113) 1962. 
In dogs, Richards (1120) 1956, found maximal 
adrenocortical stimulation in all animals exposed 
to 20 percent carbon dioxide, a response which 
persisted for as long as four hours. This adreno- 
cortical response was abolished by hypophy- 
sectomy. Barcroft, Basnayake, Celander, Cob- 
bold, Cunningham, Jukes and Young (1110) 
1957, concluded in human studies that carbon 
dioxide enhanced the respiratory response to 
norepinephrine. According to Cross and Silver 
(1112) 1962, hypercapnia in rabbits (80 percent 
carbon dioxide and 20 percent oxygen) for 5 to 
15 seconds induced a sympathetic discharge re- 
sembling that obtained from hypothalmic stimu- 
lation. These effects were reversibly blocked by 
thorocolumbar spinal anesthesia. The response 
elicited by hypercapnia was not impaired by dis- 
crete bilateral lesions in the septum, hippo- 
campus and medial thalamus. Hypothalamic 
lesions on the other hand often reduced and 
occasionally prevented the central discharge. 
Manley and Woodbury (1119) 1964, found that 
dogs ventilated with 15 percent carbon dioxide 
in oxygen showed a significant reduction of posi- 
tive chronotropic response to 2 ug/Kg epine- 
phrine within a ten minute hypercapnic period. 
When 30 percent carbon dioxide was used the 
positive chronotropic response was virtually elim- 
inated and the positive inotropic response was 
reduced. Pretreatment with phentolamine (6.25 
mg/Kg) provided marked potentiation of the 
blocking effects caused by carbon dioxide. Equiv- 
alent cardiac stimulation elicited by acetyl- 
choline (500 ug/Kg) given to the atropinized 
dogs was unaltered during a ten minute hyper- 
capnic period induced by inhalation of 30 per- 
cent carbon dioxide. The effect of hypercapnia 
upon epinephrine-induced cardiac stimulation 
was also investigated in dogs pretreated with 
atropine, chlorisondamine (P-286), acute bi- 
lateral adrenalectomy or reserpine. These treat- 
ments under the experimental conditions of the 
authors caused no reduction of the positive 
chronotropic response to epinephrine and pro- 
duced only minor alterations in the positive 
inotropic response. Reduction of the pressor re- 
sponse to epinephrine by hypercapnia was found 
to be significantly less in those animals which had 
experienced a reduction of available catechola- 
mine stores. 
Schaefer, King, Mego and Williams (1121) 
1954, have reported in normal male guinea pigs 
exposed to 1.5 percent carbon dioxide over PHYSIOLOGICAL EFFECTS OF HIGH CARBON DIOXIDE—ENDOCRINES 
periods of 42 days and 91 days that there is an 
initial decrease in body weight lasting for 13 days 
followed by an increase. After a latent period 
of seven days adrenal cortical activity increased 
during exposure to 1.5 percent carbon dioxide as 
indicated by a decrease in adrenal cholesterol 
content and notable eosinopenia and lympho- 
penia. The blood sugar did not change while 
liver glycogen and muscle glycogen decreased 
significantly during exposure to the carbon diox- 
ide. Erythrocytes, hemoglobin and hematocrit 
increased during carbon dioxide exposure after 
a latent period of seven days. The observed rise 
in the reticulocyte counts indicate a slight ery- 
thropoietic stimulation. A further paper by 
Tenney (1122) 1956, may be consulted for evi- 
dence that carbon dioxide serves as a potent 
stimulus to increase the titer of circulating sym- 
pathetico-adrenal catecholamines in the cat. 
Chen, Sabel and Lyons (1111) 1963, found in 
experiments on human subjects that the ventila- 
tory response to four and six percent carbon diox- 
ide inhalation in air was increased by administra- 
tion of progesterone. 
Johnson and Bean (1114) 1955, have pointed 
out that although it is well known that a small 
increase of carbon dioxide augments most toxic 
reactions to oxygen under high pressure, in- 
formation concerning influence on lung damage 
in oxygen under high pressure is deficient. Ex- 
periments on adult albino rats exposed to OHP 
as well as animals exposed to OHP plus carbon 
dioxide (40 mm. Hg partial pressure) showed 
that carbon dioxide enhances lung damage in- 
duced by OHP. Earlier work of these authors 
indicated that the sympathetico-adrenal system 
contributes importantly to lung damage in OHP 
and to ascertain whether the carbon dioxide en- 
hancement of OHP lung damage might be due 
to sympathetic involvement. Test rats were in- 
jected with a sympatholytic agent, SKF501 (10 
mg/Kg) and a control group with a saline blank 
were exposed in pairs to OHP plus carbon 
dioxide (80 mm. Hg). Some rats injected with 
SKF501 were used as air controls. All saline in- 
jected oxygen controls showed gross lung damage 
and most succumbed whereas only 12 percent 
SKF injected oxygen exposed animals showed 
comparable lung damage although 50 percent 
succumbed. Several SKF501 animals in OHP 
showed small patches of hemorrhage but lung 
weight was unchanged, in contrast to a 250 per- 
cent lung weight increase in saline controls. The 
data indicate that carbon dioxide augments pul- 
monary damage by OHP and that sympathetic 
blockage protects against this augmentation as 
well as against the damage by OHP itself. This 
augmentation by carbon dioxide, like that of the 
pulmonary effect of OHP itself is in large meas- 
ure mediated through the sympathetico-adrenal 
system and possibly through the hypothalamus. 
Tenney {1122) 1956 has pointed out that carbon 
dioxide serves as a potent stimulus to increase 
the titer of circulating sympathetico-adrenal 
catechol amines in the cat. In man Barcroft, 
Basnayake, Celander, Cobbold, Cunningham, 
Jukes and Young (1110) 1957, have demonstrated 
an enhancing effect of carbon dioxide on the res- 
piratory response to nor-epinephrine. Adminis- 
tration of 10 ug. of nor-epinephrine per minute 
for 15 minutes to human subjects breathing car- 
bon dioxide and air mixtures was carried out. 
The carbon dioxide percentage varied from two 
to five percent. A sustained increase of 20-50 
percent in pulmonary ventilation was obtained 
in spite of a small fall in alveolar Pc02 which 
accompanied hyperpnea. At alveolar Pco., ten- 
sions of around 43 mm. Hg ventilation was in- 
creased by about 10 L/min. by infusion of nor- 
epinephrine. 
The reader should consult a paper by Tenney 
(1123) 1960, on the effect of carbon dioxide on 
neurohumoral and endocrine mechansms. Criti- 
cal concentrations of carbon dioxide appear to 
be essential for optimal synthesis of acetylcho- 
line. With regard to the sympathetic nervous 
system and the adrenal medulla there is also evi- 
dence that carbon dioxide actually enhances the 
excitability of sympathetic fibers to electrical 
stimuli. Higher concentrations of carbon dioxide 
initiate the release of catecholamines from the 
adrenal medulla. The role of carbon dioxide in 
certain aspects of adrenal funtion have been 
demonstrated by King (1115) 1962. 
Adult male rats were exposed for 10 and 30 
minutes as well as one, two, three and four hours 
to 30 percent carbon dioxide and a reduction 
was found in adrenal cortical ascorbic acid rang- 
ing from 500 mg. percent to 280 at 10 and 30 
minutes and 320 mg. percent at one hour. In SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
rabbits under urethane anesthesia Cross and 
Silver (1112) 1962, found that hypercapnia in- 
duced by inhalation of a mixture of 80 percent 
carbon dioxide and 20 percent oxygen for from 
5-15 seconds, produced a sympathetic discharge 
resembling that from hypothalamic stimulation. 
The effect was similar to that of hypoxia, but 
the hypercapnia was more potent than the hy- 
poxia. The effects were reversibly blocked by 
thorcolumbar spinal anesthesia. Placements of 
discrete bilateral lesions in the septum, hippo- 
campus and medial thalamus did not impair the 
sympathetic activity elicited by hypercapnia. 
Hypothalamic lesions on the other hand often 
reduced and occasionally prevented the central 
sympathetic discharge. Epinephrine-induced car- 
diac stimulation had been blocked by carbon 
dioxide inhalation in studies on dogs carried 
out by Manley and Woodbury (1119) 1964. 
Dogs were ventilated with 15 percent carbon 
dioxide and demonstrated a significant reduction 
of positive chronotropic response to 2 ug./Kg. 
of epinephrine within ten minutes after carbon 
dioxide inhalations started. When 30 percent 
carbon dioxide was employed the positive chrono- 
tropic response was almost entirely eliminated 
and the positive inotropic response reduced. The 
effect of hypercapnia upon epinephrine-induced 
cardiac stimulation has also been investigated in 
dogs pretreated with atropine, acute bilateral 
adrenalectomy or reserpine. These treatments 
under the experimental conditions of the authors 
caused no reduction of the positive chronotropic 
response to epinephrine and produced only minor 
alteration of the positive inotropic response. 
Reduction of the pressor response to epinephrine 
by hypercapnia was found to be significantly less 
in those animals which had experienced a reduc- 
tion of available catecholamine stores. 
In male guinea pigs the effects of prolonged 
exposure to 1.5 percent carbon dioxide in air for 
periods up to 91 days have been studied by 
Schaefer, King, Mego and Williams (1121) 
1954, In two experiments normal male guinea 
pigs, Connaught strain, were exposed to 1.5 per- 
cent carbon dioxide over periods of 42 days and 
91 days. The carbon dioxide tension in the 
blood rose significantly and the pH dropped 
slightly during exposure to carbon dioxide. Body 
weight showed a biphasic change, an initial de- 
crease lasting for a period of 13 days followed 
by an increase. After a latent period of seven 
days adrenal cortical activity was found to be 
increased during exposure to 1.5 percent carbon 
dioxide as indicated by a decrease in adrenal 
cholesteral content and marked eosinopenia and 
lymphopenia. Blood sugar did not change, while 
liver glycogen and muscle glycogen decreased 
significantly during exposure to carbon dioxide. 
Erythrocytes, hemoglobin and hematocrit in- 
creased during carbon dioxide exposure after a 
latent time of seven days. The observed rise in 
the reticulocyte counts indicated a slight erythro- 
poietic stimulation. The increased activity of the 
adrenal-pituitary system found during exposure 
to 1.5 percent carbon dioxide may play a role in 
the loss of body weight since stimulation of the 
adrenal medulla with epinephrine release en- 
hances the metabolic rate. 
A study of the effect of carbon dioxide ex- 
posure on adrenal 17-hydroxycorticosteroid 
secretion in dogs has been reported by Richards 
(1120) 1956. Male mongrel dogs with polyethy- 
lene cannulas in the right adrenal vein and 
carotid artery were placed in a recompression 
chamber at atmospheric pressure. Oxygen and 
carbon dioxide content of the chamber were 
measured by continuous sampling through a 
Beckman oxygen analyzer and a Liston-Becker 
infrared carbon dioxide analyzer. Following a 
control period of 30 minutes during which ad- 
renal venous and arterial blood samples were 
collected, the dogs were subjected to various con- 
centrations of carbon dioxide in air. Experi- 
ments were divided into the following groups: 
unanesthetized dogs exposed to 2.5, 5 and 10 
percent carbon dioxide for periods of one hour 
each; anesthetized dogs exposed to 2.5, 5 and 10 
percent carbon dioxide for one hour each; 10, 20 
and 30 percent carbon dioxide for one hour each; 
20 percent carbon dioxide for four hours; and 
anesthetized hypophysectomized dogs exposed 
to 20 percent carbon dioxide for three hours. 
Intermittent arterial and venous blood samples 
were obtained during the carbon dioxide ex- 
posure periods. Adrenal venous bloods were 
analyzed for 17-hydroxycorticosteroids. Arterial 
bloods were collected under oil and analyzed for 
pH, carbon dioxide content and in some cases 
for oxygen content. Adrenocortical stimulation PHYSIOLOGICAL EFFECTS OF HIGH CARBON DIOXIDE—KIDNEY 
1110-1124 
was correlated with decreased pH and increased 
carbon dioxide content in the arterial blood. 
Maximal adrenocortical stimulation occurred in 
all dogs exposed to 20 percent carbon dioxide and 
this response persisted for as long as four hours. 
Hypophysectomy abolished the adrenocortical re- 
sponse to carbon dioxide exposure. 
King, Williams, Mego and Schaefer {1116) 
1954, exposed normal and hypophysectomized 
rats to 1.5 percent carbon dioxide for 42 days. 
Both groups of animals demonstrated a marked 
eosinopenia and lymphopenia, correlated with a 
drop in adrenal cholesterol and ascorbic acid. 
The blood sugar was maintained at a normal 
level, apparently at the expense of liver and mus- 
cle glycogen stores. During this exposure to car- 
bon dioxide adrenal cortical activity was in- 
creased and had not returned to initial levels 
when the animals were sacrificed at intervals 
during a ten day recovery period in normal air. 
The results of the blood and adrenal studies in- 
dicate that prolonged exposure to 1.5 percent 
carbon dioxide produces a stress on the pituitary- 
adrenal system which is not reversed during a 
ten day recovery period. 
1110. Barcroft, H., V. Basnayake, O. Celander, 
A. F. Cobbold, D. J. C. Cuningham, M, G. M. Jukes 
and I. M. Young. The effect of carbon dioxide on the 
respiratory response to noradrenaline in man. J. Physiol., 
1957,137: 365-373. 
1111. Chen, H. C., B. Savel and H. A. Lyons. C02 
response curves after administration of progesterone and 
NaHC03. Fed. Proc., 1963, 22: 221. 
1112. Cross, B. A. and L. A. Silver. Central activa- 
tion of the sympathetico-adrenal system by hypoxia and 
hypercapnia. /. Endocrin., 1962, 24: 91-103. 
1113. Hamolsky, M. W. and M. Stein. Effects of 
2-amino-2-hydroxy-methyl-l, 3-propane-diol, pCO,, and 
pH on plasma protein binding of the thyroid hormones. 
Ann. N. Y. Acad. Sci., 1961, 92: 528-538. 
1114. Johnson, P. C. and J. W. Bean. Carbon di- 
oxide and the sympathoadrenal system in G2 at high pres- 
sure (OHP). Fed. Proc., 1955, 14: 81. 
1115. King, C. T. G. Carbon dioxide and certain 
aspects of adrenal function, pp. 117-126 in: Man’s depend- 
ence on the earthly atmosphere. Edited by K. E. Schaefer. 
The MacMillan Company, New York, 1962, 416 pp. 
1116. King, C. T. G., E. E. Williams, J. L. Mego 
and K. E. Schaefer. Effects of prolonged exposure to 
carbon dioxide in air on pituitary-adrenal interrelations 
in the male albino rat. U.S. Navy. Submarine base, New 
London, Conn. Medical research laboratory. Project NM 
002 015.11, Kept. no. 3, 16 March 1954. 
1117. Langley, L. L., P. W. Scokel and E. J. 
Moore. Role of hypoglycemia and carbon dioxide in the 
reaction to stress. Endocrinology, 1954, 54: 425-430. 
1118. Loomis, W. F. Sexual differentiation in Hydra; 
control by carbon dioxide tension. Science, 1957, 126: 
735-739. 
1119. Manley, E. S., Jr. and R. A. Woodbury. 
Blockade of epinephrine-induced cardiac stimulation by 
carbon dioxide inhalation. Fed. Proc., 1964, 23: 125. 
1120. Richards, J. B. and S. N. Stein. Effect of 
carbon dioxide exposure on adrenal 17-hydroxy corticoste- 
roid secretion in dogs. Fed. Proc., 1956,15: 151. 
1121. Schaefer, K. E., C. T. G. King, J. L. Mego 
and E. E. Williams. Effects of prolonged exposure to 
1.5% carbon dioxide in air for periods up to 91 days on 
body weight, carbohydrate metabolism, and adrenal cor- 
tical activity in guinea pigs. U. S. Navy. Submarine base, 
New London, Conn. Medical research laboratory. Project 
NM 002 015.11.05, 12 October 1954, 21 pp. 
1122. Tenney, S. M. Sympathoadrenal stimulation 
by carbon dioxide and the inhibitory effect of carbonic 
acid on epinephrine response. Amer. J. Physiol., 1956, 187: 
341-346. 
1123. Tenney, S. M. The effect of carbon dioxide on 
neurohumoral and endocrine mechanisms. Anesthesiology, 
1960, 21: 674-685. 
I. SWEATING 
Inhalation of carbon dioxide causes an in- 
crease of sweating as shown by Bullard {1124) 
1964. The inhalation of six percent carbon 
dioxide by male subjects exposed to three ambi- 
ent room temperatures gave an increase of sweat- 
ing as measured by resistance hygrometry. The 
increase reached approximately 100 percent over 
control levels. All measured body temperatures 
were reduced during or following the carbon 
dioxide exposure. In the recovery a striking re- 
duction of sweating occurred which ended as the 
skin temperature rose. 
1124. Bullard, R. W. The effects of carbon dioxide 
inhalation on sweating. J. appl. Physiol., 1964, 19: 137-141. 
J. KIDNEY 
For a general discussion of the effect of carbon 
dioxide on the kidney, a paper by Kennedy 
(7745) 1960, may be consulted. Electrolyte 
changes under carbon dioxide have been reported 
by Nichols and Schaefer {1140) 1962. Data on 
rats exposed to 24 percent carbon dioxide in air 
from 30 minutes to 48 hours indicate the rapid 
development of respiratory acidosis within 30 
minutes. Hypercapnia in dogs causes an immedi- 
ate increase in bicarbonate reabsorption by the 
kidneys irrespective of pH changes. In man after SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
30 minutes of 7 percent carbon dioxide inhala- 
tion, urinary pH falls, titratable acid and hydro- 
gen ion increases, and phosphate and chloride 
ion increases. Potassium secretion falls, ammon- 
ium ion increases a small but significant amount 
and sodium excretion increases. 
Breathing carbon dioxide leads to a rise in 
urine flow. Barbour, Bull, Evans, Jones and 
Logothetopoulos {1126) 1953, found that breath- 
ing 5-7 percent carbon dioxide causes a marked 
increase in urine flow in the recumbent normal 
subject, but no regular change in the sitting 
subject. During the diuresis induced by carbon 
dioxide, urine specific gravity falls and there is 
a slight rise in the excretion of total moles per 
minute. Urea contributes most of this increase 
and there is no significant change in the excretion 
per minute of creatinine, sodium, chloride or 
potassium. The glomerular filtration rate and 
renal plasma flow are not altered. The diuresis 
ordinarily induced by carbon dioxide can be 
inhibited by pitressin. The freezing point of 
plasma is not significantly altered by breathing 
carbon dioxide. Thus haemodilution is not con- 
sidered by the authors to be responsible for the 
diuresis. In fact, the diuresis may persist despite 
hemoconcentration. The probable mechanism of 
the carbon dioxide diuresis, according to the 
authors, is an inhibition of pitressin release. 
Currie and Ullmann {1130) 1961, also called 
attention to increased urine flow associated with 
carbon dioxide inhalation. According to Valtin, 
Wilson and Tenney {1131) 1959, carbon dioxide 
is probably mediated via nonosmotic influences 
on the supra-opticohypophyseal system. Since 
the left atrial stretch receptor mechanism is one 
such nonosmotic system which carbon dioxide 
might influence, experiments were designed by 
the authors to elucidate its role. It was found 
that carbon dioxide diuresis may be abolished 
by erect posture or by applying tourniquets 
high on the thighs while supine, and that it may 
be restored by standing in a tank of water or by 
mild exercise. Increases in plasma volume, total 
blood volume, or pulmonary blood volume, 
which conceivably might stretch the left atrium, 
did not occur during the carbon dioxide diure- 
sis. Voluntary hyperventilation mimicking that 
which accompanies carbon dioxide inhalation 
resulted in a much smaller diuresis and one 
which unlike that of carbon dioxide was accom- 
panied by increased sodium excretion. Main- 
taining normal alveolar PCOo during voluntary 
hyperventilation by simultaneous inhalation of 
two percent carbon dioxide in no way altered this 
result. Bilateral vagus section in animals does 
not abolish carbon dioxide diuresis, but may 
enhance it. It was concluded by the authors, 
therefore, that the left atrial stretch receptor 
mechanism is not the afferent system for carbon 
dioxide diuresis. 
In a study of the effect of prolonged exposure 
to carbon dioxide, 20 subjects were exposed to 
1.5 percent- carbon dioxide for 42 days, by 
Nichols, Schaefer and Carey (7747) in 1957. 
This exposure resulted in a slight uncompensated 
respiratory acidosis which lasted for 23 days and 
was followed by compensatory respiratory acido- 
sis. The red cells exhibited an increased sodium 
content and commensurately decreased potassium 
content during exposure to carbon dioxide and 
during nine days of recovery in air. Caloric 
intake decreased during exposure. Sodium bal- 
ance studies showed a biphasic pattern, retention 
during the phase of uncompensated respiratory 
acidosis, followed by an increased excretion dur- 
ing the phase of compensated respiratory acidosis, 
and during the nine day recovery period on air. 
The potassium balance, however, remained es- 
sentially unchanged and exhibited only an ad- 
justment of excretion to the reduced intake. 
Electrolyte excretion during acute respiratory 
acidosis in man has also been studied by Elkin- 
ton, Singer, Barker and Clark {1132) 1953. In 
normal subjects exposure to inhalation of 7.5 per- 
cent carbon dioxide was imposed for approxi- 
mately 30 minutes. At the end of this inhalation 
the average change in electrolyte excretion rate 
over the individual mean control values in 
uEq./min. were as follows: HC03‘ — 63, P04~ -f- 
10, K+ — 71, NH4+ -f 8, Na+ and Cl- + 5. 
In experiments of Epstein, Branscome and 
Levitin {1133) 1957, rats were exposed to 7.5 
percent or 12 percent carbon dioxide in air for 
one to four days and sacrificed at the end of 
the experiment. Renal losses of CL and K+ in- 
creased on the first day of hypercapnia to produce 
a negative balance of these ions at the end of 
24 hours, after which no further net loss occurred. 
Ammonia excretion was increased on exposure PHYSIOLOGICAL EFFECTS OF HIGH CARBON DIOXIDE—KIDNEY 
1125-1141 
to carbon dioxide and returned promptly to 
normal when the rats were given room air to 
breathe. The data of these authors suggest renal 
compensation characterized by excretion of Cl- 
in association with K+ and NH4+, plays an im- 
portant role in adjustments to chronic respira- 
tory acidosis in the rat. The renal response to 
acute respiratory acidosis has already been re- 
ported by Dorman, Sullivan and Pitts (1131) 
1954. In normal dogs receiving infusions of 
sodium bicarbonate, acute respiratory acidosis 
induced by breathing 12 percent carbon dioxide 
results in a significant increase in the rate of 
reabsorption of bicarbonate bound base, whether 
expressed in absolute or relative terms. In acute 
respiratory acidosis, a change in PCOo of the body 
fluids is the effective stimulus in enhancing the 
reabsorption of bicarbonate bound base. A 
change in pH does not per se affect this reabsorp- 
tive mechanism. The hypothesis proposed to 
account for these observations postulated a 
mechanism involving exchange of hydrogen ions 
for basic ions, operating throughout the renal 
tubule. This mechanism, enzymatically facili- 
tated by carbonic anhydrase, is depressed by car- 
bonic anhydrase inhibitors. 
The effects of exposure to carbon dioxide in 
air and oxygen on carbonic anhydrase activity 
in blood and kidney have been reported by 
Killion and Schaefer (1136) 1954. In these 
studies guinea pigs were exposed to 30 percent 
carbon dioxide in air, and in oxygen for one 
hour. Carbonic anhydrase activity in blood and 
kidney homogenates were determined. Carbonic 
anhydrase activity of the kidney homogenates 
showed no change after ten minutes of exposure 
to 30 percent carbon dioxide in air, but in- 
creased significantly after 60 minutes of exposure 
to 30 percent carbon dioxide in air, and was 
found to return to control levels after two days 
of recovery. Schaefer (1145) 1955, studying 
guinea pigs exposed to various carbon dioxide 
concentrations found that the effect on carbonic 
anhydrase activity of the kidneys exhibited in- 
dividual variations. According to Schwartz, Fal- 
briard and Lemieux (1146) 1959, the rate limit- 
ing process in bicarbonate reabsorption during 
acute respiratory acidosis is an enzymatic reac- 
tion involving carbonic anhydrase. 
1125. Baratz, R. A., A. N. Welter and L, H. 
Hamilton. Ventilatory, hemodynamic and renal response 
to I-V infusions of C02, with observations on the effects of 
a CO, buffer. Fed. Proc., 1961, 20: 42S. 
1126. Barbour, A., G. M. Bull, B. M. Evans, N. 
C. H. Jones and J. Logothetopoulos. The effect of 
breathing 5 to 7% carbon dioxide on urine flow and 
mineral excretion. Clin. Sci., 1953, 12: 1-13. 
1127. Brazeau, P. and A. Gilman. Effect of plasma 
CO, tension on renal tubular reabsorption of bicarbonate. 
Amer. J. Physiol, 1953,175: 33-38. 
1128. Brazeau, P. and A. Gilman. Effects of C02 
tension on renal tubular bicarbonate reabsorption. Fed. 
Proc., 1953, 12: 19. 
1129. Carter, N. W., D. W. Seldin and H. C. Teng. 
Tissue and renal response to chronic respiratory acidosis. 
J. din. Invest., 1959, 38: 939-960. 
1130. Currie, J. C. M. and E. Ullmann. Polyuria 
during experimental modifications of breathing. J. Physiol, 
1961, 155: 438-455. 
1131. Dorman, P. J., W. J. Sullivan and R. F. 
Pitts. The renal response to acute respiratory acidosis. 
J. din. Invest., 1954, 33: 82-90. 
1132. Elkinton, J. R., R. B. Singer, E. S. Barker 
and J. K. Clark. Effects of acute respiratory acidosis on 
electrolyte excretion in man. Fed. Proc., 1953,12: 38. 
1133. Epstein, F. H., W. Branscome and H. Levi- 
tin. The mechanism of hypochloremia in chronic respira- 
tory acidosis. Clin. Res., 1957, 5: 17. 
1134. Kaim, J. T., G. Carrasquer, R. Shapiro and 
W. A. Brodsky. Diffusion of C02 across the renal tubule. 
Fed. Proc., 1957, 16: 69. 
1135. Kennedy, T. J. The effect of carbon dioxide on 
the kidney. Anesthesiology, 1960, 21: 704-716. 
1136. Killion, P. J. and K. E. Schaefer. Effects of 
exposure to 30% C02 in air and in G2 on carboni an- 
hydrase activity in blood and kidney. Fed. Proc., 1954, 13: 
78. 
1137. Kloos, K. and K. J. Muller. Karyometrische 
und zytologische Nierenbefunde bei akuter und subakuter 
experimentellen Hyperkapnie. Zbl allg. Path. path. Anat., 
1960, 100: 464-172. 
1138. Kozlov, N. B. The effect of carbon dioxide gas 
on the content of ammonia, glutamine, and urea in the 
blood of animals after injection of solutions of ammonium 
chloride. Bull exp. Biol Med., 1961, 50: 1048-1052. 
1139. Longson, D. and J. N. Mills. Excess carbon 
dioxide and morning urine. J. Physiol, 1952, 118: 6P. 
1140. Nichols, G., Jr. and K. E. Schaefer. Exchange 
of electrolytes under carbon dioxide, pp. 145-146 in: 
Man’s dependence on the earthly atmosphere. Edited by 
K. E. Schaefer. The MacMillan Company, New York, 1962, 
416 pp. 
1141. Nichols, G., Jr., K. E. Schaefer and C. R. 
Carey. The effect of prolonged exposure to low concen- 
trations of carbon dioxide on acid base balance and elec- 
trolytes in blood and urine. U.S. Navy. Submarine Base, 
New London, Conn. Medical research laboratory. Rept. 
no. 292. Project NM 24 01 20, Rept. no. 1 on Subtask no. 
1, 2 December 1957, 10 pp. 1142-1153 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
1142. Rector, F. C., Jr., D. W. Seldin, A. D. 
Roberts, Jr. and J. S. Smith. The role of plasma C02 
tension and carbonic anhydrase activity in the renal re- 
absorption of bicarbonate. J. din. Invest., 1960, 39: 1706- 
1721. 
1143. Reiman, A. S., B. Etsten and W. B. 
Schwartz. The regulation of renal bicarbonate reabsorp- 
tion by plasma carbon dioxide tension. J. din. Invest., 1953, 
32: 972-978. 
1144. Schaefer, K. E. Respiration and acid base 
balance during exposure to 1.5 per cent carbon dioxide for 
nine days. U.S. Navy. Submarine Base, New London, Conn. 
Medical research laboratory. Project NM 002 015.03, Kept, 
no. 9, 1952. 
1145. Schaefer, K. E. Stress of CO, and activation of 
kidney carbonic anhydrase. Fed. Proc., 1955,14: 131. 
1146. Schwartz, W. B., A. Falbriard and G. Le- 
mieux. The kinetics of bicarbonate reabsorption during 
acute respiratory acidosis. J. din. Invest., 1959, 38: 939-944. 
1147. Schwartz, W. B., G. Lemieux and A. Fal- 
briard. Renal absorption of bicarbonate during acute 
respiratory alkalosis. J. din. Invest., 1959, 38: 2197-2201. 
1148. Scribner, B. H., G. M. Bogardus, K. Fre- 
mont-Smith and J. M. Burnell. Potassium intoxication 
during and immediately following respiratory acidosis. 
J. din. Invest., 1954, 33: 965. 
1149. Scribner, B. H. and J. M. Burnell. The effect 
of respiratory alteriations of pH on the internal equilib- 
rium of potassium. J. din. Invest., 1955, 34: 919. 
1150. Valtin, H. and S. M. Tenney. Carbon dioxide 
diuresis at high altitude. Fed. Proc., 1960, 19: 362. 
1151. Valtin, H., I. D. Wilson and S. M. Tenney. 
C02 diuresis, with special reference to role of the left atrial 
stretch receptor mechanism. J. appl. Physiol., 1959, 14: 844- 
848. 
K. SPLEEN 
Studies of Ramlo and Brown (1152) 1959, in- 
dicate that splenic contraction produced in dogs 
by breathing 30 percent carbon dioxide is medi- 
ated by both splenic nerves and by the adrenal 
glands. Nerve stimulation appears to act more 
rapidly, but contraction still occurs in the 
absence of all innervation. Neither bilateral 
adrenalectomy nor splenic denervation alone 
completely blocked the splenic response. In 
order to block the splenic response completely, 
both denervation of the spleen and bilateral 
adrenalectomy were necessary. 
1152. Ramlo, J. H. and E. B. Brown, Jr. Mechan- 
isms of splenic contraction produced by severe hypercap- 
nia. Amer. J. Physiol., 1959,197: 1079-1082. 
L. TOLERANCE 
According to Chapin (1153) 1955, survival 
times of mice exposed to high carbon dioxide 
varied with different oxygen concentrations. 
Longer survival times were encountered when 
the carbon dioxide concentration was lowest, 
and with exposures to 40 percent carbon dioxide 
when oxygen concentrations were between 12 and 
20 percent. Oxygen under high pressure failed 
to produce convulsions in the presence of high 
carbon dioxide concentrations, 
1153. Chapin, J. L. Survival of mice in high C02 en- 
vironments at varying 02 tensions, pp. 255-258 in: Studies 
in respiratory physiology. Second series. Chemistry, me- 
chanics, and circulation of the lung. Edited by H. Rahn 
and W. O. Fenn. Wright Air Development Center, Dayton, 
Ohio. Aero medical laboratory. WADC Tech. Kept. 55-537, 
November 1955, 438 pp. 
M. ACCLIMATIZATION 
For studies of acclimatization to carbon dioxide 
and respiratory responses to carbon dioxide dur- 
ing altitude acclimatization, the following biblio- 
graphic papers should be consulted: Kellogg, 
Reed and Todd (.1158) 1958; Kellogg (1157) 
1961; and Kellogg (1156) 1960. 
The effects of chronic hypercapnia on elec- 
trolyte and acid-base equilibrium have been re- 
ported by Polak, Haynie, Hays and Schwartz 
(1159) 1961. These studies were carried out in 
dogs exposed to atmospheres of 11 to 13 percent 
carbon dioxide for periods of 6 to 15 days . A 
consistent pattern of response was found, charac- 
terized by a sharp rise in plasma bicarbonate con- 
centration during the first day of exposure and 
a subsequent slower rise over the next 5 or 6 
days, to a final concentration ranging from 35-38 
mEq./L. 
Schaefer, Nichols and Carey (1162) 1960, have 
reported that human subjects exposed to 3 per- 
cent carbon dioxide in 21 percent oxygen for 
prolonged periods, showed a characteristic res- 
piratory adaptation, which consisted among other 
factors in a reduction of the normal ventilatory 
response to increased concentration of carbon 
dioxide. In further subjects exposed to 1.5 per- 
cent carbon dioxide in 21 percent oxygen for 42 
days, the respiratory minute volume and alveolar 
carbon dioxide tensions were found to be in- 
creased throughout the exposure. No significant 
changes were observed in vital capacity, inspira- 
tory and expiratory reserve, or tidal volume. A 
slight respiratory acidosis was present during 
the first 23 days of exposure, as indicated in the PHYSIOLOGICAL EFFECTS OF HIGH CARBON DIOXIDE-PATHOLOGICAL CHANGES 1154-1163 
lowering of pH, which was associated with a 
decreased carbon dioxide excretion in the expired 
air and urine. A phase of compensated respira- 
tory acidosis followed, during which the pH, as 
well as the carbon dioxide excretion, returned 
to the initial level. After transition to air the 
carbon dioxide excretion in expired air and urine 
reached a peak and returned to normal values 
within a week. At the end of the exposure to 1.5 
percent carbon dioxide, a significant depression 
of the ventilatory response to 5 percent carbon 
dioxide was found, similar to the results under 3 
percent carbon dioxide. Similar studies were re- 
ported by Schaefer, Hastings, Carey and Nichols 
(1161) 1963. 
1154. Balke, B. The effect of altitude acclimatization 
on C02 tolerance. Fed. Proc., 1959,18: 7. 
1155. Chapin, J. L. Evidence for simultaneous lower- 
ing of upper and lower limits of CO, tolerance. Fed. Proc., 
1956, 15: 34. 
1156. Kellogg, R. H. Acclimatization to carbon di- 
oxide. Anesthesiology, 1960, 21: 634-641. 
1157. Kellogg, R. H. The role of CO, in altitude ac- 
climatization. pp. 379-395 in: The regulation of human 
respiration. Edited by D. J. C. Cunningham and B. B. 
Lloyd. F. A. Davis Co., Philadelphia, 1961, 591 pp. 
1158. Kellogg, R. H., D. J. Reed and A. R. Todd. 
Comparison of acid-base balance and respiratory response 
to C02 during altitude acclimatization. Fed. Proc., 1958, 
17: 84. 
1159. Polak, A., D. G. Haynie, R. M. Hays and W. 
B. Schwartz. Effects of chronic hypercapnia on electrolyte 
and acid-base equilibrium. I. Adaptation. J. din. Invest., 
1961,40: 1223-1237. 
1160. Schaefer, K. E. A concept of triple tolerance 
limits based on chronic carbon dioxide toxicity studies. 
Aerospace Med., 1961, 32: 197-204. 
1161. Schaefer, K. E., B. J. Hastings, C. R. Carey 
and G. Nichols, Jr. Respiratory acclimatization to carbon 
dioxide. J. appl. Physiol, 1963, 18: 1071-1078. 
1162. Schaefer, K. E., G. Nichols and C. R. Carey. 
Respiratory adaptation to chronic C02 exposure. Fed. 
Proc., 1960, 19: 381. 
1163. White, C. S., J. H. Humm, E. D. Armstrong 
and N. P. V. Lundgren. Human tolerance to acute ex- 
posure to six percent carbon dioxide in air and in oxygen. 
USAF, Randolph Field, Texas. School of aviation medi- 
cine. Project 21-1402-0001, Kept. no. 1, March 1953, 13 pp. 
N. PATHOLOGICAL CHANGES 
Studies of pathological changes resulting from 
experimental exposure to high concentrations of 
carbon dioxide, published before 1951, draw at- 
tention to irreversible changes, including damage 
of the alveolar walls of the lungs and cell necrosis 
with dead cells and debris in the liver, kidney 
and brain. High degrees of hyperemia of the 
lung have been found, as well as pulmonary 
edema in some cases. In some cases the alveoli 
of the lungs were dilated, as in emphysema, with 
dense infiltration of leukocytes in extensive areas. 
Hyperemia has also been found extensively 
throughout the liver. In some liver cells the 
nuclei! were pycnotic. Some cases revealed 
hyperemia and necrosis of the kidneys. In some 
animals there were irreversible changes in the 
central neurons. The liver and kidneys appeared 
to be the first organs to be impaired. The 
straight uriniferous tubules showed vacuolar de- 
generation and necrosis. With high carbon 
dioxide concentrations there were also fat de- 
posits in the renal pyramids and the glomeruli 
were swollen. Regarding nervous system dam- 
age, those neurons most sensitive to hypoxia, 
such as those in the cerebral cortex, were found 
to be protected from severe histopathological 
changes. Following exposure to carbon dioxide, 
the cells of the more primitive levels of the 
brain, less sensitive to oxygen lack, sustained 
the greatest structural damage as a result of high 
carbon dioxide inhalation. In acute exposures to 
carbon dioxide the cell changes were generally 
reversible but irreversible changes were observed 
in some large motor cells. In acute experiments 
neurons showed slight swelling with chromatoly- 
tic changes, more marked in the periphery of 
the cells. The nuclei were swollen, as were 
also the nucleoli and there was also vacuolation. 
In chronic experiments there was severe swell- 
ing of the cells with chromatolysis. Vacuolar 
degeneration of cells of the hypophysis was also 
reported. More recently, Kaplan, Williams, 
Carpenter, Annegers and Lee (1164) 1956, have 
carried out studies on monkeys to examine the 
possible toxic effects of high carbon dioxide 
concentrations. They exposed animals to 3 and 
4.5 percent carbon dioxide for periods up to 112 
days. The oxygen concentration was maintained 
at 21 percent. In the 3 percent carbon dioxide 
experiment, 10 animals were exposed to carbon 
dioxide while 10 others were kept at ordinary 
atmospheric conditions and served as controls. 
In the 4 percent carbon dioxide experiment, 10 
animals were kept at ordinary atmospheric con- 
ditions for three weeks to obtain control meas- 1164-1187 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
urements prior to the exposure. The following 
constituents of the blood or plasma were meas- 
ured: carbon dioxide content, pH, PCo2> NPN, 
calcium, phosphorus, glucose, sodium, potassium, 
chloride, bilirubin, cephalin flocculation, oxygen 
content, hemoglobin, hematocrit, sedimentation 
rate, white blood cell and eosinophil counts. 
Autopsies were performed on the animals during 
or at the end of the exposure period. During 
exposure to 3 percent carbon dioxide, the animals 
maintained their weights and showed no signifi- 
cant alterations in the constitutents of their 
blood. However, during exposure to 4.5 percent 
carbon dioxide they developed anorexia, dyspnea, 
cough, dehydration and loss of weight. The only 
changes observed recorded in the constituents 
of the plasma were elevation of the carbon 
dioxide content and PCOo and reduction of the 
hydrogen ion concentration. Morphologic find- 
ings in the group exposed to 4.5 percent carbon 
dioxide included: 1) a diffuse pneumonitis, and 
2) hepatic edema, manifested by intracellular 
watery vacuoles and perisinusoidal edema. The 
lungs showed some features in common with 
the socalled uremic pneumonitis. The most 
severe changes were seen in animals with the 
most severe respiratory acidosis. A possibility 
that the pathological findings might have been 
due to pulmonary infestation was not ruled out. 
1164. Kaplan, S. A., S. N. Stein, R. B. Williams, 
H. M. Carpenter, J. Annegers and R. E. Lee. Effects 
of prolonged exposure of monkeys to carbon dioxide. Fed. 
Proc., 1956, 15: 105. 
1165. Millikan, C. H. Evaluation of carbon dioxide 
inhalation for acute focal cerebral infarction. Arch. Neurol. 
Psychiat., 1955, 73: 324-328. 
1166. Schaefer, K. E., M. Avery and K. Bensch. 
Effect of C02 intoxication on the surface characteristics of 
lungs and morphology of alveolar epithelial cells. Fed. 
Proc., 1963, 22: 339. 
V. INERT GASES 
A. GENERAL STUDIES 
For papers dealing generally with the effects 
of the inert gases, the reader should consult the 
references listed in the following section. 
1167. Carpenter, F. G. Depressant action of inert 
gases on the central nervous system in mice. Amer. J. 
Physiol, 1953,172: 471-474. 
1168. Carpenter, F. G. Anesthetic action of inert and 
unreactive gases on intact animals and isolated tissues. 
Amer. J. Physiol., 1954, 178: 505-509. 
1169. Carpenter, F. G. Inert gas narcosis, pp. 124- 
130 in: Proceedings of the underwater physiology sympo- 
sium. Edited by L. G. Goff. National Research Council, 
Washington, D. C. N.R.C. Publication 477, 1955, 153 pp. 
1170. Carpenter, F. G. Alteration in mammalian 
nerve metabolism by soluble and gaseous anesthetics. 
Amer. J. Physiol., 1956, 187: 573-578. 
1171. Carpenter, F. G. Kinetics of blockade in pe- 
ripheral nerve fibers produced by anesthetic gases. Fed. 
Proc., 1959, 18: 23. 
1172. Cook, G. A. Argon, helium and the rare gases. 
The elements of the helium group. Volume I. Interscience 
Publishers, New York, 1961, 392 pp. 
1173. Cook, G. A. Argon, helium and the rare gases. 
The elements of the helium group. Volume II. Interscience 
Publishers, New York, 1961, 818 pp. 
1174. Cook, S. F. The effect of helium and argon on 
metabolism and metamorphosis. J. cell. comp. Physiol., 
1950, 36: 115-127. 
1175. Cook, S. F. and H. A. Leon. Physiological 
effects of inert gases. USAF. Holloman Air Force Base, 
Mexico. Missile development center. Tech. Kept. AFMDC- 
TR-59-26, June, 1959, 35 pp. 
1176. Davis, H. S., W. F. Collins, C. T, Randt and 
W. H. Dillon. Effect of anesthetic agents on evoked 
central nervous system responses: gaseous agents. Anes- 
thesiology, 1957, 18: 634-642. 
1177. Ebert, M., S. Hornsey and A. Howard. 
Effect of inert gases on oxygen-dependent radiosensitivity. 
Nature, Lond., 1958, 181: 613-616. 
1178. Featherstone, R. M. and C. A. Muehl- 
baecher. The curent role of inert gases in the search for 
anesthesia mechanisms. Pharmacol. Rev., 1963, 15: 97. 
1179. Frankel, J. and H. A. Schneiderman. The 
effects of nitrogen, helium, argon and sulfur hexafluoride 
on the development of insects. J. cell. comp. Physiol., 1958, 
52: 431-451. 
1180. Johnson, W. J. and J. H. Quastel. Narcotics 
and biological acetylations. Nature, Lond., 1953, 171: 602- 
605. 
1181. Lanphier, E. H. Nitrogen-oxygen mixture 
physiology. Phases I and II. U.S. Navy, EDU, Naval Gun 
Factory, Washington, D.C. Rept. 7—55, Proj. NS185—005, 
Subtask 5, 30 June 1955, 35 pp. 
1182. Lord, G. P., G. F. Bond and K. E. Schaefer. 
Pulmonary function in man breathing a helium-oxygen- 
nitrogen atmosphere at 7 atmospheres absolute pressure 
for 12 days. Fed. Proc., 1964, 23: 117. 
1183. Miller, S. L. A theory of gaseous anesthetics. 
Proc. nat. Acad. Sci., Wash., 1961, 47: 1515-1524. 
1184. Naimark, G. M. and W. A. Mosher. Pepsin in- 
activation by inert gases. J. Franklin Inst., 1952, 254: 344. 
1185. Pauling, L. A molecular theory of general 
anesthesia. Science, 1961, 134: 15-21. 
1186. Powell, H. M. Clathrate compounds or inert 
gases. XXII Inter. Congr. physiol. Sci., Leiden, 1962, Vol. 
I, Part I, pp- 546-547. 
1187. Rinfret, A. P. and G. F. Doebbler. Physiolog- 
ical and biochemical effects and applications, pp. 727-764 
in: Argon, helium and the rare gases. Volume II. Edited 
by G. A. Cook. Interscience Publishers, New York, 817 pp. INERT GASES—NITROGEN 
1188-1194 
1188. Schilder, D. P., A. Roberts and D. L. Fry. 
Effect of gas density and viscosity on the maximal expira- 
tory flow-volume relationship. J. din. Invest., 1963, 42: 
1705-1713. 
1189. Schreiner, H. R. Other biological effects of the 
noble gases. XXII Inter. Congr. physiol. Sci., Leiden, 1962, 
Vol. I, Part I, pp. 535-539. 
1190. Sears, D. F. and W. O. Fenn. Narcosis and 
emulsion reversal by inert gases. J. gen. Physiol., 1956-57, 
40: 515-520. 
1191. South, F. E., Jr. and S. F. Cook. Argon, 
xenon, hydrogen, and the oxygen consumption and gly- 
colysis of mouse tissue slices. J. gen. Physiol., 1954, 37: 
335-341. 
1192. Steinberg, H. Selective effects of an anaesthetic 
drug on cognitive behaviour. Quart. J. exp. Psychol., 1954, 
6: 170-180. 
1193. Tenney, S. M. Effect of gas density on alveolar 
ventilation. Fed. Proc., 1959, 18: 157. 
1194. Wulf, R. J. and R. M. Featherstone. A corre- 
lation of van der Waals constants with anesthetic potency. 
Anesthesiology, 1957, 18: 97-105. 
B. NITROGEN 
Nitrogen narcosis (1222), characterized by 
symptoms similar to alcohol intoxication, be- 
comes evident first at a depth of about 100 feet 
and causes ineffectiveness in most divers at 200 
feet. Like alcohol the effects of nitrogen vary 
with the individual person and its hazards can 
be minimized within limits by conscious effort. 
Similar to other inert gases, which are soluble 
in oil or fat, its anesthetic potency increases 
under pressure. Argon, krypton and xenon have 
even greater narcotic effects than nitrogen. The 
general subject of nitrogen narcosis has been 
treated by Miles (1217) 1962. At levels of 100 
to 150 feet depth there is light-headedness, in- 
creased self-confidence and loss of fine discrimina- 
tion. At 150 to 200 feet subjects become jovial 
and garrulous, and there is some dizziness. At 
200 to 250 feet there is laughter and possibly 
hysteria, with lessened powers of concentration 
and some peripheral numbness and tingling with 
delayed stimulus response. At 300 feet there is 
depression and impaired neuromuscular coordi- 
nation. At 350 feet consciousness may be lost 
and there is increased danger of oxygen toxicity. 
All of these symptoms are seen with air under 
pressure. It appears that resistance to nitrogen 
narcosis is improved with diving experience but 
the adaptation is not permanent. In order to 
maintain the adaptation, dives once a week to 
300 feet seem to be required. Only a few 
minutes at depth is needed. As Burnett (1206) 
1955, has stated, the exact cause of nitrogen 
narcosis has as yet not been definitely estab- 
lished, although means of combating the effect 
of compressed air on human subjects at great 
depths are available by the use of helium in 
substitution for nitrogen. For a discussion of 
the theories of inert gas narcosis, a paper by 
Miller (1218) 1963, may be consulted. Rahn 
(1219) 1961, has discussed the role of nitrogen 
gas, in general, in various biological processes. 
According to Rashbass (1220) 1955, and Lanp- 
hier and Busby (1213) 1962, carbon dioxide 
retention can be ruled out as a primary cause 
of nitrogen narcosis. That nitrogen narcosis 
does not depend on an increase of arterial Pc02 
has also been reported by Lanphier (1214) 1963. 
In a review of the physiological effects of high 
pressures with nitrogen and oxygen, Fenn (1208) 
1961, states that nitrogen under high pressure 
and argon under high pressure, but not helium, 
act like other anesthetics in favoring water-in-oil 
rather than oil-in-water emulsions of dilute 
NaOH solutions in olive oil. The effect is small 
but appears to be real. This suggests that inert 
gases may make the lipoidal surface layer of cells 
relatively more continuous and therefore less 
permeable. 
To test the hypothesis that nitrogen narcosis 
is really carbon dioxide narcosis, Taylor (1221) 
1962, caused human subjects to hyperventilate 
in order to reduce carbon dioxide under condi- 
tions of supposed nitrogen narcosis. The narcotic 
effect was determined by comparison of the num- 
ber of correct answers during two minutes of 
arithmetic at 250 feet with the number correct 
answers under control conditions. At a simulated 
depth of 250 feet there was a marked reduction 
in the correct number of sums and a small but 
significant rise in carbon dioxide concentration. 
Five minutes of normal breathing abolished in- 
creased alveolar carbon dioxide and there was a 
reduction in alveolar carbon dioxide concentra- 
tion with no further alleviation of the narcosis. 
Therefore, with the possible exception of the first 
few minutes, carbon dioxide was considered by 
the author not to contribute to the causation 
of the narcosis. 
Lambertsen (1213) 1961, has pointed out that 
inert gases differ in the partial pressures required SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
to produce a narcotic effect. For full unconsci- 
ousness and analgesia from nitrogen, 38 at- 
mospheres or 1200 feet depth is required, but 
euphoria occurs between 3.5 and 5 atmospheres 
(80-120 feet depth), and a state of severe “al- 
coholic” intoxication is obtained at 250 feet. 
No narcotic effect of helium has been found yet 
(up to 1000 feet). The narcotic effect increases 
with molecular weight and with the solubility 
of the gas in lipids. It is noteworthy that the 
British experience in recent diving trials demon- 
strates some narcosis from helium at 750 to 800 
feet depth. 
In an important paper on the neuropharma- 
cologic and neurophysiologic changes in inert 
gas narcosis, Bennett (1199) 1963, has reported 
the response of rats to electroshock as a measure 
of the extent of inert gas narcosis (argon and 
nitrogen at 180 lbs. per sq. in.) before and after 
Frenquel administration. The experiments dem- 
onstrate that argon is more narcotic than nitro- 
gen and nitrogen in turn is more narcotic than 
helium. The administration of Frenquel pro- 
tected against inert gas narcosis. The increase 
in ventilation at 180 psi in air was 50.2 percent, 
±4 percent, whereas with Frenquel it was 1.21 
percent, ±2.45 percent (not significantly differ- 
ent from atmospheric pressure). The dosage of 
Frenquel was 40 mg. When three men were 
compressed to 10 ATA Frenquel in doses of 10, 
300 and 900 mg. had no protective effect against 
narcosis, as measured by arithmetic and manual 
dexterity tests. At 300 feet depth on air there 
was a significant rise in the critical fusion fre- 
quency, but when 3600 mg. of Frenquel was 
given no increase was seen, but there were some 
drug side effects. Synaptic potentials evoked by 
sciatic nerve stimulation were depressed by in- 
creased inert gas pressures. When argon (220 
psi) with 15 psi oxygen were used, there was an 
initial depression of potential followed by a 
period of augmentation and then a progressive 
depression and sometimes blockade. With nitro- 
gen the effect was less; with helium there was no 
effect. In experiments reported by Bennett and 
Glass (1204) 1957, cortical electrodes were in- 
serted into the skull of rabbits with the tips of 
the electrodes just resting on the dura. Record- 
ings were taken at sea level and at various simu- 
lated depths to a maximum of 250 feet, and at 
different stages of decompression. The animals 
appeared more restless at depth than at the sur- 
face and the EEG confirmed these findings. After 
decompression the slower activity (5-6 cycles 
per second from the cortex) returned. When a 
20-25 percent nitrous oxide mixture was given 
(isonarcotic with air at 250 feet depth) the EEG 
was slower and resembled sleep. In human 
studies divers were the subjects of EEG record- 
ing. Control EEG records with the subjects eyes 
closed revealed a 9-11 cycle pattern of 20-30 
uV. This was blocked by opening the eyes 
(alpha blocking). Mental tasks were also ad- 
ministered, and it was found that the blocking 
of the alpha rhythm by mental problems was 
abolished after varying times at pressure. At 
higher pressures this time was short and at lower 
pressures it was longer. This relationship be- 
tween time and abolition of blocking at depth 
suggested to the authors a diffusion process. It 
was found that a high partial pressure of nitrogen 
was primarily responsible for this effect. A sug- 
gested site of action of nitrogen is the reticular 
activating system in the brain stem. It was con- 
cluded that isonarcotic concentration of nitrous 
oxide studies suggest that the tables by Carpenter 
are not strictly applicable to human subjects. In 
the latter there is a tendency to a higher degree 
of narcosis than would be found at an equivalent 
depth of compressed air. Related studies are 
reported by Bennett and Glass (1205) 1961, 
and Bennett (1196) 1958. In a study of the 
fusion frequency of flicker and nitrogen satura- 
tion, Bennett (1200) 1959, carried out experi- 
ments to measure the flicker fusion frequency of 
men exposed to raised pressure of compressed 
air. In five subjects tested, four showed and 
maintained a slight fall and the other a rise in 
fusion frequency while at pressure. Each subject 
was tested at seven different pressures. The time 
required for this change in perception of fusion 
frequency or the nitrogen threshold was found 
to be inversely proportional to the square of 
the pressure. 
Ch’un (1207) 1959, found that the reflex ac- 
tivity of the spinal cord was lowered in decere- 
brate cats at a pressure of 9 atmospheres of nitro- 
gen partial pressure. 
In experimental studies of prevention of nar- 
cosis by inert gases at high pressures, Bennett INERT GASES—NITROGEN 
(1198) 1963, developed a technique for quanti- 
tative evaluation of inert gas narcosis in rats. 
The response of 46 adult Wistar rats to minimal 
electroshock was used in 102 experiments to de- 
termine the narcotic effect of nitrogen at 12.6 
and 13.5 ATA and argon at 12.6 ATA, before 
and after the oral, intraperitoneal or intravenous 
administration of Frenquel. This drug controlled 
the narcotic effect produced by these inert gases 
at pressure without, so far as could be observed, 
the supervention of undesirable side effects. The 
effective dose was 40 mg. (130-150 mg./Kg. body 
weight). Lower doses were only partially effec- 
tive, and the maximum protective action of the 
drug was observed about 48 hours after its 
administration. Similar studies are reported by 
Bennett, Dossett and Kidd (1202) 1959. These 
same authors (1203) 1960, found in rats that the 
least narcotic effect was produced by mixtures of 
65 psi of oxygen and 130 psi of nitrogen. In a 
comparison of the effects of drugs on nitrogen 
narcosis and oxygen toxicity in rats, Bennett 
(1197) 1962, found that Frenquel, phenacetin, 
Carbachol, Doriden and aspirin all protected 
against nitrogen narcosis and also delayed the 
onset of oxygen convulsions. There was varia- 
tion among the drugs in the protection afforded; 
Carbachol was most effective. Some drugs, such 
as methedrine, enhanced the sensitivity of rats 
to narcotic effects of nitrogen and oxygen con- 
vulsions. Adrenalin, Scopolamine and Physostig- 
mine had little effect. The author concluded that 
both nitrogen and oxygen involved impairment 
of at least some similar mechanisms and that 
drugs which control or enhance impairment pro- 
duced by one gas will act similarly with the other. 
Psychomotor testing indicates a detriment in 
performance of subjects during air dives to five 
atmospheres. Hesser (1210) 1963, in a study of 
factors responsible for compressed air narcosis, 
examined human performance alterations in- 
duced through exposure to different nitrogen- 
oxygen partial pressures at increased ambient 
pressure. In these studies 12 subjects were sub- 
jected to psychomotor tasks in a dry chamber. 
A rise in air pressure from 1-5 atmospheres re- 
sulted in a slight tendency towards impaired per- 
formance if oxygen was added (39.8 percent 
oxygen in nitrogen). At 6.6 atmospheres the 
impairment in performance was increased. From 
this experiment the author concluded that the 
narcosis is not due to interference with the 
oxidative processes in the tissues. In a further 
study of performance impairment as a function 
of nitrogen narcosis, Kiessling and Maag (1211) 
1960, and (1212) 1962, carried out some studies 
in which Navy divers individually performed air 
dives in a high pressure chamber for 40 minutes 
at a simulated depth of 100 feet. Each experi- 
mental session consisted of three phases: (1) a 
measure of performance on choice reaction time, 
motor coordination, and conceptual reasoning 
at sea level in the chamber; (2) three 12 minute 
periods at a pressure equivalent to 100 feet of sea 
water, during which equal time was allocated to 
each of the three tests; and (3) a final measure 
during the decompression stop at 10 feet. Statis- 
tically significant decreases in performance for 
all subjects on all tests were found with the 
greatest decrement occurring on the reasoning 
test, the least on motor coordination. Decreased 
performance occurred as the pressure increased 
and remained relatively constant with duration 
of exposure. 
In a study of the role of nitrogen in breath- 
holding at increased pressures, Hesser (1209) 
1962, conducted studies to test the hypothesis 
that the increased ability to hold the breath at 
increased ambient pressure is due to increased 
nitrogen pressure in addition to the concomitant 
increase in oxygen tension. In Hesser’s studies 
eight experienced subjects were exposed to air, 
100 percent oxygen, or 5 percent oxygen in nitro- 
gen, in a dry recompression chamber at pressures 
from 1-4 ATA for 15 minutes before breathhold- 
ing. The average expiratory reserve volume at 
the breaking point ranged from 1.02 to 1.34 
liters. With air the maximum breathholding 
time (2.8 times longer at four than at one at- 
mosphere) and the breaking point of PCo2 
increased with increasing pressure. The break- 
ing points after 5 percent oxygen in nitrogen at 
three and four atmospheres were located on the 
same curve as air breathing or reduced pressure, 
suggesting no effect of nitrogen on breathholding 
ability. Breathholding time with air at four 
atmospheres was significantly longer and the 
Pcoo significantly higher than oxygen breathing 
at one atmosphere, despite a higher Pco2 in 
the latter. After testing the theory that 15 1195-1219 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
minutes was not long enough for the chemosensi- 
tive control mechanisms to come into equili- 
brium with a new oxygen tension, the original 
hypothesis was still disproved within the pressure 
range studied. It was also demonstrated at ambi- 
ent pressure that an oxygen threshold exists of 
350 mm. Hg above which the breaking point is 
entirely PCOo dependent. The PCOo threshold 
was 60 mm. Hg. No symptoms of oxygen toxicity 
were noted in five hours of 100 percent oxy- 
gen breathing at pressures from 0.3 to 2.5 
atmospheres. 
1195. Behnke, A. R. Effects of nitrogen and oxygen 
on consciousness, pp. 117-131 in: Environmental effects on 
consciousness. Edited by K. E. Schaefer. The MacMillan 
Company, New York, 1962, 146 pp. 
1196. Bennett, P. B. Flicker fusion frequency and 
nitrogen narcosis. A comparison with EEG changes and 
the narcotic effect of argon mixtures. Gt. Brit. MRC, 
RNPRC, UPS. Rept. R.N.P. 59/935, U.P.S. 176, April 1958, 
12 pp. 
1197. Bennett, P. B. Comparison of the effects of 
drugs on nitrogen narcosis and oxygen toxicity in rats. 
Life Sci., 1962, 12: 721-727. 
1198. Bennett, P. B. Prevention in rats of narcosis 
produced by inert gases at high pressures. Amer. J. 
Physiol, 1963, 205: 1013-1018. 
1199. Bennett, P. B. Neuropharmacologic and neuro- 
physiologic changes in inert gas narcosis, pp. 209-225 in: 
Second symposium on underwater physiology. Edited by 
C. J. Lambertsen and L, J. Greenbaum, Jr. National Re- 
search Council, Washington, D.C. N.R.C. Publication 1181, 
1963, 296 pp. 
1200. Bennett, P. B. and A. V. C. Cross. The fusion 
frequency of flicker and nitrogen saturation. Gt. Brit. 
MRC, RNPRC, UPS. Rept. R.N.P. 60/999, U.P.S. 191, 
December 1959, 6 pp. 
1201. Bennett, P. B. and A. V. C. Cross. Alterations 
in the fusion frequency of flicker correlated with electro- 
encephalogram changes at increased partial pressures of 
nitrogen. J. Physiol, 1960, 151: 28P-29P. 
1202. Bennett, P. B., A. N. Dossett and D. J. 
Kidd. Prevention in rats of the narcotic effect produced 
by inert gases at high partial pressure. Gt. Brit. MRC, 
RNPRC, UPS. Rept. R.N.P. 60/998, U.P.S. 190, October 
1959, 7 pp. 
1203. Bennett, P. B., A. N. Dossett and D. J. Kidd. 
The effect of rate of increasing pressure on the narcosis 
produced in rats by high partial pressures of oxygen and 
nitrogen. Gt. Brit. MRC, RNPRC, UPS. R.N.P. 60/1001, 
U.P.S. 192, June 1960, 12 pp. 
1204. Bennett, P. B. and A. Glass. The electro- 
encephalograph and narcosis under high partial pressures 
of nitrogen and isonarcotic concentrations of nitrous oxide. 
Gt. Brit., MRC, RNPRC, UPS. Rept. R.N.P. 59/937, 
U.P.S. 170, December 1957, 29 pp. 
1205. Bennett, P. B. and A. Glass. Electroencephalo- 
graphic and other changes induced by high partial pres- 
sures of nitrogen, EEG din. Neurophysiol., 1961, 13: 91-98. 
1206. Burnett, W. A. The problem of nitrogen nar- 
cosis. J.R. nav. med. Serv., 1955, 41: 188-192. 
1207. Ch’un, C. Vliianie povyshennogo davleniia 
azota na reflektornuiu deiatel’nost’ spinnogo mozga. [The 
effect of raised nitrogen pressure on the reflex activity of 
the spinal cord.] Sechenov J. Physiol., 1959, 45: 605-609. 
1208. Fenn, W. O. Physiological effects of high pres- 
sures of nitrogen and oxygen. Circulation. 1961, 26 (Sup- 
pi.): 1135-1143. 
1209. Hesser, C. M. The role of nitrogen in breath- 
holding at increased pressures, pp. 327-334 in: Man’s 
dependence on the earthly atmosphere. Edited by K. E. 
Schaefer. The MacMillan Company, New York, 1962, 416 
pp. 
1210. Heser, C. M. Measurement of inert gas narcosis 
in man. pp. 202-208 in: Second symposium on underwater 
physiology. Edited by C. J. Lambertsen and L. J. Green- 
baum, Jr. National Research Council, Washington, D.C. 
N.R.C. Publication 1181, 1963, 296 pp. 
1211. Kiessling, R. J. and C. H. Maag. Perform- 
ance impairment as a function of nitrogen narcosis. U.S. 
Navy. Naval Weapons Plant, EDU. Project NS 185-005, 
sub task no. 5, test no. 12, 1 June 1960, 19 pp. 
1212. Kiessling, R. J. and C. H. Maag. Performance 
impairment as a function of nitrogen narcosis. J. appl. 
Physiol, 1962, 46: 91-95. 
1213. Lambertsen, C. J. Harmful effects of oxygen, 
nitrogen, carbon dioxide, and carbon monoxide. Nitrogen 
narcosis, pp. 719-720 in; Medical physiology. Edited by 
P. Bard, C. V. Mosby Company, St. Louis, 1961, 1339 pp. 
1214. Lanphier, E. H. Influence of increased ambient 
pressure upon alveolar ventilation, pp. 124-133 in: Sec- 
ond symposium on underwater physiology. Edited by C. J. 
Lambertsen and L. J. Greenbaum, Jr. National Research 
Council, Washington, D.C. N.R.C. Publication 1181, 1963, 
296 pp. 
1215. Lanphier, E. H. and D. E. Busby. Alveolar 
and arterial PCOa in man under increased ambient pres- 
sures. XXII Inter. Congr. physiol. Sci., Leiden, 1962, 2: 
Abstr. 301. 
1216. Miles, S. The nitrogen narcosis hazard and the 
self contained diver. Gt. Brit. MRC, RNPRC, UPS. Rept. 
R.N.P. 60/995, U.P.S. 184, May 1959, 4 pp. 
1217. Miles, S. Nitrogen narcosis, pp. 100-116 in; 
Underwater medicine. J. J. Lippincott Co., Philadelphia, 
1962, 328 pp. 
1218. Miller, S. L. A theory of inert gas narcosis, 
pp. 226-240 in: Second symposium on underwater physi- 
ology. Edited by C. J. Lambertsen and L. J. Greenbaum, 
Jr. National Research Council, Washington, D. C. N.R.C. 
Publication 1181, 1963, 296 pp. 
1219. Rahn, H. The role of N2 gas in various biological 
processes with particular reference to the lung. Harvey 
Led., 1961, 55: 173-199. INERT GASES—KRYPTON 
1220-1232 
1220. Rashbass, C. The unimportance of carbon di- 
oxide as a cause of nitrogen narcosis. Gt. Brit. MRC, 
RNPRC, UPS. Rept. R.N.P. 55/854, U.P.S. 153, October 
1955, 8 pp. 
1221. Taylor, H. J. Neurological effects of nitrogen. 
pp. 47-52 in Environmental effects on consciousness. Edited 
by K. E. Schaefer. The MacMillan Company, New York, 
1962, 146 pp. 
1222. U.S. Navy. Nitrogen narcosis, pp. 70 in: U.S. 
Navy Diving Manual. BuShips, NAVSHIPS 250-538, 1958- 
1959, 433 pp. 
C. XENON 
The anesthetic properties of xenon have been 
studied in both animals and human subjects by 
Cullen and Gross (1223) 1951. Human subjects 
inhaled either 50-50 mixtures of xenon and oxy- 
gen or 50-50 mixtures of nitrous oxide and oxy- 
gen from a closed system spirometer with soda 
lime in the circuit. Oxygen was added according 
to the metabolic requirements of the individual. 
Pain threshold measurements indicated a uni- 
form 15 percent increase in pain threshold with 
either gas mixture. Each subject reported more 
pronounced subjective symptoms of narcosis with 
the xenon mixture than with nitrous oxide. Two 
human subjects who inhaled a mixture contain- 
ing 70 percent xenon and 30 percent oxygen 
for three minutes experienced pronounced nar- 
cotic effects with partial loss of consciousness. It 
appeared that xenon had anesthetic properties 
approximately equivalent to ethylene. 
The basis of the anesthetic action of xenon is 
not understood. Comparative in vitro studies of 
guinea pig brain oxidations, as influenced by 
xenon and nitrous oxide and conducted by 
Pittinger, Featherstone, Cullen and Gross (1228) 
1951, have shown that xenon and nitrous oxide 
in 80-20 mixtures with oxygen did not suppress 
in vitro oxygen uptake of guinea pig brain 
tissue, either before or after addition of glucose 
as a substrate. The addition of the substrate did 
result in significant increases in oxygen consump- 
tion but no significant difference existed among 
80-20 xenon-oxygen, nitrous oxide-oxygen, or 
nitrogen-oxygen mixtures in this respect. 
1223. Cullen, S. C. and E. G. Gross. Anesthetic prop- 
erties of xenon in animals and human beings with some 
additional observations on krypton. Fed. Proc., 1951, 10: 
290. 
1224. Cullen, S. C. and E. G. Gross. The anesthetic 
properties of xenon in animals and human beings, with 
additional observations on krypton. Science, 1951, 113: 
580-582. 
1225. Featherstone, R. M. Anesthesia: Xenon, pp. 
22 in: Medical physics. Vol. III. O. Glasser, Editor. Year 
Book Publishers, Chicago, 1960, 754 pp. 
1226. Levy, L. and R. M. Featherstone. The effect 
of xenon and nitrous oxide on in vitro guinea pig brain 
respiration and oxidative phosphorylation. J. Pharmacol., 
1954, 110: 221-225. 
1227 Morris, L. E., J. R. Knott and C. B. Pit- 
tinger. Electroencephalographic and blood gas observa- 
tions in human surgical patients during xenon anesthesia. 
Anesthesiology, 1955, 16: 312-319. 
1228. Pittinger, C. B., R. M. Featherstone, S. C. 
Cullen and E. G. Gross. Comparative in vitro study of 
guinea pig brain oxidations as influenced by xenon and 
nitrous oxide. J. Lab. din. Med., 1951, 38: 384-387. 
1229. Pittinger, C. B., E. F. Van Epps and R. A. 
Utterback. Xenon in encephalography. Neurology, 1956, 
6: 429-443. 
D. KRYPTON 
Krypton is referred to here because it is an 
inert gas which can be readily used for satura- 
tion and desaturation studies of animals or men 
at sea level or under pressure. The gas is par- 
ticularly convenient because it can be readily 
tagged and has a short half life. Krypton is thus 
a potentially important research tool in that it 
can be used to follow the distribution of inert 
gases throughout the body. No evidence has 
been found in the literature of any physiological 
effect of krypton at sea level pressures. The radio- 
active isotope krypton 85 has been used to meas- 
ure blood flow (Brun, Crone, Davidsen, Fab- 
ricius, Hansen, Lassen and Munck (1230), 1955) 
coronary blood flow (Hansen, Haxholdt, Hus- 
feldt, Lassen, Munck, S0rensen and Winkler 
(1231), 1956) and cerebral blood flow (Lassen 
and Munck (1232), 1955). 
1230. Brun, C., C. Crone, H. G. Davidsen, J. Fab- 
ricius, A. T. Hansen, N. A. Lassen and O. Munck. 
Renal blood flow in anuric human subject determined by 
use of radioactive krypton 85. Proc. Soc. exp. Biol., N.Y., 
1955, 89: 687-690. 
1231. Hansen, A. T., B. F. Haxholdt, E. Husfeldt, 
N. A. Lassen, O. Munck, H. R. S0rensen and K. 
Winkler. Measurement of coronary blood flow and cardiac 
efficiency in hypothermia by use of radioactive krypton 85. 
Scand. J. din. Lab. Invest., 1956, 8: 182. 
1232. Lassen, N. A. and O. Munck. The cerebral 
blood flow in man determined by the use of radioactive 
krypton. Acta physiol, scand., 1955,33: 30-49. SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
1233-1239 
1233. Lassen, N. A. and O. Munck. Cerebral blood 
flow in arteriovenous anomalies of the brain determined 
by use of radioactive krypton 85. Acta psychiat., Kbh., 1956, 
31: 71-80. 
1234. Long, R. T. L., E. Braunwald and A. G. 
Morrow. Intracardiac injection of radioactive krypton. 
Clinical applications of new method for characterization 
of circulatory shunts. Circulation, 1960, 21: 1126-1133. 
1235. Long, R. T. L. and W. F. Cornell. Experi- 
mental detection of left-to-right circulatory shunts with 
injection of krypton85. Proc. Soc. exp. Biol., N.Y., 1959, 
101: 836-838. 
1236. Long, R. T. L„ J. A. Waldhausen, W. P. 
Cornell and R. J. Sanders. Detection of right-to-left 
circulatory shunts: A new method utilizing injections of 
krypton85. Proc. Soc. exp. Biol., N.Y., 1959, 102: 456-458. 
1237. Sanders, R. J. Use of a radioactive gas (Kr85) in 
diagnosis of cardiac shunts. Proc. Soc. exp. Biol., N.Y., 1958, 
97: 1-4. 
1238. Sanders, R. J. and A. G. Morrow. The iden- 
tification and quantification of left-to-right circulatory 
shunts. A new diagnostic method utilizing the inhalation 
of a radioactive gas, Kr85. Amer. J. Med., 1959, 26: 508-516. 
1239. Steinfield, W. Suppression of gastric acidity by 
radio krypton. Proc. Soc. exp. Biol., N.Y., 1952, 81: 636-638. 
E. HELIUM 
The use of helium-oxygen mixtures has not 
only increased the depths to which divers can 
descend, but it has also greatly enhanced their 
performance at these depths. By the use of 
helium-oxygen mixtures the respiratory effort is 
greatly diminished. The practical uses of helium- 
oxygen mixtures in diving are discussed in a later 
section. 
The use of helium-oxygen mixtures in alleviat- 
ing symptoms in patients with bronchial asthma 
has been examined by Schiller, Lowell, Lynch 
and Franklin (1249) 1955. In severely ill patients 
no significant change was observed in expiratory 
reserve volume, inspiratory capacity, vital ca- 
pacity or in speed of flow during performance of 
the vital capacity testing. On the other hand in 
the same measurements using less seriously ill 
patients slightly larger values were obtained with 
helium, thus the use of helium has definite 
therapeutic limitations. 
The use of helium-oxygen mixtures, because 
of lower density, causes a characteristic high- 
pitched “Donald Duck” voice production with 
important effects on speech intelligibility. Sev- 
eral studies have been undertaken to examine 
this problem. Sergeant (1232) 1963, carried out 
a study to see if the “Donald Duck” voice effect 
would remain on prolonged exposure to helium- 
oxygen mixtures or whether adaptation would 
occur. In general, the effects tend to persist. 
However, Sergeant reported in sea level studies 
that intelligibility showed deterioration after 
two days of exposure to helium-oxygen mixtures, 
but by the fourth to sixth day’s exposure a re- 
turn to more normal speech was found. For 
further studies on speech quality and frequency 
during respiration of helium-oxygen mixtures, 
papers by Sergeant (1231) 1963, Dublin, Baldes 
and Williams (1243) 1940, and Beil (1240) 1962, 
should be consulted. Research is needed on the 
development of electronic speech unscramblers to 
convert this “Donald Duck” type of voice into 
more intelligible speech. 
Cook and South (1242) 1953, have shown 
that helium increases the rate of oxygen con- 
sumption of mouse brain slices in vitro. The 
same authors (1233) 1953, found that the use 
of helium relative to nitrogen under anaerobic 
conditions causes a depression of the glycolytic 
rates in both mouse liver slices and diaphragm. 
There is also an increase in the carbon dioxide 
evolution and lactic acid production of mouse 
liver homogenates oxidizing either glucose and 
hexose diphosphate, or hexose diphosphate alone. 
It is hypothesized that helium does not alter the 
substrate utilized by the tissue. Also it is believed 
that the gas interferes in some way with the 
cyanide-cytochrome oxidase bond, but may not 
affect cytochrome oxidase in the absence of 
cyanide. The citric acid cycle is not subject to 
the influence of helium in tissue slices but is 
altered in an unexplained fashion in homogen- 
ates. It is postulated that a rearrangement of 
particular surfaces may be the significant factor 
here. The glycolytic process is the site of both 
an inhibitory and an acceleratory effect of helium. 
The locus of the inhibition lies above the aldolase 
reaction and that of the acceleration between 
the aldolase and enolase reactions. 
Cross (1244) 1953, has reported the effect of 
increased atmospheric pressures and inhalation 
of 95 percent oxygen and helium-oxygen mix- 
tures on the viability of the bowel wall and 
the absorption of gas in closed loop obstructions 
in dogs. Comparisons were made in groups of 
dogs breathing air at pressures of 1 to 4 atmos- 
pheres for 6 to 24 hours; breathing 95 percent INERT GASES—HELIUM 
1240-1244 
oxygen at pressures of 1 to 2.5 atmospheres for 
periods of 6 to 12 hours; breathing helium-oxygen 
mixtures at 1 to 2 atmospheres for periods of 
6 to 24 hours with observations on the effect 
of increased atmospheric pressure on the mainte- 
nance of viability of the bowel in closed loop ob- 
structions. It was found that the absorption 
rate of injected air from closed loops was in- 
creased under conditions of increased atmospheric 
pressure no matter what gas had been inhaled, 
the magnitude of the increase being directly 
proportional to the increase in atmospheric pres- 
sure. Ninety-five percent oxygen inhalation 
caused the best absorption rates of gas from the 
closed loops whether breathed at 1 atmosphere or 
under conditions of increased pressure. The 
limiting factor in the use of oxygen was the on- 
set of oxygen intoxication. The dogs tolerated 
95 percent oxygen at 2 atmospheres for 6 hours, 
or for 12 hours at 1 atmosphere, but the incidence 
of oxygen intoxication was high in those dogs 
breathing oxygen for 6 hours at 214 atmospheres 
or for 12 hours at 2 atmospheres of pressure. 
This oxygen intoxication could be avoided when 
the dogs breathed helium-oxygen mixture, but 
the absorption rates of the bile gas were up to 
17 percent less than with oxygen breathing for 
any given pressure or time period. The helium 
diffused into the bowel as the nitrogen diffused 
out, and the distention was maintained. Not 
only was there an increased absorption of gas 
from the bowel under conditions of increased 
pressure but also the viability of the bowel wall 
was well maintained. In a study of the mecha- 
nism by which helium increases metabolism in 
small mammals Leon and Cook {1248) 1960, 
studied the oxygen consumption of male rats 
determined at three different ambient tempera- 
tures in air and the equivalent helium-oxygen 
mixture. It was found that when the ambient 
temperature is near the skin temperature of the 
rat the effect of helium is insignificant. If the 
ambient temperature is lowered helium induces 
an increased metabolic rate over air at the same 
temperature. Since helium has a thermal con- 
ductivity about six times greater than nitrogen 
it was concluded that the accelerated metabolism 
is in response to greater heat loss in the presence 
of helium and that the magnitude of this re- 
sponse is proportional to the thermal gradient 
between the animal and the environment. Young 
and Cook (1256) 1953, have reported on the 
effect of helium on the gas exchange of mice as 
modified by body size and thyroid activity. Two 
groups of male mice, one averaging 25 games 
in weight and the other 30 grams, were tested 
in air and in a mixture of 20 percent oxygen 
in helium. Helium accelerated the oxygen con- 
sumption in both groups. The degree of accelera- 
tion was greater in the heavier group in which 
the standard metabolism in air was lower. 
Similar experiments were performed with normal 
mice, with mice which had been radiothyroidec- 
tomized with I131, and with mice which had been 
fed heavy doses of desiccated thyroid gland. The 
acceleration of oxygen consumption due to 
helium was greatest in the slowly metabolizing 
thyroidectomized group (intermediate with the 
normals and least with the hyperthyroid ani- 
mals) . It was concluded that the effect of helium 
is inversely proportional to the level of the stand- 
ard metabolism regardless of the nature of the 
factors which initially determine that level. An 
interesting new biological effect of helium has 
been reported by Schreiner, Gregoire and Lawrie 
{1250) 1962, in studies which show a close cor- 
relation of growth rate with the molecular weight 
of the inert gas in a gaseous mixture containing 
oxygen. The mold neurospora crassa was grown 
in gaseous environments of helium, neon, argon, 
krypton, zenon or nitrogen containing 5 percent 
oxygen. There was a close correlation of growth 
rate R (in millimeters/hour at 30°C.) with 
molecular weight MW (MW of the chemically 
inert gas). This relationship is described by the 
empirical equation: R = 3.88 — 0.1785 (MW) 1/2- 
1240. Bell, R. G. Frequency analysis of vowels pro- 
duced in a helium-rich atmosphere. /. acoust. Soc. Amer., 
1962, 34: 347-349. 
1241. Briscoe, W. A. Further studies on the intra- 
pulmonary mixing of helium in normal and emphysema- 
tous subjects. Clin. Sci., 1952, 11: 45-58. 
1242. Cook, S. F. and F. E. South, Jr. Helium and 
comparative in vitro metabolism of mouse tissue slices. 
Amer. J. Physiol., 1953, 173: 542-544. 
1243. Cook, S. F., F. E. South, Jr. and D. R. 
Young. Effect of helium on gas exchange of mice. Amer. 
J. Physiol., 1951 164: 248-250. 
1244. Cross, F. S. The effect of increased atmospheric 
pressures and the inhalation of 95 per cent oxygen and 
helium-oxygen mixtures on the viability of the bowel ivall 
and the absorption of gas in closed loop obstructions. 
Thesis (Med.), University of Minnesota, 1953. 1245-1257 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
1245. Dublin, W. B., E. J. Baldes and M, M. D. 
Williams. Voice changes with a mixture of helium and 
oxygen. Proc. Mayo Clin., 1940,15: 586-588. 
1246. Grape, B., E. Channin and J. M. Tyler. The 
effect of helium and oxygen mixtures on pulmonary resist- 
ances in emphysema. Amer. Rev. resp. Dis., 1960, 81: 823- 
829. 
1247. Green, R. and B. L. Day. Preoperative admin- 
istration of helium in respiratory obstruction. Lancet, 1954, 
266: 602-603. 
1248. Leon, H. A. and S. F. Cook. A mechanism by 
which helium increases metabolism in small mammals. 
Amer. J. Physiol., 1960, 199: 243-245. 
1249. Schiller, I. W., F. C. Lowell, M. T. Lynch 
and W. Franklin. The effect of helium-oxygen mixtures 
on pulmonary function in asthmatic patients. J. Allergy, 
1955,26: 11-15. 
1250. Schreiner, H. R., R. C. Gregoire and J. A. 
Lawrie. New biological effect of the gases of the helium 
group. Science, 1962,156: 653-654. 
1251. Sergean, R. L. Speech during respiration of a 
mixture of helium and oxygen. Aerospace Med., 1963, 54: 
826-829. 
1252. Sergeant, R. L. Speech intelligibility during 
prolonged exposure to helium-oxygen. U.S. Navy, Sub- 
marine Base, New London, Conn. Medical research labora- 
tory. Kept. 65-8, MR 005.14-1001-A.02, 13 May 1963, 6 pp. 
1253. South, F. E., Jr. and S. F. Cook. Effect of 
helium on the respiration and glycolysis of mouse liver 
slices. J. gen. Physiol., 1953, 56: 513-528. 
1254. Trowbridge, W. V., A. E. Bayless and J. D. 
French. An inquiry concerning the practical value of 
helium as an encephalographic medium. J. int. Coll. Surg., 
1954, 21: 441-446. 
1255. Walser, M. and S. N. Stein. Determination of 
specific gravity of intact animals by helium; comparison 
with water displacement. U.S. Navy. National Naval Medi- 
cal Center, Bethesda, Maryland. Naval medical research 
institute. Project NM 000 018.07, Memorandum Rep. 55-7, 
22 April 1953, 6 pp. 
1256. Young, D. R. and S. F. Cook. The effect of 
helium on the gas exchange of mice as modified by body 
size and thyroid activity. J. cell. comp. Physiol., 1953, 42: 
319-325. 
1257. Anon. Living on oxygen and helium 200 feet 
under the sea. New Scient., 1962, 15: 596. 
VI. HEAT AND HUMIDITY 
PROBLEMS 
A. PHYSIOLOGICAL EFFECTS OF RAISED 
TEMPERATURES 
There are many compensatory mechanisms 
which serve to protect the organism from high 
heat levels and to maintain the constancy of the 
internal temperature of the body. Under certain 
conditions of stress, as in violent exercise, ele- 
vated temperatures of the body are observed 
with no untoward effects. Although rectal tem- 
peratures as high as 106-108°F. have been ob- 
served in short foot races in athletes without 
harm, such hyperpyrexia if prolonged for several 
hours leads to thermal injury of certain body 
cells, particularly in the central nervous system. 
Dehydration and circulatory collapse may result 
from prolonged heat exposure. Compensatory 
mechanisms leading to increased blood volume 
and re-direction of circulation through the peri- 
phery, as well as loss of body fluid stores, may 
lead to circulatory shock even before the body 
temperature begins to rise significantly (heat 
collapse). In some instances of severe exposure 
to heat associated with muscular work there may 
be rapid failure of circulatory adjustments and 
sweating so that true body hyperthermia results 
(heat stroke). For a general review of pathologi- 
cal effects of heat on man a review by Carter 
(1262) 1960, may be consulted. In a study of 
cardiovascular responses to acute heat stress, 
Marshall, Koroxenidis and Shepherd (1277) 
1961, have examined cardiac output, digital heat 
flow and forearm blood flow simultaneously in 
healthy subjects. Initially with subjects cool the 
cardiac index was 3.00 liters, the heart rate 66, 
the stroke volume 85 ml. and digital heat flow 
30 BTU/M.2/hr. (mean values). Indirect heat- 
ing was then imposed for 45 minutes. The h«_at 
flow rapidly increased to a plateau when sweat- 
ing was first noted 15 minutes after heating be- 
gan. In contrast, gradual and parallel increases 
in output and forearm flow occurred throughout 
the 45 minute period. At the end when the 
subjects were sweating profusely and the oral 
temperature was 99.5°F. or more, cardiac index 
rose to 4.70 liters, the heart rate to 94, the stroke 
volume to 95 ml. and the heat flow to 240 
BTU/M.2/hr. Thus increased skin blood flow 
during heat stress is sufficient to increase cardiac 
output by more than 50 percent, and this in- 
crease in output is achieved mainly by tachycar- 
dia. Kanter (1270) 1956, has experimentally 
investigated glucose regulation in dogs exposed 
to high environmental temperatures. Exposure 
of 12 dogs to 120°F. four hours without access 
to water resulted in an average fall of whole 
blood glucose of 19 percent and of plasma glu- 
cose by 13 percent, in spite of an average final 
dehydration of 5.6 percent in body weight. One HEAT AND HUMIDITY—PHYSIOLOGICAL EFFECTS 
might expect dehydration to cause an increase in 
concentration, yet under the experimental con- 
ditions imposed hypoglycemia resulted. That 
the fall in glucose levels was the result of de- 
hydration per se therefore seemed unlikely. To 
test this point, seven experiments were conducted 
in which dogs were exposed to heat but the water 
balance was maintained by administration of 
water through a stomach tube. Here hypo- 
glycemia again was found but the regime of the 
experiment was not responsible for the hypo- 
glycemia. It appears that the fall in glucose 
concentration is associated with the increase in 
deep body temperature, for when dogs were ex- 
posed to milder air temperatures (100°F.) de- 
hydration, but only slight elevation in rectal 
temperature, occurred with no fall in glucose 
levels. A finding of hyperglycemia in man ex- 
posed to desert-like conditions has been reported 
(in contrast to the hypoglycemia found in dogs), 
and may possibly be explained by the presence 
of dehydration but with an absence of elevation 
of deep body temperature in human studies. 
Salt losses of men working in hot environments 
have been examined by Weiner and van Heynin- 
gen {1285) 1952. Loss of chlorides in sweat and 
urine occurs in human subjects working in hot 
conditions for short periods. Acclimatization to 
heat is accompanied by a decrease in chloride 
concentration of body sweat, only if negative 
chloride balance is induced by restriction of 
chloride intake. Sweating for short periods (two 
hours) in unacclimatized subjects brings about 
compensatory reduction of urinary chlorides 
manifested after the subject leaves the hot en- 
vironment. This reduction is so great that total 
loss of chloride may be less on days in which 
sweating occurs. Malhotra, Sharma and Sivara- 
man {1276) 1959, have presented data on salt 
requirements in the tropics based on observations 
on 24 acclimatized Indian subjects given diets 
containing 16.2, 11.2, 8.7, 6.2 and 3.1 gms. of salt 
per day. The adequacy of the salt diet was tested 
by measurements of chloride secretion in the 
urine, by changes observed in thiocyanate space 
and plasma chloride concentration at the start 
and after the subjects had been on the restricted 
salt diet for a week. Sweat and chloride losses 
in different environmental temperatures were 
studied. The salt requirements of subjects walk- 
ing for two hours in the sun at a speed of about 
2.5 miles per hour was found to be about 6.2 
gms. per day when the mean maximum environ- 
mental temperature was 100.7°F. (dry bulb). 
The requirement was found to increase by 0.063 
gm. per degree rise in dry bulb temperature for 
two hours exercise. Kanter has reported a de- 
crease in glomerular filtration rate and renal 
plasma flow as a result of hyperthermia. This 
study was carried out on anesthetized dogs using 
creatinine clearance to measure the glomerular 
filtration rate and PAH clearance to measure 
renal plasma flow. The glomerular filtration rate 
in eight mildly dehydrated dogs fell from a con- 
trol value of 67.6 ± 5.2 ml. per minute at a 
rectal temperature of 39.0°C. to a glomerular 
filtration rate of 38.5 -f- 10.1 ml. per minute at a 
rectal temperature of 41.6°C. at the end of 4.5 
hours of exposure to heat. The final dehydration 
averaged -1.0 percent body weight. The fall in 
glomerular filtration rate and renal plasma flow 
was not considered by the author to be due to de- 
hydration since in a group of five hydrated dogs 
(with -j-4 percent body weight at the end) 
similar results were observed. No change in 
glomerular filtration rate or renal plasma flow 
occurred in either hydrated or dehydrated dogs 
until severe hyperthermia (greater than 41.2°C.) 
was present. This alteration did not occur before 
3.5 to 4.0 hours of exposure to heat. Although 
there was a decline in the blood pressure towards 
the end of each exposure in both groups, the 
decrease in glomerular filtration rate and renal 
plasma flow preceded any marked fall in blood 
pressure. The dehydrated group exhibited an in- 
crease in hematocrit at the end of 4.5 hours ex- 
posure to heat. There was a gradual increase in 
plasma volume. The decrease in glomerular 
filtration rate and renal plasma flow demon- 
strated in these studies appears to the author to 
be directly related to the hyperthermia. 
In an attempt to elucidate some of the 
mechanisms underlying the process of acclimati- 
zation to heat in man, Bass, Kleeman, Quinn, 
Henschel and Hegnauer {1259) 1955, carried out 
studies of the effects of prolonged heat exposure 
on body fluid distribution, adrenocortical ac- 
tivity, sweat composition and nitrogen and elec- 
trolyte metabolism. Five young men were accli- 
matized to heat by living and working for a SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
period of 14 consecutive days in a chamber 
maintained at 120°F. during 12 daytime hours 
each day, and at 100°F. during the nights. The 
experimental period of heat exposure was pre- 
ceded by a three weeks control period at 76°F. 
and was followed by an 11 days recovery period 
at 76°F. The subjects performed standard work 
tasks daily and measurements were made of 
antipyrine, thiocyanate and T-1824 spaces, sweat 
concentration of sodium, chloride, potassium, 
nitrogen and creatinine. Sodium and electrolyte 
balance and indices of adrenocortical activity 
(circulating eosinophils and urinary 17-ketoste- 
roids) as well as pulse rates and rectal tempera- 
ture were examined. Progressive dehydration 
and salt deficiency were minimized by replacing 
sweat losses with 0.2 percent saline. The authors 
observed that successful acclimatization to heat 
was obtained within the first week. The sweat 
glands progressively excreted more water relative 
to all solutes measured during the first week with 
little change thereafter. Isotonic expansion of ex- 
tracellular fluid in all subjects was accomplished 
by renal retention in the first four days of sodium 
and chloride in excess of that required to sup- 
port swreat losses of these electrolytes. The 
authors concluded that the major physiological 
adaptation resulting in improved ability to work 
in the early days of acclimatization to heat are 
probably cardiovascular in nature. The kidney 
has an important role in these adaptations. It 
conserves sodium and chloride in excess of 
amounts required to compensate for sweat losses 
with the result that plasma and interstitial fluid 
volumes are isotonicly expanded. It was con- 
cluded that increased activity of the pituitary- 
adrenal system is not a prepotent factor in the 
adaptation observed in this study. That changes 
in the excretion of urinary adrenocortical steroids 
during heat stress can occur has been demon- 
strated by Heilman, Collins, Gray, Jones, Lun- 
non and Weiner (1266) 1956. These investi- 
gators studied the output of urinary adrenocorti- 
coids in 32 healthy subjects between the ages of 
19 and 45 years before, during and after exposure 
to high environmental temperatures. While there 
was no significant change in the excretion of 
17-hydroxycorticoids, cortisone and cortisol, or 
of tetrahydrocortisone and tetrahydrocortisol, 
there was a significant increase in the output of 
aldosterone. 
Respiratory changes resulting from conditions 
causing a rise in body temperature were studied 
by Barltrop (1238) 1954, in 12 subjects placed 
in a circulated bath. Rectal and oral tempera- 
tures were recorded. It was found that a 2°C. 
rise in body temperature caused an average in- 
crease of 3.8 liters in the minute volume (with 
a range from 0.2 to 14.2 liters). The Pc02 
diminished by an average of 4.8 mm. with a range 
from 1.9 to -|- 26.8 mm. Hg. 
As Ranter (1269) 1953, has concluded, the 
kidneys in dogs exposed to heat conserve both 
salt and water. In these experiments the hot 
room was designed to maintain an air temper- 
ature of 48°C. which was sufficient to dehydrate 
the animals at a rate of approximately 1.0 per- 
cent body weight per hour. Fresh air was con- 
stantly drawn through a thermostatically regu- 
lated steam heating unit and blown into the hot 
room so that the relative humidity never attained 
levels that would limit evaporation. The author 
found no significant difference in urine flows in 
the hot room with or without access to water and 
indeed, while a dog was in negative weight bal- 
ance and given water, there was no stimulation 
of diuresis, unless the water load exceeded the 
deficit. The urine chloride concentration re- 
mained below the plasma chloride concentration 
while the dog was in the hot room, with or with- 
out access to water. Dehydration up to 10 per- 
cent body weight had no appreciable effect on 
urine flows nor on the low urine chloride con- 
centration. This low urine chloride concentra- 
tion was not considered to be due to dehydration 
since heat by itself had a depressing effect on 
chloride excretion. High environmental tem- 
perature does not limit the ability of the kidneys 
to concentrate exogenous chloride. The urine 
chloride concentration also rises when the dog is 
removed to a cool environment. Drinking plays 
a major role in the regulation of imbalance in 
the hot room, for the addition of water alone 
usually suffices to restore balance rapidly. Dogs 
with all the available water they wish to drink 
failed to maintain control body weight while in 
the hot room, since they did not actually drink 
enough water during exposure to heat. The 
drinking pattern showed individual character- HEAT AND HUMIDITY—PHYSIOLOGICAL EFFECTS 
istics. Some dogs took fewer large drafts, others 
many small drafts. However, the total water in- 
take was dependent on the nature of the experi- 
ment and not on the drinking pattern. 
Human heat loss during exercise at various en- 
vironmental temperatures has been studied by 
Minard, Kitzinger and Benzinger (1278) 1957. 
Heat loss was recorded before, during and after 
standard 40 minute exercises performed by each 
of two subjects in a human gradient calorimeter. 
The subjects were exposed to five temperatures 
ranging from 29.5° to 21.1°C. In each test the 
ergometer registered 23-24 kilocalories of ex- 
ternal work. At 29.5°C. evaporative heat loss 
rose steeply as work began, reaching a high pla- 
teau in 20 minutes. Radiative and convective 
heat loss contributed essentially nothing to the 
excess heat appearing during work and recovery. 
The total excess heat was 100 kilocalories. At 
21.1°C. evaporative heat loss during work rose 
only slightly, the major fraction of excess heat 
being radiative and convective. The total excess 
heat was only 24 kilocalories. Thus in a cool en- 
vironment heat produced during work is largely 
retained in the body and might serve to restore 
heat to tissues cooled during the preceding rest 
period. 
For a report of physiological observations on 
men working under conditions of high humidity 
and low air movement, a paper by Ladell (1272) 
1955, may be consulted. The conditions under 
which the studies were carried out were in a deep 
West African gold mine in which heat stress 
was avoided by frequent rests and enforced with- 
drawal during blasting at midshift to cooler, 
well-ventilated parts of the mine. Men on an 
eight hour shift in District A (dry bulb tempera- 
ture 93 to 93.5°F.; wet bulb temperature 92 to 
92.5°F.; air movement 60 to 70 ft. per minute, 
effective temperature 91.59°F.) and in District B 
(dry bulb 95.5°F.; wet bulb 93.5°F,; air move- 
ment 80 to 90 feet per minute, effective tempera- 
ture 93.0°F.) and truckers (dry bulb 86°F.; wet 
bulb 85°F. and air movement 200 feet per 
minute) were studied. The rectal temperature 
rise of 17 men in Districts A and B was 1.5 ± 
0.15°F. and in 5 truckers 1.5°F. The mean fall 
in 15 men from station to surface was 0.5 ± 
0.13°F. The overall weight loss in 22 men was 1.5 
Kg. ± 0.145. Truckers showed a slow steady rise 
in rectal temperature while the men in Districts 
A and B showed sharp rises during the beginning 
and end of the shifts with a lull or even a fall 
during the mid-shift period. In work tests there 
was no significant difference in temperature rise 
between novices and trained subjects. The pulse 
rates and sweat rates were higher in novices than 
in trained subjects. However, there was no evi- 
dence that the West African deep miners had an 
unusually high heat tolerance. 
The influence of thermal environments on re- 
covery from exposure to severe heat has been 
reported by Riedesel, Belding and Ross (1281) 
1957. In these studies semi-nude subjects were 
exposed for 30' minutes in heat conditions which 
resulted in the production of 0.6 liters of sweat 
and progressive rises of rectal temperature with 
an average of 100.6°F., skin temperature of 100°F. 
and heart rates up to 140 beats per minute. Re- 
covery from these exposures was observed during 
one hour of rest under four different environ- 
mental conditions: 
a) dry bulb 96°F. and vapor pressure 25 mm. Hg; 
b) dry bulb 86°F. and vapor pressure 25 mm. 
Hg; 
c) dry bulb 86°F. and vapor pressure 12 mm. Hg; 
d) dry bulb 76°F. and vapor pressure 12 mm. 
Hg- 
Greater strain accompanied recovery under con- 
dition a) while the differences under the other 
recovery conditions were significant in only a 
few instances. The trends consistently indicated 
progressively less strain as the temperature was 
lower and the conditions less humid. It did not 
seem to matter whether the subjects were clothed 
or semi-nude. 
With exposures to tolerable heat conditions, 
histopathological changes do not generally occur. 
Local exposure to heat, viz. testicles, definite 
disturbances were observed. For example, Stein- 
berger and Dixon found that 15 minute expo- 
sures of the testicles of rats to a temperature of 
45°C. produced a progressive destruction of the 
entire germinal epithelium, the earliest cytologic 
changes being observed in the spermatids. 
According to Ladell (1273) 1962, a full ac- 
climatization develops only when the environ- 
ment is hotter than the body, and interference 
with non-evaporative heat losses causes a skin 
temperature rise. This does not occur in the 1258-1285 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
wet tropics, which explains the apparent anomaly 
of relative unacclimatization under these condi- 
tions. Full acclimatization with sweating would 
be of no advantage because of poor evaporation 
consequent on high humidity and wastage of wa- 
ter and salt. 
1258. Barltrop, D. The relation between body tem- 
perature and respiration. J. Physiol., 1954, 125: 19-20P. 
1259. Bass, D. E., C. R. Kleeman, M. Quinn, A. 
Henschel and A. H. Hegnauer. Mechanisms of acclima- 
tization to heat in man. Medicine, 1955, 54: 323-380. 
1260. Belding, H. S. Acceptance of heat applied to 
human skin. Fed. Proc., 1959, 18: 9. 
1261. Burton, A. C., W. G. Leach and R. A. 
Snyder. A specific effect of humidity on the physiological 
responses to cold of unclothed men. Fed. Proc., 1955, 14: 
24. 
1262. Carter, E. T. Heat: pathologic effects on man. 
pp. 289-291 in: Medical physics. Vol. 111. O. Glasser, 
Editor. Year Book Publisher, Chicago, 1960, 754 pp. 
1263. Folk, G. E., E. W. Sybil and S. M. Horvath. 
Effects of confining perspiration near the skin. Fed. Proc., 
1954, 15: 45. 
1264. Fox, R. H., R. Goldsmith and H. E. Lewis. 
Acclimatization to heat in man by passive elevation of body 
temperature. XXII Inter. Congr. physiol. Sci., Leiden. 1962, 
2: Abstr. 669. 
1265. Hall, J. F. and J. W. Polte. Physiological in- 
dex of strain and body heat storage in hyperthermia. Fed. 
Proc., 1960, 19: 177. 
1266. Heilman, K., K. J. Collins, C. H. Gray, R. 
M. Jones, J. B. Lunnon and J. S. Weiner. The ex- 
cretion of urinary adrenocortical steroids during heat 
stress. J. Endocrin., 1956, 14: 206-216. 
1267. Hertig, B. A. and H. S. Belding. Rates of 
adjustment of sweating and body temperatures following 
exposure to heat. Fed. Proc., 1961, 20: 211. 
1268. lampietro, P. F. and E. R. Buskirk. Effects 
of high and low humidity on heat exchanges of lightly 
clothed men. J. appl. Physiol., 1960, 15: 212-214. 
1269. Kanter, G. S. Heat and hydropenia; their effects 
on thirst and chloride regulation in dogs. Amer. J. Physiol., 
1953, 174: 95-105. 
1270. Kanter, G. S. Heat and hypoglycemia in dogs. 
Fed. Proc., 1956,15: 104. 
1271. Kanter, G. S. The effect of hyperthermia on 
glomercular filtration rate and renal plasma flow. Fed. 
Proc., 1959, 18: 78. 
1272. Ladell, W. S. S. Physiological observations on 
men working in supposedly limiting environments in a 
West African gold-mine. Brit. J. industr. Med., 1955, 12: 
111-125. 
1273. Ladell, W. S. S! Temperature regulation in a 
hot wet climate. XXII Inter. Congr. physiol. Sci., Leiden. 
1962, 2: Abstr. 670. 
1274. Lamport, H. Tolerance to heat exposure of 
thirsting mammal. Fed. Proc., 1956, 15: 115. 
1275. Lind, A. R. and R. F. Hellon Assessment of 
physiological severity of hot climate. /. appl. Physiol., 1957, 
11: 35-40. 
1276. Malhotra, M. S., B. K. Sharma and R. Siva- 
raman. Requirements of sodium chloride during summer 
in the tropics. /. appl. Physiol., 1959,14: 823-828. 
1277. Marshall, R. J., G. T. Koroxenidis and J. T. 
Shepherd. Cardiovascular response to acute heat stress. 
Fed. Proc., 1961, 20: 130. 
1278. Minard, D., C. Kitzinger and T. H. Ben- 
zinger. Human heat loss during exercise at various en- 
vironmental temperatures. Fed. Proc., 1957, 16: 88. 
1279. Nottie, H. R. Effect of a hot, humid atmosphere 
on the pack fitness index. J. appl. Physiol., 1954, 7: 105- 
108. 
1280. Pepler, R. D. Extreme warmth and sensori- 
motor coordination. J. appl. Physiol., 1959, 14: 383-386. 
1281. Riedesel, M. L., H. S. Belding and D. M. 
Ross. Influence of thermal environments on recovery 
from exposure to severe heat. Fed. Proc., 1957, 16: 106. 
1282. Sharma, D. C. and N. D. Kehar. Effect of en- 
vironmental temperature and humidity on intake and 
digestion of nutrients. J. appl. Physiol., 1961, 16: 611-616. 
1283. Steinberger, E. and W. J. Dixon. Some ob- 
servations on the effect of heat on the testicular germinal 
epithelium. Fertil. Steril., 1959, 10: 578-594. 
1284. Strydom, N. B., J. F. Morrison, J. Booyens 
and J. Peter. Comparison of oral and rectal tempera- 
tures during work in heat. J. appl. Physiol., 1955-56, 8: 
406-408. 
1285. Weiner, J. S. and R. E. Van Heyningen. Salt 
losses of men working in hot environments. Brit. J. in- 
dustr. Med., 1952, 9: 56-64. 
B. PERFORMANCE 
The effects of drinking water or saline, or not 
drinking at all, and of taking salt alone, on fully 
acclimatized men working in a hot and humid 
environment have been investigated in a number 
of experiments by Ladell (1286) 1955. In some 
tests the amount of water drunk and/or of salt 
taken was equated to the amounts of these sub- 
stances lost in the sweat. In others saline of fixed 
strength was given in varying amounts. Sub- 
jective effects were more marked than were ob- 
jective effects. The chances of failure to complete 
a given task in the heat increased with increas- 
ing water deficit. Fatigue, usually of sudden on- 
set, was more pronounced when the water debt 
was high. Sweat rate tended to be lower in the 
men drinking saline. Abstention from water had 
no effect on the sweat rate until water debts of 
more than 2.5 liters had occurred. In this re- 
spect sweat secretion behaves similarly to urine 
excretion and salivation during dehydration. 
Thermal equilibrium was established at a higher COLD EXPOSURE PROBLEMS—PHYSIOLOGICAL EFFECTS 
1286-1290 
level in men who abstained from drinking than 
in those who did drink and in those not taking 
salt than in those taking salt. The heart rate in 
recovery increased with rectal temperature less 
rapidly when the subjects were taking salt or 
saline than when they were not drinking or drink- 
ing only water. In those taking salt the heart 
rates were faster at low rectal temperatures and 
slower at high rectal temperatures than in those 
taking water only. Exercise tolerance was better 
maintained by subjects when they drank water or 
saline than when they did not drink or took salt 
only. 
For a paper on the upper limits of thermal 
stress for human subjects the report by Largent 
and Ashe (1287) 1958, should be consulted. 
These authors have studied the problem of safe 
upper limits of thermal stress for workmen in 
Indian textile mills. They have suggested a line 
described by 85°F./85°F. and 110°F./82°F. (dry 
bulb/wet bulb temperatures), as upper safe 
limits of thermal stress for acclimatized workmen. 
The location of this line appears to have been 
reasonably a good choice and gives relatively wide 
margins of safety under the conditions studied. 
Somewhat lower limits may be desirable for un- 
acclimatized workmen. 
The problem of exposure to raised water tem- 
peratures in underwater swimming cannot be 
ignored although exposure to cold in diving has 
received most attention. Underwater swimming 
in shallow tropical waters may subject personnel 
to water temperatures near or above skin tem- 
perature, (1290) 1956. In the actively swimming 
individual the metabolic heat production is high 
and if dissipation of this heat is impeded, con- 
siderable discomfort and physiologic derange- 
ment can result. Ordinarily heat dissipation is 
considerably abetted by the high conductivity 
of water, but if the water temperature is above 
skin temperature this physical factor is no longer 
an aid to the swimmer and body temperature 
must rise. 
1286. Ladell, W. S. S. The effects of water and salt 
intake upon the performance of men working in hot and 
humid environments. ]. Physiol., 1955, 127: 11-46. 
1287. Largent, E. J. and W. F. Ashe. Upper limits 
of thermal stress for workmen. Amer. ind. Hyg. Ass. J., 
1958, 19: 246-250. 
1288. Malhotra, M. S., S. S. Ramaswamy and S. N. 
Ray. Effect of environmental temperature on work and 
resting metabolism. J. appl. Physiol., 1960, 15: 769-770. 
1289. Payne, R. B. Tracking proficiency as a function 
of thermal balance. J. appl. Physiol., 1959, 14: 387-389. 
1290. U.S. NRC. High temperature, p. 24 in: Status 
of research in underwater physiology. U.S. NRC-CUW, 
Kept. 468, March 1956, 24 pp. 
VII. COLD EXPOSURE PROBLEMS 
A. GENERAL PHYSIOLOGICAL EFFECTS 
For a general consideration of cold exposure 
problems the monograph by Burton and Edholm 
(1297) 1955, may be consulted. This volume 
covers the subject fully and contains pertinent 
reference lists at the end of each chapter. 
Regarding the effects of cooling on peripheral 
blood flow, evidence has been presented by Eagan 
(1302) 1960, that initiation of cold-induced vaso- 
dilatation is due to the intersection of vascular 
transmural pressure and critical closing pressure 
of the arteriovenous anastomoses. Eagan has re- 
ported experiments supporting the involvement 
of critical closing pressure on four subjects in 
which vascular occlusion (300 mm. Hg) of one 
finger was produced for various periods, and the 
corresponding contralateral finger served as con- 
trol. It was found in these studies (with immer- 
sion of both fingers in ice water at 0°C.) that 
occlusion for five minutes before immersion 
usually, but not invariably, had no effect on cold 
induced vasodilatation. When an effect occurred 
it was one of earlier dilatation. Occlusion from 
five minutes before to five minutes after immer- 
sion had no effect upon the time of dilatation 
but the test finger tended to warm more. Oc- 
clusion from five minutes before to one minute 
after had a marked effect. Following release of 
the occlusion, an increase in finger temperature 
occurred and there was no phase of intense vaso- 
constriction subsequently. This evidence sug- 
gests that metabolites which cause reduction of 
critical closing pressure of the arteriovenous 
anastomoses and resistance vessels are not flushed 
out of the finger by the low blood flow existing 
at one minute after occlusion, so that in spite of 
the intense cold stimulus a true reactive hy- 
peremia occurs. 
Exposure to cold results in increased catechola- 
mine and adrenal steroid output. Thus Arnett 
and Watts (1291) 1960, observed that there was 
a significant increase in the excretion of epine- 
phrine and norepinephrine in the urine in male 
subjects exposed to a cold stress of 6.5°C. for one SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
hour. One hour urine samples were collected in 
acid immediately before and after the exposure. 
The increase in epinephrine excretion was more 
marked than that of norepinephrine ,and it was 
concluded that the secretion of these catechola- 
mines is involved in the chemical control of heat 
production during exposure to cold. Egdahl and 
Richards {1305) 1956, exposed unanesthetized 
dogs to environmental temperatures of —46° to 
—50°C. for 2-28 hours and —75° to —79°C. for 
4-5 hours. Adrenal venous blood samples were 
collected prior to and during periods of cold ex- 
posure and analyzed for 17-hydroxycorticoste- 
roids. In both temperature ranges a marked in- 
crease in adrenal steroid output occurred soon 
after the onset of exposure in the 10 dogs studied. 
In 9 of the 10 animals this response persisted for 
1-3 hours after which adrenal steroid secretion 
returned to control pre-exposure levels despite 
continued cold exposure. The intravenous ad- 
ministration of 40 international units of ACTH 
produced a subsequent increase in adrenal 
17-hydroxcoritcosteroid output. Healthy dogs 
exposed to temperatures of —47°C. for 28 hours 
and —79°C. for 5 hours did not become 
hypothermic. 
As Laties and Weiss {1325) 1959, have demon- 
strated, rats in a cold room will press a lever 
to obtain bursts of heat from a heat lamp. When 
working at 2°C. hypothyroid rats begin to work 
for heat at a steady rate earlier in a 16 hour ses- 
sion than do euthyroid rats. This rate is both 
higher and more steady for hypothyroid than for 
euthyroid rats. Euthyroid and hypothyroid rats 
working at 5°C. show a difference only in the 
time required to attain their steady rate. In one 
experiment the chronic administration of 1-tri- 
iodithyronine to hypothyroid rats led to a signifi- 
cant decrease of lever presses as compared to the 
performance of normal rats. Discontinuance of 
1-triiodothyronine caused a gradual recovery of 
the high rate. The differences in this kind of 
behavior between hypothyroid and euthyroid 
animals were attributed by the authors to differ- 
ences in the drive state arising from the tendency 
of body temperature of hypothyroid animals to 
decline more rapidly in the cold. 
Burton, Snyder and Leach {1298) 1955-56, 
exposed nine human subjects lying unclothed in 
four experiments of 100 minutes duration at 
48°F. and 58°F. with low (30 percent) and high 
(80 percent) relative humidity. There was a 
significantly greater rise of rectal temperature on 
exposure to cold when the humidity was low in- 
dicating a greater physiological response to vaso- 
constriction and a greater increase in metabolism. 
Shivering was considerably greater, both in in- 
cidence and severity, when the humidity was 
low. This was significant even at the higher tem- 
peratures. This could explain the higher thoracic 
temperatures in low humidity because of in- 
creased blood flow to the shivering thoracic 
muscles. Sensations of cold were also significantly 
greater in low humidity at both temperatures 
studied in spite of the fact that skin temperatures 
were not affected by humidity. Pilomotor re- 
sponses were consistently seen at the lower tem- 
peratures and were not significantly related to 
humidity. The degree of vasoconstrictor response 
was estimated by calculating the insulation of 
the tissues. This was about maximal at both tem- 
peratures with some indication that vasoconstric- 
tion was slightly greater (except for the thorax) 
in the low humidities. In studies by lampietro, 
Vaughan, Goldman, Kreider, Masucci and Bass 
{1316) 1960, healthy young men were exposed 
nearly nude for two hours or less to various en- 
vironmental conditions (dry-bulb temperature 
90°F. to 20°F.; wind speed 1, 5 and 10 mph.). 
Oxygen consumption was recorded at intervals 
during exposure. The results showed that even 
under conditions where no visible shivering was 
observed there was an increase in heat produc- 
tion. Exposure to very low temperatures (20°F.) 
with low winds did not evoke the largest increase 
in heat production. The greatest mean heat pro- 
duction (370 Cal./hr.) was associated with the 
highest wind speed (10 mph.) and this value 
approached the maximum heat production which 
can be obtained by shivering (mean value about 
425 Cal./hr.). Thus, increasing the wind speed 
has a greater impact on heat production than de- 
creasing the dry-bulb temperature. The relation- 
ships between heat production and wind speed 
and heat production and dry-bulb temperature 
were nonlinear. Spurr, Hutt and Horwath 
{1336) 1957, studied skin and rectal tempera- 
tures, oxygen consumption, respiratory minute 
volume, carbon dioxide production, respiratory 
quotient and shivering in 11 experiments on 9 COLD EXPOSURE PROBLEMS—PHYSIOLOGICAL EFFECTS 
nude male adults before, during and after sud- 
den exposure to a 10°C. environment. The re- 
sults were compared statistically with those of 
experiments in an ambient temperature of -3°C. 
In the 10°C. environment the first tremors of 
shivering appeared in 6.3 minutes and general- 
ized shivering was observed in 10.25 minutes. 
These times were significantly longer than those 
observed in the —3°C. environment. However, 
the average mean skin and mean body tem- 
peratures of the two groups of subjects were not 
significantly different at the time the first tremors 
of shivering and generalized shivering com- 
menced, suggesting that the temperature recep- 
tors may sense absolute temperature as well as 
responding to rate of change. The respiratory 
minute volume, oxygen consumption and respira- 
tory quotient showed significant increases as a 
result of the exposure to 10°C. and shivering. 
From a consideration of the data on the ventila- 
tion eqiuvalent and percentage of carbon dioxide 
in expired air, it is suggested by the authors that 
the rise in respiratory quotient observed in both 
ambient temperatures was a true increase and 
not due entirely to overventilation on the part of 
the subjects. It was estimated that in the 10°C. 
environment shivering was approximately 5.9 
percent efficient in protecting the body against 
heat loss. This was significantly reduced below 
the value of 11.6 percent observed at —3°C. It 
appeared, therefore, that shivering afforded rela- 
tively greater partial protection to the total body 
heat content in the colder environment. 
The question of heat loss via the respiratory 
route is a critical one in low temperature opera- 
tions where the inert gas used possesses qualities 
of high heat conductivity. In studies of oral ex- 
pired air Brebbia, Goldman and Buskirk (1294) 
1957, collected the water vapor in oral expired 
air during rest and exercise in a subarctic environ- 
ment in 26 experiments on three men. Heat 
loss via this route was about 9 percent of the 
total energy expenditure and water vapor loss 
was directly proportional to ventilation volume. 
In studies on immersion in cold water and 
body tissue insulation, Carlson, Hsieh, Full- 
ington and Eisner (1300) 1958, worked with 
subjects in whom fat constituted 8-32 percent of 
the body weight. These men were immersed at 
33°C., 25°C., 20°C. and in some cases at 9°C. 
All experiments began with a control period at 
33°C., and water temperature was then lowered 
to the desired level. Body insulation calculated by 
the Burton equation, varied directly with specific 
gravity, ranging from 0.10°C./cal./m.2/hr. to 
0.40°C./cal./m.2/hr. However, the fraction of the 
body calculated to be involved as insulation was 
always greater than the estimated fat content. 
Visible shivering always was accompanied by a 
reduction in body insulation. These results to 
the authors to explain the wide variation in sur- 
vival times during cold water immersion. Can- 
non and Keatinge (1929) 1960, found that the 
metabolic rate of both fat and thin young men 
in heat balance in water rose when the bath tem- 
perature was lowered below 33°C., although the 
fat men did not achieve maximum tissue insula- 
tion until the water temperature was much lower. 
The commonly used concept of “critical tempera- 
ture” is therefore considered by the authors not 
valid in the case of fat men. The metabolic rate 
rose less in fat than in thin men when the bath 
temperature was lowered below 33°C. The stable 
rectal temperature of thin men was much lower 
in cold than in warm water while that of the 
fattest men was not. It was concluded that fat 
men’s small metabolic response to cold was due 
to reflexes from the skin while in these men they 
were reinforced by a fall in deep temperature 
and consequent stimulation of deep temperature 
receptors. Fat men achieved higher maximum 
tissue insulation than thin men and could stabi- 
lize their body temperature in water down to 
10-12°C. Work accelerated the fall in rectal 
temperature of both fat and thin men in water 
just too cold for them to stabilize their rectal tem- 
perature when still. Keatinge (1318,1319) 1960, 
found that the fall in rectal temperature of 
young men immersed motionless for 30 minutes 
in stirred water at 15°C. varied little in succes- 
sive immersions and was closely related to the 
subject’s subcutaneous fat thickness. The falls 
bore relatively little relation to finger blood 
flow, which was always low during immersions, 
but both were slightly greater when the men were 
hot rather than cool at the time of immersion. 
Metabolic rates during immersion were substan- 
tially lowered by a small increase in body tem- 
perature at the time of immersion and increased 
by exposure to cold air, though not by moderate SPECIAL ANATOMY. PHYSIOLOGY, AND BIOCHEMISTRY 
exercise several hours before immersion. In the 
first 10 minutes of immersion the metabolic rates 
of thin men were slightly higher than those of 
fat men with a number of substantial and con- 
sistent individual differences not related to fat 
thickness or fall in rectal temperature. In the 
last 20 minutes of immersion the metabolic rates 
of thin men increased but those of fat men did 
not. 
Exposure to cold in military operations raises 
the special issue of the practical problems of 
special vulnerability of particular parts of the 
body, such as the head and the hands. Two separ- 
ate practical problems are the reduction of the 
total heat loss from the head, as by insulated 
helmets and protection from frostbite, as by face 
masks. These problems have been raised by Ed- 
wards and Burton {1304) 1960. Solution of both 
problems benefits from knowledge of the distribu- 
tion of skin temperature. Temperatures in Bur- 
ton and Edwards’ studies were measured with 
thermocouples at several points on three subjects, 
in the steady state, at environmental tempera- 
tures of 0°C. Topographical differences were 
similar for the three subjects. Temperatures at 
a large number of points were measured on a 
single subject and isothermal maps were drawn 
from the results. These showed that the areas 
needing most protection from frostbite are the 
tip of the nose, the rim of the ears, the chin and 
the cheekbones. The areas of highest tempera- 
ture (greatest heat loss) are those covered by the 
conventional insulated helmets. A face mask 
need not cover the area around the mouth where 
tactile sensitivity may make it uncomfortable. 
The isothermal map is correlated with the ana- 
tomical distribution of arterial blood supply. 
Froese and Burton {1307) 1956, have suggested 
from calculations that there may be excessive 
heat loss from the head in cold. This has been 
verified with a temperature gradient calorimeter 
made of thin Styrofoam sheets. Resistance meas- 
urement of wires covering the inside and out- 
side surfaces of the walls gave the total flux, 
which by Gauss’ theorem is proportional in the 
steady state to the magnitude of the heat source. 
The breath was led outside the calorimeter; thus 
heat loss from the head was measured on three 
subjects (27 runs at 14 different room tempera- 
tures) . The average temperature over the inside 
surfaces of the calorimeter walls ranged from 32 
to —21°C. Cheek temperatures were measured in 
a few cases. A linear regression between heat 
loss and calorimeter temperature was found. The 
coefficient of correlation was 0.97 ± 11.3°C. 
(9.4°F.) equal to half the total resting metabolic 
rate. Extrapolating to zero heat loss, the ‘brain 
temperature’ was found to be 37.4°C. This tem- 
perature was used to calculate the insulation from 
the brain to the calorimeter wall. An average 
value of 0.71 ± 0.12 standard do units was ob- 
tained. The contribution of the tissue insula- 
tion to this total is estimated as 0.25 do units. 
It appears therefore that there is no detectable 
peripheral constriction in the head during ex- 
posure to cold. This would seem to favor keep- 
ing the brain temperature normal. 
Differential rates of cooling are found, the 
fingers being more vulnerable. Hall, Poke and 
Kelley (1311) 1954, carried out studies in which 
men wearing immersion suits were submerged 
in water (32-39°F.) and the hands were found to 
cool most rapidly. An increase of 0.6-1.1 do 
units reduced this temperature drop. When the 
hands were kept out of the water, less rapid rates 
of hand cooling were observed. The feet cooled 
at much slower rates. The rates of average skin 
cooling were progressively reduced when body 
(trunk, arm and leg) insulation was increased 
from 2.3 to 3.7 and 4.7 do units. Maximum body 
insulation did not alter the critical cooling rate 
of the immersed hands. On the basis of the rate 
of upper extremity and average skin temperature 
cooling, a body insulation of approximately 
3.0-3.5 do units is indicated for cold water 
(32-39°F.) immersion exposure. A metabolic 
increase of 54-93 percent was reported under 
these conditions. Immersion time was 40 minutes 
with 10 minutes control recording in air. In a 
study of finger numbness and skin temperature 
Mills (1331) 1956, found that the tactile dis- 
crimination of the right index finger tips of men 
exposed to a cold environment decreased with 
the skin temperature of the same area. The meas- 
ure of tactile discrimination with minimum 
separation between two edges at which they could 
be discriminated is two. The log of this separa- 
tion was inversely proportional to the skin tem- 
perature between 0°C. and -j-33°C. If the finger 
was rewarmed by a phase of spontaneous vaso- COLD EXPOSURE PROBLEMS—PHYSIOLOGICAL EFFECTS 
dilatation, which generally developed after about 
15 minutes of exposure to —18 to —23°C,, tactile 
discrimination recovered with the rise in skin 
temperature. If spontaneous rewarming did not 
occur at that temperature, frostbite usually en- 
sued. Practical studies have been conducted by 
LeBlanc, Hildes and Heroux. In the work of 
these authors a group of Gaspe fishermen accus- 
tomed to cold water immersion and a group of 
control subjects from the same vicinity were 
studied to determine if the fishermen’s hands 
were adapted to cold. With one hand immersed 
in cold water, the pressor response was greater in 
the control subjects; the fishermen maintained 
a higher finger temperature and complained less 
of pain. Heat flow from the fishermen’s hands 
was greater than in the control group. Finger 
numbness was measured by a modification of 
Mackworth’s V-test, and this was variable and 
not significantly different in the two groups. Skin 
biopsies revealed no differences in the skin thick- 
ness or cell size, but there was a significantly 
greater number of mast cells in the fishermen’s 
skin. The differences between the fishermen 
and the control subjects may be related to re- 
peated exposure by the former. 
Tactile discrimination is impaired under cold 
conditions. Provine and Morton {1334) 1960, 
immersed the index finger of 10 subjects in water 
at 0.75°C. for 40 minutes. Two-edge threshold 
discrimination was tested during cooling of the 
finger and subsequent spontaneous rewarming 
due to cold vasodilatation. There was a marked 
deterioration of tactile discrimination at finger 
skin temperatures below about 8°C., although the 
curve showing the mean decrease of numbness 
with increasing skin temperature was displaced 
relative to the curve, showing the mean increase 
of numbness with decreasing skin temperature. 
Tactile discrimination was also tested on five 
subjects at each of six water bath temperatures 
(2, 4, 6, 8, 15 and 30°C.). At each temperature 
the finger was immersed for 20 minutes and 
the finger circulation arrested after the first 
five minutes. There was little impairment of two- 
edge discrimination after 15 to 20 minutes im- 
mersion of the finger at temperatures of 6°C. or 
higher. At 4°C. there was marked impairment, 
and at 2°C. all subjects experienced complete 
numbness at the test site. A further study by 
Morton and Provins {1332) 1960, is also of in- 
terest. Twenty subjects exposed the index finger 
to air at —22°C. and a wind speed of 300 ft./min. 
until the indicated skin temperature fell to —5°C. 
The finger was then returned to room tempera- 
ture conditions (19°C.) and the subject tested 
on each of two tasks involving tactile discrimina- 
tion until the finger had fully recovered. The 
degree of impairment on both sensory motor tasks 
at a given skin temperature varied appreciably 
from subject to subject, although most subjects 
showed little impairment above 8°C. The evi- 
dence suggests that while finger numbness, as 
measured by Mackworth’s V-test, may indicate 
a corresponding impairment of performance in 
accuracy of pressure reproduction, testing sub- 
jects on either task at normal skin temperature 
will have little predictive value for their relative 
performance after cold exposure in the present 
situation. 
Metabolic rate tends to accelerate in human 
subjects exposed to cold. Thompson, Buskirk, 
Moore and Whedon {1338) 1960, drew attention 
to the fact that various methods have been ap- 
plied in the past to the measurement of metabo- 
lic rate in the cold, and that these methods have 
been based upon interval sampling of expired 
gas concentrations. Although the discrete 
sampling approach has established sample to 
sample differences in metabolic rate, the moment 
to moment changes have not been identified. 
By using methods for continuous gas analysis it 
has been possible to delineate previously ob- 
scrued features of the metabolic response (oxy- 
gen consumption) to cold. In the authors’ 
studies young subjects varying in body composi- 
tion and clothed only in shorts, were individually 
exposed for approximately three hours on two 
or more occasions to 26°C. (control environ- 
ment) or 10°C. air. Notable inter-individual 
differences were observed in the metabolic re- 
sponse of these subjects to cold, both in the delay 
before initiation and the magnitude attained. 
Characteristic features of the metabolic response 
were its cyclic nature associated with intermittent 
shivering and an underlying general increase in 
oxygen consumption for approximately two 
hours following its onset. Cyclic changes in oxy- 
gen consumption were not reflected by changes 
in any of the measured body temperatures. The SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
influence of cold upon the metabolism and body 
temperature of wild rats, albino rats and albino 
rats conditioned to cold, has been reported by 
Krog, Monson and Irving (1323) 1955. After 
exposure to low temperatures for 2.5 hours the 
maximum metabolic effort for white rats condi- 
tioned to 5°C. occurred at —30°C., compared 
with —10°C. for white rats normally kept at 30°C. 
The difference was accounted for by the ability 
of cold-conditioned rats to maintain higher meta- 
bolic rates at all temperatures. Wild Norwegian 
rats survived lower temperatures than cold-con- 
ditioned white rats. This corresponded with the 
fact that wild rats could increase their metab- 
olism in proportion to body to air temperature 
gradients 4.5 to 6 times over basal level as com- 
pared with a triple increase possible for white 
rats. The basal metabolic rate of white rats kept 
in cold was 60 percent above that appropriate 
to animals of their size. This elevation suggests 
that cold induced a compensatory metabolic 
change not normal to the species. Wild rats re- 
sponded to exposure to cold in a manner normal 
to wild animals of cold climate. White rats de- 
viated from the pattern of animals naturally 
living in cold climates. The body temperature 
in cold-conditioned white rats showed no appreci- 
able fall after 2.5 hours exposure to —10°C.; the 
corresponding tolerance level for normal white 
rats was 10°C. The difference corresponded to 
that observed in metabolic curves, except that 
critical points in body temperature measurements 
showed up at higher temperatures because the 
rats were partially immobilized by thermocou- 
ples. When corresponding parts of the tempera- 
ture curves were compared, the body temperature 
of cold-conditioned rats was shown to be a little 
lower than in normal animals. 
Reynafarje and Chaffee (1335) 1960, have con- 
cluded that the mechanism of cold acclimatiza- 
tion involved a metabolic adjustment resulting 
in increased heat production. It is also clear 
that oxidation of triphosphopyridinenucleotide 
(TPNH) plays an important role in this acclima- 
tization. Furthermore, the increment in activity 
of these reductases, which occurs only in micro- 
somes and not in mitochondria, are regarded as 
the oxidative units in the cell and may signify 
that utilization of oxygen is not involved in the 
process. 
Oxygen consumption and body temperature 
during sleep in cold environments has been 
studied by Kreider and lampietro (1322) 1959. 
Six young soldiers slept at ambient temperatures 
of 25.5 to 26.0°C. (78-80°F.); 15 to 18.5°C. (60- 
65°F.); and -32 to —34.5°C. (-25 to —30°F). 
The rectal temperature and skin temperatures 
were recorded and mean weighted skin temper- 
ature was calculated at one-half hour intervals 
every night. Oxygen consumption was measured 
at six minute intervals on occasional nights. Dur- 
ing sleep at a ‘comfortable’ temperature 
(25.5°C.) the rectal temperature and the mean 
weighted skin temperature and the oxygen con- 
sumption decreased below the resting level which 
was measured just before retiring. During sleep 
in cold environments the rectal temperature and 
mean skin temperature dropped to still lower 
levels with the lowest values recorded at an early 
hour of the night. The oxygen consumption dur- 
ing sleep in cold did not differ from values re- 
corded during sleep at 25.5°C. The lowest values 
measured during sleep in the coldest environ- 
ment were 35.5, 30.5 and 78 Cal./m.2 for rectal 
temperature and mean skin temperature and 
body heat debt respectively. These values may 
represent, according to the authors, the limits 
of body cooling comparable with substantially 
continuous sleep in the cold. 
The critical temperature in naked male sub- 
jects performing exercise on a bicycle ergome«.er 
in a cold room has been studied by Erikson, 
Krog, Anderson and Scholander (1306) 1956. 
Letting the subjects do just enough to avoid be- 
coming cold, the critical temperature was found 
to be 26°C., confirming earlier studies. 
The question of preventing immersion hypo- 
thermia is an important one. Beavers and Co- 
vino (1292) 1956, for example, have studied the 
effect of glycine upon immersion hypothermia. 
The intravenous administration of a 5 percent 
glycine solution was found to cause a significant 
increase of 34.6 minutes in the time required to 
lower the rectal temperature from 38 to 26°C. in 
dogs. Total rewarming time was decreased by 
34.3 minutes in the glycine treated group. The 
differences in cooling and rewarming rates be- 
tween the treated and nontreated animals was 
believed to be due to the increased heat produc- 
tion observed in the dogs receiving glycine. COLD EXPOSURE PROBLEMS—PHYSIOLOGICAL EFFECTS 
1291-1317 
The effect of acute cold exposure on renal 
function in dogs has been studied by Nungesser 
(/5J3) 1955. This author used unanesthetized 
trained female dogs with bladder cannuli im- 
planted. These animals were repeatedly exposed 
to cold room temperatures, decreasing to lows of 
4.0 to 1.8°C. for periods of one hour following 45 
minute control observations at room tempera- 
tures of 22-24°C. Rectal temperatures and skin 
temperatures of foot and back were recorded. 
Renal clearances of creatinine and PAH and 
also water and chloride excretion were deter- 
mined. Cold exposure resulted in a sharp de- 
crease in foot temperatures and smaller de- 
creases in back temperatures, both suggesting a 
decrease in peripheral blood flow. Shivering oc- 
curred in these animals and little change oc- 
curred in rectal temperatures. Usually the cold 
results in a decrease in renal plasma flow and 
chloride excretion. Glomerular filtration rate 
and water excretion were less frequently and 
less markedly decreased. 
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excretion in men exposed to cold. J. appl. Physiol, 1960, 
15: 499-500. 
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hypothermia: effect of glycine. Proc. Soc. exp. Biol, N.Y., 
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from rest periods spent in a cool environment. Fed. Proc., 
1960,19: 179. 
1338. Thompson, R. H., E. R. Buskirk, R. Moore 
and G. D. Whedon. Continuous measurement of meta- 
bolic rate in human subjects exposed to cold 10° C. Fed. 
Proc., 1960, 19: 44. 
1339. Weiss, A. K. and W. G. Moss. Effects of sub- 
total hepatectomy on response of the rat to cold exposure. 
J. appl. Physiol, 1957, 10: 131-136. 
1340. Wyndham, C. H. and G. E. Jacobs. Loss of 
acclimatization after six days of work in cool conditions on 
the surface of a mine. /. appl. Physiol., 1957, 11: 197-198. 
B. ACCLIMATIZATION 
In acclimatization increased heat production 
caused by cold exposure is not as large as in 
unacclimatized subjects. This was reported by 
LeBlanc (1349) 1956, who observed evidence of 
acclimatization in soldiers exposed for four 
months to Arctic winter climate and who fre- 
quently experienced thermal discomfort. The 
subjects were exposed three times during the 
winter to the same standard cold stress. At the 
end of the winter the increased heat production 
caused by this standard cold exposure was not 
as great as in the autumn. Since the same ob- 
servations have been made by various workers 
on laboratory animals, this result is interpreted 
as evidence of acclimatization to cold. Practical 
studies of Scholander, Hammel, Lange-Anderson 
and Loyning {1351) 1957, involved exposure of 
human subjects to conditions in the Norwegian 
mountains above the tree line. In September 
and October, eight men lived under these condi- 
tions in essentially summer clothing and with 
insufficient night protection. Snow and sleet 
were common and night temperatures were 
usually between 0 and -(-5°C. The men had 
enough food and were kept busy hiking, fishing 
and hunting. The nights were spent beneath a 
tarpaulin rigged as a rainproof shelter with one 
side open. The subjects slept naked except for 
socks and shorts in a single blanket sleeping bag 
with a hydrophobic cover. After six weeks in the 
field they had acquired considerable acclimatiza- 
tion; tests showed that they then stayed warm 
from head to foot all night and slept well. Heat 
production remained 50-60 percent higher than 
the basal production all night while they were 
asleep. Shivering, visible or detectable by elec- 
tromyography, occurred frequently during sleep. COLD EXPOSURE PROBLEMS—ACCLIMATIZATION 
Control subjects had less elevated metabolic rates 
and were unable to rest and sleep due to chilling, 
especially of the feet. In the acclimatized men 
therefore an increased heat production alleviated 
the shell cooling from which unacclimatized peo- 
ple suffer. When bicycling naked in just enough 
cold to maintain the rectal temperature the cold 
acclimatized men used as much oxygen as the 
controls so neither during exercise nor during 
rest did acclimatization result in increased in- 
sulation by shell cooling. Metabolic acclimatiza- 
tion to cold is well known in other homeotherm- 
ous systems. Davis, Johnston and Bell have car- 
ried out studies to determine the existence of 
physiologic acclimatization to cold in man. Sub- 
jects were exposed in a cold chamber 8 hours 
daily for 31 days. By the tenth day, shivering 
significantly decreased while heat production re- 
mained elevated 30-40 percent above basal levels 
throughout the period of exposure. Basal meta- 
bolic rate did not change; rectal temperature re- 
mained at pre-exposure levels for the first ten 
days but on the fourteenth day it fell to signifi- 
cantly lower values and remained there for the 
remainder of the experiment. Skin temperatures 
showed some significant fluctuations on the 
eighth and fourteenth days but returned to pre- 
exposure levels thereafter. Of the eight surface 
areas measured for temperature, no significant 
alterations took place as a result of the total 
period of exposure. On the basis of shivering 
decrease and rectal temperature change it was 
concluded that men can be artificially cold-ac- 
climatized. Failure of cold-elevated heat produc- 
tion to decrease in the face of a significant de- 
crease in shivering indicates to the authors the 
presence of nonshivering thermo-genesis in man. 
Peripheral and extermity temperature alterations 
do not take place as a result of chronic artificial 
cold exposure. The authors recommend that 
studies should be undertaken to determine the 
retainability of acclimatization induced by cold 
chamber exposure together with studies to de- 
termine the effect of heat acclimatization on cold 
acclimatization. 
Cold acclimatization affects hepatic carbohy- 
drate and lipid metabolism (Felts and Masoro 
(1343) 1959). Acclimatization of rats to low 
environmental temperatures was found to alter 
the hepatic metabolic response to fasting for one 
day at 0-2°C. Liver glycogen was stabilized, 
fatty infiltration of the liver did not occur, and 
liver slices were better able to oxidize acetate 
and palmitate to carbon dioxide. These results 
provide an example of an acclimatization process 
occurring at the molecular level. In a previous 
paper Masoro and Felts (1350) 1959, pointed out 
that cold acclimatization greatly modifies the 
hepatic response of rats to fasting at low environ- 
mental temperatures. Liver glycogen almost com- 
pletely disappeared in control rats fasted for 24 
hours at 2°C., but is maintained at the surpris- 
ingly high level of 2 percent of net weight in cold 
acclimatized rats similarly treated. Of equal in- 
terest is the finding that cold acclimatization 
prevents the fatty infiltration of the liver that 
usually accompanies fasting in a cold environ- 
ment. In a consideration of the effects of aging 
on adaptation to cold, Weiss (1352) 1959, has 
questioned whether the decreased ability of older 
and larger rats to adapt to cold is due to aging 
or to altered insulating properties of the tissues. 
Six weeks old male Holtzman rats who are 
depilated by clipping before cold-exposure at 
5± 2°C. show a mean survival rate of less than 
two days in the cold. Cold exposure for seven 
days before clipping allows the animals to adapt 
and withstand cold-exposure after clipping. One- 
and-one-half year-old clipped rats die soon after 
cold-exposure, whether pretreated with cold be- 
fore clipping or not. Injection of tri-iodothryo- 
nine acetate (100 ug./lOO gm. body weight, in- 
tramuscularly) on three alternate days during 
pretreatment with cold prolongs the survival of 
the older animals after clipping. Additional 
doses of the compound prolong maintenance in 
the cold when the animals are clipped twice 
weekly. It was suggested by the author that the 
older animals do not adapt as well at 5°C., but 
are protected in some measure from the cold by 
their fur. After clipping the tissues alone cannot 
furnish adequate insulation protection for sur- 
vival. It is therefore concluded that aging does 
reduce the ability of the rat to adapt to cold, but 
adaptation in older rats can be brought about 
artificially by administration of thyroid hormone. 
For a study of the relationship between chang- 
ing levels of physical fitness and cold acclimatiza- 
tion, a report by Heberling and Adams (1344) 
1960, may be consulted. In this study five adult 1341-1352 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
male subjects were exposed nude in a cold cham- 
ber at 10°C. for one hour before and after physi- 
cal training program and following a six week 
winter field bivouac in interior Alaska. Body 
temperatures during the acute cold exposure were 
the criteria by which the effects of the changing 
levels of physical and of the “cold-acclimatizing” 
field encampment were judged. After the physi- 
cal training program (before bivouac) the skin 
and extremity temperatures were significantly 
higher than pre-training measurements, but no 
differences in these values were seen after the 
field bivouac when physical training levels re- 
mained unchanged and the variable of cold ex- 
posure operated alone. These data confirm an 
earlier suggestion that these indices of acclimati- 
zation may appear as a result of chronically ele- 
vated activity levels. Dietary measurements 
showed equal caloric intakes in the training and 
bivouac phases, although formal activity require- 
ments were discontinued in the latter test period. 
These data open for question the interpretation 
of physiological changes observed after winter 
bivouac or field exposure as being “cold induced”. 
Amongst the various metabolic changes oc- 
curring in cold adaptation is an increase in bile 
flow as demonstrated by Intoccia and Van Mid- 
dlesworth {1346) 1958. 
Immersion of personnel in cold water after 
shipwreck or aircraft disaster over the sea con- 
stitutes a continuing survival problem. It has not 
been known clearly what advice to give men 
about immersion in water under such conditions. 
Keatinge {1347) 1959, has concluded that in 
general men who have thick and close-fitting 
clothing lose heat relatively slowly in cold water 
and adaptation is possible. It is therefore of 
practical importance that personnel should if 
possible dress appropriately before abandoning 
ship or escape from a submarine. 
1341. Davis, T. R. A., D. R. Johnston and F. C. 
Bell. Experimental cold acclimatization in man. U.S. 
Army. Fort Knox, Kentucky. Medical research laboratory. 
Rept. no. 457, 3 November 1960, 8 pp. 
1342. Depocas, F. Metabolic response of warm and 
cold acclimated rats to very cold environments. Fed. Proc., 
1956, 15: 48. 
1343. Felts, J. M, and E. J. Masoro. Effects of cold 
acclimation on hepatic carbohydrate and lipid metabolism. 
Amer. J. Physiol., 1959,197: 34-36. 
1344. Heberling, E. J, and T. Adams. Relationship 
of changing levels of physical fitness to human cold aclima- 
tization. Fed. Proc., 1960, 19: 43. 
1345. Herous, O., J. S. Hart and F. Depocas. 
Metabolism and muscle activity of anesthetized warm and 
cold acclimated rats on exposure to cold. /. appl. Physiol., 
1956, 9: 399-403. 
1346. Intoccia, A. and L. Van Middlesworth. Bile 
flow increased by cold adaptation. Fed. Proc., 1958, 17: 77. 
1347. Keatinge, W. R. The effect of work, clothing 
and adaptation on the maintenance of the body tempera- 
ture in water. Gt. Brit. MRC, RNPRC, SS. Kept. R.N.P. 
60.977, S.S. 97, October 1959, 8 p. 
1348. Laties, V. G. and B. Weiss. Behavior in the 
cold after acclimatization. Fed. Proc., 1960, 19: 43. 
1349. LeBlanc, J. A. Evidence and meaning of ac- 
climatization to cold in man. J. appl. Physiol., 1956, 9: 395- 
398. 
1350. Masoro, E. J. and J. M. Felts. Effects of ac- 
climation to cold on hepatic metabolism. Fed. Proc., 1959, 
18: 99. 
1351. Scholander, P. F., H. T. Hammel, K. Lange- 
Andersen and Y. Loyning, Metabolic acclimation to 
cold in man. Fed. Proc., 1957,16: 114. 
1352. Weiss, A. K. Effects of aging on adaptation to 
cold. Fed. Proc., 1959, 18: 168. 
C. EFFECTS OF COLD ON 
PERFORMANCE 
For information on the effects of exposure to 
cold and manual dexterity as well as other per- 
formance, papers by LeBlanc {1354) 1956, Pro- 
vins and Clarke {1356) 1960, Rubin {1357) 1957, 
and Teichner and Kobrick {1359) 1955, may be 
consulted. The literature on the subject is re- 
viewed by Provins and Clarke. Hand skin tem- 
peratures are reached at which dexterity is im- 
paired by cold. According to LeBlanc, when the 
fingers alone are cooled performance of tests in- 
volving little movement of a joint may be slightly 
enhanced, whereas impairment is large when 
the joint movements are increased. This is in- 
terpreted as evidence for the hypothesis that in- 
creased viscosity of the synovial fluid is a factor 
in decreasing finger dexterity in the cold. How- 
ever, this is not the only factor since cooling of 
the arm, even when the hands are kept warm, 
apparently causes a large decrement in finger 
dexterity. As Rubin has demonstrated, one of 
the problems in testing the effect of cold on 
manual dexterity is to design laboratory tasks 
which correlate with actual military tasks. In 
Rubin’s study male volunteers from the Army 
Chemical Center performed four tasks: a nut and 
bolt task, a screwdriver task, a washer task and COLD EXPOSURE PROBLEMS—IMMERSION 
1353-1364 
a military task (manipulation of a kit to detect 
chemicals). There was no significant correlation 
between any of the dexterity tasks when the bare 
hands were used. When the hands were gloved 
significant correlation was found between labora- 
tory dexterity tasks but no laboratory task corre- 
lated significantly with the military task. In these 
studies manual dexterity was affected by hand 
conditions of the experiment although tempera- 
ture conditions between 25°F. and 100°F. and 
duration of exposure from 40 to 120 minutes had 
no significant effect on dexterity. In Teichner 
and Kobrick’s studies five subjects lived in a 
constant temperature chamber for 41 days. For 
the first 16 days the temperature was held at 
75°F., for the next 12 days at 55°F. and for the 
remaining 13 days at 75°F. Subjects were given 
15 trials daily on a pursuit motor. Visual motor 
performance markedly and immediately deterio- 
rated in cold and recovered gradually, but to 
lower levels rather than to optimal temperature 
conditions. The authors concluded that impair- 
ment of visual motor performance in low tem- 
peratures is the result of lowering of the final 
limit of performance rather than reduction of 
the rate of limit of learning. 
1353. Carlton, P. L., R. A. Marks and B. Smith. 
Heat reinforced operant behavior as a function of pro- 
longed cold exposure. U.S. Army. Fort Knox, Kentucky. 
Medical research laboratory. Kept. no. 325, 13 January 
1958, 9 pp. 
1354. LeBlanc, J. A. Impairment of manual dexter- 
ity in the cold. J. appl. Physiol., 1956, 9: 62-64. 
1355. Newton, J. M., M. Meketon, J. Roote and 
R. Stargel. An investigation of tracking performance in 
the cold with two types of controls. U.S. Army. Fort Knox, 
Kentucky. Medical research laboratory. Kept. no. 324, 6 
February 1958, 13 pp. 
1356. Provins, K. A. and R. S. J. Clarke. The effect 
of cold on manual performance. J. occup. Med., 1960, 2: 
169-176. 
1357. Rubin, L. S. Manual dexterity of the gloved 
and bare hand as a function of the ambient temperature 
and duration of exposure. J. appl. Psychol., 1957, 41: 377- 
383. 
1358. Teichner, W. H. Manual dexterity in the cold. 
appl. Physiol., 1957,11: 333-338. 
1359. Teichner, W. H. and J. L. Kobrick. Effects 
of prolonged exposure to low temperature on visual-motor 
performance. J. exp. Psychol., 1955, 49: 122-126. 
1360. Teichner, W. H. and R. F. Wehrkamp. 
Visual-motor performance as a function of short duration 
ambient temperature. J. exp. Psychol., 1954, 47: 447-450. 
1361. U.S. NRC. Low temperature, pp. 23-24 in: 
Status of research in underwater physiology. U.S. NRC- 
CUW, Kept. 468, March 1956, 24 pp. 
D. IMMERSION IN COLD WATER 
The effects of immersion in cold water depend 
upon the condition of the individual at the time 
of immersion, the temperature of the water and 
the duration of exposure. The immediate effects 
are stimulatory upon metabolic rate, heart rate, 
etc., depending upon the degree of cold. The 
compensatory changes supervened as cold is en- 
dured. Keatinge and Evans (1364) 1960, have 
reported on the effect of food, alcohol and 
hyoscine on body temperature and reflex re- 
sponses of men immersed in cold water. Neither 
75 ml. of alcohol, nor a heavy meal, nor 1/100 
gr. hyoscine, taken 45 minutes before immersion 
significantly affected the rate at which men’s 
rectal temperatures fell during 30 minutes of im- 
mersion in water at 15°C. It was found that 
under these conditions the blood flow in the 
fingers always was reduced rapidly to low levels 
and that the fall was significantly less rapid after 
alcohol. Several of the subjects developed ven- 
tricular extrasystoles on immersion; most of these 
were observed after hyoscine or a heavy meal and 
not after alcohol. Alcohol greatly reduced the 
men’s subjective discomfort and sensation of cold 
in the water. Also, alcohol usually reduced the 
rise in metabolic rate and the increase in heart 
rate during immersion. Hyoscine reduced the 
metabolic rates and abolished the increase in 
heart rates but unlike alcohol it did not affect 
subjective sensation of cold. For other papers on 
the effect of cold immersion, those by Goff, Bru- 
bach, Specht and Smith (1363) 1956; McCally 
and Graveline (1363) 1963, may be consulted. 
1362. Beckman, E. L. Thermal protection during im- 
mersion in cold water, pp. 247-266 in: Second symposium 
on underwater physiology. Edited by C. J. Lambertsen 
and L. J. Greenbaum, Jr. National Research Council, 
Washington, D.C. N.R.C. Publication 1181, 1963, 296 pp. 
1363. Goff, L. G., H, F. Brubach, H. Specht and 
N. Smith. Effect of total immersion at various tempera- 
tures on oxygen uptake at rest and during exercise. J. 
appl. Physiol., 1956, 9: 59-61. 
1364. Keatinge, W. R. and M. Evans. Effect of 
food, alcohol and hyoscine on body-temperature and re- 
flex responses of men immersed in cold-water. Lancet, 
1960, 2: 176-178. 1365-1375 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
1365. McCally, M. and D. E. Graveline. Urinary 
adrenaline and noradrenaline response to water immer- 
sion. Fed. Proc., 1963, 22: 508. 
VIII. VISUAL PROBLEMS 
A. GENERAL CONSIDERATIONS 
For general considerations of visual problems, 
reference should be made to Volume II of this 
Sourcebook. The reader may also consult papers 
by Schwartz and Sandberg {1366, 1367) 1954. 
These authors have determined the visual charac- 
teristics of 1064 submariners by means of Snellen 
wall charts and the Bausch and Lomb Ortho- 
Rater. From the Snellen scores the group showed 
peak acuity at better than 20/20 with about four 
percent falling below 20/30. Ortho-Rater scores 
were distributed normally around 20/20 with one 
percent falling below the equivalent of 20/30. 
The lateral phoria scores showed a definite ten- 
dency to exophoria at near, with 12 percent of 
the men exceeding five prism diopters. The 
visual characteristics of these 1064 submariners 
were also compared with those of 2354 candidates 
for the U.S. Naval Submarine School. With in- 
creased time in the submarine service a decrease 
of visual acuity for distance and for near, ac- 
companied by a tendency toward esophoria, was 
found to be characteristic of the submarine popu- 
lation. This loss of visual efficiency may be re- 
lated to the confining nature of the submarine 
environment. 
1366. Schwartz, I. and N. E. Sandberg. Visual char- 
acteristics of the submarine population. U.S. Navy. Sub- 
marine Base, New London, Conn. Medical research labora- 
tory. Project NM 003 041.57.02, 12 June 1954, 12 pp. 
1367. Schwartz, I. and N. E. Sandberg. The effect 
of time in submarine service on vision. U.S. Navy. Sub- 
marine Base, New London, Conn. Medical research labora- 
tory. Project NM 003 041.57.03, 30 August 1954, 9 pp. 
B. ACUITY 
The references cited below may be consulted 
for information on visual acuity. Special men- 
tion should be made of a paper by Sweeney, Kin- 
ney and Ryan {1375) 1959. These-investigators 
have developed a new scotopic sensitivity test 
at the Medical Research Laboratory. The test 
presents small spots of light of various sizes at a 
number of locations in the visual field and yields 
scores of the total number correctly located. A 
group of 108 enlisted men have been tested on 
this night vision test and the results show signifi- 
cant differences in scotopic sensitivity and a fairly 
normal distribution of scores. The reliability of 
the test measured on two consecutive days was 
83. Several measures made to indicate the in- 
ternal validity of the test gave positive results. In 
addition, various questions concerning the most 
efficient means of administering and scoring the 
test have been answered. 
1368. Hillman, B. M. Relationship between stimulus 
size and threshold intensity in the fovea measured at four 
exposure times. J. opt. Soc. Amer., 1958, 48: 422-428. 
1369. Hillmann, B. B. Relationship between stimulus 
size and threshold intensity measured at four exposure 
times. U.S. Navy. Submarine Base, New London, Conn. 
Medical research laboratory. Project NM 22 01 20.01, 
Kept. no. 6, 1958. 
1370. Kinney, J. A. S. Comparison of scotopic, me- 
sopic and photopic spectral sensitivity curves. U. S. Navy. 
Submarine Base, New London, Conn. Medical research 
laboratory. Project NM 22 01 20.01, Kept. no. 4, 1958. 
1371. Kinney, J. A. S., E. J. Sweeney and A. P. 
Ryan. A new test of scotopic sensitivity. U. S. Navy. 
Submarine Base, New London, Conn. Medical research 
laboratory. Project MR005.14-2001-4, Kept. no. 4, 3 No- 
vember 1960. 
1372. Luria, S. M. and I. Schwartz. Visual acuity 
under red vs. white illumination. U.S. Navy. Submarine 
Base, New London, Conn. Medical research laboratory. 
Project MR 005.14-1001-10, 14 January 1960, 8 pp. 
1373. Schwartz, I. and F. L. Dimmick. Comparison 
of high acuity scores on Snellen and ortho-rater tests. 
Amer. J. Optom, 1958, 35: 309-313. 
1374. Sperling, H. G. and G. B. Lee. The area- 
intensity relationship at threshold for three stimulus dura- 
tions in the human fovea. U.S. Navy. Submarine Base, 
New London, Conn. Medical research laboratory. Project 
NM 22 01 20, 20 May 1957, 6 pp. 
1375. Sweeney, E. J., J. A. S. Kinney and A. P. 
Ryan. Scotopic sensitivity test. U.S. Navy. Submarine 
Base, New London, Conn. Medical research laboratory. 
Project NM 23 01 20, March 1959, 4 pp. 
C. COLOR VISION 
The references cited below provide a selection 
of studies on color vision with particular refer- 
ence to their applicability to submarine medicine. 
Of special interest is the report by Farnsworth 
(1381) 1956. This investigator has reported 
studies on tritanomalous vision as a threshold 
function. This study was undertaken to ascer- 
tain how individuals with inherited tritanopia 
(commonly referred to as yellow-blue color blind- 
ness) perceived colors as compared to normal in- 
dividuals, using the most sensitive portion of 
their eye (foveal vision). It was found that 
subjects with tritanopia perceive colors in the VISUAL PROBLEMS—COLOR VISION 
1376-1391 
same manner and degree as do normal individ- 
uals using foveal vision. This in essence con- 
firms previous findings that the most sensitive 
portion of the eye (fovea) is yellow-blue blind. 
Malone {1388) 1953, has carried out a prelimi- 
nary field evaluation of the relative detectability 
of colors for air-sea rescue. The relative detect- 
ability of a series of Munsell reds, fluorescent 
paints, International Orange and the standard 
lifeboat yellow, was the subject of this research. 
Observations were made from an aircraft flying 
at an altitude of 1000 and 500 feet and at 
distances of three-quarters of a mile to one and 
three-quarters miles from the targets. The targets 
were spheres of spun aluminum 34 inches in di- 
ameter which were towed in groups of five by a 
retriever. Observations were made during the 
spring and summer on sunny days with a mini- 
mum of haze. Colors from 2.5 red to 7.5 red were 
detected first and second a significantly greater 
percentage of the time than the standard lifeboat 
yellow. The fluorescents and International 
Orange also showed greater detectability than 
lifeboat yellow did. A photometric survey of the 
red lighting installation on the USS Darter was 
conducted by Moody, Squires, Lewis and Huff 
(1390) 1956. It was concluded that the overall 
red lighting installation was unsatisfactory. The 
general brightness level in the Attack Center was 
found to be too high and that in the living quar- 
ters too low. It was concluded that the purpose 
of red lighting in the Attack Center is to render 
optimal periscope viewing at night. This purpose 
has been defeated by the red lighting equipment 
installed at the time of study. Excessive bright- 
ness from non-directional overhead luminaries, 
together with high glare (both direct and in- 
direct) , plus white light leaks were found to be 
present. This lighting situation was reported to 
be incompatible with efficient periscope viewing. 
The “jewels” on panels in various compartments 
were uniformly too bright and too various in 
color to meet red light standards. 
1376. Brindley, G. S. The effects on colour vision of 
adaptation to very bright lights. J. Physiol., 1953, 122: 332- 
350. 
1377. Dimmick, F. L. and R. E. Wienke. How red 
is red? Amer. J. Psychol., 1958, 71: 298-304. 
1378. Farnsworth, D. An introduction to the princi- 
ples of color deficiency. U.S. Navy. Submarine Base, New 
London, Conn. Medical research laboratory. Project NM 
003 041. 60.01, 8 September 1954, 15 pp. 
1379. Farnsworth, D. Tritanomalous vision as a 
threshold function. Farbe, 1955, 4: 185-196. 
1380. Farnsworth, D. Exposure test of fluorescent 
paints to sun and salt water. U.S. Navy. Submarine Base, 
New London, Conn. Medical research laboratory. Project 
NM 002 014.09.05, 3 January 1956, 5 pp. 
1381. Farnsworth, D. Tritanomalous vision as a 
threshold function. U.S. Navy. Submarine Base, New 
London, Conn. Medical research laboratory. Project NM 
002 014.09, Kept. no. 3, 1956. 
1382. Farnsworth, D. and B. Hillmann. A compari- 
son of specifications for dark adapted red. U.S. Navy. 
Submarine Base, New London, Conn. Medical research 
laboratory. Project NM 002 014.01.01, 2 February 1953, 18 
pp. 
1383. Halsey, R. M. Identification of signal lights: I. 
Blue, green, white and purple: II. Elimination of the pur- 
ple category. U.S. Navy. Submarine Base, New London, 
Conn. Medical research laboratory. Project NW 22 02 20.03, 
Kept. no. 1, 22 May 1959. 
1384. Hillmann, B., K. Connolly and D. Farns- 
worth. Color perception of small stimuli with central 
vision. U.S. Navy. Submarine Base, New London, Conn. 
Medical research laboratory. Project NM 002 014.09.02, 
26 October 1954, 22 pp. 
1385. Katz, M. S., A. Morris and F. L. Dimmick. 
Effect of various durations of red adaptation on the course 
of subsequent dark adaptation. U.S. Navy. Submarine 
Base, New London, Conn. Medical research laboratory. 
Project NM 003 041.58.01, 27 April 1954, 9 pp. 
1386. Kelsey, P. A. and I. Schwartz. Nature of the 
limit of the color zone in perimetry. U.S. Navy. Submarine 
Base, New London, Conn. Medical research laboratory. 
Project MR 005.14-1001.1, Kept. no. 9, 20 October 1959. 
1387. Kenney, J. A. S. Comparison of scotopic, me- 
sopic and photopic spectral sensitivity curves. J. opt. Soc. 
Amer., 1958, 48: 185-190. 
1388. Malone, F. L. A preliminary field evaluation 
of the relative detectability of colors for air-sea rescue. 
U.S. Navy. Submarine Base, New London, Conn. Medical 
research laboratory. Project NM 002 014.09.01, 23 Novem- 
ber 1953, 10 pp. 
1389. Moody, J. A., P. C. Squires and W. G. 
Lewis. Photometric survey of the red lighting installation 
on the USS Seawolf. U.S. Navy. Submarine Base, New 
London, Conn. Medical research laboratory, Project NM 
002 014.08.13, 24 September 1956, 6 pp. 
1390. Moody, J. A., P. C. Squires, W. G. Lewis 
and J. W. Huff. Photometic survey of the red lighting 
installation in the USS DARTER (USS 576). U.S. Navy. 
Submarine Base, New London, Conn. Medical research 
laboratory. Project NM 002 014.08.11, 13 December 1956, 
6 pp. 
1391. Sexton, M. S., F. L. Malone and D. Farns- 
worth. The relative detectability of red-purples, reds, and 
yellow-reds, in air-sea rescue. U.S. Navy. Submarine Base, 
New London, Conn. Medical research laboratory. Project 
NM 003 041.35.02, 19 March 1952, 15 pp. 1392-1408 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
1392. VonSchelling, H. Charts for measuring the 
effect of illumination on color vision. U.S. Navy. Submarine 
Base, New London, Conn. Medical research laboratory. 
Project NM 003 041.33, Kept. no. 1, 1952. 
1393. VonSchelling, H. Thickness adjustment of 
glass filters to given total transmittance. U.S. Navy. Sub- 
marine Base, New London, Conn. Medical research labora- 
tory. Project NM 003 041.40, Kept. no. 2, 10 March 1952. 
1394. Wienke, R. E. Refractive error and the green/ 
red ratio. U.S. Navy. Submarine Base, New London, Conn. 
Medical research laboratory. Project MR 005.14-1001-1, 
Rept. no. 19, 6 June 1960. 
1395. Wienke, R. E. and I. Schwartz. Effect of con- 
tact lenses on the red/green ratio. U.S. Navy. Submarine 
Base, New London, Conn. Medical research laboratory. 
Project MR 005.14-1001-1, Rept. no. 12, 26 January 1960. 
1396. Willis, M. P. and D. Farnsworth. Compara- 
tive evaluation of anomaloscopes. U.S. Navy. Submarine 
Base, New London, Conn. Medical research laboratory. 
Project NM 003 041.26.01, 18 August 1952, 88 pp. 
1397. U.S. Navy. Analysis of colors used in Dvorine 
color perception testing charts. U.S. Navy. Submarine Base, 
New London, Conn. Medical research department. Project 
NM 003 041.10, Rept. no. 52-9, 28 August 1952, 10 pp. 
D. VISUAL PERFORMANCE 
Reference should be made to the report of 
Kinney and Pratt {1403) 1954, on the effect of 
refractive error on acuity through binoculars. 
The authors made a study of visual acuity 
through binoculars and of the extent to which 
refractive errors can be corrected by adjusting 
the eye pieces of standard binoculars. The acuity 
of individuals with various types of refractive 
errors was measured by a liminal method using a 
number of dioptric settings in the binoculars. It 
was shown that the acuity was best at a setting 
indicated by the results of refractions. The acui- 
ties of a group of naval enlisted men were tested 
using their optimum binocular settings and a 
comparison was made between the performance 
of men who did and who did not have unaided 
acuity of 20/20. Persons whose unaided acuity 
was poor due to simple sypherical errors per- 
formed as well with binoculars as those whose un- 
aided acuity was 20/20. The type of refractive 
error was shown to give a more adequate predic- 
tion of the individuals who perform well with 
binoculars than does the 20/20 standard. It was 
found that astigmatism of less than one-half 
diopter did not impair acuity under any of the 
conditions tested, but larger amounts of astigma- 
tism had a marked effect. 
Attention should also be directed to an evalua- 
tion by Workman and Prickett {1409) 1957, to 
determine the limitation of the visual field perim- 
eters and distortion within this perimeter for 
various diving masks. The authors describe the 
use of the perimeter detector and measurement of 
visual field and distortion while wearing various 
diving masks. Restriction of the visual field by 
the diving masks evaluated was found to be from 
40-50 degrees. Distortion was found only in the 
outer two degrees of the visual field. The results 
are discussed by the authors and recommenda- 
tions made for masks with the least restricted 
visual field. The authors also outline a standard 
evaluation procedure for use in determining 
visual field restriction and distortion. 
1398. Bakan, P. Discrimination decrement as a func- 
tion of time in a prolonged vigil. J. exp. Psychol., 1955, 
50: 387-390. 
1399. Colquhoun, W. P. The effect of ‘unwanted’ 
signals on performance in a vigilance task. Ergonomics, 
1961, 4: 41-51. 
1400. Hillman, B., G. B, Lee and H. G. Sperling. 
Brighteness thresholds as a function of target contrast and 
retinal position. U.S. Navy. Submarine Base, New London, 
Conn. Medical research laboratory. Project NM 002 
014.09.04, Kept. no. 4, 11 July 1955. 
1401. Jenkins, H. M. The effect of signal-rate on per- 
formance in visual monitoring. Amer. J. Psychol., 1958, 71: 
647-661. 
1402. Kappauf, W. E. and W. E. Powe. Perform- 
ance decrement at an audio-visual checking task. J. exp- 
Psychol., 1959, 57: 49-56. 
1403. Kinney, J. A. S. and C. H. Pratt. The effect 
of refractive error on acuity through binoculars. U.S. Navy. 
Submarine Base, New London, Conn. Medical research 
laboratory. Project NM 003 041.57, Kept. no. 1, 2 April 
1954. 
1404. Squires, P. C. New digit designs for use under 
reflected red light of low brightness. U.S. Navy. Submarine 
Base, New London, Conn. Medical research laboratory. 
Project NM 22 02 20, 20 May 1957, 11 pp. 
1405. Squires, P. S. Stereo-distance identification. 
U.S. Navy. Submarine Base, New London, Conn. Medical 
research laboratory. Project NM 22 02 20, 22 May 1957, 3 
pp. 
1406. Squires, P. C. and W. G. Lewis. Photometric 
survey of lighting installation on the submersible craft 
X-l (SSX-1). U.S. Navy. Submarine Base, New London, 
Conn. Medical research laboratory. Project NM 002 
014.08.12, 29 February 1956, 6 pp. 
1407. Tanner, W. P., Jr. and J. A. Swets. A deci- 
sion-making theory of visual detection. Psychol. Rev., 1954, 
61: 401-409. 
1408. White, C. T. and A. Ford. Eye movements 
during simulated radar search. /. opt. Soc. Amer., 1960, 
50: 909-913. AUDITORY PROBLEMS 
1409-1421 
1409. Workman, R. D. and C. M. Prickett. Visual 
field perimeter and distortion in diving masks. U.S. Navy. 
Naval Weapons Plant, EDU. Project NS 185-005, sub task 
no. 4, test no. 34, 1 February 1957, 5 pp. 
E. NIGHT VISION AND DARK 
ADAPTATION 
Of the references cited below, the paper by De 
Dodge and Smith (1412) 1952, is selected 
for special mention. These investigators explored 
the night sensitivity of the eye by using a spot of 
light of different brightness presented at nine 
points between one and 27 degrees from fixa- 
tion, in each of four positions: up, down, right 
and left. A total of 13,000 judgments were made 
by three observers. Overall sensitivity was found 
to increase rapidly to a peak between seven and 
twelve degrees from fixation and then to decrease 
steadily into the periphery. Sensitivity in the 
upper, lower, nasal and temporal quadrants 
follow the same general pattern but with certain 
specific differences. The nasal quadrant had the 
best sensitivity over the largest area. 
1410. Adams, J. A. Vigilance in the detection of low- 
intensity visual stimuli. J. exp. Psychol., 1956, 52: 204-208. 
1411. Arden, G. B. and R. A, Weale. Nervous me- 
chanisms and dark-adaptation. J. Physiol., 125: 417-426. 
1412. De Groot, S. G., J. M. Dodge and J. A. 
Smith. Factors in night vision sensitivity: the effect of 
Medical research laboratory. Project NM 003.041.09.04, 18 
brightness. U.S. Navy. Submarine Base, New London. 
Conn. Medical research laboratory. Project NM 003.041.09 
.04, 18 March 1952, 17 pp. 
1413. De Groot, S. C., J. M. Dodge and J. A. 
Smith. Factors in night vision sensitivity. III. The inter- 
relation of size, brightness, and location. U.S. Navy. Sub- 
marine Base, New London, Conn. Medical research labora- 
tory. Project NM 003 041.09.05, 14 September 1953, 13 pp. 
1414. Fooks, G., E. J. Sweeney and F. L. Dim- 
mick. Pilot studies of a scotopic sensitivity test. U.S. Navy. 
Submarine Base, New London, Conn. Medical research 
laboratory. Project NM 23 01 20, 14 June 1957, 7 pp. 
1415. Luria, S. M. and I. Schwartz, Effect of red vs 
white adaptation and target illumination on the temporal 
course of scopotic acuity. U.S. Navy. Submarine Base, New 
London, Conn. Medical research laboratory. Project 
MR005.14-1001-1, Rept. no. 20, 27 December 1960. 
1416. Smith, S. W. and F. L. Dimmick. Measure- 
ment of the light adaptation of the rods. J. opt. Soc. Amer., 
1957,47: 391-393. 
1417. Sweeney, E. J. Effect of test stimulus on the 
measurement of dark adaptation. J. opt. Soc. Amer., 1959, 
49: 667-668. 
1418. Sweeney, E. J. Effect of test stimulus on meas- 
urement of dark adaptation. U.S. Navy. Submarine Base, 
New London, Conn. Medical research laboratory. Project 
NM 22 01 20.01, Rept. no. 8, 8 September 1959. 
F. UNDERWATER VISION 
Miles {1421) 1962, has found that considerable 
absorption of light by water takes place. The 
light intensity is reduced to one-quarter at 15 
feet and to one-eighth at 50 feet. Bathyscaphes at 
1500 feet have shown that this is the limit of 
penetration by light from above. The type or 
character of the water alters these values. Colors 
become deceptive because light is unevenly ab- 
sorbed. Blue light penetrates further than red 
light; the best color for artificial light under 
water is yellow (the mid-spectrum). The intro- 
duction of an air space between the eye and the 
water (as is the case in wearing face masks) 
causes distortion at the interface. The change 
in density at the interface causes refraction of 
all rays except the perpendicular ones. This re- 
sults in the sensation of objects appearing closer 
than they really are, in fact they appear to be only 
three-quarters of their actual distance away. A 
report in press by Kenneth Faust constitutes an 
evaluation of underwater contact lenses. These 
lenses were developed by the Navy for under- 
water swimmers to obviate the use of face masks 
and the consequent limitation of lateral vision. 
1419. Arion, M. Verres de contact pour la vision sous- 
marine. Marseille tried., 1961, 98: 721-722. 
1420. Barnard, E. E. P. Visual problems under water. 
Proc. R. Soc. Med., 1961, 54: 755-756. 
1421. Miles, S. Vision, hearing and special senses, pp. 
148-157 in: Underwater medicine. J. B. Lippincott Co., 
Philadelphia, 1962, 328 pp. 
IX. AUDITORY PROBLEMS 
The reader is referred to a survey report on 
basic problems of underwater acoustics research 
published by the NRG Committee on Undersea 
Warfare (1457) 1950. Auditory problems in sub- 
marine operations include those pertinent to 
sonar operators and sound communication on a 
background of noise. One of the most important 
tasks of the sonar operator is the detection of 
an auditory signal which is more or less masked 
by a background of sound. Thus studies of mask- 
ing are of major practical importance in under- 
water acoustics. Sound thresholds in noise (1450) 
1959, and recovery times from noise and auditory 
fatigue (1452, 1453) 1952, are subjects of 
importance. 
A large number of the items included in this 
section are reports of auditory research conducted 1422-1450 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
at the Medical Research Laboratory, U.S. Sub- 
marine Base, New London, Connecticut. 
1422. Broadbent, D. E. Failure of attention in selec- 
tive listening. Gt. Brit. MRC, RNPRC. Kept. R.N.P. 
52,698, O.E.S. 210, A.P.U. 168/51, 1952, 8 pp. 
1423. Broadbent, D. E. A review of multiple channel 
listening experiments. Gt. Brit. MRC, RNPRC, OES. 
Rept. R.N.P. 55/833, O.E.S. 257, April 1955, 9 pp. 
1424. Close, P. and R. G. Ireland. Alterations in the 
pure tone threshold following changes in both absolute 
and differential pressures upon the ear. U.S. Navy. NATB, 
Pensacola, Fla. School of Aviation Medicine. Project no. 
MR 005.13-1002, subtask 13, Rept. no. 1, 1 November 1960, 
9 pp. 
1425. Faucett, R. E. The effect of Dramamine on 
visual and auditory acuity. U.S. Navy. Submarine Base, 
New London, Conn. Medical research laboratory. Project 
NM 002 015.09, Rept. no. 1, 3 April 1953. 
1426. Glorig, A. and H. P. House. A new concept 
in auditory screening. Arch. Otolaryng., 1957, 66: 228- 
232. 
1427. Harris, J. D. The decline of pitch discrimina- 
tion with time. U.S. Navy. Submarine Base, New London, 
Conn. Medical research laboratory. Project NM 003 
041.22.03, 28 January 1952, 13 pp. 
1428. Harris, J. D. An historical and critical review of 
loudness recruitment. U.S. Navy. Submarine Base, New 
London, Conn. Medical research laboratory. Project NM 
003 041.21.07, 20 May 1952, 47 pp. 
1429. Harris, J. D. Pitch discrimination. U.S. Navy. 
Submarine Base, New London, Conn. Medical research 
laboratory. Project NM 003 041.22.04, 20 June 1952, 22 pp. 
1430. Harris, J. D. The roles of sensation level and 
of pressure in producing reversible auditory fatigueXaryn- 
goscope, St. Louis, 1954, 64: 89-97. 
1431. Harris, J. D. The roles of sensation level and of 
sound pressure in producing reversible auditory fatigue. 
U.S. Navy. Submarine Base, New London, Conn. Medical 
research laboratory. Project NM 003 041.56, Rept. no. 2, 
19 April 1954. 
1432. Harris, J. D. Revisions of the Navy Sonar Pitch- 
Memory Test. U.S. Navy. Submarine Base, New London, 
Conn. Medical research laboratory. Project NM 003 
041.55.01, 20 April 1954, 11 pp. 
1433. Harris, J. D. Peak vs. total energy in thresholds 
for very short tones. Acta oto-laryng., Stockh., 1957, 47: 
134-140. 
1434. Harris, J. D. The relation between the audio- 
gram, contact’detection, and sonar operation performance. 
U.S. Navy. Submarine Base, New London, Conn. Medical 
research laboratory. Project NM 22 03 20.3.03, 15 Novem- 
ber 1957, 15 pp. 
1435. Harris, J. D., H. L. Haines and C. K. Myers. 
A helmet-held bone conduction vibrator. Laryngoscope, 
St. Louis, 1953, 63: 998-1007. 
1436. Harris, J. D., H. L. Haines and C. K. Myers. 
A new formula for using the audiogram to predict hear- 
ing loss for speech. U.S. Navy. Submarine Base, New Lon- 
don, Conn. Medical research laboratory. Project NM 003 
041.56.07, 24 February 1956, 28 pp. 
1437. Harris, J. D., H. L. Haines and C. K. Myers. 
Brief- tone audiometry. Arch. Otolaryng., 1958, 67: 699- 
713. 
1438. Harris, J. D., H. L. Haines and C. K. Myers. 
Brief tone audiometry: temporal integration in the hy- 
pacusic. U.S. Navy. Submarine Base, New London, Conn. 
Medical research laboratory. Project NM 22 01 20.03, Kept, 
no. 3, 1958. 
1439. Harris, J. D., H. L. Haines and C. K. Myers. 
The importance of hearing at 3 KC for understanding 
speeded speech. U.S. Navy. Submarine Base, New London, 
Conn. Medical research laboratory. Project MR 005.14- 
1001-2, Kept. no. 5, 11 April I960. 
1440. Harris, J. D. and C. K. Myers. Experiments 
on fluctuation of auditory acuity. U.S. Navy. Submarine 
Base, New London, Conn. Medical research laboratory. 
Project NM 003, 041.21.08, 22 June 1952, 29 pp. 
1441. Harris, J. D. and A. I. Rawnsley. The locus 
of short duration auditory fatigue on “adaptation.” U.S. 
Navy. Submarine Base, New London, Conn. Medical 
research laboratory. Project NM 003 041.56.01, 22 January 
1954. 
1442. Kelsey, P. A. and A. I. Rawnsley. Adaptation 
of the ear to sound stimuli. The intensity time relation- 
ship. U.S. Navy. Submarine Base, New London, Conn. 
Medical research laboratory. Project NM 003 041.34.06, 
20 May 1953, 9 pp. 
1443. Knight, J. J. and R. R. A. Coles. Determina- 
tion of the hearing thresholds of naval recruits in terms of 
British and American standards. /. acoust. Soc. Amer., 1960, 
32: 800-804. 
1444. Kohl, O. A. and W. F. Searle, Jr. Subjective 
and articulation tests of deep and shallow water divers 
communication. U.S. Navy. Naval. Weapons Plant, EDU. 
Project NS 185-005, sub task no. 2, test no. 10, 19 August 
1957, 25 pp. 
1445. Lawrence, M. and P. A. Yantis. Thresholds 
of overload in normal and pathological ears. Arch. 
Otolaryng., 1956, 63: 66-77. 
1446. Loeb, M. and E. A. Schmidt. Influence of time 
on task and false information on efficiency of responding 
to pure tones. U.S. Army. Fort Knox, Kentucky. Medical 
research laboratory. Kept. no. 426, 20 April 1960, 8 pp. 
1447. Mackworth, J. F. and N. H. Mackworth. 
The overlapping of signals for decisions. Amer. J. Psychol., 
1956, 69: 26-47. 
1448. O’Hare, J. J. The effect of visual stimulus on 
threshold of auditory acuity. U.S. Navy. Submarine Base, 
New London, Conn. Medical research laboratory. Project 
NM 003 041.21, Kept. no. 9, 1952. 
1449. O’Hare, J. J., J. D. Harris, R. H. Ehmer and 
B. H. Cohen. Some primary auditory abilities in pitch 
and loudness. U.S. Navy. Submarine Base, New London, 
Conn. Medical research laboratory. Project NM 22 01 20.02, 
Kept. no. 2, 15 September 1959. 
1450. Pettie, C. R. The loudness difference limen for 
tones in noise. U.S. Navy. Submarine Base, New London, 
Conn. Medical research laboratory. Project NM 22 01 
20.02.01, 7 August 1959, 5 pp. NOISE—PHYSIOLOGICAL AND PATHOLOGICAL EFFECTS 
1451-1468 
1451. Poulton, E. C. The optimal perceptual load in 
a paced auditory inspection task. Brit. J. Psychol., 1960, 
51: 127-139. 
1452. Rawnsley, A. I. and J. D. Harris. Studies in 
short duration auditory fatigue. IV. Recovery time. U.S. 
Navy. Submarine Base, New London, Conn. Medical re- 
search laboratory. Project NM 003 041.34.03, 30 January 
1952, 11 pp. 
1453. Rawnsley, A. I. and J. D. Harris. Studies in 
short duration auditory fatigue. V. An investigation of 
the spread of fatigue within narrow frequency limits. U.S. 
Navy. Submarine Base, New London, Conn. Medical re- 
search department. Project NM 003 041.34.04, 16 May 1952, 
14 PP- 
1454. Rawnsley, A. I. and J. D. Harris. Compara- 
tive analysis of normal speech and speech with delayed 
side-tone by means of spectrograms. U.S. Navy. Submarine 
Base, New London, Conn. Medical research laboratory. 
Project NM 003 041.56.03, 27 April 1954, 5 pp. 
1455. Schmidt, P. H. and H. A. E. van Dishoeck. 
The effect on cochlear potentials of positive and negative 
pressures in the outer ear of the guinea-pig. Acta physiol, 
pharm. neerl., 1959, 8: 298-299. 
1456. U.S. Navy. Report of effects of pressure on vari- 
ous units of USN USL voice communication system for 
underwater demolition teams. U.S. Navy. Submarine Base, 
New London, Conn. Medical research laboratory. Project 
NM 002 014.06. 01, 15 February 1954, 6 pp. 
1457. U.S. NRC. A survey report on basic problems 
of underwater acoustics research. U.S. NRC, Committee 
on Undersea Warfare, Washington, D.C., 1950, 137 pp. 
1458. White, C. E. Relative evaluation of earphones 
by search tube microphone techniques as applied to the 
Permoflux PDR-8 ano the Telex Twinset units. U.S. Navy. 
Submarine Base, New London, Conn. Medical research 
laboratory. Project NM 003 041.21.09, 6 May 1953, 20 pp. 
1459. Wing, K. G. A progress report on hypoglycemia 
and cochlear microphonics. U.S. Navy. Submarine Base, 
New London, Conn. Medical research laboratory. Project 
NM 002 015.15, Kept. no. 1, 28 June 1954. 
X. NOISE 
A. GENERAL STUDIES 
The principal noise problems in submarine 
operations are 1) effects of noise on hearing, 2) 
disturbance of performance due to noise, 3) 
effects of noise upon sound communication. For 
a good review of the subject a chapter by Par- 
rack {1464) 1961, may be consulted. Although 
much of the information presented does not 
apply to submarine noise, Parrack’s chapter is 
valuable not only in providing useful data but 
also in presenting a basic reference source. 
Except for noise in the area of the sonar head 
nuclear powered submarines operate quietly. 
Fleet type submarines powered with diesel en- 
gines are noisy and the noise level varies. Harris 
and White {1462) 1953, have analyzed the am- 
bient noise in the engineroom of the USS Harder 
at six duty stations. In these studies either one, 
two or three engines were running at idling speed 
and again at full load. All conditions were run 
both with and without silencing hoods on the 
engine. The weakest reading, with one engine 
idling, was 108.9 db at one microphone position. 
The loudest reading, with three engines fullload, 
hoods off, was 129 db. With two engines full 
load, hoods on, the noise levels were always over 
115 db. and ranged up to 124.2 db. With three 
engines full load, hoods on, the levels were 
about 120 db. ranging up to 125.5 db. The effect 
of the silencing hoods was almost negligible be- 
low 300 cycles per second, but ranged up to 5 or 
6 db. at the higher frequencies. The overall noise 
levels were reduced on the average three db. by 
the silencing hoods. 
1460. Burns, W. and T. S. Littler. Noise, pp. 249- 
267 in: Modern trends in occupational health. Edited by 
R.S.F. Schilling. Butterworth and Co., Ltd., London, 1960, 
313 pp. 
1461. Cox, J. R., Jr. Industrial noise and the con- 
servation of hearing, pp. 621-693 in: Industrial hygiene 
and toxicology. Volume I. Edited by F. A. Patty, Inter- 
science Publishers, Inc., New York, 1958, 830 pp. 
1462. Harris, J. D. and C. E. White. Analysis of 
ambient noise in engineroom of USS HARDER (SS568). 
U.S. Navy. Submarine Base, New London, Conn. Medical 
research laboratory. Project NM 003 041.56, 21 December 
1953, 11 pp. 
1463. Lund-Iversen, L. Noise and hearing conditions 
on board Norwegian motor torpedo boats and submarines. 
Acta oto-laryng., Stockh., 1957, 47: 50-63. 
1464. Parrack, H. O. Effects of acoustic energy, pp. 
284-323 in: Aerospace medicine. Edited by H. G. Arm- 
strong, Williams and Wilkens Co., Baltimore, 1961, 633 pp. 
1465. Peterson, A. P. G. and E. E. Gross, Jr. 
Handbook of noise measurement. General Radio Company, 
West Concord, Mass., 1960, 132 pp. 
1466. Slager, U. T. Noise and vibration, pp. 241-257 
in: Space medicine. Prentice-Hall, Inc., Englewood Cliffs, 
N.J., 1962, 388 pp. 
1467. White, C. E. Memorandum on noise measure- 
ment. U.S. Navy. Submarine Base, New London, Conn. 
Medical research laboratory. Project NM 003 041.34, 24 
July 1953, 11 pp. 
1468. Yaffe, C. D. and H. H. Jones. Noise and hear- 
ing. U.S. HEW, PHYS, Div. Occupational Health. Govt. 
Printing Office, Washington, D.C., 1961, 72 pp. 
B. PHYSIOLOGICAL AND PATHOLOGICAL 
EFFECTS 
In a study of the threshold of aural pain to 
high intensity sound, Ades, Morrill and Graybiel SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
{1469) 1959, exposed deaf and normal human 
subjects monaurally to high intensity noise stim- 
uli, including pure tone and broad band noise. 
The threshold of aural pain resulting from sound 
stimulation was found to lie in the range from 
140 db and above in the normal ear, and 150 db 
and above in the nerve deaf ear with intact 
drum. There was evidence of slight interaction 
of hearing and pain perception. The ear drum 
contains the principal pain perceptive mechan- 
ism. Aural pain is without value as a warning 
mechanism for acoustic trauma by high intensity 
sound. It was found that there was considerable 
variation of thresholds for deaf subjects which 
were slightly higher than for normal persons. 
According to Sackler, Weltman, Bradshaw and 
Jurtshuk {1489) 1959, significant endocrine 
changes occur in a female Wistar strain rat sub- 
jected to intense auditory stimulation with a 
mean intensity of 110 db at frequencies of 
375-500 cps. There was a reduction in weight 
gain and serious changes both in endocrine 
weight and histologic structure of endocrine or- 
gans. There was adrenal hyperplasia, partial in- 
hibition of ovarian activity, reduction in weight 
and vascularity of the uterus and loss in liver 
weight. Although no changes were found in 
either the pituitary or thyroid weight there were 
significant changes in the pituitary cell type and 
in thyroid colloid storage. The influence of high 
intensity noise on visual thresholds has been 
studied by Coleman and Krauskopf {1477) 1956. 
Using the psychophysical method of limits, thres- 
holds for three visual stimuli were determined 
during noise and quiet conditions. Noise intensi- 
ties were varied between 110 and 140 db. It was 
found that noise had no general effect on visual 
thresholds at any of the intensities used in the 
experiments. No differential effect of noise on 
the thresholds for the three visual stimuli used 
was demonstrated. There were consistent indi- 
vidual differences in visual threshold changes 
during noise. Absence of any demonstrable gen- 
eral effect of noise was due to cancellation of 
opposite effects in individuals. A possible factor 
contributing to these individual differences was 
investigated by showing the subjects’ spurious 
curves, purported to represent their performance 
during previous sessions. The subject’s perform- 
ance did seem to be influenced by the fake curves, 
although statistical significance was not demon- 
strated. Krauskopf, Coleman and Kalla {1482) 
1956, investigated the effect of monaural and 
binaural stimulation with high intensity noise 
on the amplitude of eye movement occurring dur- 
ing fixation. It was found that 137 db noise de- 
livered binaurally produced a significant in- 
crease in eye movement records. A partial analy- 
sis of records of the eye movements suggested 
that the increase in total movement was due to 
an increase in the high frequency fine tremor 
components of the record. Monaural stimulation 
with noise of the same intensity failed to produce 
any significant change in the records. 
For studies on gastrointestinal reactions during 
a noise avoidance task a report by Davis and 
Berry {1478) 1961, should be consulted. Bio- 
chemical and histological changes in the cochlea 
of rabbits and guinea pigs have been observed 
after exposure to noise by Koide, Konno, Yoshi- 
kawa, Yoshida, Naakno, Nagaba and Morimoto 
{1481) 1960. For related studies attention is 
drawn to a paper by Misrahy, Arnold, Mundie, 
Shinabarger and Garwood {1484) 1958. Oleneva 
{1485) 1961, found that sound stimulation in 
rats produced visible disturbances in the blood 
vessels of the brain and changes in nerve cell 
dendrites and myelin fibers. These changes ap- 
peared to be localized chiefly in the medial 
geniculate body, and related cortex. 
Palmgren {1496) 1960, has conducted an 
otorhinolaryngologic investigation of construc- 
tion workers employed in the Stockholm under- 
ground railway from 1953 to 1957. These con- 
struction operations were carried out in caissons 
under excess pressure and noisy conditions. The 
highest pressure measured from 1.3 to 1.4 at- 
mospheres (gauge). In addition to a general 
medical examination, all workers were subjected 
to otorhinolaryngologic investigations. Of 173 
applicants accepted on the basis of the general 
medical examination, 24 were rejected because 
of changes in the ear, nose and throat region. 
Nine were rejected because of earlier noise dam- 
age, two because of perceptive deafness in the 
greater part of the frequency range from 125 to 
8000 cps, ten because of deviation of the nasal 
septum, two because of pathologic tympanic 
membranes following earlier acute otitis media, 
and one because of inward bulging of the tym- NOISE—HEARING DEFECTS 
1469-1492 
panic membranes after test compression at three 
atmospheres. Audiograms were taken in 1953 
and in 1957 on all workers subjected to follow-up 
examination. Of those examined 21 had normal 
audiograms on both occasions; four were normal 
in 1953 but showed incipient noise damage in 
1957. In 1953 24 men already presented noise 
damage. Eleven of these had unchanged audio- 
grams in 1957, while six showed 15 db deteriora- 
tion of hearing and seven a deterioration of 
more than 15 db. The total caisson working 
time was 1233 days. The highest measured 
noise level for the loading machine which pro- 
duced most of the noise was 100 db at 1000 cps. 
1469. Ades, H. W., S. N. Morrill and A. Graybiel. 
Threshold of aural pain to high intensity sound. Aero- 
space Med., 1959, 30: 678-684. 
1470. Anthony, A. Effects of noise on eosinophil levels 
of audiogenic-seizure-susceptible and seizure-resistant mice. 
J. acoust. Soc. Amer., 1955, 27: 1150-1153. 
1471. Anthony, A. Changes in adrenals and other 
organs following exposure of hairless mice to intense 
sound. J. acoust. Soc. Amer., 1956, 28: 270-274. 
1472. Anthony, A. and E. Ackerman. Effects of 
noise on the blood eosinophil levels and adrenals of mice. 
J. acoust. Soc. Amer., 1955. 27; 1144-1149. 
1473. Anthony, A. and S. Babcock. Effects of in- 
tense noise on adrenal and plasma cholesterol of mice. 
Experentia, 1958, 14: 104-105. 
1474. Bagley, W. P. Biological effects of high in- 
tensity noise. J. environ. Sci., 1960, 3: 24—26; 29. 
1475. Bugard, P. L’action des bruits sur 1’organisme, 
I’im-portance des effets non specifiques. Rev. Cps. SantS 
milit., 1960,1: 58-72. 
1476. Busnengo, E. Alcuni effetti dell'esposizione dell’ 
uomo ai rumori e alle vibrazioni di motori a turbopropul- 
sione. Riv. Med. aero., 1959, 22; 73-84. 
1477. Coleman, P. D. and J. Krauskopf. The in- 
fluence of high intensity noise on visual thresholds. U.S. 
Army. Fort Knox, Kentucky, Medical research laboratory. 
Rept. no. 222, 22 February 1956, 26 pp. 
1478. Davis, R. C. and F. Berry. Gastrointestinal 
reactions during a noise avoidance task. U.S. Army Office 
of Surgeon General. Tech. Rept. DA-49-I93-HD 2063, 
July 1961, 7 pp. 
1479. Hines, M. The effects of intense vibration. U.S. 
Army. Fort Knox, Kentucky. Medical research laboratory. 
Rept. no. 358, 10 October 1958, 57 pp. 
1480. Kiang, N. Y. and M. H. Goldstein, Jr. Re- 
sponses from auditory cortex to repeated bursts of noise. 
Fed. Proc., 1956, 15: 110. 
1481. Koide, Y., M. Konno, Y. Yoshikawa, M. 
Yoshida, Y. Nakano, M. Nagaba and M. Morimoto. 
Some aspects of the biochemistry of acoustic trauma. Ann. 
Otol., etc., St. Louis, 1960, 69: 661-697. 
1482. Krauskopf, JM P. D. Coleman and R. Kalla. 
The effect of noise on eye movements. U.S. Army. Fort 
Knox, Kentucky, Medical research laboratory. Kept. no. 
218, 15 February 1956, 8 pp. 
1483. Lawrence, M. The effects of intense vibration. 
U.S. Army. Fort Knox, Kentucky. Medical research labora- 
tory. Kept. no. 358, 10 October 1958, 57 pp. 
1484. Misrahy, G. A., J. E. Arnold, J, R. Mundie, 
E. W. Shinabarger and V. P. Garwood. Genesis of 
endolymphatic hypoxia following acoustic trauma. /. 
acoust. Soc. Amer., 1958, 30: 1082-1088. 
1485. Oleneva, G. N. Narusheniia krovoobrashcheniia 
i gistopatologicheskie izmeneniia v golovnom mozgu belykh 
krys pri deistvii zvuka. [Circulatory disturbances and histo- 
pathological changes in the brain of white rats due to the 
action of sound.] Vestn. Otorhinolaryng., Leningr., 1961, 
23: 34-40. 
1486. Palmgren, R. Work under compression and in 
noisy environments. An oto-rhinolaryngologic investiga- 
tion of construction workers building the Stockholm under- 
ground railway from 1953 to 1957. Acta oto-laryng., Stockh., 
1960. 51: 165-174. 
1487. Riopelle, A. J. The effects of intense vibration. 
U.S. Army. Fort Knox, Kentucky. Medical research labora- 
tory. Kept. no. 358, 10 October 1958, 57 pp. 
1488. Ruedi, L. Different types and degrees of acoustic 
trauma by experimental exposure of the human and ani- 
mal ear to pure tones and noise. Ann. Otol., etc., St. Louis, 
1954, 63: 702-725. 
1489. Sackler, A. M., A. S. Weltman, M. Bradshaw 
and P. Jurtshuk, Jr. Endocrine changes due to auditory 
stress. Acta endocr., Copenhagen, 1959, 31: 405-418. 
1490. Sackler, A. M., A. S. Weltman and P. Jurt- 
shuk, Jr. Endocrine aspects of auditory stress. Aerospace 
Med., 1960, 31: 749-759. 
1491. Schaefer, V. H., R. G. Ulmer, H. J. Link, 
R. H. Bouchard, D. H. Yost and R. L. Jacobs. Some 
behavioral and physiological studies in vibration. U.S. 
Army. Fort Knox, Kentucky. Medical research laboratory. 
Kept. no. 389, 12 June 1959, 28 pp. 
1492. Wever, E. G. and M. Lawrence. Patterns of 
injury produced by overstimulation of the ear. /. acoust. 
Soc. Amer., 1955, 27; 853-858. 
C. HEARING DEFECTS FROM EXPOSURE 
TO NOISE 
Studies on the effect of short exposures to sub- 
marine engine noise on auditory acuity have 
been reported by Harris {1484) 1952. These 
workers presented tape-recorded noise from the 
engineroom of the submarine USS HARDER to 
Submarine School candidates at levels up to 
110 db for 30 minutes. Pre- and post-exposure 
audiograms were collected. Levels of 105 db 
could be withstood easily for 30 minutes by all 
but the most fatigue-susceptible subjects. Levels 
of 100 db left residual losses sufficiently signifi- 1493-1502 
SPECIAL ANATOMY, PHYSIOLOGY, AND BIOCHEMISTRY 
cant to reduce speech communicability for a half- 
hour or more. This is a noise level commonly 
reached in fleet type submarines. The relation 
of occupational noise exposure to loss of hearing 
acuity has been reported by Pell (1499) 1957, 
who studied audiograms of 1049 males exposed to 
continuous and steady-state noise for five years. 
Over-all noise level categories included: 1) less 
than 75 db; 2) 75-84 db; 3) 85-90 db. These 
studies showed that hearing acuity of persons 
with normal audiograms was affected by five years 
occupational noise from 75 to 90 db. With Stage 
1 hearing loss at the onset (no hearing loss from 
250 to 2000 cps and moderate hearing loss at 
4000 and/or 8000 cps) acuity was affected by 
exposure to 85 to 90 db, but was not affected be- 
tween 75 and 84 db. With Stage 2 hearing loss 
at the onset (no hearing loss from 250 to 2000 
cps, but severe hearing loss at 4000 and/or 8000 
cps) the loss was not affected up to 90 db. It was 
found that hearing loss begins rapidly and pro- 
ceeds slowly in its advanced stages. Persons over 
45 were found to be more susceptible to trau- 
matic hearing loss. 
Webster and Solomon (1502) 1954, have 
studied the prevalence of hearing losses among 
submariners. They administered the Naval Elec- 
tronics Laboratory warble tone hearing test to 
1053 submariners. Hearing losses of less than 5 
db could not be measured at 500 cps due to 
ambient noises in the training areas. At the other 
test frequencies (1000, 2000, 4000 and 7000 cps) 
any positive value of hearing loss could be meas- 
ured. It was found that approximately 10 per- 
cent of all the subjects tested had high frequency 
hearing losses of 18 db or greater (at 4000 and 
7000 cps). Comparison of hearing losses of 
engine men to those of all others as a function of 
time on the boat for each frequency showed in 
general that engine men had greater losses at all 
frequencies although there were minor reversals. 
The amount of loss was somewhat less than ex- 
pected from previous findings. In a study of 
recovery following stimulation up to 140 db, 
Harris (1495) 1953, have three fatigue-resistant 
subjects stimulation at 120 to 140 db sound pres- 
sure level (750 cps) for up to ten minutes. Re- 
covery to normal threshold at 1000 cps was 
studied with especial care. The shape of the re- 
covery curve was found to depend on both the 
intensity and duration of stimulation, the best 
predictor being a combination of both factors. 
Hearing loss is a linear function of stimulus 
duration, the function having a different slope 
for each stimulus intensity. To a less reliable ex- 
tent, hearing loss is also a linear function of 
stimulus intensity when the stimulus duration is 
the parameter. A family of equi-noxious curves 
appears from these data, showing the combina- 
tions of intensity and duration which produce 
equally deleterious effects on the auditory thres- 
hold. These results will predict the hearing losses 
(at frequencies important in speech communica- 
tion) by being immersed in the noise band of 
600 to 1200 cps for up to ten minutes at sound 
pressure levels up to 140 db. 
1493. Ehmer, R. H. Masking by tones vs. noise bands. 
U.S. Navy. Submarine Base, New London, Conn. Medical 
research laboratory. Project MR 005.14-1001-2, Kept. no. 
4, 14 April 1960. 
1494. Harris, J. D. Effect on auditory acuity of short 
exposures to submarine engine noise. U.S. Navy. Sub- 
marine Base, New London, Conn. Medical research depart- 
ment. Project NM 003 041.34, 18 December 1952, 9 pp. 
1495. Harris, J. D. Recovery curves and equinoxious 
exposures in reversible auditory fatigue following stimula- 
tion up to 150 DB plus. Laryngoscope, St. Louis, 1953, 63: 
660-673. 
1496. Harris, J. D. Recovery curves and equinoxious 
exposures in reversible auditory fatigue following stimula- 
tion up to 140 DB. U.S. Navy. Submarine Base, New Lon- 
don, Conn. Medical research laboratory. Project NM 003 
041.34, Kept. no. 5, 22 November 1953, 
1497. Harris, J. D. Auditory fatigue following high 
frequency pulse trains. U.S. Navy. Submarine Base, New 
London, Conn. Medical research laboratory. Project NM 
22 03 20.2, January 1959, 9 pp. 
1498. Lawrence, M. and C. L. Blanchard. Predic- 
tion of susceptibility to acoustic trauma by determination 
of threshold distortion. Univ. Mich. med. Bull., 1954, 20: 
81-92. 
1499. Pell, S. The relation of occupational noise ex- 
posure to loss of hearing acuity. Arch. Otolaryng., 1957, 
66: 79-92. 
1500. Sataloff, J. Effect of prolonged exposure to in- 
tense noise on hearing acuity. Arch. Otolaryng., 1953, 58: 
62-80. 
1501. Schulthess, G. V. Evaluation of hearing impair- 
ment due to industrial noise. Arch. Otolaryng., 1957, 65: 
512-520. 
1502. Webster, J. C. and L. N. Solomon. Hearing 
losses among submariners and their relation to Navy audi- 
tory tasks. U.S. Navy. Naval Electronics Laboratory, San 
Diego, Calif., Res. Rept. 549, 25 October 1954, 16 pp. NOISE—EFFECTS ON EFFICIENCY 
D. EFFECTS OF NOISE ON EFFICIENCY 
It has earlier been suggested on the basis of 
tests that aside from the engine rooms, no com- 
partments in the fleet type submarines is noisy 
enough to reduce auditory acuity noticeably or 
to diminish psychomotor or physiological effici- 
ency. However, it does appear that reduction in 
performance can result from certain intensities 
and durations of noise. Such a study has been re- 
ported by Broadbent (1503) 1951. Performance 
on noisy days under test conditions was worse 
than on quiet days. When lights were used the 
performance decrement was diminished. Broad- 
bent (1503) 1953, has shown that under noisy 
conditions vigilance tasks are performed less 
well. Broadbent (1507) 1954, had demonstrated 
that a high-pitched noise causes more errors in 
performance than those of lower pitch, the dif- 
ference being most apparent at the highest in- 
tensity of noise (100 db). In a study of the ef- 
fects of noise on visual performance Broadbent 
(1508) 1954, found in a group of 10 subjects 
that impaired performance (watch keeping on a 
display made up of steam pressure gauges) was 
greater in a condition of 100 db noise as com- 
pared with 70 db. On easier tasks of watch keep- 
ing (a display of small lights) another group of 
20 subjects showed no overall effect of noise. 
With continued exposure the performance on 
light watching tended to become relatively less 
efficient in noise so that some parts of the task 
were still adequately carried out while others 
were not. Thus noise effects are functions of in- 
dividual differences, of visibility of signals and 
of length of performance in noise. In a further 
study of the effect of noise on intellectual tasks, 
Broadbent (1509) 1957, studied three groups of 
Naval ratings who worked for two sessions with 
a subtraction task involving a memory load. 
One group had both sessions in relative quiet 
(70 db) while the other group had the first 
session at 100 db and the second session in quiet. 
A third group had noise and quiet in the re- 
verse order. In the first session, the noise group 
slowed down at solving subtraction problems as 
time proceeded. This was greater than in groups 
working under quiet conditions. Subjects who 
had been subjected to noise in a previous session 
exhibited an after-effect in the subsequent session. 
Slowing down of performance with time of ex- 
posure to noise was in all groups most marked 
in subjects described as extroverts. Thus it was 
concluded by the author that intellectual work 
must be regarded as endangered by noises, and 
that there may be harmful after-effects of noise. 
In order to investigate whether performance is 
affected by short bursts of loud sound, Woodhead 
{1510) 1957, subjected two groups of 12 subjects 
each to a visual matching task with these con- 
ditions: the task ran for four minutes and four 
noise bursts were given at irregularly spaced in- 
tervals during that time; each of these bursts 
lasted for four seconds and reached a peak in- 
tensity of 100 db. One group of subjects was 
given more information about the test than 
the other; the informed group also received 
verbal encouragement and knowledge of results. 
The aim of these apparently more favorable 
testing conditions was to discover whether or not 
any performance deterioration after noise could 
be lessened by alerting the men to the danger 
and encouraging them to overcome it. It was 
concluded that bursts of loud noise heard by men 
engaged on a visual task caused immediate de- 
terioration in the performance of most of the 
men, with complete recovery within the next 
half minute. The results demonstrated a general 
tendency to deteriorate immediately after noise, 
even when the operators were aware of this 
possibility and were trying to deal with it. Small 
variations in the task, such as a warning light, 
did not prevent deterioration. Prior verbal alert- 
ing and instruction to some operators enabled 
only a third of these to avoid the detrimental 
effects. In a further study Woodhead {1512) 
1958, studied effects of low frequency noise 
bursts at 85, 95 and 115 db on a rapid decision- 
making task. The intention was to determine 
whether the unfavorable effects of a missile noise 
on performance might vary with the level of in- 
tensity of the noise. Tests endured for four 
minutes with 70 rapid decisions the rate of work 
varying rapidly with the changing rate of dis- 
play on the screen. Four versions were given, 
timing the noise differently and once in silence. 
It was found that performance deteriorated 
progressively with the increased noise level. That 
is to say, 85 db affected work considerably less 1503-1518 
SPECIAL ANATOMY. PHYSIOLOGY, AND BIOCHEMISTRY 
In all other respects differences among listeners 
were small. 
1514. Hoffman, H. S. The detection of signals and 
their attributes. U.S. Navy. Submarine Base, New London, 
Conn. Medical research laboratory. Project NM 003 
041.55.02, 25 September 1956, 6 pp. 
1515. Pestalozza, G. and A. Lazzaroni. Noise effect 
on speech perception in clinical and experimental types 
of deafness. Acta oto-laryng., Stockh., 1954, 44\ 350-358. 
F. PROTECTION AGAINST NOISE 
Considerable attention has been given in the 
literature to the development and use of ear de- 
fender devices with the purpose of providing ade- 
quate insulation against high level sound inten- 
sities so that the magnitude of the sound reach- 
ing the ear drums is reduced to non-injurious 
levels. A report by Harris (1517) 1955, provides 
an evaluation of ear defender devices: two ear- 
plugs, four cushions and three combinations. 
This author has pointed out that the standard 
Navy ear defender (V-51R) is unsatisfactory in 
some respects; some people receive little protec- 
tion, and the device is apparently uncomfortable 
for some and cannot be used with hypersensitive 
ears or with infected ears. A foam rubber type 
of earplug (impregnated with moldable wax) 
was found to be as effective for the average per- 
son, and to give more protection to those individ- 
uals for whom the latter apparently had little 
value. For individuals who were unable to toler- 
ate any type of plug, four types of earmuffs were 
investigated. One of these was found to be 
appreciably better than the other three al- 
though this model was somewhat bulky for use 
in close spaces. In any situation it was found that 
maximum protection could be achieved by using 
an earplug in combination with any of several 
small lightweight earmuffs. For papers on con- 
servation of hearing in occupational noise and 
problems of noise in industry, those by Bums and 
Littler (1516) and Reilly (1518) may be con- 
sulted. 
1516. Burns, W. and T. S. Littler. Conservation of 
hearing in occupational noise. Gt. Brit. MRC, RNPRC, 
OES, Kept. R.N.P. 57/881, O.E.S. 292, H P. 7, 1957, 7 pp. 
1517. Harris, J. D. An evaluation of ear defender 
devices: two earplugs, four cushions and three combina- 
tions. U.S. Navy. Submarine Base, New London, Conn. 
Medical research laboratory. Project NM 003 041.56, Rept. 
no. 6, 15 December 1955. 
1518. Reilly, N. The problem of noise in industry. 
Med. J. Aust., 1959, 1: 700-703. 
than did 95 and 115 db. It was considered that a 
level of 90 db was critical. 
1503. Broadbent, D. E. The twenty dials and twenty 
lights test under noise conditions. Gt. Brit. MRC, 
RNPRC. Rept. R.N.P. 52/699, A.P.U. 160/51, 1951, 8 pp. 
1504. Broadbent, D. E. Noise, paced performance and 
vigilance tasks. Gt. Brit. MRC, RNPRC. Rept. R.N.P. 
52/697, O.E.S. 209, A.P.U. 165/51, 1952, 10 pp. 
1505. Broadbent, D. E. Noise, paced performance 
and vigilance tasks. Brit. J. Psychol., 1953, 44: 295-303. 
1506. Broadbent, D, E. Listening between and dur- 
ing practised auditory distractions. Gt. Brit. MRC, 
RNPRC. Rept. R.N.P. 54/801, O.E.S. 247, A.P.U. 208, 
1954, 11 pp. 
1507. Broadbent, D. E. Effects of noises of high and 
low pitch on behavior. Gt. Brit. MRC, RNPRC, OES. Rept. 
R.N.P. 54/814, O.E.S. 253, September 1954, 9 pp. 
1508. Broadbent, D. E. Some effects of noise on 
visual performance. Quart. J. exp. Psychol., 1954, 6: 1-5. 
1509. Broadbent, D. E. An effect of noise on an 
‘intellectual’ task. Gt. Grit. MRC, RNPRC, OES. Rept. 
R.N.P. 57/892, O.E.S. 298, July 1957, 7 pp. 
1510. Woodhead, M. M. Effects of bursts of loud 
noise on a continuous visual task. Gt. Brit. MRC, RNPRC, 
OES. Rept. R.N.P. 57/891, O.E.S. 297, July 1957, 10 pp. 
1511. Woodhead, M. M. Effects of brief loud noise 
on the performance of a visual task — III: Bursts of one 
second with a peak intensity of 110 DB. Gt. Brit. MRC, 
RNPRC, OES. Rept. R.N.P. 58/914, O.E.S. 308, February 
1958, 9 pp. 
1512. Woodhead, M. M. Effects of brief loud noise 
on the performance of a visual task — IV: An experiment 
with single bursts at three intensities. Gt. Brit. MRC, 
RNPRC, OES. Rept. R.N.P. 58/931, O.E.S. 321, December 
1958, 4 pp. 
1513. Woodhead, M. M. The effects of brusts of loud 
noise on a continuous visual task. Brit. J. industr. Med., 
1958, 15: 120-125. 
E. SOUND COMMUNICATION IN NOISE 
In a study by Hoffman (1514) 1956, on the 
detection of signals and their attributes, a series 
of signals was presented against a background of 
noise. Listeners were required to detect these 
signals and to specify their separate attributes. 
One attribute (chopping) was produced by 
periodically interrupting the signal. The second 
attribute (modulation) consisted of a periodic 
change in signal band width. A given signal was 
either chopped, modulated, chopped and modu- 
lated or steady. It was found that though the 
four signals were equally detectable, detectability 
of the separate attributes varied as a function 
of their nature and number. Listeners differed in 
the extent to which modulation detection was 
adversely affected by the presence of chopping. Biology of Very High Hydrostatic 
Pressures 
The subject of the effects of raised hydrostatic 
pressure upon the activity of living cells and 
tissues lies at the periphery of the main interest 
of this Sourcebook. Nevertheless, papers in this 
area have been discussed in previous volumes 
of the sourcebook (especially Volume I). Many 
physical and metabolic alterations occur at very 
high hydrostatic pressures for example, fluids 
are compressed to some extent, proteins are 
stated to be coagulated at pressures of 5000- 
12,000 atmospheres and above 10,000 atmos- 
pheres the activity of enzymes become greatly 
diminished. Diphtheria and tetanus toxins have 
found to be destroyed by 13,500 atmospheres 
while antitoxins remain unaffected. Protozoan 
activity is said to cease at 400-600 atmospheres, 
but this is apparently reversible even after one 
to two days. Of the more recent literature only 
a few papers are here considered. 
Haywood (1320) 1953, tested the hypothesis 
that nitrogen at high pressure exerts a general 
narcotic action by subjecting the fertilized eggs 
of the sea urchin, Arbacia punctulata, to a pres- 
sure of nitrogen of 61 atmospheres in the pres- 
ence of air at atmospheric pressure. A series was 
also run with helium at the same pressure. 
Neither nitrogen or helium at 61 atmospheres 
affected the time of appearance of the first cleav- 
age, however, as low as 2.3 atmospheres of nitr- 
ous oxide caused a definite delay of cleavage. The 
action of high pressure on the adenosinetriphos- 
phatase activity of myosin has been studied by 
Ivanov, Mirovich and Parshina (1321) 1959. 
These investigators found that solutions of re- 
precipitated myosin lose completely their adeno- 
sinetriphosphatase activity under the influence of 
a pressure of 4000 atmospheres. Spyropoulos 
(1322) 1956-57 studied the properties o£ the 
giant axon of the squid Loligo pealii at different 
hydrostatic pressures (14.7 to 16,000 psi). At 
4,000 psi the resting potential, the membrane 
resistance, membrane capacity, the conduction 
velocity, the amplitude of the action potential 
and the maximal change in the membrane im- 
pedance during activity, were only slightly af- 
fected. At the same pressure, the duration of 
the falling phase of the action potential was in- 
creased by about 40 to 60 percent and the dura- 
tion of the rising phase by about 20 to 35 per- 
cent. The duration of the membrane impedance 
change during activity was increased by 50 to 
100 percent at 4000 psi. At about 3000 to 7000 
psi fiber fired spontaneously. At pressures con- 
siderably above 5000 psi the membrane resistance 
decreased to about one-half to one-third the 
original value. The narcotizing effect upon the 
nerve fiber of 3 to 7 percent ethanol was partly 
or almost completely opposed by low tempera- 
tures or high pressures. 
1519. Gershfeld, N. L. and A. M. Shanes. The in- 
fluence of high hydrostatic pressure on cocaine and vera- 
trine action in a vertebrate nerve. J. gen. Physiol., 1959, 
42: 647-653. 
1520. Haywood, C. The cleavage times of fertilized 
eggs of the sea urchin, Arhacia punctulata, at high pres- 
sures of nitrogen, helium, and nitrous oxide. J. cell. comp. 
Physiol, 1953, 41: 335-343. 
1521. Ivanov, I. I., N. I. Mirovich and E. A. 
Parshina. The action of a high pressure on the adenos- 
inetriphatase activity of myosin. Bull. exp. Biol. Med., 
1959, 47: 690-692. 
1522. Spyropoulos, C. S. The effects of hydrostatic 
pressure upon the normal and narcotized nerve fiber. J. 
gen. Physiol, 1956-57, 40: 849-857. 
1523. ZoBell, C. E. Bacterial life at the bottom of 
the Philippine Trench. Science, 1952, 115: 507-508. Diseases and Accidents in 
Submarine Personnel, Divers and 
Compressed Air Workers 
I. EAR, NOSE AND THROAT 
DISTURBANCES 
A. GENERAL STUDIES OF OTORHINO- 
LARYNGOLOGICAL DISTURBANCES 
Providing they are uniformly distributed 
throughout the body, great pressures can be 
tolerated by the human organism. However, 
when the pressure outside is in excess of inside 
body air space and as long as equalization of 
pressure is impossible, this pressure differential 
causes traumatic effects including edema and effu- 
sion of blood or fluids into the space, capillary 
dilation or rupture of tissue. Thus, in the sinuses 
or the middle ear, pressure must be equalized by 
admission of air during descent to depth to 
avoid the development of destructive differences 
in pressure. Also during ascent the air must vent 
freely as pressure decreases; the latter is usually 
not a problem. “Squeeze” effects in the middle 
ear are usually taken care of by training per- 
sonnel how to equalize pressure through the 
eustachian tubes. This is done by swallowing, 
cracking the jaw or by the valsalva maneuver. 
Temporary conditions (such as colds) which 
cause blockage of the eustachian tubes may pre- 
vent equalization of pressure causing otitis media 
and may even rupture the eardrum. The latter 
can occur as a result of as little as 10 feet of un- 
equalized descent, such as may be the case if a 
diver falls. Blockage of the openings of the 
sinuses may also cause pain and trauma and 
exposure to pressure should be avoided during 
acute nose and throat conditions. 
The papers listed in this section have been 
chosen because they give a general overview of 
ear, nose and throat disturbances associated with 
diving and caisson operations. The reader will 
observe in Volume II of this Sourcebook that 
more space was given to ear, nose and throat 
disturbances than is given in the present Volume. 
This reflects a greater previous interest in various 
modalities of treatment and prevention such as 
irradiation therapy, dental therapy and surgical 
and physical procedures. Presently it is con- 
ceded that prevention is best accomplished by 
avoiding exposure under conditions of acute 
nasopharyngeal abnormality. Vasoconstrictors 
are of value in prevention since they may open 
up airway and may also be of value in treatment; 
if infection supervenes antibiotics are used as 
indicated. 
1524. Bertoin, R. Evolution clinique des accidents 
labyrinthiques survenant chez les ouvriers travaillant en 
air comprim£. Arch. Mai. prof., 1953, 14: 221-224. 
1525. Bertrand, M. Contribution a 1’etude des sinu- 
sites barotraumatiques. Rev. Laryng., Paris, 1954, 75: 784- 
813. 
1526. Bruzzi, B. Sindromi otorinoiatriche nella ma- 
lattia dei cassoni. Folia rned., Napoli, 1958, 41: 780-783. 
1527. Campbell, P. A. Aero-otology. Ch. XXVIII in: 
Otolaryngology. W. F. Prior Co., Inc., Hagerstown, Md. 
1960, Vol. 2. 
1528. Campbell, P. A. Sinus barotrauma. Ch. XII in: 
Otolargngology. W. F. Prior Co., Inc., Hagerstown, Md. 
1960, Vol. 3. 
1529. Chossegros, H., L. Roche and L. Migeon. 
Les atteintes vestibulaires graves dans la maladie des 
caissons. Arch. Mai. prof., 1953,14: 211-220. 
1530. Coles, R. R. A. and J. J. Knight. Aural and 
audiometric survey of qualified divers and submarine es- 
cape training tank instructors. Gt. Brit. MRC, RNPRC, 
HeS. Kept. R.N.P. 61 /1011, He.S. 29, August 1961, 29 pp. 
1531. De Vita, C. Contribute alio studio delle sinusiti 
barotraumatiche. Folia med., Napoli, 1959, 42: 781-793. 
1532. Flottes, L., L. Devilla, R. Guillerm, R. Riu 
and B. Broussolle. La pathologic du monde du silence. 
Rev. Laryng., Paris, 1958, 79: 659-702. DECOMPRESSION SICKNESS—GENERAL CONSIDERATIONS 
1533-1562 
1533. Guillerm, R. La codification des epreuves 
O.R.L. d’ aptitude & la navigation a£rienne et sous-marine. 
Rev. Med. nav., 1955, 10: 157-165. 
1534. Heller, M. F. Skin diving injury. Arch. 
Otolaryng., 1960, 72: 358-360. 
1535. Jarrett, A, Reversed-ear syndrome and the mech- 
anism of barotrauma. Brit. med. J., 1961, 5250: 483-486. 
1536. Jarrett, A. S. Ear injuries in divers. J. R. nav. 
med. Serv., 1961, 47: 13-19. 
1537. Jones, G. M. Pressure changes in the middle ear 
after altering the composition of contained gas Acta oto- 
laryng., Stockh., 1961, 53: 1-11. 
1538. Jordan, L. W. Traumatic rupture of the tym- 
panic membrane. Laryngoscope, 1952, 62: 615-622. 
1539. Kalinin, P. I. Sravnitel’naia otsenka nekotorykh 
metodov opredeleniia barofunktsii ukha. [Comparative 
evaluation of some methods of determination of the baro- 
function of the ear.] Vo.-med. Zh., 1961, 5; 76-77. 
1540. Keller, A. P., Jr. A study of the relationship of 
air pressure to myringorupture. Laryngoscope, St. Louis, 
1958, 68: 2015-2029. 
1541. Laba, L. and J. Ruszel. About permanent in- 
jury of the ear in divers. Bull. Inst. mar. Med. Gdansk., 
1960, 11: 165-172. 
1542. May, R. T. A preliminary report on the use of 
“Eskornade” in the treatment of eustachian tube block in 
divers under training. J. R. nav. med. Serv., 1960, 46: 201- 
204. 
1543. May, R. T. and W. M. Hollyhock. The 
treatment of eustachian catarrh in diving and submarine 
personnel with “Eskronade.” J. R. nav. med. Serv., 1961, 
47: 143-147. 
1544. Moslener, C.-D. Gehorschadigungen bei Tauch- 
ern. Med. Mschr., 1961, 15: 294-297. 
1545. Mungo, A. and G. Sessa. Modificazioni radiog- 
rafiche dei seni paranasali nei lavoratori dei cassoni. Folia 
med., Napoli, 1958, 41: 307-315. 
1546. Picard, D., A. Appaix and P. Nourrit. Lesions 
histologiques de 1’oreille interne consecutives <4 des baro- 
traumatismes experimentaux chez le Cobaye. C.R. Soc. 
Biol., Paris, 1959,153: 1230-1232. 
1547. Robert, P., R. Bordes and P. Blanc. Le baro- 
traumatisme et la surdite des aviateurs. Rev. Cps., Sante 
milit., 1960,1: 701-712. 
1548. Rozsahegyi, I. and G. Gomori. Otologische 
Untersuchungen bei Caissonarbeiten. Arch. Gewerbepath., 
1961,18: 384-393. 
1549. Schulte, J. H. Aerotitis media and aerosinusitis 
in submarine trainees; a prophylactic study. U.S. Forces 
med. J., 1957, 8: 1571-1576. 
1550. Shelby, R. W. Prevention and minimization of 
barotraumati injuries associated with scuba diving. J. 
Amer. osteop. Ass., 1961, 60 896-902. 
1551. Sims, R. O. S. and S. Watson. Otitic baro- 
trauma in divers. Med. J. Aust., 1961, 1040-1041. 
1552. Taylor, G. D. The otolaryngologic aspects of 
skin and scuba diving. Laryngoscope, 1959, 69: 809-858. 
1553. Taylor, G. D. The otolaryngologic aspects of 
skin and SCUBA diving. Trans. Amer. laryng. rhin. otol. 
Soc., 1959, 409-459. 
1554. White, C. E. Report on effect of increased at- 
mospheric pressure upon hearing. U.S. Navy. Submarine 
Base, New London, Conn, Medical research laboratory. 
Project NM 002014.06.03, 21 December 1955, 6 pp. 
II. OTITIS EXTERNA THERAPY 
Otitis externa is still a problem with under- 
water swimmers and military personnel on tropi- 
cal duty. It is caused by any of a variety of 
bacteria and fungi. The condition may be pre- 
vented by correct hygiene of the external ear, 
this means essentially drying the ears well after 
exposure. 
Fabricant {1556) 1957, has shown that the pH 
of the affected cutaneous surface of the external 
auditory meatus in otitis externa is on the alka- 
line side of neutral. Treatment according to this 
author requires converting this abnormal alka- 
line state to the normal physiologic acid state. 
In this connection Ochs {1559, 1560) 1950, has 
used topically aluminum acetate as a wet dress- 
ing and has added acetic acid to make a solution 
of about two percent strength. 
For further consideration of the treatment of 
otitis externa as is generally practised, reference 
should be made to a paper by Waite quoted in 
Volume II of this Sourcebook {3721) 1951. 
1555. Conley, J. J. Evaluation of fungous disease of 
the external auditory canal. Arch. Otolaryng., 1948, 47: 721- 
745. 
1556. Fabricant, N. D. The pH factor in treatment 
of otitis externa. Arch. Otolaryng., 1957, 65: 11-12. 
1557. Jenkins, B. H. Treatment of otitis externa and 
swimmer’s ear. J. Amer. med. Ass., 1961, 175: 402-404. 
1558. Moretti, G. La terapia e la prevenzione delle 
otiti esterne nel personale subacqueo. Ann. Med. Nav., 
1963, 68: 443-454. 
1559. Ochs, I. L. Use of vinegar as an antibiotic in 
the treatment of chronic middle ear disease. Arch Oto- 
laryng., 1950, 52: 935-941. 
1560. Ochs, I. L. Treatment of external otitis: a 
simple and effective technic. J. Amer. med. Ass., 1950, 142: 
1361-1362. 
1561. Senturia, B. H. and C. Carruthers. Prophy- 
laxis of external otitis; preliminary report. Ann. Otol., etc., 
St. Louis, 1954, 63: 97-100. 
1562. Anon. External and middle ear infections. J. 
Amer. med. Ass., 1959, 171: 554. 
III. DECOMPRESSION SICKNESS 
A. GENERAL CONSIDERATIONS 
The term “decompression sickness” includes 
the signs, symptoms and basic underlying path- 
ological processes caused by rapid reduction of 1563-1580 
DISEASES AND ACCIDENTS 
barometric pressure from high pressures to one 
atmosphere, or from any higher to any lower 
level of pressure. Such conditions occur in cais- 
son work and diving. Decompression sickness is 
likewise a problem in rapid ascent in aircraft 
which are unpressurized or in which there is an 
explosive loss of pressure in the cabin atmos- 
phere. The condition is characterized by pains 
(bends), painful breathing (chokes) and paraly- 
sis. There also may be visual and other sensory 
disturbances as well as convulsions and other 
signs of central nervous system disorder. In some 
cases the victim may die suddenly. 
It appears that decompression has its etiology 
in the liberation of inert gas bubbles directly 
into various tissues or into the blood stream in 
which they are carried to find lodgment in vari- 
ous parts of the body. Decompression sickness oc- 
curs when the decompression rate is too rapid to 
allow desired gradual diffusion of excess inert 
gas from the tissue fluids into the blood. Only in 
extremely rapid decompression or in severe de- 
compression sickness do bubbles appear in the 
arterial blood. With the extreme decompression 
rates bubbles in the returning venous blood 
may become lodged in the pulmonary capillaries 
causing the acute respiratory distress which we 
have referred to as “chokes”. Those bubbles that 
pass through the pulmonary filter may enter and 
obstruct the capillary beds of vital organs such as 
the brain and the heart. 
For general consideration of decompression 
sickness the paper by Lambertsen (1581) 1961, 
should be consulted. Reference is made also to 
the report made by Lewis and Paton (1582) 
1957. This paper describes some of the factors in 
the pathogenesis of decompression sickness. Rec- 
ommendations for lowering the rate of decom- 
pression sickness in a caisson operation are made 
in this paper. 
1563. Agadzhanian, N. A. and D. V. Abaev. De- 
kompressionnye rasstroistva v usloviiakh ponizhennogo 
atmosfernogo davleniia. (Obzor literatury.) [Decompres- 
sion disorders under conditions of reduced atmospheric 
pressure. (Review of the literature.)] Vo.-med. Zh., 1960, 1: 
58-62. 
1564. Aver’ianov, V. A. Vliianie vysokoi temperatury 
vozdukha na vozniknovenie dekompressionnoi bolezni. 
The effect of high air temperature on the development of 
decompression sickness. Patol. Fiziol. exp. Ter., 1961, 6: 
36-39. 
1565. Behnke, A. R. Decompression sickness. Milit. 
Med., 1955, 117: 257-271. 
1566. Behnke, A. R. Outline of problems of decom- 
pression and bends, pp. 50-52 in: Proceedings of the un- 
derwater physiology symposium. Edited by L. G. Goff, 
National Research Council, Washington, D.C. N.R.C. 
Publication 377, 1955, 153 pp. 
1567. Berry, C. A. and A. H. King. Severe dysbarism 
in actual and simulated flight. U.S. Forces med. J., 1959, 
10: 3-15. 
1568. Brain, W. R. Caisson disease, pp. 623-624 in: 
Diseases of the nervous system. Oxford University Press, 
London, 1962, 879 pp. 
1569. Bucklitsch, W. and K. Pfeifer. Das Tauchens 
mit Pressluftgeraten. Dtsch. Gesundheitwes., 1960 15: 1561- 
1566, 
1570. Cerchia, F. Osservazioni cliniche su alcuni in- 
fortuni sul lavoro occorsi a palombari civili assistiti dal 
servizio sanitario di maricentrosub la spezia. Ann. Med. 
Nav., 1953, 58: 506-526. 
1571. Clamann, H. G. Decompression sickness, pp. 
175-188 in: Aerospace medicine. Edited by H. G. Arm- 
strong, Williams and Wilkens Co., Baltimore, 1961, 633 pp. 
1572. Darling, R. C. Decompression sickness, pp. 478- 
480 in: A textbook of medicine. Edited by R. L. Cecil and 
R. F. Loeb, W. B. Saunders Co., Philadelphia, 1959, 1665 
pp. 
1573. Dewey, A. W., Jr. Decompression sickness, an 
emerging recreational hazard. A discussion, with an illus- 
trative case history of an increasingly common, but not 
yet widely understood, sports injury. New Engl. J. Med., 
1962, 267: 759-765. 
1574. Dewey, A. W., Jr. Decompression sickness, an 
emerging recreational hazard (concluded). A discussion 
with an illustrative case history for an increasingly 
common, but not yet widely understood, sports injury. 
New Engl. J. Med., 1962, 267: 812-820. 
1575. Donald, K. W. J- S. Haldane’s contributions to 
applied physiology in the armed forces, with special ref- 
erence to diving, pp. 83-91 in: The regulation of human 
respiration. Edited by D. J. C. Cunningham and B. B. 
Lloyd, Blackwell Scientific Publications, Oxford, 1963, 591 
pp. 
1576. Hansen, A. Periculum in mora. Ugeskr. Laeg., 
1952,114: 33. 
1577. Hunter, D. Occupational diseases with neuro- 
logical symptoms and signs. Practitioner, 1953,171: 48-58. 
1578. Kern, J. D. The etiology and pathological physi- 
ology of decompression sickness. U.S. Navy. Submarine 
Base, New London, Conn. Medical research laboratory. 
Project MR005.14-3100-2, Rept. no. 2, 15 December 1960. 
1579. Kindwall, E. P. Some observations on decom- 
pression sickness. Yale University. Thesis (Med.), 1960. 
1580. Lamphier, T. A., M. Spaulding, F. Boodro, 
J. A. Scholl, E. Tynan, R. I. Goldberg, R. Buck and 
J. Haggerty. Decompression illness (aeroembolism). 
Industr. Med. Surg., 1962, 31: 239-248. DECOMPRESSION SICKNESS—CLINICAL PICTURE 
1581-1594 
1581. Lambertsen, C. J. Harmful effects of oxygen, 
nitrogen, carbon dioxide and carbon monoxide. Decom- 
pression sickness, pp. 720-721 in: Medical physiology. 
Edited by P. Bard, C.V. Mosby Company, St. Louis, 1961, 
1339 pp. 
1582. Lewis, H. E. and W. D. M. Paton. Decom- 
pression sickness during the sinking of a caisson. A study 
of some factors in the pathogenesis of caisson disease. Brit. 
J. industr. Med., 1957. 14: 5-12. 
1583. Lindgren, G. Kasunarbete och tryckfallssjuka. 
Caisson work and decompression sickness. K. L. B. Bok- 
tryckeri, Stockholm, 1958, 58 pp. 
1584. Meester, J. N. Caissonziekte. Caisson sickness. 
E. F. Bohn, Haarlem, 1958, 131 pp. 
1585. Palmieri, V. M. Medicina legale del cassonism. 
Folia med., Napoli., 1958, 41: 784-792. 
1586. Perrimond-Trouchet (N). Les accidents de 
decompression. Definition, description, traite- 
ment. Marseille mdd., 1961, 98: 761-766. 
1587. Pfrommer, J. R. Decompression sickness: The 
state of the art. U.S. Forces med. J., 1959, 10: 1292-1298. 
1588. Sensing, J. Drucklufterkrankungen. Hefte z. 
Unfallheilk., 1960, 62: 71-78. 
1589. Thibault, P. Les accidents des plongeurs. Pr. 
med., 1959, 66: 225. 
1590. U.S. Air Force. Physiology of flight. USAF 
Manual 160-30, July 1953. 
1591. U.S. Navy. Decompression, pp. 40-42 in: Div- 
ing notes. U.S. Navy, Naval Gun Factory, Washington, 
D.C., PRNC, DSDS-6, October 1952, 382 pp. 
1592. Wunsche, O. Die Druckfallrankheit des H6- 
henfliegers. Wien. med. Wschr., 1956, 106: 686-689. 
1593. Anon. Convegno sulla malattia dei cassoni 
(Napoli, 19 Gennaio 1958). Folia med., Napoli, 1958, 41: 
761-764. 
1594. Anon. New studies of decompression sickness. 
Brit. med. J., 1961, 5218: 45-46. 
B. CLINICAL PICTURE 
For a modern succinct statement on decom- 
pression sickness reference should be made to a 
chapter on the subject by E. H. Lanphier, ap- 
pearing as chapter VI, in Fundamentals of Hy- 
perbaric Medicine, Publication No. 1298, Na- 
tional Academy of Sciences, National Research 
Council, Washington, D.C., 1966. In discussing 
the clinical manifestations, Lanphier considers 
first of all acute phenomena, namely localized 
pain and neurologic, pulmonary or circulatory 
effects. This localized pain, or bends, is present 
in over 90 percent of cases and is according to 
Lanphier the sole symptom in 95 percent of tun- 
nel work cases. It is accompanied by other symp- 
toms in about a third of the cases occurring in 
divers. Eighty-five percent of the tunnel cases 
exhibit pain in the legs while upper limb pain 
is predominate in the divers. Pain other than in 
the extremities is more frequent in divers than 
it is in tunnelers. The neurologic pulmonary 
and circulatory effects are more frequent among 
divers. The neurological symptoms are most pre- 
dominant and very variable. There is frequent 
vertigo in tunnel workers, while muscular weak- 
ness and sensory defects are most common in 
divers. It appears that paraplegia is much more 
frequent in compressed air workers than in 
divers and that neurologic manifestations in 
divers more commonly involve changes of con- 
sciousness, brain stem or cortical symptoms. 
Chokes are relatively infrequent and seem to be 
present in about two percent of the divers and 
occur with a frequency of less than one percent 
in tunnel workers in some studies. Signs of shock 
have been noted in nearly half of tunnel worker 
cases with other symptoms besides pain. 
In addition to these major signs there are a 
variety of minor manifestations including itching 
and mottling of the skin. There is also unusual 
fatigue. 
There may be late or chronic changes, mainly 
aseptic bone necrosis and enduring neurologic 
defects. The necrotic changes in the bone have 
been commonly observed among caisson and 
tunnel workers but have not been seen in naval 
divers. They are infrequently diagnosed within 
a year following exposure. The bone changes do 
not usually produce symptoms except where there 
is undermining of an articular surface, as for ex- 
ample in the head of the femur where there may 
be considerable pain and disability. Paraplegia 
due to spinal cord damage is the most common 
of the enduring neurological defects. Such neuro- 
logical sequelae of decompression sickness most 
often are the result of delayed or inadequate 
treatment where there is acute central nervous 
system involvement. 
The clinical features of decompression sickness 
during the construction of the Dartford Tunnel 
have been described by Golding, Griffiths, Hem- 
pieman, Paton and Walder {1599) 1960. In this 
operation, over a period of two years, 1200 men 
were employed on eight hour shifts at pressures 
up to 28 psi. There were 689 cases of decompres- 
sion sickness out of 122,000 compressions, an 
incidence of 0.56 percent. The majority of cases 
(94.9 percent) were “simple” bends. The re- 1595-1612 
DISEASES AND ACCIDENTS 
mainder (5.1 percent) exhibited symptoms and 
signs other than pain and were more serious. 
All cases were treated successfully and no fatality 
or permanent disability occurred. In two serious 
cases cysts in the lungs were discovered and it was 
suggested that these gave rise to air embolism 
when these workers were decompressed and it 
may be that pulmonary defects may contribute 
more than hitherto believed to the pathenogene- 
sis of bends. The paper includes descriptions of 
other features of decompression sickness. The 
bends rate was higher for the back shift (3:00 
p.m. and 11 p.m.) and for the night shift (11:00 
p.m. to 7:00 a.m.) than it was for the day shift. 
In the treatment of decompression sickness it 
appears to be more satisfactory to use the mini- 
mum pressure required for relief of symptoms, 
followed by slow decompression with occasional 
“soaks” than to attempt to drive the causative 
bubbles into solution with high pressures. The 
decompression tables recently prescribed by the 
Ministry of Labour were used. Existence of ac- 
climatization to pressure was confined; thus the 
bends rate may fall within two to three weeks 
to 0.1 percent to the incidence on the first day of 
exposure. Acclimatization is lost again with a 
“half-time” of about seven days, if a man is 
away from work. 
Although itching is a common manifestation 
of decompression sickness, it has received little 
attention from investigators in this field. In 
view of its trivality in comparison with the pain- 
ful maiming or even fatal consequences which 
can arise from diving procedures this neglect is 
scarcely surprising. Rashbass {1609) 1957, has 
justified an investigation of itching of decompres- 
sion on the basis that the occurrence of itching 
is an indication that the dive may have been 
close to the borderline of safety. It appears that 
itching is consistently a manifestation of decom- 
pression sickness arising in a tissue whose time- 
constant is shorter than that of tissues responsible 
for the more severe effects. Thus itching is com- 
mon in deep dives of short duration and absent 
in shallow dives of long duration. The im- 
mediate cause of itching seems to be the release 
of bubbles into the skin or subcutaneous tissue. 
Even sludging of blood may be responsible for 
cutaneous manifestations. 
1595. Berry, C. A. Severe dysbarism in Air Force op- 
erations and training. U.S. Forces med. J., 1958, 9: 937- 
948. 
1596. Berry, C. A. and H. H. Wayne. Grade IV 
chamber reactions or neurocirculatory collapse occurring 
in the USAF, 1950-1955. J. Aviat. Med., 1957, 28: 192. 
1597. Buscaino, V. M. Sindromi neurologiche nella 
malattia dei cassoni. Folia med., Napoli, 1958, 41: 773-779. 
1598. Caccuri, S. Pathogenesi e clinica della malattia 
dei cassoni. Folia med., Napoli, 1958, 41: 764-773. 
1599. Golding, F. C., P. Griffiths, H. V. Hemple- 
man, W. D. M. Paton and D. N. Walder. Decompres- 
sion sickness during construction of the Dartford Tunnel. 
Brit. J. industr. Med., 1960, 17: 167-180. 
1600. Halbouty, M. R. and J. J. Neisler. Severe 
neurocirculatory collapse at simulated altitude. U.S. Forces 
med. J., 1955, 6: 1363-1370. 
1601. Hollyhock, W. M. An unusual case of decom- 
pression urticaria. J. R. nav. med. Serv., 1960, 46: 93-95. 
1602. Hook, O. and G, Lindgren. Tryckfallssjuka 
och kasonarbete. En oversikt och nagra erfarenheter fran 
tunnel banearbetena i Stockholm 1953-1957. [Decompres- 
sion sickness and caisson work. Survey and experiences 
among underground railway workers in Stockholm 1953- 
1957.] Svenska Lakartidn., 1958, 55: 365-384. 
1603. Kaiser, M. H., T. M. Lin, G. Roback, L. 
Pevsner, H. K. Ivy, P. K. Moon and A. C. Ivy. Bone 
marrow and cutaneous circulation during decompression. 
USAF. Randolph Field, Texas. School of Aviation Medi- 
cine, Project no. 21-23-019, Kept. no. 6, August 1954, 19 pp. 
1604. Kindwall, E. P. Metabolic rate and animal size 
correlated with decompression sickness. Amer. J. Physiol., 
1962, 203: 385-388. 
1605. Kindwall, E. P., L. O. Boreus and B. Wes- 
terholm. Failure to show change in rat tissue histamine 
and serotonin after rapid decompression. Amer. J. Physiol., 
1962, 203: 389-390. 
1606. Nazarkin, V. la. O nekotorykh prichinakh baro- 
travmy legkikh. [On some causes and manifestations of 
barotrauma of the lungs.] Vo.-med. Zh., 1961, 3: 65-67. 
1607. Parsons, V. Forced expiratory spirograms fol- 
lowing decompression sickness. Aerospace Med., 1959, 30: 
821-824. 
1608. Piccoli, P. Comportamento delle proteine 
seriche nella malattia dei cassoni. Folia med., Napoli, 1958, 
41: 841-846. 
1609. Rashbass, C. The aetiology of itching on de- 
compression. Gt. Brit. MRC, RNPRC, UPS. Kept. R.N.P. 
57/894, U.P.S. 167, 1957, 3 pp. 
1610. Sessa, T. Funzionalita’ respiratoria nei cassoni- 
sti. Folia med., Napoli, 1958, 41: 837-840. 
1611. Shust, V. K voprosu o dekompressionnykh iz- 
meneniiakh krovi. [On decompression changes in the 
blood.] Fiziol. Zh. SSSR Sechenov, 1960, 46: 618-622. 
1612. Snyder, J. F. Dive reaction scale study. U.S. 
Navy. Naval Weapons Plant, EDU. Project NS 185-005, 
sub task no. 5, test no. 10, 13 March 1958, 6 pp. DECOMPRESSION SICKNESS—CASE REPORTS 
1613. Viadro, M. D. and A. S. Panfilov. O dekom- 
pressionnykh rasstroistvakh u letnogo sostava v polete. 
[On decompression disorders in flight personnel during 
flight.] Vo-med. Zh., 1960, 1: 62-65. Milit. med. J., 1960, 
1: 99-103. 
C. CASE REPORTS 
Case histories of decompression sickness have 
been quite well documented on pages 121-137 of 
the first volume of this Sourcebook and on pages 
161-163 of the second volume. Of the reports 
given below, several may be discussed in some 
detail. The first is a report given by Aston 
(1615) 1957, of a serious case of decompression 
sickness occurring on 27 May 1957 in a Nor- 
wegian civilian diver working from the Nor- 
wegian salvage ship Nyhavn on the sunken 
Swedish ship Akka off Clock Point in the Fifth of 
Clyde. The diver had been at a depth of 80 feet 
for one and a quarter hours wearing standard 
equipment and breathing air. According to the 
Royal Navy diving tables, such a dive would 
merit a total decompression time of 32 minutes, 
but owing to a breakdown in communications 
between the diver and his surface attendant, he 
was brought up in only three minutes. The 
patient, a 48 year old, well-built, muscular man, 
had had one previous attack of bends in one 
shoulder when he surfaced too quickly as a result 
of “blowing up”. On the day of the reported in- 
cident his symptoms commenced relatively sud- 
denly ten minutes after surfacing. A civilian 
doctor recognizing this as a case of decompression 
illness contacted H.M.S. Adamant by telephone. 
The patient was transferred by ambulance to a 
point where he was met by a medical officer and 
a diving officer and brought to the ship. On ar- 
rival he was placed directly in the recompression 
chamber. The estimated time between surfacing 
and entering the chamber was one and three- 
quarters to two hours. Initially the patient was 
conscious but semi-collapsed; there was pain 
in both lower limbs. There was also pain in the 
lower back, abdomen and lower half of the 
chest. There was vomiting and staggering. The 
patient had some cyanosis and respiratory dis- 
tress, but these were not marked. The pulse rate 
was about 100. Therapeutic recompression was 
carried out in accordance with the Royal Navy 
Diving Manual. He was recompressed at 25 feet 
a minute to 165 feet where his symptoms were 
relieved. Decompression was then started ac- 
cording to Table III of the Manual. When he 
had been at the 30 foot level for three hours he 
suddenly developed severe cardiac and respira- 
tory embarrassment, becoming almost uncon- 
scious. The pulse was almost imperceptible and 
the rate was over 100. On recompression to 60 
feet he recovered rapidly, but again felt a pain 
in his left lower limb, which, however, was only 
temporary. From this time on he was brought 
to the surface according to Table IV; in the last 
three-quarters of an hour of each of the stops 
at 30, 20 and 10 feet he was given oxygen. The 
total time spent in the chamber was 40.5 hours. 
In the last four hours the patient was encouraged 
to use his limbs gently and some massage was 
given. On leaving the chamber the patient was 
transferred to a sick bay where he was retained 
for 48 hours. He was then transferred to Lark- 
field Hospital for further observation, since it 
was thought possible that some permanent dam- 
age may have been done, because of the rela- 
tively sudden onset of severe symptoms and the 
delay before he could be recompressed. In the 
hospital electrocardiographic and radiological 
examinations were negative as was a general 
neurological exam. The patient returned to 
Norway within two weeks after admission to the 
hospital. 
Johnson (1624) 1957, reported the case of a 
SCUBA diver in whom decompression sickness 
simulated an infectious myelitis. The author has 
pointed out that the popularity of skin diving 
is not paralleled by knowledge of the hazards 
and safeguards or facilities for treatment of 
decompression sickness and air embolism. In the 
case reported the diver made four consecutive 
dives to 90 feet for 20 minutes each, surfacing 
after the last dive in one minute. He had symp- 
toms of severe pain in the left infrascapular para- 
vertebral area, followed by numbness and tingl- 
ing in arms and legs. Six to eight hours later he 
reported to a civilian clinic with a sensation of 
pressure in the back and legs. The temperature 
was 102°F. and there was a recent history of up- 
per respiratory infection. The white count was 
14,000. Complete paralysis of the right lower 
extremity followed and there was a positive Ba- 
binski bilaterally. There were no abdominal or 
cremasteric reflexes. There was loss of perception DISEASES AND ACCIDENTS 
of pain from the umbilicus down. The patient 
was unable to void. After 10 hours delay a 38 
hour standard recompression procedure was un- 
dertaken. Paraplegia persisted, and in retrospect 
the author considered that the bubble formation 
was at the level of the 10th thoracic segment. 
McCallum and Walder (1626) 1953, have drawn 
attention to the importance of early and ade- 
quate treatment. A few minutes may make the 
difference between gross central nervous system 
damage and complete recovery. The authors re- 
port two cases in which there was continuing 
and severe disability. These cases are reported 
from work at the Tyne Tunnel at 34 psi. Work- 
ers were decompressed according to a fixed sched- 
ule so that tissue supersaturation pressure should 
fall to 18 psi before removal from the lock. In 
the first case an experienced man exited from the 
dequipment lock, disregarded decompression 
after two hours at 34 psi. This resulted in paraly- 
sis of both legs and bladder distension. He was 
recompressed to 40 psi five times and decom- 
pressed by methods prescribed for bends. A year 
later the patient still walked with crutches and 
had urinary and some fecal incontinence. In 
such severe cases compression should have been 
maintained for 24 hours. In a second case a nov- 
ice had experienced two or three minor attacks 
of bends plus one other attack which resulted 
in temporary loss of the use of the legs (which 
should have indicated unsuitability for caisson 
work) . After three and three-quarters hours 
work at 34 psi the patient developed bends dur- 
ing the process of correct decompression. How- 
ever, decompression was then accelerated and 
this added to the severity of the case. The au- 
thors point out that he should have been re- 
compressed immediately for 24 hours instead of 
for a much shorter and delayed period. 
Richter and Behnke (1631) 1959, have re- 
ported the case of a skin diver aged 22 who de- 
veloped severe spinal cord involvement after 
ascending too rapidly from a depth of 350 feet. 
There was blurring of vision, constriction of 
peripheral vision, numbness and loss of conscious- 
ness. After being pulled aboard the stand-by 
boat the victim was able to stand, but in two to 
three minutes had pains in the chest and in the 
posterior neck area as well as stabbing, hammer- 
ing pain through the right arm. The legs be- 
came numb. The patient was placed in a recom- 
pression chamber two hours after the accident 
and remained there for 48 hours. He was at 
three to six atmospheres for 12 hours and then 
was slowly decompressed for 36 hours. In ef- 
forts to combat shock he was given fluids by 
mouth. Hematocrit and red blood count re- 
turned to normal after 48 hours. The patient 
received Demerol and Meprobamate for pain 
and anxiety. In spite of his symptoms he was 
coherant, well oriented and there was no im- 
pairment of special senses. Twenty-two hours 
after the beginning of recompression a neurologi- 
cal examination showed severe generalized weak- 
ness of both lower extremities (more on the 
left). There was moderate, general weakness of 
the upper extremities; there was also ankle 
clonus and a positive Babinski. These and other 
signs and symptoms suggested multiple lesions in 
the spinal cord, especially in the thoracic region. 
There was improvement after 36 hours, but there 
was still considerable difficulty. One month after 
the accident there was residual weakness, spastic- 
ity, and sensory loss in the lower extremities. 
Three months after the accident the patient was 
able to walk unaided and there were no G.U. 
disturbances. Residual proprioceptive and cuta- 
neous sensory disturbances were present. In 
general there was a remarkable freedom of 
involvement of the central nervous system in 
decompression sickness, even with widespread air 
embolism. Of all the CNS areas, the spinal cord 
is most susceptible to involvement and usually 
it is the thoracic region. 
Haymaker, Johnston and Downey (1623) 1956, 
have reported fatal decompression sickness dur- 
ing jet aircraft flight. This report is concerned 
with two nearly identical cases of collapse during 
jet aircraft flight. Signs of central nervous system 
damage were observed in both. The clinical 
course was fulminant with death supervening in 
11.5 and in 6 hours respectively. Pathologically 
the chief features were: 1) evidence of circula- 
tory collapse; 2) the presence of intense, gen- 
eralized lipemia and of fat emboli in the kidney 
in one case and fat emboli in the lungs and in the 
brain in the other; 3) a patent foramen ovale in 
both, with enlargement of the heart in one; 4) 
many foci of ischemic necrosis in the brain, in- 
distinguishable from those due to air embolism; DECOMPRESSION SICKNESS—CASE REPORTS 
1614—1630 
and 5) acute ischemic change in the spinal cord 
in one of the cases. Piecing together the ob- 
servations, it is postulated by the authors that 
the following series of events occurred: as a con- 
sequence of fairly rapid decompression fat de- 
posits became supersaturated with gas, gas bub- 
bles formed in fat cells, rupturing them and as a 
consequence fat gained access to the venous blood 
stream. Gas bubbles thought to have emanated 
from the region of fat depots were carried to 
the right side of the heart and thence to the 
lungs where many bubbles and fat emboli were 
filtered out. The authors concede that many may 
have passed the pulmonary filter. This tampon- 
ade of the pulmonary circulation produced an 
elevation of pulmonary blood pressure which 
was reflected in the right heart, enabling blood 
laden with bubbles to traverse the foreman ovale 
and enter the general circulation. Thus bubbles 
were carried in sufficient number to the brain 
to contribute to the acute circulatory collapse 
and death. 
Pressures greater than one atmosphere have 
been used to treat decompression sickness oc- 
curring in flight personnal. Donnell and Nor- 
ton (1620) 1960, have reported the successful 
use of the recompression chamber in severe de- 
compression sickness with neurocirculatory col- 
lapse. A 39 year old obese Air Force command 
pilot experienced severe decompression sickness 
with neurocirculatory collapse following a rou- 
tine refresher training course in the altitude 
chamber. Approximately one hour after com- 
pletion of a chamber flight to 43,000 feet, the 
individual developed nausea and vomiting, left 
hemiplegia, a fall in blood pressure to shock 
levels and disorientation. His condition pro- 
gressively deteriorated. Approximately three 
hours later he was placed in a recompression 
chamber at, a nearby Naval installation. He was 
immediately recompressed to six atmospheres and 
over a period of 36 hours was gradually brought 
back to one atmosphere. Approximately two 
hours after being placed in the recompression 
chamber, the patient began a steady and pro- 
gressive return to normal mental and physical 
status. Upon removal from the recompression 
chamber he had no essential pathological resid- 
uals. One week later the neurological examina- 
tion including electroencephalograms was nor- 
mal. A review of the literature by the authors 
indicates that this is the first altitude decompres- 
sion sickness case to be treated by the use of 
recompression to pressures higher than one at- 
mosphere. The authors concluded that had re- 
compression not been available this patient 
would not have survived. 
1614. Albretsen, C. S. Bends ved trykkfallsyke 
(dykkersyke). [Bends in decompression sickness.] Tidsskr. 
norske Laegeforen., 1955, 75: 50-51. 
1615. Aston, F. R. A case of decompression sickness. 
J. R. nav. med. Serv., 1957, 45: 162-164. 
1616. Berry, C. A. Dysbarism; An inflight case and a 
discussion of the present status. Aerospace Med., 1961, 52: 
107-112. 
1617. Briantseva, R. G. K voprosu o dekompression- 
noi bolezni. [On the problem of decompression sickness.] 
Zh. Nevropat. Psikh. Korsakov, 1961, 61: 860-861. 
1618. Cotes, J. E. Decompression sickness with post- 
decompression collapse. Gt. Brit., FPRC, RAF Institute of 
Aviation Medicine, F.P.R.C. Rept. no. 825, April 1953, 10 
pp. 
1619. Dbbeln, von W. and O. Hook. Olycksfall vid 
undertruckskammarprov. [Accident in decompression test.] 
Medd. flyg. Navmed., 1954, 4: 14-16. 
1620. Donnell, A. M., Jr. and C. P. Norton. Suc- 
cessful use of the recompresison chamber in severe de- 
compression sickness with neurocirculatory collapse. Aero- 
space Med., 1960, 51: 1004-1009. 
1621. Flinn, D. E. and G. J. Womack. Neurological 
manifestations of dysbarism: a review and report of a 
with multiple episodes. Aerospace Med., 1963, 54: 956-962. 
1622. Halbouty, M. R. and D. R. Long. Neurocircu- 
latory collapse in aircraft flight: report of a case. J. Aviat. 
Med., 1953, 24: 301-307. 
1623. Haymaker, W., A. D. Johnston and W. M. 
Downey. Fatal decompression sickness during jet aircraft 
flight. J. Aviat. Med., 1956, 27: 2-17. 
1624. Johnson, J. E., III. Decompression sickness 
simulating infectious myelitis in a SCUBA diver. New 
Engl. J. Med., 1957, 256: 1138-1141. 
1625. Malette, W. G., J. B. Fitzgerald and A. T. 
K. Cockett. Dysbarism. A review of 55 cases with sug- 
gestions for therapy. USAF, Aerospace Medical Center 
(ATC), School Aviation Medicine, Brooks Air Force Base, 
Texas. 1961, 61 pp. 
1626. McCallum, R. I. and D. N. Walder. Com- 
pressed-air illness on Tyneside. Lancet, 1953, 1: 464-467. 
1627. Nashimoto, I. and M. Furuhashi. Un cas de 
pneumo thorax spontand chez un travailleur en caisson. 
Marco med., 1961, 428: 522-525. 
1628. Odland, L. T. Fatal decompression illness at an 
altitude of 22,000 feet. Aerospace Med., 1959, 50: 840-846. 
1629. Rait, W. L. Post-decompression shock. Med. J. 
Aust., 1952, 2: 533-534. 
1630. Rawlins, J. S. P. An unusual diving incident. 
J. R. nav. med. Sen>., 1958, 44: 201-204. 1631-1655 
DISEASES AND ACCIDENTS 
1631. Richter, R. W. and A. R. Behnke. Spinal cord 
injury following a scuba dive to a depth of 350 feet. U.S. 
Forces med. J., 1959,10: 1227-1234. 
1632. Rising, J. D. and M. Delp. Sudden knee and 
abdominal pain, dyspnea, nausea, and collapse occurring 
in an obese aerial photographer. J. Kans. med. Soc., 1960, 
61: 473-447. 
1633. Rudolph, S. J., Jr., M. E. Herring and D. A. 
Vavala. Neurocirculatory collapse associated with reduced 
barometric pressure. Aerospace Med., 1961, 32: 1023-1025. 
1634. Schneck, S. A. Decompression sickness at me- 
dium altitude. U.S. Forces med. J., 1957, 8: 1366-1370. 
1635. Soskin, V. V. O klinicheskikh proiavleniiakh 
barotravmy legkikh. [On the clinical manifestations of 
barotrauma of the lungs.] Vo.-med. Zh., 1959, 8: 46-48. 
1636. Steward, D. J. Decompression illness. A case 
report. Med. Serv. J., Canada, 1961, 17: 475-479. 
1637. Taylor, W. L., G. W. Santos and A. R. 
Behnke. Localization of spinal cord injury in a deep sea 
diver. U.S. Forces med. J., 1959, 10: 1223-1226. 
1638. Viadro, M. D. and A. S. Panfilov. O dekom- 
pressionnykh rasstroistvakh u letnogo sostava v polete. [On 
decompression disorders in flying personnel during flight.] 
Vo-med. Zh., 1960,1: 62-65. 
1639. Wortmann, H. Ein kasuistischer Beitrag zur 
Begutachtung angeblichen Pressluftschadens. Medizinische, 
1959, 18: 894-895. 
1640. Anon. Decompression sickness. U.S. Forces med. 
J., 1955, 6: 1787-1799. 
D. INCIDENCE, DIAGNOSIS AND 
PROGNOSIS 
For the principle reports on this subject refer- 
ence should be made to Volume II of this 
Sourcebook, pages 163-164. Additional refer- 
ences are given below. 
1641. Fimiani, R. and G. Colicchio. II sistema neuro- 
vegetativo nella malattia da cassone. Folia med., Napoli, 
1960, 43: 661-674. 
1642. Hall, A. L., M. M. Shrinegesh and M. N. 
Johnson. The effects of decompression on subjects re- 
peatedly exposed to 43,000 feet while using standard 
pressure breathing equipment: incidence of aeroembolism 
in an individual subjected to 82 exposures, a case report. 
U.S. Navy. Pensacola, Fla. School of Aviation Medicine. 
Project NM 001 059.21.03, 15 June 1952. 
1643. Isomaki, A. M. and P. T. Hanninen. Tila- 
stollis-kliininen tutkimus maassamme 1916-55 sattuneista 
sukellustapaturmista ja sukeltajien nykyisesta terveydentil- 
asta. A statistical clinical study of the diving accidents 
occurring in Finland in the period 1916-55 and of the 
present health of divers. Duodecim, 1958, 74: 314-323. 
1644. Kleinfeld, M. and J, T. Wilson. Decompres- 
sion sickness (compressed-air illness) in a tunneling opera- 
tion. Arch, industr. Hlth., 1956, 14: 539-542. 
1645. Kooperstein, S. I. and B. J. Schuman. Acute 
decompression illness. A report of forty-four cases. Industr. 
Med. Surg., 1957, 26: 492-496. 
1646. Marbarger, J. P., W. E. Kemp, W. Kadetz 
and J. Hansen. Studies in aeroembolism. J. Aviat. Med., 
1958, 29: 291-300. 
1647. Marbarger, J. P., W. E. Kemp, W. Kadetz, 
D. Variakojis and J. Hansen. Studies in aeroembolism. 
USAF. Randolph Field, Texas. School of Aviation Medi- 
cine. Kept. no. 57-44, February 1957, 11 pp. 
1648. Paton, W. D. M. and D. N. Walder. Com- 
pressed air illness. An investigation during the construc- 
tion of the Tyne Tunnel 1948-50. Gt. Brit. MRC. Special 
Kept., Series no. 281, 1954, 44 pp. 
E. ETIOLOGY 
It is most generally agreed that the formation 
of bubbles causes decompression sickness and 
references on this research as well as comments 
are to be found on pages 164-165 of Volume II 
of this Sourcebook. It has not yet been agreed 
whether or not the bubbles are usually in the 
blood stream or in the tissues; also controversial 
is the question as to whether bubbles are often 
or always present even if there are no symptoms. 
It is possible that bubbles may exist in parts of 
the body without giving rise to symptomatic 
manifestations. If so, such bubbles may cause 
chronic delayed damage such as aseptic bone 
necrosis. 
1649. Buscaino, V. M. Sindromi neurologiche nella 
malattia del cassoni. Folia med., Napoli, 1958, 41: 773-779. 
1650. Gribble, M. de G. A comparison of the “high- 
altitude” and high pressure” syndrome of decompression 
sickness. Brit. J. industr. Med., 1960, 17: 181-186. 
1651. Hickey, J. L. and V. A. Stembridge. Occur- 
rence of pulmonary fat and tissue embolism in aircraft 
accident fatalities. J. Aviat. Med., 1958, 29: 787-793. 
1652. Ivanov, P. N., A. G. Kuznetsov, V. B. 
Malkin and E. O. Popova. Dekompressionnye iavleniia 
v organizme cheloveka v usloviiax kraine nizkogo baro- 
metricheskogo davleniia atmosfery. [Decompression phe- 
nomena in the human body under conditions of extremely 
low barometric pressure of the atmosphere.] Biofizika, 
1960, 5; 704-709. 
1653. Walder, D. N. A possible explanation for some 
cases of severe decompression sickness in compressed air 
workers, pp. 570-572 in: The regulation of human respira- 
tion. Edited by D. J. C. Cunningham and B. B. Lloyd, 
F. A. Davis Co., Philadelphia, 1961, 591 pp. 
1654. Wiinsche, O. Zur Pathogenese und Prophylaxe 
der Druckfall krankheit des Hohenflegers II. Der Einfluss 
narkotischer und sedativer Mittel auf die intravasale 
Gasblasenbildung im Drucksturzversuch. Int. Z. angew. 
Physiol., 1958, 17: 303-315. 
1655. Anon. Panel-floor discussion of decompression 
and bends, pp. 84-88 in: Proceedings of the underwater 
physiology symposium. Edited by L. G. Goff, National Re- 
search Council, Washington, D.C. N.R.C. Publication 377, 
1955, 153 pp. DECOMPRESSION SICKNESS—PATHOLOGICAL LESIONS 
1656-1682 
F. PATHOLOGICAL LESIONS 
On pages 142-162 of the first Volume of this 
Sourcebook there is given a detailed description 
of pathological lesions encountered in decom- 
pression sickness, including post-mortem findings, 
lesions of the central nervous system, lesions of 
the eye, ear lesions and bone and joint lesions. 
This treatment of the subject is supplemented by 
material on pages 165-167 of Volume II of the 
Sourcebook. This latter discussion deals prin- 
cipally with bone and joint lesions. 
Because of the detailed attention given to 
pathological lesions in Volumes I and II, they 
will not be discussed fully here. The references 
that follow deal principally with bone changes. 
Although aseptic bone necrosis is common 
among caisson and tunnel workers, it is virtually 
not found in trained Naval divers. A report is 
given by Sloerdahl (1683) 1953, of aseptic necro- 
sis of bone in three cases among 13 divers ex- 
amined by X-ray. The first had aseptic necrosis 
of the upper end of both femors and humeri; the 
second had involvement of both humeri, while 
in the third there was necrosis of the left humerus 
only. Dale (1660) 1952, published two examples 
of professional divers with necrosis of the femoral 
head and of the humeral head respectively. 
1656. Baillarge, J. and P. Merer. Contribution h 
1’etude des ostto-arthropathies des caissons. Considerations 
sur vingt observations. Arch. Mai. prof., 1953, 14: 225-229. 
1657. Berry, C. A. and G. L. Hekhuis. X-ray survey 
for bone changes in low-pressure chamber operators. 
Aerospace Med., 1960, 31: 760-765. 
1658. Bruzzi, B. Otopatie e Sinusopatie da Baro- 
trauma nei Laboratori dei Cassoni. S. Pipola, Napol, 1959, 
334 pp. 
1659. Coburn, K. R. Preliminary investigation of bone 
change associated with decompression sickness. J. Aviat. 
Med., 1956, 27: 163. 
1660. Dale, T. Bone necrosis in divers. Acta chir. 
scand., 1952, 104: 153-156. 
1661. Davidson, J. K. Radiology in decompression 
sickness: the Clyde tunnel. Scot. med. J., 1964, 9: 1-9. 
1662. Deak, P., I. Rozsahegyi and J. Devai, Echte 
spontane Abbildung des Gelenkspaltes bei Caissonarbei- 
tern. Acta med. Hung., 1955, 8: 125-131. 
1663. Friind, R. Caissonkrankheit im Schultereckgel- 
enk. Z. Orthopdd., 1956, 87: 571-575. 
1664. Guitard, J. Considerations sur les signes de 
debut des osteo-arthrites baro-traumatiques Arch. Mai. 
prof., 1953,14: 230-232. 
1665. Haymake, W. and A. D. Johnston. Pathology 
of decompression sickness. A comparison of the lesions in 
airmen with those in caisson workers and divers. Milit. 
Med., 1955, 117: 285-306. 
1666. Hook, O. Dysbarism manifested by anterior 
spinal artery syndrome. J. Aviat. Med., 1958, 29: 540-543. 
1667. Kettunen, K. O. Sukeltajan tauti ja arthrosis 
deformans. [Diver’s disease and arthrosis deformans.] Duo- 
decim, 1955, 71: 863-869. 
1668. Koledinov, V. I., T. A. Osipkova and G. I. 
Markman. Rentgenologicheskoe izuchenie serdtsa i 
legkikh u vodolazov. Roentgenological study of the heart 
and lungs in divers. Vestn. Rentgenol. Radiol., 1959, 6: 
24-29. 
1669. Laarmann, A. Kahnbeinpseudarthrose und 
Mondbeinnekrose als Pressluftschaden. Untersuchungen 
iiber Entstehungsweise und Wesen dieser Sonderformen 
der Berufskrankheit. Nr. 20. Dtsch. med. ]., 1961, 12: 189- 
197. 
1670. Liess, G. Knochen- und Gelenkveranderungen 
bei der Caisson-Krankheit. Fortschr. Rontgenstr., 1956, 84: 
472-477. 
1671. Markman, G. I. and T. A. Osipkova. K rent- 
genologicheskomu izucheniiu funktsional’nogo sostoianiia 
legkikh u vodolazov. On the roentgenological study of the 
functional state of the lungs in divers. Trud. Leningr. 
sanit. Med. Inst., 1959, 53: 168-182. 
1672. Mauro, M,, Jr. La patogenesi della malattia dei 
cassoni e degli altri barotraumi con particolare riguardo 
alle forme osteo-mio-artralgiche. Folia med., Napoli, 1958, 
41: 847-871. 
1673. McCallum, R.I., J. K. Stanger, D. N. Walder 
and W. D. M. Paton. Avascular necrosis of the femoral 
heads in a compressed air worker. J. Bone Jt. Surg., 1954, 
36B: 606-611. 
1674. Mungo, A. and G, Sessa. Alterazioni radiolo- 
giche dello scheletro nei lavoratori dei cassoni. Folia med., 
Napoli, 1958, 41: 819-836. 
1675. Poppel, M. H. and W. T. Robinson. The 
roentgen manifestations of caisson disease. Amer. J. 
Roentgenol., 1956, 76: 74-80. 
1676. Raymond, V, Arthroses baro-traumatiques. 
Maroc med., 1961, 428: 502-508. 
1677. Robie, R. R., F. W. Lovell and F. M. Town- 
send. Pathological findings in three cases of decompres- 
sion sickness. Aerospace Med., 1960, 31: 885-896. 
1678. Rombola, G. Sindromi morbose da baro-traumi 
in lavoratori subacquei. (Mezzi preventivi e terapeutici.) 
Riv. Infort., 1952. 39: 1067-1083. 
1679. Rozsahegyi, I. Die chronische Osteoarthro- 
pathie der Caissonarbeiter. Arch. Gewerbepath., 1956, 14: 
483-510. 
1680. Sacchitelli, F, and G. Sacchitelli. Sull’azione 
antalgica delle microonde radar nella malattia dei cassoni. 
Minerva Fisioter., 1960, 5: 201-203. 
1681. Schroeder, G. Klinisch-rontgenologischer Beit- 
rag zum Problem des Knocheninfraktes bei Caissonarbeit- 
ern. Mschr. Unfallheilk., 1956, 59: 161-167. 
1682. Sillery, R. J. Decompression sickness. Arch. 
Path., 1958, 66: 241-246. 1683-1697 
DISEASES AND ACCIDENTS 
1683. Sloerdahl, J. Aseptisk bennerose ved dykkersyke. 
Aseptic necrosis of bone in caisson disease. Tidsskr. norske 
Laegeforen., 1953, 73: 300-304. 
1684. Solodkov, A. S. Ob endotelial’nykh reaktsiiakh 
u vodolazov. On endothelial reactions in divers. Vo.-med. 
Zh., 1961, 9: 69-70. 
1685. Suntych, F. and M. Suntychova. Kostni zmeny 
u kesonov£ nemoci. Bone changes in caisson disease. Acta 
chir. orthop. traum. Cech., 1961, 28: 108-114. 
1686. Thomson, J. D. and A. B. Young. Aseptic 
necrosis of bone in caisson disease. Brit. J. industr. Med., 
1958,15: 270-272 
G. PREVENTION AND TREATMENT, 
INCLUDING PRESELECTION TESTS 
1. GENERAL STUDIES 
For a comprehensive approach to prevention 
and treatment of decompression sickness, a chap- 
ter by Miles (1693) 1962, should be consulted. 
This chapter gives the symptoms, historical back- 
ground, diagnosis, treatment and prevention of 
decompression sickness. A comparison of the 
techniques of development of decompression 
tables for air diving is presented. 
1692. Los Angeles County. Underwater recreation. 
County of Los Angeles, Dept, of Parks and Recreation, 
1964, 72 pp. 
1693. Miles, S. Decompression, pp. 158-185 in: Under- 
wate medicine. J. B. Lippincott Co., Philadelphia, 1962, 
328 pp. 
1694. New York State. Work in compressed air (as 
amended). The industrial code, rule no. 22. State of New 
York, Department of Labor, Board of Standards and Ap- 
peals, 15 October 1960, 33 pp. 
1695. Shchupakov, N. N. Profilaktika i lechenie kes- 
sonnoi belezni. [Prevention and therapy of caisson disease.] 
Moskow, 1962, 185 pp. 
1696. Trouillez, M. Un aspect de la m£decine portu- 
aire: les travaus en caisson. Maroc med., 1961, 428: 518- 
521. 
1697. Washington, State of. Safety standards for 
compressed air work. State of Washington, Dept, of Labor 
and Industries, Div. of Safety. Chapter 20, Part 2, 1 Febru- 
ary 1963, 66 pp. 
2. DECOMPRESSION PROCEDURES 
The reader may refer to reference 1728 for a 
description of the decompression tables in use 
in the U. S. Navy. These are reproduced from 
the U.S. Navy Diving Manual and are prescribed 
for all dives where air is the breathing medium. 
Figure 1 reproduces Table 1-5 U.S. Navy stand- 
ard air decompression table. Figure 2 of Table 
1-17, the surface decompression table using oxy- 
gen; Figure 3 is a reproduction of Table 1-18, the 
surface decompression table using air. The pro- 
cedure for the calculation of decompression fol- 
lowing repetitive diving is presented in table 
form in the Manual. 
For investigative studies into the diving tables 
in the Royal Navy a report by Crocker (1702) 
1957, may be consulted. This report (VII) de- 
scribes sea trials of proposed new diving tables. 
These were given a stringent trial in the sea by 
suited divers under practical conditions. The 
dives finally chosen were as follows: 1) 120 feet 
for 30 minutes; 2) 140 feet for 30 minutes; 3) 
160 feet for 25 minutes. These were the dives 
which effected the greatest saving of decompres- 
sion time at the depths indicated. To these 
were added a fourth dive: 120 feet for 50 min- 
utes, which was the longest dive at the depth for 
which the new stops were of shorter duration. 
Fifty-three dives were carried out by 23 subjects. 
Seven cases of decompression sickness and 17 
cases of mild symptoms (not requiring recom- 
pression) occurred. They were distributed 
among the four test schedules as follows: 
Table 
Depth 
DurationTime at Stops 
mins. 
Total 
Time 
ft. 
mins. 
30 ft. 
20 ft. 
30 ft. 
mins. 
HALDANE 
120-132 
15-30 
8 
10 
15 
33 
RASHBASS 
130 
20-30 
4 
9 
13 
CROCKER 
120-130 
25-30 
5 
20 
25 
U.S. NAVY 
130 
30 
4.8 
18 
22.8 
FRENCH 
125 
30 
27 
27 
Miles gives as his opinion the view that the 
United States’ practice of timing to the nearest 
minute for the stops and fractions of minutes 
in ascent time to the first stop is somewhat un- 
realistic. He believes that Crocker’s five minute 
grading is simpler and less likely to cause error. 
1687. Besse, F. Calcul d’une table de plong£e. Marine 
Nationale. GERS, Toulon. Kept. 10/62 G.E.R.S., no. 560, 18 
December 1962, 24 pp 
1688. Didonna, P. La prevenzione della malattia del 
cassoni. Folia med., Napoli, 1958, 41: 792-801. 
1689. Duffner, G. J. Decompression sickness and its 
prevention among compressed air workers. City of Seattle, 
Washington, 20 December 1962, 35 pp. 
1690. Gt. Britain. The work in compressed air special 
regulations, 1958. Gt. Britain, Minister of Labour and 
National Service. Her Majesty’s Stationery Office, 1960, 
16 pp. 
1691. Kratochvil, C. H. The contributions of Al- 
honse Jaminet to an understanding of decompression 
sickness. /. Aviat. Med., 1956, 27: 59-63. DECOMPRESSION SICKNESS—PROCEDURES 
U.S. NAVY DIVING MANUAL 
Depth 
Bottom 
Time to 
Decompression stops 
Total 
Repet. 
(f« 
time 
first 
ascent 
group 
(mins) 
stop 
50 40 30 20 10 
time 
200 
0 
0.7 
. 
210 
0.5 
2 
2.5 
N 
40 
230 
0.5 
7 
7.5 
N 
250 
0.5 
11 
11.5 
O 
270 
0.5 
15 
15.5 
O 
300 
0.5 
19 
19.5 
z 
100 
0 
0.8 
. 
110 
0.7 
3 
3.7 
L 
120 
0.7 
5 
5.7 
M 
140 
0.7 
10 
10.7 
M 
50 
160 
0.7 
21 
21.7 
N 
180 
0.7 
29 
29,7 
O 
200 
0.7 
35 
35.7 
O 
220 
0.7 
40 
40.7 
z 
240 
0.7 
47 
47.7 
z 
60 
0 
1.0 
» 
70 
0.8 
2 
2.8 
K 
80 
0.8 
7 
7.8 
L 
100 
0.8 
14 
14.8 
M 
60 
120 
0.8 
26 
26.8 
N 
140 
0.8 
39 
39.8 
O 
160 
0.8 
48 
48.8 
Z 
180 
0.8 
56 
56.8 
z 
200 
0.6 
1 69 
70.6 
z 
50 
0 
1.2 
* 
60 
1.0 
8 
9.0 
K 
70 
1.0 
14 
15.0 
L 
80 
1.0 
18 
19.0 
M 
90 
1.0 
23 
24.0 
N 
100 
1.0 
33 
34.0 
N 
70 
no 
0,8 
2 41 
43.8 
O 
120 
0.8 
4 47 
51.8 
O 
130 
0.8 
6 52 
58.8 
0 
140 
0.8 
8 56 
64.8 
z 
150 
0.8 
9 61 
70.8 
z 
160 
0.8 
13 72 
85.8 
z 
170 
0.8 
19 79 
98.8 
z 
40 
0 
1.3' 
. 
50 
1.2 
10 
11.2 
K 
60 
1.2 
17 
18.2 
L 
70 
1,2 
23 
24.2 
M 
80 
1.0 
2 31 
34.0 
N 
80 
90 
1.0 
7 39 
47.0 
N 
100 
1.0 
11 46 
58.0 
O 
no 
1.0 
13 53 
67.0 
O 
120 
1.0 
17 56 
74.0 
z 
130 
1.0 
19 63 
83.0 
z 
140 
1.0 
26 69 
96.0 
z 
150 
1.0 
32 77 
110.0 
z 
30 
0 
1.5 
• 
40 
1.3 
7 
8.3 
J 
50 
1.3 
18 
19.3 
L 
60 
1.3 
25 
26.3 
M 
70 
1.2 
7 30 
38.2 
N 
90 
80 
1.2 
13 40 
54.2 
N 
90 
1.2 
18 48 
67.2 
O 
100 
1.2 
21 54 
76.2 
z 
no 
1.2 
24 61 
86.2 
z 
120 
1.2 
32 68 
101.2 
z 
130 
1.0 
5 36 74 
116.0 
z 
25 
0 
1.7 
» 
30 
1.5 
3 
4.5 
I 
40 
1.5 
15 
16.5 
K 
50 
1.3 
2 24 
27.3 
L 
60 
1.3 
9 28 
38.3 
N 
100 
70 
1.3 
17 39 
57.3 
O 
80 
1.3 
23 48 
72.3 
O 
90 
1.2 
3 23 57 
84.2 
z 
100 
1.2 
7 23 66 
97,2 
z 
no 
1.2 
10 34 72 
117.2 
z 
120 
1.2 
12 41 78 
132.2 
z 
20 
0 
1.8 
« 
25 
1.7 
3 
4.7 
H 
30 
1.7 
7 
8.7 
J 
40 
1.5 
2 21 
24.5 
L 
no 
50 
1.5 
8 26 
35.5 
M 
60 
1.5 
18 36 
55.5 
N 
70 
1.3 
1 23 48 
73.3 
O 
80 
1.3 
7 23 57 
88.3 
Z 
90 
1.3 
12 30 64 
107.3 
z 
100 
1.3 
15 37 72 
125.3 
z 
Depth 
Bottom 
Time to 
Decompression stops 
Total 
Repet. 
(ft) 
time 
first 
ascent 
group 
(mins) 
stop 
50 
40 
30 
20 
10 
time 
15 
0 
2.0 
♦ 
20 
1.8 
2 
3.8 
H 
25 
1.8 
6 
7.8 
1 
30 
1.8 
14 
15.8 
J 
40 
1.7 
5 
25 
31.7 
L 
120 
50 
1.7 
15 
31 
47.7 
N 
60 
1.5 
2 
22 
45 
70.5 
O 
70 
1.5 
9 
23 
55 
88.5 
O 
80 
1.5 
15 
27 
63 
106.5 
z 
90 
1.5 
19 
37 
74 
131.5 
z 
100 
1.5 
23 
45 
80 
149.5 
z 
10 
0 
2.2 
* 
15 
2.0 
1 
3.0 
F 
20 
2,0 
4 
6.0 
H 
25 
2.0 
10 
12.0 
J 
30 
1.8 
3 
18 
22.8 
M 
130 
40 
1.8 
10 
25 
36.8 
N 
50 
1.7 
3 
21 
37 
62.7 
O 
60 
1.7 
9 
23 
52 
85,7 
Z 
70 
1.7 
16 
24 
61 
102.7 
z 
80 
1.5 
3 
19 
35 
72 
130.5 
z 
90 
1.5 
8 
19 
45 
80 
153.5 
z 
10 
0 
2.3 
* 
15 
2.2 
2 
4.2 
G 
20 
2.2 
6 
8.2 
I 
25 
2.0 
2 
14 
18.0 
J 
140 
30 
2.0 
5 
21 
28,0 
K 
40 
1.8 
2 
16 
26 
45.8 
N 
50 
1.8 
6 
24 
44 
75.8 
0 
60 
1.8 
16 
23 
56 
96.8 
z 
70 
1.7 
4 
19 
32 
68 
124.7 
z 
80 
1.7 
10 
23 
41 
79 
154.7 
z 
5 
0 
2.5 
c 
10 
2.3 
1 
3.3 
E 
15 
2.3 
3 
5.3 
G 
20 
2.2 
2 
7 
11.2 
H 
25 
2.2 
4 
17 
23.2 
K 
150 
30 
2.2 
8 
24 
34.2 
L 
40 
2.0 
5 
19 
33 
59.0 
N 
50 
2.0 
12 
23 
51 
88.0 
O 
60 
1.8 
3 
19 
26 
62 
111.8 
Z 
70 
1.8 
11 
19 
39 
75 
145.8 
z 
80 
1.7 
1 
17 
19 
50 
84 
172.7 
z 
5 
0 
2.7 
D 
10 
2.5 
1 
3.5 
F 
15 
2.3 
1 4 
7.3 
H 
20 
2.3 
3 
11 
16.3 
J 
160 
25 
2.3 
7 
20 
29.3 
K 
30 
2.2 
2 
11 
25 
40.2 
M 
40 
2.2 
7 
23 
39 
71.2 
N 
50 
2.0 
2 
16 
23 
55 
98.0 
Z 
60 
2.0 
9 
19 
33 
69 
132,0 
Z 
70 
1.8 
1 
17 
22 
44 
80 
165.8 
Z 
5 
0 
2.8 
D 
10 
2.7 
2 
4.7 
F 
15 
2.5 
2 
5 
9.5 
H 
20 
2.5 
4 
15 
21.5 
J 
170 
25 
2.3 
2 
7 
23 
34.3 
L 
30 
2.3 
4 
13 
26 
45.3 
M 
40 
2.2 
1 
10 
23 
45 
81.2 
O 
50 
2.2 
5 
18 
23 
61 
109.2 
Z 
60 
2.0 
2 
15 
22 
37 
74 
152.0 
Z 
70 
2.0 
8 
17 
19 
51 
86 
183.0 
z 
5 
0 
3.0 
D 
10 
2.8 
3 
5.8 
F 
15 
2.7 
3 
6 
11.7 
I 
20 
2.5 
1 
5 
17 
25.5 
K 
180 
25 
2.5 
3 
10 
24 
39.5 
L 
30 
2.5 
6 
17 
27 
52.5 
N 
40 
2.3 
3 
14 
23 
50 
92.3 
O 
50 
2.2 
2 
9 
19 
.30 
65 
127.2 
Z 
60 
2.2 
5 
16 
19 
44 
81 
167.2 
Z 
5 
0 
3.2 
D 
10 
2.8 
1 3 
6.8 
G 
15 
2.8 
4 
7 
13.8 
I 
20 
2.7 
2 
6 
20 
30.7 
K 
190 
25 
2.7 
5 
11 
25 
43.7 
M 
30 
2.5 
1 
8 
19 
32 
62.5 
N 
40 
2.5 
8 
14 
23 
55 
102.5 
O 
50 
2,3 
4 
13 
22 
33 
72 
146.3 
z 
60 
2.3 
10 
17 
19 
50 
84 
182.3 
z 
*See table 1-6 for repetitive groups in “no decompression” dives. 
(Rev. 1958) 
Table 1-5. — U.S. Navy standard air decompression table. 
Figure 1 DISEASES AND ACCIDENTS 
1** 
2** 
3** 
4** 
5»* 
6** 
7** 
Time (min.) 
Approxi- 
Depth 
in feet 
Time 
lime (mm.) at 
at 40' 
water stops 
breathing air at 
stop 
pression 
oxygen 
time (min.) 
60' 
50' 
40' 
30’ 
52 
0 
0 
0 
0 
0 
3 
90 
0 
0 
0 
0 
15 
24 
70 
*120 
0 
0 
0 
0 
23 
32 
150 
0 
0 
0 
0 
31 
40 
180 
0 
0 
0 
0 
39 
48 
40 
0 
0 
0 
0 
0 
3 
70 
0 
0 
0 
0 
14 
23 
85 
0 
0 
0 
0 
20 
29 
80 
100 
0 
0 
0 
0 
26 
35 
*115 
0 
0 
0 
0 
31 
40 
130 
0 
0 
0 
0 
37 
46 
150 
0 
0 
0 
0 
44 
53 
Cf) 
w 
H 
O 
32 
0 
0 
0 
0 
0 
H 
CC 
4 
60 
0 
0 
0 
0 
p 
14 
w 
CQ 
24 
70 
0 
0 
0 
0 
20 
30 
80 
0 
0 
0 
0 
25 
<z 
ffi w 
uO 
35 
90 
*90 
0 
0 
0 
0 
Q 
30 
40 
100 
0 
0 
0 
0 
w 
w 
CJ 
34 
zx 
44 
110 
0 
0 
0 
0 
39 
-o 
49 
120 
0 
0 
0 
0 
X 
w 
43 
wg 
P 
53 
130 
0 
0 
0 
0 
o 
48 
58 
26 
0 
0 
0 
0 
H 
0 
w 
4 
50 
0 
0 
0 
0 
z 
14 
£ cc 
23 
24 
60 
0 
0 
0 
0 
20 
cc 
* w 
30 
70 
0 
0 
0 
0 
> 
26 
36 
100 
*80 
90 
0 
0 
0 
0 
0 
0 
0 
0 
cc 
w 
H 
32 
38 
zs 
wx 
42 
48 
100 
0 
0 
0 
0 
z 
44 
54 
110 
120 
0 
0 
0 
0 
0 
0 
0 
3 
w 
CJ 
< 
49 
53 
59 
66 
cc 
22 
0 
0 
0 
0 
p 
(/) 
0 
s 
5 
40 
0 
0 
0 
0 
12 
CM 
23 
50 
0 
0 
0 
0 
19 
30 
60 
0 
0 
0 
0 
26 
37 
110 
*70 
0 
0 
0 
0 
33 
44 
80 
0 
0 
0 
1 
40 
52 
90 
0 
0 
0 
2 
46 
59 
100 
0 
0 
0 
5 
51 
67 
no 
0 
0 
0 
12 
54 
77 
18 
0 
0 
0 
0 
0 
5 
30 
0 
0 
0 
(I 
9 
20 
120 
40 
0 
0 
0 
0 
16 
27 
50 
0 
0 
0 
0 
24 
35 
*60 
0 
0 
0 
2 
32 
45 
GENERAL PRINCIPLES OF DIVING 
1** 
2** 
3** 
4** 
5»* 
6** 
7** 
Time (min.) 
Approxi- 
Depth 
in feet 
Time 
1 ime (mm.) at 
water stops 
breathing air at 
stop 
pression 
time (min.) 
oxygen 
60' 
50' 
40' 
30' 
70 
0 
0 
0 
4 
39 
54 
120 
80 
0 
0 
0 
5 
46 
62 
90 
0 
0 
3 
7 
51 
72 
100 
0 
0 
6 
15 
54 
86 
15 
0 
0 
0 
0 
0 
5 
30 
0 
0 
0 
0 
12 
23 
40 
0 
0 
0 
0 
21 
32 
130 
50 
0 
0 
0 
3 
29 
43 
*60 
0 
0 
0 
5 
37 
53 
70 
0 
0 
0 
7 
45 
63 
80 
0 
0 
6 
7 
51 
76 
90 
0 
0 
10 
12 
56 
90 
cn 
w 
H 
O 
13 
0 
0 
0 
0 
0 
H 
ec 
6 
25 
0 
0 
0 
0 
D 
11 
u 
SC yr 
Su 
23 
30 
0 
0 
0 
0 
15 
27 
35 
0 
0 
0 
0 
20 
CO 
32 
40 
0 
0 
0 
2 
Q 
24 
ox 
38 
140 
45 
0 
0 
0 
4 
w 
29 
7° 
45 
50 
0 
0 
0 
6 
CJ 
33 
-o 
hZ 
51 
*55 
0 
0 
0 
7 
u 
38 
US 
57 
60 
0 
0 
0 
8 
o 
43 
63 
65 
70 
0 
0 
0 
2 
3 
7 
7 
7 
H 
H 
O 
48 
51 
C u 
70 
80 
11 
0 
0 
0 
0 
0 
OS J 
6 
25 
0 
0 
0 
0 
< 
> 
13 
25 
30 
0 
0 
0 
0 
os 
18 
T 
W W 
Oo 
30 
150 
35 
0 
0 
0 
4 
E- 
23 
39 
40 
0 
0 
3 
6 
z 
27 
< Us 
49 
45 
0 
0 
5 
7 
w 
33 
58 
*50 
0 
2 
5 
8 
< 
38 
66 
55 
2 
5 
9 
4 
u* 
OS 
44 
z 
78 
cn 
9 
0 
0 
0 
0 
0 
CM 
7 
20 
0 
0 
0 
0 
11 
24 
25 
0 
0 
0 
0 
16 
29 
160 
30 
0 
0 
0 
2 
21 
35 
35 
0 
0 
4 
6 
26 
49 
40 
0 
3 
5 
8 
32 
62 
*45 
3 
4 
8 
6 
38 
73 
7 
0 
0 
0 
0 
0 
7 
20 
0 
0 
0 
0 
13 
26 
170 
25 
0 
0 
0 
0 
19 
32 
30 
0 
0 
3 
5 
23 
44 
35 
0 
4 
4 
7 
29 
58 
*40 
4 
4 
8 
6 
36 
73 
•These are the optimum exposure times for each depth which repre- 
sent the best balance between length of work period, safety and amount 
of useful work for the average diver. Exposure beyond these times is 
permitted only under special conditions. 
•‘Notes on columns. 
Column 1. Depth —In feet, gage. 
Column 2. Time —Interval from leaving the surface to leaving the 
bottom. 
Column 3. Water stops —Time spent at tabulated stops using air. 
If no water stops are required use a 25 foot per minute rate of ascent 
to the surface. When water stops are required use a 25 foot per minute 
rate of ascent to first stop. Take an additional minute between stops. 
Use one minute for the ascent from 30 feet to the surface. 
Column 4. Surface interval —The surface interval shall not exceed 
5 minutes and is composed of the following elements: 
(a) Time of ascent from the 30-foot water stop to the surface 
(1 minute). 
(b) Time on surface for landing the diver on deck and undressing 
(not to exceed 3Va minutes). 
(c) Time of descent in the recompression chamber from the surface 
to 40 feet (about V2 minute). 
Column 5. During the period while breathing oxygen the chamber 
shall be ventilated. 
Column 6. Surfacing—Oxygen breathing during this 2-minute 
period shall follow the period of oxygen breathing tabulated in Column 
5 without interruption. 
Column 7. Total decompression time —This includes 
(a) Time of ascent from bottom to first stop at 25 feet per minute. 
(b) Sum of tabulated water stops, column 2. 
(c) One minute between water stops. 
(d) Surface interval. 
(e) Time at 40 feet in recompression chamber, column 4. 
(f) Time of ascent, an additional 2 minutes, from 40 feet in the 
recompression chamber to the surface, column 5. 
The Approximate Total Decompression Time may be shortened only 
by decreasing the time required to undress the diver on deck. 
Table 1-17.— Surface decompression table using oxygen. 
Figure 2 DECOMPRESSION SICKNESS—PROCEDURES 
U.S. NAVY DIVING MANUAL 
Depth 
(ft.) 
Bottom 
time 
(min.) 
Time to 
first 
stop 
Time at 
water stops 
Chamber 
stops (air) 
Total 
ascent 
time 
30 
20 
10 
30 
20 
10 
40 
230 
0.5 
3 
7 
10.5 
250 
0.5 
3 
11 
14.5 
270 
0.5 
3 
15 
18.5 
300 
0.5 
3 
19 
22.5 
50 
120 
0.7 
3 
5 
8.7 
140 
0.7 
3 
TIME ON SURFACE NOT TO EXCEED 3.5 MINUTES 
10 
13.7 
160 
0.7 
3 
21 
24.7 
180 
0.7 
3 
29 
32.7 
200 
0.7 
3 
35 
38.7 
220 
0.7 
3 
40 
43.7 
240 
0.7 
3 
47 
50.7 
60 
80 
0.8 
3 
7 
10.8 
100 
0.8 
3 
14 
17.8 
120 
0.8 
3 
26 
29.8 
140 
0.8 
3 
39 
42.8 
160 
0.8 
3 
48 
51.8 
180 
0.8 
3 
56 
59.8 
200 
0.7 
3 
3 
69 
75.7 
70 
60 
1.0 
3 
8 
12.0 
70 
1.0 
3 
14 
18.0 
80 
1.0 
3 
18 
22.0 
90 
1.0 
3 
23 
27.0 
100 
1.0 
3 
33 
37.0 
no 
0.8 
3 
3 
41 
47.8 
120 
0.8 
3 
4 
47 
54.8 
130 
0.8 
3 
6 
52 
61.8 
140 
0.8 
3 
8 
56 
67.8 
150 
0.8 
3 
9 
61 
73.8 
160 
0.8 
3 
13 
72 
88.8 
170 
0.8 
3 
19 
79 
101.8 
80 
50 
1.2 
3 
10 
14.2 
60 
1.2 
3 
17 
21.2 
70 
1.2 
3 
23 
27.2 
80 
1.0 
3 
3 
31 
38.0 
90 
1.0 
3 
7 
39 
50.0 
100 
1.0 
3 
11 
46 
61.0 
no 
1.0 
3 
13 
53 
70.0 
120 
1.0 
3 
17 
56 
77.0 
130 
1.0 
3 
19 
63 
86.0 
140 
1.0 
26 
26 
69 
122.0 
150 
1.0 
32 
32 
77 
142.0 
90 
40 
1.3 
3 
7 
11.3 
50 
1.3 
3 
18 
22.3 
60 
1.3 
3 
25 
29,3 
70 
1.2 
3 
7 
30 
41.2 
80 
1.2 
13 
13 
40 
67.2 
90 
1.2 
18 
18 
48 
85.2 
100 
1.2 
21 
21 
54 
97.2 
no 
1.2 
24 
24 
61 
110.2 
120 
1.2 
32 
32 
68 
133.2 
130 
1.0 
5 
36 
36 
74 
152.0 
100 
40 
1.5 
3 
15 
19.5 
50 
1.3 
3 
3 
24 
31.3 
60 
1.3 
3 
9 
28 
41.3 
70 
1.3 
3 
17 
39 
60.3 
80 
1.3 
23 
23 
48 
95.3 
90 
1.2 
3 
23 
23 
57 
107.2 
100 
1.2 
7 
23 
23 
66 
120.2 
no 
1.2 
10 
34 
34 
72 
151.2 
120 
1.2 
12 
41 
41 
78 
173.2 
no 
30 
1.7 
3 
7 
11.7 
40 
1.5 
3 
3 
21 
28.5 
50 
1.5 
3 
8 
26 
38.5 
60 
1.5 
18 
18 
36 
73.5 
70 
1.5 
1 
23 
23 
48 
96.5 
80 
1.3 
7 
23 
23 
57 
111.3 
90 
1.3 
12 
30 
30 
64 
137.3 
100 
1.3 
15 
37 
37 
72 
162.3 
Depth 
(ft.) 
Bottom 
Time to 
Time at 
water stops 
Chamber 
stops (air) 
Total 
(min.) 
stop 
50 
40 
30 
20 
10 
30 
20 
10 
time 
25 
1.8 
3 
6 
10.8 
30 
1.8 
3 
14 
18.8 
40 
1.7 
3 
5 
25 
34.7 
50 
1.7 
15 
15 
31 
62.7 
120 
60 
1.5 
2 
22 
22 
45 
92.5 
70 
1.5 
9 
23 
23 
55 
111.5 
80 
1.5 
15 
27 
27 
63 
133.5 
90 
1.5 
19 
37 
37 
74 
168.5 
100 
1.5 
23 
45 
45 
80 
194.5 
25 
2.0 
3 
10 
15.0 
30 
1.8 
3 
3 
18 
25.8 
40 
1.8 
10 
10 
25 
46.8 
130 
50 
1.7 
3 
21 
21 
37 
83.7 
60 
1.7 
9 
23 
23 
52 
108.7 
70 
1.7 
16 
24 
24 
61 
126.7 
80 
1.5 
3 
19 
35 
35 
72 
165.5 
90 
1.5 
8 
19 
45 
45 
80 
198.5 
20 
2.2 
3 
(S) 
w 
6 
11.2 
25 
2.0 
3 
H 
3 
14 
22.0 
30 
2.0 
5 
z 
5 
21 
33.0 
140 
40 
1.8 
2 
16 
16 
26 
61.8 
50 
1.8 
6 
24 
24 
44 
99.8 
60 
1.8 
16 
23 
c6 
23 
56 
119.8 
70 
1.7 
4 
19 
32 
Q 
32 
68 
156.7 
80 
1.7 
10 
23 
41 
W 
W 
41 
79 
195.7 
20 
2.2 
3 
X 
w 
3 
7 
15.2 
25 
2.2 
4 
4 
17 
27.2 
30 
2.2 
8 
o 
8 
24 
42.2 
150 
40 
2.0 
5 
19 
19 
33 
78.0 
50 
2.0 
12 
23 
b 
23 
51 
111.0 
60 
1.8 
3 
19 
26 
z 
26 
62 
137.8 
70 
1,8 
11 
19 
39 
w 
39 
75 
184.8 
80 
1.7 
1 
17 
19 
50 
CJ 
< 
50 
84 
222.7 
20 
2.3 
3 
s 
3 
11 
19.3 
25 
2.3 
7 
Cf) 
7 
20 
36.3 
30 
2.2 
2 
11 
z 
11 
25 
51.2 
160 
40 
2.2 
7 
23 
o 
1 23 
39 
94.2 
50 
2.0 
2 
16 
23 
W 
23 
55 
121.0 
60 
2.0 
9 
19 
33 
s 
33 
69 
165.0 
70 
1.8 
1 
17 
22 
44 
H 
44 
80 
209.8 
15 
2.5 
3 
1 3 
5 
13.5 
20 
2.5 
4 
4 
15 
25.5 
25 
2.3 
2 
7 
7 
23 
41.3 
170 
30 
2.3 
4 
13 
13 
26 
58.3 
40 
2.2 
1 
10 
23 
23 
45 
104.2 
50 
2.2 
5 
18 
23 
23 
61 
132.2 
60 
2.0 
2 
15 
22 
37 
37 
74 
187.0 
70 
2.0 
8 
17 
19 
51 
51 
86 
234.0 
15 
2.7 
3 
3 
6 
14.7 
20 
2.5 
1 
5 
5 
17 
30.5 
25 
2.5 
3 
10 
10 
24 
49.5 
180 
30 
2.5 
6 
17 
17 
27 
69.5 
40 
2.3 
3 
14 
23 
23 
50 
115.3 
50 
2.2 
2 
9 
19 
30 
30 
65 
155.2 
60 
2.2 
5 
16 
19 
44 
44 
81 
211.2 
15 
2.8 
4 
4 
7 
17.8 
20 
2.7 
2 
6 
6 
20 
36.7 
25 
2.7 
5 
11 
11 
25 
54.7 
190 
30 
2.5 
1 
8 
19 
19 
32 
81.5 
40 
2.5 
8 
14 
23 
23 
55 
125.5 
50 
2.3 
4 
13 
22 
33 
33 
72 
179.3 
60 
2.3 
10 
17 
19 
50 
| 50 
84 
232.3 
TABLE 1-18. —Surface decompression table using air. 
Figure 3 DISEASES AND ACCIDENTS 
Cases 
Minor 
No. of 
Test schedule 
of bends 
symptoms 
dives 
1. 120 ft. for 30 min. 
2 
4 
20 
2. 120 ft. for 50 min. 
2 
4 
14 
3. 140 ft. for 30 min. 
1 
5 
11 
4. 160 ft. for 25 min. 
2 
4 
8 
to be successful for depths down to 300 feet if a 
modified technique is used. A depth of 190 feet 
had been the previous limit. Experiments on 
human subjects confirmed the safety of the 
method down to 230 feet. For a report of sea 
trials on the surface decompression routine, Mac- 
kay’s paper (1716) 1958, may be perused. Two 
hundred and ten dives were carried out to test a 
new routine of surface decompression in sheltered 
sea waters with an overall incidence of major de- 
compression sickness of 4.29 percent. The range 
of depths for the dives was 80 to 180 feet and the 
duration of the dives was chosen to test the tables 
more fully. These dives were work dives, consist- 
ing of bottom sorties of linkcutting. Rate of 
descent was precisely regulated to one foot per 
second with decompression carried out in a 
chamber aboard ship. The diver was brought 
from the bottom immediately to the surface, 
placed in the chamber and recompressed to a 
depth 30 feet below the dive depth. (The time 
required to accomplish should not exceed five 
minutes.) The chamber was kept at the 30+ 
depth for five minutes and then decompression 
was carried out as scheduled for a dive of ten 
minutes longer than the actual dive performed. 
One minute was used to get to the first new 
stop. The author recommended that the routine 
for surface decompression be accepted to replace 
the Royal Navy Diving Manual routine. For an 
additional paper on surface decompression, that 
by Workman (1721) 1957, may be consulted. 
Here a method is reported on surface decom- 
pression for diving to depths of 190 feet, employ- 
ing modified standard air decompression tables. 
Essentially the procedure is to bring the diver 
to the surface following minimal decompression 
in the water and to recompress him in a chamber 
within 3.5 minutes. The excess inert gas ten- 
sion can be tolerated during such a brief in- 
terval. The last water stop is repeated in the 
chamber and the remainder of the prescribed de- 
compression completed. This procedure was 
tested by the author during 76 working dives 
at simulated depths of 80 to 190 feet. The method 
was found to be satisfactory within the test 
limits. 
The advantages of surface decompression are: 
1) The diver can be removed at once to a warm, 
safe, reasonably comfortable decompression 
It is concluded by the author that the margin 
of safety in the more critcial dives is too narrow 
for the tables to be adopted by the services in 
their entirety. Crocker has given a further re- 
port on the revised tables {1703). Kiessling and 
Duffner (1712) 1960, reported the development 
of a test to determine the adequacy of decom- 
pression following a dive. In these studies Navy 
divers performed working dives in a pressure 
tank for 30 minutes at simulated depths of 90, 
110 and 125 feet. The work consisted of swim- 
ming on an ergometer and weight lifting. Fol- 
lowing the dive the subjects were decompressed 
to atmospheric pressure at a rate of 60 feet per 
minute. Upon surfacing the subjects observed 
the following routine: 0-15 minutes, unsuper- 
vised activity; 15-45 minutes, exercise (five deep 
knee bends and five push-ups every five minutes); 
45-50 minutes, ascent to simulated altitude of 
18,000 feet; 50-105 minutes, at altitude exercis- 
ing (ten deep knee bends every five minutes). 
The times of occurrence of any signs or symp- 
toms of decompression sickness were recorded. 
The experiment was terminated when the subject 
could no longer tolerate his symptoms. These 
three exposures were considered to represent 
different decompression sickness hazard levels 
and hence were designated as GREEN, YEL- 
LOW and RED dives. The following mean end- 
points in terms of time at altitude were observed: 
GREEN 47.5, YELLOW 21.4 and RED 7.2. Sta- 
tistical analysis demonstrated that these mean 
differences did not occur by chance, but as a 
product of the experimental conditions. The 
authors concluded that this procedure will quan- 
titatively measure the adequacy of decompres- 
sion. 
For studies of decompression and inert gas- 
oxygen mixtures in the U.S. Navy a report by 
Workman {1722) 1963, should be consulted. 
Davidson and Taylor {1704) 1952, have car- 
ried out animal and human experiments on sur- 
face decompression procedures. Animal studies 
have shown that surface decompression is likely DECOMPRESSION SICKNESS—PROCEDURES 
1698-1717 
chamber. 2) In the chamber the actual pressure 
depth at a given stop can be precisely controlled 
in contrast to the condition in the water in heavy 
seas where depth control may be difficult. 
For a report presenting the theoretical basis 
for a calculation of decompression schedules for 
nitrogen-oxygen and helium-oxygen mixtures 
used in diving, a report by R. D. Workman (Cal- 
culation of decompression schedules for nitro- 
gen-oxygen and helium-oxygen dives, Research 
Report 6-65, Project No. SF-001-06-05; Task 
No. 11514, Sub-task 5, 26 May 1965) should be 
consulted. This report appeared too late for in- 
clusion in the citation list for the present Source- 
book. This report includes definition, theory of 
exponential saturation and de-saturation and 
theory of limiting values of excess saturation per- 
mitted at various ambient pressures with helium 
and oxygen. An attempt has been made to 
simplify the presentation of the calculation pro- 
cedures to implement the theoretical method. 
The necessary tables and work sheets used in 
calculations are presented by the author and 
there are also sample calculations of dive sched- 
ules. This discussion describes and appraises 
other methods of calculation developed in recent 
years. 
1698. Albano, G. Tavole per la decompressione con 
aria o con ossigeno ad uso dei sommozzatori. Ann. Med. 
Nav., 1962, 67: 609-620. 
1699. Behnke, A. R. Oxygen decompression, pp. 61- 
73 in: Proceedings of the underwater physiology sym- 
posium. Edited by L. G. Goff, National Research Council, 
Washington, D.C. N.R.C. Publication 377, 1955, 153 pp. 
1700. Besse, F, Studies of decompression, pp. 14-21 
in: Second symposium on underwater physiology. Edited 
by C. J. Lambertsen and L. J. Greenbaum, Jr. National 
Research Council, Washington, D.C. N.R.C. Publication 
1181, 1963, 296 pp 
1701. Brestkin, A. P. and A. G. Zhironkin. Otsenka 
razlichnykh sposobov primeneniia kisloroda pri dekom- 
pressii vodolazov. [Evaluation of different methods of 
administration of oxygen for the decompression of divers.] 
Fiziol. Zh. SSSR Sechenov, 959, 45: 865-871. 
1702. Crocker, W. E. Investigation into the decom- 
pression tables. Rept. VII. Sea trials of proposed new div- 
ing tables. Gt. Brit. MRC, RNPRC, UPS, Rept. R.N.P. 
57/885, U.P.S. 162, February 1957, 3 pp. 
1703. Crocker, W. E. Investigation into decompres- 
sion tables. Report IX. Revised tables. Gt. Brit. MRC, 
RNPRC, UPS. Rept. R.N.P. 58/902, U.P.S. 171, December 
1957, 20 pp 
1704. Davidson, W. M. and H. J. Taylor. Surface 
decompression. Gt. Brit. MRC, RNPRC. Kept. R.N.P. 
52 j705, U.P.S 130, D.P. 6, 1952, 6 pp. 
1705. Des Granges, M. Standard air decompression 
table. U.S. Navy. EDU, Naval Gun Factory, Washington, 
D.C. Res. Rept. 5-57, Proj. NS 185-005, Subtask 5, Test 3, 
3 December 1956, 35 pp. 
1706. Des Granges, M. Repetitive diving decompres- 
sion tables. U.S. Navy. EDU, Naval Gun Factory, Washing- 
ton, D.C. Res. Rept. 6-57, Proj. NS 185-005, Subtask 5, 
Test 3, 9 January 1957, 40 pp. 
1707. Dwyer, J. V. Calculation of air decompression 
tables. U.S. Navy. EDU, Naval Gun Factory, Washington, 
D.C. Res. Rept. 4-56, Proj. NS 185-005, Subtask 5, Test 3, 
29 November 1955, 27 pp. 
1708. Hempleman, H. V. Investigation into the de- 
compression tables. Report VIII. Further basic facts on 
decompression sickness. Gt. Brit. MRC, RNPRC, UPS. 
Rept. R.N.P. 57/896, U.S.P 168, August 1957, 7 pp. 
1709. Hempleman, H. V. Tissue inert gas exchange 
and decompression sickness, pp. 613 in: Second symposium 
on underwater physiology. Edited by C. J. Lambertsen and 
L. J. Greenbaum, Jr. National Research Council, Wash- 
ington, D.C. N.R.C. Publication 1181, 1963, 296 pp. 
1710. Hempleman, H. V., W. E. Crocker and H. 
J. Taylor. Investigation into the decompression tables. 
Report III. Part A. A new theoretical basis for the calcula- 
tion of decompression tables. Part B. A method of calculat- 
ing decompression stages and the formulation of new 
diving tables. Gt. Brit. MRC, RNPRC, UPS. Rept. R.N.P. 
52/708, U.P.S. 131, June 1952, 30 pp. 
1711. Jullien, G., M. Leandri, G. Auge and C. 
Rampal. Etude sur les tables de decompression utilises 
par les ouvierstubistes. Projet d’une methode de decom- 
pression a F oxygene pur. Marco med., 1961,428: 509-517. 
1712. Kiessling, R. J. and G. J. Duffner. The de- 
velopment of a test to determine the adequacy of de- 
compression following a dive. U.S. Navy. Naval Weapons 
Plant, EDU. Res. Rept. no. 2-60, 15 February 1960, 16 pp. 
1713. Kiessling, R. J. and W. B. Wood. The devel- 
ment of a test to determine the adequacy of decompression 
following a dive. Phase II. U.S. Navy. Naval Weapons 
Plant, EDU. 30 June 1961, 47 pp. 
1714. Lanphier, E. H. Use of nitrogen-oxygen mix- 
tures in diving, pp. 74-78 in: Proceedings of the under- 
water physiology symposium. Edited by L. G. Goff, Na- 
tional Research Council, Washington, D.C. N.R.C. Pub- 
lication 377, 1955,153 pp. 
1715. Logan, J. A. An evaluation of the equivalent 
air depth theory. U.S. Navy. Naval Weapons Plant, EDU. 
Project NS 185-005, sub task no. 5, test no. 1, 28 July 1960, 
10 pp. 
1716. Mackay, E. Sea trials of new surface decom- 
pression routine. Gt. Brit. MRC, RNPRC, UPS. Rept. 
U.P.S. 181, August 1958, 9 pp. 
1717. Rashbass, C. Investigation into the decompres- 
sion tables. Report VI. New tables. Gt. Brit. MRC, 
RNPRC, UPS. Rept. R.N.P. 55/847, U.P.S. 151. October 
1955, 27 pp. 1718-1728 
DISEASES AND ACCIDENTS 
1718. Rashbass, C. and W. J. Eaton. The effect of 
oxygen concentration on the occurrence of decompression 
sickness. Gt. Brit. MRC, RNPRC, UPS. Rept. R.N.P. 
57/897, U.P.S. 169, July 1957, 3 pp. 
1719. Raymond, V. La prevention physiologique des 
coups de pression, Les tables de decompression. Arch. Mai. 
prof., 1953,14: 248-251. 
1720. Workman, R. D. Calculation of air saturation 
decompression tables. U.S. Navy. Naval Weapons Plant, 
EDU. Project NS 185-005, sub task no. 5, test no. 7, 20 
June 1957, 16 pp. 
1721. Workman, R. D. Surface decompression from 
air dives. U.S. Navy. Naval Weapons Plant, EDU. Project 
NS 185-005, sub task no. 5, test no. 8, 20 June 1957, 10 pp. 
1722. Workman, R. D. Studies of decompression and 
inert gas-oxygen mixtures in the U.S. Navy. pp. 22-28 in: 
Second symposium on underwater physiology. Edited by 
C. J. Lambertsen and L. J. Greenbaum, Jr. U.S. National 
Research Council, Washington, D.C. N.R.C. Publication 
1181, 1963, 296 pp. 
1723. U.S. NRC. Decompression, pp. 13-15 in; Status 
of research in underwater physiology. U.S. NRC-CUW, 
Rept. 468, March 1956, 24 pp. 
1724. U.S. NRC. Mixed gas diving, pp. 16-18 in: 
Status of research in underwater physiology. U.S. NRC- 
CUW, Rept. 468, March 1956, 24 pp. 
1725. U.S. Navy. Navy standard decompression tables, 
pp. 52-57 in: Submarine medicine practice. U.S. Navy, 
BuMed. NAVMED — P 5054, Gov’t. Printing Office, Wash- 
ington, D.C., 1956, 357 pp. 
1726. U.S. Navy. Decompression tables, pp. 109-121 
in: Curriculum for submarine medical officers (Diving 
medicine). U.S. Navy, BuPers, Washington, D.C. NAVPERS 
92427, February 1957, 167 pp. 
1727. U.S. Navy. Nitrogen-oxygen decompression 
tables, p. 106 in: U.S. Navy diving manual. BuShips. 
NAVSHIPS 250-538, 1959, 433 pp. 
1728. U.S. Navy. Air decompression tables, pp. 95- 
106 in: U.S. Navy diving manual. BuShips. NAVSHIPS 
250-538, 1959, 433 pp. 
3. HELIUM—OXYGEN ADMINISTRATION 
The rationale for using helium-oxygen mix- 
tures in diving has been given on page 295 of 
Volume I of this Sourcebook. On pages 170 and 
171 of the second Volume, helium-oxygen ad- 
ministration has been further discussed. At 
present helium is the only “non-depressant” in- 
ert gas which is known to be fully practical as 
a substitute for nitrogen in breathing mixtures 
(1736). In 1956 the current record depth of 
diving with helium and oxygen was 561 feet ( in 
a pressure tank) and 500 feet (in the open sea). 
Since then a dive has been made to 1000 feet 
with helium as one of the constituent inert gases. 
Helium provides an advantage for long, deep 
dives, since it reduces respiratory resistance; but 
it is not known yet whether the elimination of 
carbon dioxide from the lungs is significantly 
interfered with by increasing the gas density at 
depth. Helium would therefore be helpful for 
this reason: if medullary depression by nitrogen 
is involved in the enhanced susceptibility to 
oxygen poisoning observed in the use of nitrogen- 
oxygen mixtures, the operational objectives of 
“mixed gas” diving may have to be sought with 
helium. 
Helium-oxygen tables differ from the air tables 
in the following major respects: the partial pres- 
sure of the inert gas at depth and not the depth 
determines the use of the tables; the rate of as- 
cent from the bottom to the first stop varies; the 
rate of ascent between stops varies; the time of 
ascent from one stop to the next is included in 
the time of the subsequent stops; and repetitive 
dives are not permitted (1740). There are oxy- 
gen limits in the helium-oxygen diving proced- 
ure: for exposure times up to 30 minutes 2.0 
atmospheres oxygen is the limit, and the allow- 
able oxygen precentage under 30 minutes may 
be determined by the following formula where 
D = depth: maximum oxygen percentage equals 
(2 0 y 33) 
The main difference between air 
(D -f 33) 
and helium-oxygen decompression methods is 
the use of partial pressure of inert gas instead 
of actual depth. The compression schedules 
are given for each 10 feet of partial pressure 
from 60 to 410 feet and for bottom times of 10 
to 240 minutes. An emergency table for the 
procedure for the use of air instead of oxygen 
or a helium-oxygen mixture is given. In case 
oxygen poisoning occurs during helium-oxygen 
decompression and the diver is within five min- 
utes of surface time; start ascent at once. After 
surfacing place the diver in a chamber immedi- 
ately and proceed with surface decompression, 
doubling the missed time and adding it to the 
chamber stop, using oxygen in the chamber. 
When decompression is completed keep the diver 
close to the chamber and watch for symptoms. 
If prompt ascent is not possible, bring the diver 
up 10 feet at once, shift to helium-oxygen or air, 
put the diver on open circuit, use the emergency 
table decompression and bring up for surface 
decompression. DECOMPRESSION SICKNESS—HELIUM OXYGEN 
After the references in the present Volume of 
the Sourcebook had been tabulated, there was 
published Helium-oxygen Decompression Tables 
and Procedures, extract from U.S. Navy Diving 
Manual (NAVSHIPS 250-538), prepared by 
U.S. Naval School, Deep Sea Divers, U.S. Naval 
Weapons Plant, Washington 25, D.C., January 
1962. This report was promulgated as an aid 
in the teaching of and familiarization with the 
standard Navy helium-oxygen partial pressure 
tables and as a convenient reference for use at 
diving stations. The material is extracted from 
the U.S. Navy Diving Manual as stated and in- 
cludes changes which reflect alterations in tech- 
nique. Formulas are provided for the computa- 
tion of partial pressures of gases, for the effect 
of atmosphere, the maximum oxygen percentage 
and tables delineating oxygen partial pressure 
limits. There are tables describing the rate of 
ascent and the actual partial pressure tables. 
In recent studies of helium exchange in diving, 
Duffner (1731) 1962, and Duffner, Snyder and 
Smith (1732) 1959, have employed a theoretical 
no-decompression curve for dives in which an 80 
percent helium and 20 percent oxygen is em- 
ployed. One hundred and nine test dives were 
then performed using depth-time combinations 
following along this curve using 17 enlisted Navy 
divers as subjects. The limiting rate of ascent was 
also investigated following dives in which an 
80 percent helium-20 percent oxygen breathing 
mixture was used. Seventy-eight dives employ- 
ing decompression stops were also carried out. 
The findings were as follows: 1) there is no 
greater risk of decompression sickness with a 
helium-oxygen mixture than there is with air 
during dives to depths of less than 200 feet and 
of less than 180 minutes duration; 2) the helium 
uptake can be described with precision and ac- 
curacy for the purpose of computing decompres- 
sion tables by employing three power function 
equations; 3) rates of ascent as high as 75 feet 
per minute can be tolerated from 120 feet to 
the surface, and rates as high as 120 feet per 
minute can be tolerated from 120 feet to 30 feet. 
The authors concluded that: 1) the use of helium- 
oxygen mixtures is feasible in mixed-gas SCUBA 
diving; 2) the range of activity can be covered 
by using a 50 percent and a 70 percent helium 
mixture; 3) a short and simple decompression 
procedure can be developed. 
Since the references in the present volume of 
the Sourcebook have been compiled, there ap- 
peared by R. D. Workman and J. L. Reynolds the 
Research Report 1-65, Adaptation of Helium- 
oxygen to Mixed Gas SCUBA, Project No. F-011- 
06-01 Task 3361, Test 1, U.S. Navy, Experi- 
mental Diving Unit, Washington Navy Yard, 
Washington, D.C., 1 March 1965. The authors 
have developed a decompression procedure using 
helium-oxygen mixtures in mixed gas SCUBA 
to allow repetitive dives to a depth of 200 feet. 
This procedure employs modified Haldane prin- 
ciples. The repetitive diving procedure provides 
a system by which a diver can determine the 
necessary increase in decompression time on suc- 
cessive dives, based on the amount of excess inert 
gas tension in the body tissues after completion 
of previous dives. The amount of decompression 
required is decreased by the time interval at the 
surface between dives. The information re- 
quired for the use of this system is obtained 
from four tables: 1) the decompression table, 2) 
the no-decompression dive table, 3) the surface 
interval credit table and 4) the repetitive dive 
time table. A method for the use of oxygen de- 
compression at 30 and 20 feet water-stops is also 
provided. The validity of this procedure is 
based on tests of 486 dives in which 28 three- 
dive series and 68 oxygen decompression dives 
were made. The procedure as recorded is con- 
sidered satisfactory and is recommended for fur- 
ther testing under operational conditions in the 
field before service-wide use. 
For a case history illustrating decompression 
problems of diving to 600 feet, a report by 
Crocker and Hempleman (1730) 1957, should be 
consulted. These authors believe that postwar 
experience with helium diving tables, based on 
Haldane’s principles, indicates that they are 
unreliable for any but the shortest dives between 
360 and 500 feet, and that any dive deeper than 
500 feet might produce bends. Consequently 
when the question of providing tables for a dive 
to 600 feet arose it seemed that if the same meth- 
ods were used not only would there be a strong 
likelihood of bends, but they might well appear 
in the early stages of decompression while the 
diver was still in the surface decompression 1729-1741 
DISEASES AND ACCIDENTS 
chamber. This was too great a risk to take and it 
was therefore decided to adopt an entirely differ- 
ent approach to the problem. A new method of 
calculating decompression tables is described. 
Using this new method tables were worked out 
for dives at three depths: 300, 450 and 600 feet. 
The first part of the trial consisted of four dives 
to 300 feet. All four were completed without 
incident except for bends sustained by one of the 
surface decompression chamber attendants. The 
first attempt to carry out the 450 foot dive was 
unsuccessful because the diver exceeded the 
depth required by 36 feet. A further dive to 
450 feet was successful in every respect. The 600 
foot dive was carried out on 12 October 1956 
in a Norwegian fjord from the H.M.S. Reclaim. 
The diver arrived on the bottom of the shot-rope 
after seven minutes and started his task of shackl- 
ing wire onto a ring bolt. Two minutes later 
having had a reasonable time in which to com- 
plete his task, he was told to “stand by to come 
up,” whereupon he attempted to pass a message 
which, due to the distortion of his voice over the 
telephone by the high pressure of the helium, was 
quite unintelligible to those on the surface. 
When after a further two minutes this message 
had not been received, he was hauled up to his 
first stop at 260 feet in accordance with the de- 
compression schedule. An error was made in 
estimating the depth of the first stop; conse- 
quently the diver spent four minutes extra on 
helium at 250 feet. Subsequent decompression 
proceeded without incident until some six hours 
later when the surface decompression chamber 
was brought to atmospheric pressure from 30 
feet. The diver developed pains in both shoulders 
which got worse as he was transferred to the main 
chamber with his attendant. They were both 
recompressed to 50 feet and when all symptoms 
were fully relieved he was therapeutically decom- 
pressed. It was concluded that useful work is 
possible at 600 feet, provided heavy muscular 
effort is not required. The risk of decompres- 
sion sickness by any present method of calcula- 
tion cannot be avoided and it is recommended 
that no further dives to these depths be per- 
formed until there is a method of transferring 
divers from the surface decompression chamber 
into the main chamber without bringing them 
back to atmospheric pressure. Unless such a 
system is provided time spent on decompression 
defeats its own objective by exhausting the diver, 
1729. Barthelemy, L. and R. Perrimond-Trouchet. 
Melanges respiratoires pour profonde. Marine 
Nationale, GERS, Toulon. G.E.R.S. Kept. 241, May 1962, 
21 pp. 
1730. Crocker, W. E. and H. V. Hempleman. The 
decompression problems of diving to 600 feet. Gj. Brit. 
MRC, RNPRC, UPS. Kept. R.N.P. 57/887, U.P.S., March 
1957, 31 pp. 
1731. Duffner, G. J. Recent studies of helium ex- 
change in diving, pp. 315-326. in; Man’s dependence on 
the earthly atmosphere. Edited by K. E. Schaefer, The 
MacMillan Company, New York, 1962, 416 pp. 
1732. Duffner, G. J., J. F. Snyder and L. L. Smith. 
Adaptation of helium-oxygen to mixed-gas SCUBA. U.S. 
Navy. Naval Weapons Plant, EDU. Project NS 186-201, 
sub task no. 2, test no. 3, 27 January 1959, 18 pp. 
1733. Lambertsen, C. J. Helium, pp. 55/17—55/19 
in: Pharmacology in medicine. Edited by V. A. Drill, 
McGraw-Hill Book Co., Inc., New York, 1954. 
1734. Linaweaver, P. G., Jr. Use of helium-oxygen 
mixtures in mixed-gas scuba oxygen limits “Operation 
Pulse-Beat.” U.S. Navy. Naval Weapons Plant, EDU. 
Project NS 186-201, sub task no. 2, test no. 4, 5 January 
1961, 24 pp. 
1735. Parola, M. P. Helium-oxygen mixtures in deep- 
sea diving. Med. Tech. Bull., 1953, 4: 195-197. 
1736. U.S. NRC. Helium, pp. 10-11: Status of research 
in underwater physiology. U.S. NRC-CUW, Rept. 468, 
March 1956, 24 pp. 
1737. U.S. Navy. Helium-oxygen, pp. 116-131 in; 
Diving notes. U.S. Navy. Naval Gun Factory, Washington, 
D.C. PRNC, DSDS-6, October 1952, 382 pp. 
1738. U.S. Navy. Helium-oxygen decompression, pp. 
83-95 in: Submarine medicine practice. U.S. Navy, BuMed. 
NAVMED — P 5054, Gov’t. Printing Office, Washington, 
D.C., 1956, 357 pp. 
1739. U.S. Navy. Helium-oxygen diving techniques, 
pp. 37-42 in: Curriculum for submarine medical officers 
(Diving medicine). U.S. Navy. BuPers, Washington, D.C. 
NAVPERS 92427, February 1957, 167 pp. 
1740. U.S. Navy. Helium-oxygen decompression 
tables, pp. 106-119 in: U.S. Navy diving manual. BuShips. 
NAVSHIPS 250-538, 1959, 433 pp. 
1741. Webster, A. P. Some theoretical aspects of the 
use of multiple-gas mixtures for deep-sea diving, pp. 79- 
83 in: Proceedings of the underwater physiology sym- 
posium. Edited by L. G. Goff, National Research Council, 
Washington, D.C. N.R.C. Publication 377, 1955, 153 pp. 
4. OXYGEN ADMINISTRATION 
For a paper on the possible role of oxygen in 
the genesis of decompression sickness, a paper by 
Donald {1742) 1955, should be consulted. Rash- 
bass and Eaton {1718) 1957, have also reported 
on the effect of oxygen concentration on the oc- 
currence of decompression sickness. The experi- DECOMPRESSION SICKNESS—OXYGEN 
1742-1749 
ments carried out by these investigators indicates 
that the pressure of oxygen increases slightly the 
probability of bends and that a reasonable esti- 
mate of its contribution would be to consider it 
as nitrogen present in one-fourth to one-third 
of its concentration. Therefore air would have a 
tendency to produce bends as though it were 
some 86 percent nitrogen. 
R. D. Workman has prepared a report en- 
titled, “Oxygen decompression following air 
dives for use in hyperbaric oxygen therapy”, Re- 
search Report 2-64, Project F-011-06-01, Task 
3361, Test 7, 15 December 1964. This report ap- 
peared too late for inclusion in the citation list. 
In this study two decompression schedules with 
the use of oxygen were tested to provide three 
and four hour air exposures at 3 atmospheres 
absolute pressure, required for use in hyperbaric 
oxygen treatment. Schedules for such long ex- 
posures have not been available previously to al- 
low use of oxygen breathing during decompres- 
sion so that the decompression time can be 
shortened. Six subjects were exposed to air 
breathing in a dry pressure chamber at 70 feet 
equivalent depth in sea water for periods of 180 
and 240 minutes respectively. Decompression 
was carried out with oxygen breathing at 30, 20 
and 10 foot stops. All six subjects exposed for 
180 minutes were symptom-free following de- 
compression. Of six subjects exposed for 240 
minutes, one subject developed transient vertigo 
one hour post dive, which resolved promptly 
with oxygen breathing at a depth of 60 feet. 
Greater than average susceptibility to decom- 
pression sickness from such prolonged exposures 
in this subject is considered to be a severe test of 
adequacy for this schedule. Thus the schedules 
tested should provide efficient decompression for 
these prolonged exposures with minimal risk of 
symptoms of decompression sickness. No mani- 
festations of oxygen toxicity appeared during the 
oxygen decompression periods. Risk of oxygen 
toxicity should be minimal with the use of these 
schedules since the exposure is well within the 
safe limits for subjects at rest. Figure 4 repro- 
duces Table 1 of Workman’s report and shows 
air exposure with oxygen decompression sched- 
ules for hyperbaric oxygen therapy. 
1742. Donald, K. W. Oxygen bends. J. appl. Physiol, 
1955, 7; 639-644. 
1743. Henry, F. M. The aeroembolism problem for 
long-range missions. USAF. Wright-Patterson Air Force 
Base, Ohio. Aero Medical Laboratory. WADC Tech. Kept, 
no. 52-84, February 1952, 21 pp. 
1744. Luft, U. C. Physiological aspects of pressure 
cabins and rapid decompression, pp. 129-142 in: Handbook 
of respiratory physiology. Edited by W. M. Boothby, 
U.S.A.F. School of Aviation Medicine, Randolph Air Force 
Base, Texas. September 1954, 189 pp. 
1745. Marbarger, J. P., W. Kadetz, D. Variakojis 
and J. Hansen. The occurrence of depression sickness 
following denitrogenation at ground level and altitude. 
J. Aviat. Med., 1957, 28: 127-133. 
1746. Marotta, S. F., J. P. Marbarger, N. Ander- 
sen, J. Hansen and W. Kadetz. Incidence of bends 
following partial denitrogenation at simulated altitude. 
Aerospace Med., 1961, 32: 289-295. 
1747. Perrimond-Trouchet, P. Methode de plongees 
successives avec inhalation d’oxygene pur. Marine Na- 
tionale, GERS, Toulon. June 1956, 6 pp. 
1748. Schmitz, E. Untersuchunger ilher das Auftreten 
intravasaler Gasblasen nach rascher Druckerniedrigung 
in Abhdngigkeit von Vasotonus. Zentrale fur Wissenschaft- 
liches Berichtswessen der Deutschen Versuchsanstalt fur 
Luftfahrt e V. Miilheim. Westdeutscher Verlag, Koln, 
June 1958, 23 pp. 
1749. Wiinsche, O. Zur Pathogenese und Prophylaxe 
der Druckfallkrankheit des Hbhenfliegers. I. Uber den 
Einfluss der Hyaluronidase auf die Dauer der Sauerstoff- 
Voratmung. Int. Z. angew. Physiol, 1957, 16: 453-463. 
Figure 4 
TABLE L—AIR EXPOSURE WITH OXYGEN DECOMPRESSION 
SCHEDULES FOR HYPERBARIC OXYGEN THERAPY 
Depth 
(ft) 
Exposure 
Time 
(min) 
Time to 
First Stop 
(min) 
(ft) 
Decompression Stops 
Breathing 100% Oxygen 
30 20 
10 
Total 
Ascent 
Time 
Repet. 
Group 
70 
180 
5 
5* 
20* 
25* 
58 
Z 
70 
240 
5 
10* 
25* 
35* 
78 
Z 
* Ascent rate, between stops and surfacing is 
at 10 feet/minute. DISEASES AND ACCIDENTS 
5. RECOMPRESSION TREATMENT AND 
PROCEDURES 
An essential source on recompression treatment 
of decompression sickness is that provided by 
E. H. Lanphier in Chapter 7, Fundamentals of 
Hyperbaric Medicine, Publication No. 1298, Na- 
tional Research Council, Washington, D.C., 1966. 
As Lanphier has pointed out, the purpose of re- 
compression is to provide prompt and lasting re- 
lief of the signs and symptoms of decompression 
sickness and of air embolism. The procedure of 
recompression must be designed to reduce the 
bubbles to a size at which they become asympto- 
matic. Also the therapeutic objective is to ensure 
that no bubble again becomes symptomatic upon 
subsequent decompression. Finally, it is neces- 
sary to conduct the decompression phase in such 
a way that no new bubbles form in the process. 
There are a number of important considera- 
tions in applying recompression treatment to 
problems of decompression sickness. It is highly 
important to give treatment even in doubtful 
cases. Failure to do so can be a serious error. 
It is also significant that recompression pro- 
cedures be initiated at once and not delayed. The 
longer the delay the deeper the victim will have 
to be taken for the relief of symptoms. The 
divers should be kept near the chamber for at 
least 24 hours after recompression treatment in 
case there is a return of symptoms. It is to be 
noted that symptoms of bends may sometimes be- 
come temporarily worse if pressures are applied 
too quickly. Should this occur the compression 
should be arrested for the time being and the 
pressure then slowly raised at a rate which is 
tolerable to the diver. In all cases and especially 
in serious paralysis, the capacity of the diver 
to stand up and walk the length of the chamber 
should always be tested. This test should be 
routinely made before the diver leaves the depth 
of relief of symptoms, and also made at the com- 
pletion of the 30 foot stops. 
Figures 5 through 8 are reproduced from the 
U.S. Navy Diving Manual, BuShips (1728) 1959. 
Figure 5, which reproduces Table 1-20, outlines 
briefly the treatment of an unconscious diver. 
Figure 6 (Table 1-21) provides a treatment 
schedule for varying degrees of severity of de- 
compression sickness and air embolism. The 
Figures 7 and 8 (Table 1-22) gives a compact 
set of notes on recompression. As pointed out in 
this figure the most frequent errors related to 
treatment are the failure of the diver to report 
symptoms early, failure to treat doubtful cases, 
failure to treat promptly, failure to recognize 
serious symptoms, failure to treat adequately and 
finally failure to keep the patient near the cham- 
ber after treatment. 
For an excellent paper on recompression treat- 
ment, the report by M. W. Goodman and 
R. D. Workman, Minimal-recompression, oxygen- 
breathing approach to treatment of decompres- 
sion sickness in divers and aviators, BuShips Pro- 
ect SF Oil 06 05, Task 11513-2 (Research Report 
5-65), 15 November 1965, U.S. Navy Experi- 
mental Diving Unit, Washington Navy Yard, 
Washington, D.C. should be consulted. This re- 
port appeared subsequent to the preparation of 
the bibliographic lists for the current Volume of 
the Sourcebook. As these authors have pointed 
out, there is a growing awareness of the incre- 
mental frequency with which difficulties are en- 
countered in recompression treatment of severely 
injured patients, and of the grossly inadequate 
decompressions now characterizing the civilian 
diver casualty population applying to Naval 
recompression facilities. For this latter reason 
evaluation and clinical trials of therapeutic pro- 
cedures alternative to U.S. Navy treatment tables 
were carried out by the authors. These tech- 
niques are particularly suitable for recompres- 
sion management of aviators dysbarism when 
descent to sea level has not provided complete 
relief. The proportion of good results obtained 
with initial recompression trials with these pro- 
cedures has significantly exceeded that obtained 
in recent years with the Diving Manual tables, 
although the current series reported by the au- 
thors of 79 cases surpassed comparable casualty 
groups in average case severity. Hypothetical and 
practical aspects of the treatment concept and 
techniques are presented by the authors as well 
as contra-indications. There were no adverse 
responses to the 2.8 atmospheres absolute P0o 
and nine volunteer human subjects showed no 
impairment of timed vital capacity following 
test exposures. It was concluded that the current 
U.S. Navy recompression procedures are in gen- 
eral reliable therapeutic schedules for divers who 
have reported “bends with pain only” subsequent DECOMPRESSION SICKNESS—RECOMPRESSION TREATMENT AND PROCEDURES 
to exposures conducted in accordance with pro- 
cedures set forth by the U.S. Navy Diving Man- 
ual. Current U.S. Navy recompression proced- 
ures are generally speaking, inadequate in the 
management of severe decompression sickness 
following grossly inadequate decompressions 
from compressed air dives. The recompression 
treatment procedures reported by the authors 
have afforded complete, firm relief to divers 
stricken with severe decompression sickness. Ef- 
ficacy has also been demonstrated in 14 cases 
which followed “saturation” dives and in three 
cases of altitude dysbarism. It was reported that 
56 percent of 79 cases fulfilled the standard 
criteria for mandatory application of U.S. Navy 
treatment tables. The incidence of unsatis- 
factory first-recompression results was 3.6 per- 
cent for the group managed within the limits 
of a “minimally-adequate” routine. Overall, 
there was an 8.9 percent failure incidence, and 
for the adequately-managed cases a 2.0 percent 
failure of the initial recompression trials. The 
authors recommend taking steps and seeking 
approval for promulgation of these treatment 
procedures in the next edition of the Diving 
Manual. They believe that current U.S. Navy 
treatment tables should be retained with the 
oxygen recompression procedures alternately 
Figure 5 
Table 1-20 
TREATMENT OF AN UNCONSCIOUS DIVER 
(Loss of consciousness during or within 24 hours after a dive. See art. 1.6.4) 
1. IF NOT BREATHING, start manual artificial respiration at once. (See tables 1-23, 1-24, 
and 1-25.) 
2. RECOMPRESS PROMPTLY. (See note (d).) 
3. Examine for injuries and other abnormalities; apply first aid and other measures as required. (Secure the 
help of a medical officer as soon as possible.) 
NOTES 
Artificial respiration 
(a) Shift to a mechanical resuscitator if one is available and working properly, but never wait for it. Always 
start a manual method first. 
(b) Continue artificial respiration by some method without interruption until normal breathing resumes or 
victim is pronounced dead. Continue on way to chamber and during recompression. (Do not use oxygen 
deeper than 60 feet in chamber.) 
Recompression 
(c) Remember that an unconscious diver may have air embolism or serious decompression sickness even 
though some other accident seems to explain his condition. 
(id) Recompress unless— 
(1) Victim regains consciousness and is free of nervous system symptoms before recompression can 
be started. 
(2) Possibility of air embolism or decompression sickness can be ruled out without question. 
(3) Another lifesaving measure is absolutely required and makes recompression impossible. 
(e) Try to reach a recompression chamber no matter how far it is. 
(/) Treat according to treatment table 3 or 4 (see table 1-21), depending on response. Remember that early 
recovery under pressure never rules out the need for adequate treatment. DISEASES AND ACCIDENTS 
GENERAL PRINCIPLES OF DIVING 
Table 1—21 . — Treatment of decompression sickness and air embolism. 
Stops 
Bends —Pain only 
Serious symptoms 
Rate of de- 
scent—25 ft. 
per min. 
Rate of as- 
cent— 1 
minute 
between 
stops. 
Pain relieved at depths less 
than 66 ft. 
Use table 1—A if O2 is not 
available. 
Pain relieved at depths 
greater than 66 ft. 
Use table 2—A if O2 is not 
available. 
If pain does not improve 
within 30 min. at 165 ft. 
the case is probably not 
bends. Decompress on 
table 2 or 2-A. 
Serious symptoms include any one of the 
following: 
1. Unconsciousness. 
2. Convulsions. 
3. Weakness or inability to use arms 
or legs. 
4. Air embolism. 
5. Any visual disturbances. 
6. Dizziness. 
7. Loss of speech or hearing. 
8. Severe shortness of breath or chokes. 
9. Bends occurring while still under 
pressure. 
Symptoms re- 
lieved within 
30 minutes at 
165 ft. 
Use table 3 
Symptoms not re- 
lieved within 30 
minutes at 165 ft. 
Use table 4 
Pounds 
Feet 
Table 1 
Table 1-A 
Table 2 
Table 2—A 
Table 3 
Table 4 
73.4 
165 
30 (air) 
30 (air) 
30 (air) 
30 to 120 (air) 
62.3 
140 
12 (air) 
12 (air) 
12 (air) 
30 (air) 
53.4 
120 
12 (air) 
12 (air) 
12 (air) 
30 (air) 
44.5 
100 
30 (air) 
30 (air) 
12 (air) 
12 (air) 
12 (air) 
30 (air) 
35.6 
80 
12 (air) 
12 (air) 
12 (air) 
12 (air) 
12 (air) 
30 (air) 
26.7 
60 
30 (02) 
30 (air) 
30 (02) 
30 (air) 
30 (02) or (air) 
6 hrs. (air) 
22.3 
50 
30 (02) 
30 (air) 
30 (02) 
30 (air) 
30 (02) or (air) 
6 hrs. (air) 
17.8 
40 
30 (02) 
30 (air) 
30 (02) 
30 (air) 
30 (C>2)or(air) 
6 hrs. (air) 
13.4 
30 
5 ( 
>) 
3*) 
r 
60 (air) 
60 (02) 
2 hrs. (air) 
12 hrs. (air) 
First 11 hrs. (air) 
Then 1 hr. (O2) 
or (air) 
8.9 
20 
60 (air) 
5( 
3-2) 
r 
2 hrs. (air) 
2 hrs. (air) 
First 1 hr. (air) 
Then 1 hr. (02) 
or (air) 
4.5 
10 
2 hrs. (air) 
4 hrs. (air) 
2 hrs. (air) 
First 1 hr. (air) 
Then 1 hr. (02) 
or (air) 
Surface 
1 min. (air) 
1 min. (air) 
1 min. (air) 
1 min. (02) 
Time at all stops in minutes unless otherwise indicated. 
Figure 6 DECOMPRESSION SICKNESS—RECOMPRESSION TREATMENT AND PROCEDURES 
U.S. NAVY DIVING MANUAL 
Table 1-22 
NOTES ON RECOMPRESSION 
Explanation: All references to TABLES indicate parts of table 1-21 “Treatment of Decompression Sickness 
and Air Embolism.” 
1. General Considerations 
a. Follow treatment TABLES (table 1-21) accurately. 
b. Permit no shortening or other alteration of tables except 
on advice of trained diving medical officer or in extreme 
emergency. 
2) Complete the treatment according to TABLE 4. 
b. Following treatment: 
1) Recompress to depth giving relief. 
2) If depth of relief is less than 30 feet, 
a) Take to 30 feet. 
b) Decompress from 30-foot stop according to 
TABLE 3. 
3) If relief occurs deeper than 30 feet, 
a) Keep patient at depth of relief for 30 minutes. 
b) Complete remaining stops of TABLES. 
Note.— If original treatment was on 
TABLE 3, use TABLE 4. 
4) Examine carefully to be sure no serious 
symptom is present. If the original treat- 
ment was on TABLE 1 or TABLE 2, appear- 
ance of a serious symptom requires full 
treatment on TABLE 3 or TABLE 4. 
2. Rate of Descent in Chamber 
a. Normal rate is 25 feet per minute. 
b. Serious symptoms: rapid descent is desirable. 
c. If pain increases on descent: stop, resume at a rate 
tolerated by patient. 
3. Treatment Depth 
a. Go to full depth indicated by table 
required. 
b. Do not go beyond 165 feet except on 
decision of medical officer. 
MOST FREQUENT 
ERRORS RELATED 
TO TREATMENT 
1. Diver’s failure to report 
symptoms early. 
2. Failure to treat doubtful 
cases. 
3. Failure to treat promptly. 
4. Failure to recognize serious 
symptoms. 
5. Failure to treat adequately. 
6. Failure to keep patient 
near chamber after treat- 
ment. 
4. Examination of Patient 
(see article 1.6.2(14)) 
a. If no serious symptoms are evident 
and pain is not severe, examine thor- 
oughly before treatment. 
b. If any serious symptom is noted, do 
not delay descent for examination or 
for determining depth of relief. 
c. In “pain only” cases where relief 
is reported before reaching 66 feet, 
make sure it is complete before deciding 
on TABLE 1. 
d. On reaching maximum depth of 
treatment, examine as completely as possible to detect 
1) Incomplete relief 
2) Any symptoms overlooked 
Note.— At the very least, have patient stand and walk 
length of chamber. 
e. Recheck before leaving bottom. 
f. Ask patient how he feels before and after coming to 
each stop and periodically during long stops. 
g. Do not let patient sleep through changes of depth or for 
more than an hour at a time at any stop. (Symptoms can 
develop or recur during sleep.) 
h. Recheck patient before leaving last stop. 
ALWAYS KEEP DIVER CLOSE TO CHAM- 
BER FOR AT LEAST 6 HOURS AFTER 
TREATMENT. (Keep him for 24 hours 
unless very prompt return can be 
assured.) 
7. Use of Oxygen 
a. Use oxygen wherever permitted by 
tables unless 
1) Patient has not had oxygen 
tolerance test, or 
2) Is known to tolerate oxygen poorly. 
b. Be sure mask fits snugly. 
c. Take all precautions against fire (see table 1-29). 
d. Tend carefully, being alert for symptoms of oxygen 
poisoning such as 
1) Twitching 3) Nausea 
2) Dizziness 4) Blurring of vision 
e. Know what to do in event of convulsion. Have mouth- 
bit available. 
f. If symptoms appear, remove mask at once. 
g. If oxygen breathing must be interrupted — 
1) On TABLE 1, proceed on TABLE 1-A. 
2) On TABLE 2, proceed on TABLE 2-A 
3) On TABLE 3, continue on TABLE 3 using air. 
h. At medical officer’s discretion, oxygen breathing may be 
resumed at 40-foot stop. If this is done, complete treatment 
as follows: 
1) Resuming from TABLE 1-A: breathe oxygen: 
at 40 feet for 30 minutes 
at 30 feet for 1 hour 
2) Resuming from TABLE 2-A: breathe oxygen: 
at 40 feet for 30 minutes 
at 30 feet for 2 hours 
3) In both cases, then surface in 5 minutes still breathing 
oxygen. 
4) Resuming from TABLE 3: breathe oxygen: 
at 40 feet for 30 minutes 
at 30 feet for first hour 
(then finish treatment with air) 
5. Patient Getting Worse 
a. Never continue bringing a patient up if his condition is 
worsening. 
b. Treat as a recurrence during treatment (see 6). 
c. Consider use of helium-oxygen as breathing medium for 
patient (see 8). 
6. Recurrence of Symptoms 
a. During treatment: 
1) Take patient to depth of relief (but never to less 
than 30 feet; and not deeper than 165 feet except on 
decision of medical officer). 
(If recurrence involves serious symptom not pre- 
viously present, take patient to 165 feet.) 
Figure 7 DISEASES AND ACCIDENTS 
GENERAL PRINCIPLES OF DIVING 
Table 1-22. —Continued 
NOTES ON RECOMPRESSION 
Explanation: All references to TABLES indicate parts of table 1—21 “Treatment of Decompression Sickness 
and Air Embolism.” — Continued 
8. Use of Helium-Oxygen 
a. Helium-oxygen mixtures (ratio about 80:20) can be used 
instead of air (not in place of oxygen) in all types of treat- 
ment and at any depth. 
b. Use of helium-oxygen is especially desirable in any 
patient who 
1) Has serious symptoms that fail to clear within a short 
time at 165 feet. 
2) Has recurrence or otherwise becomes worse at any 
stage of treatment. 
3) Has any difficulty in breathing. 
Rule 2. Maximum interval between ventilations: 
a. Not using oxygen: 
Interval (min.) 
Chamber (or lock) volume (cu. ft.) 
Basic vent. req. (cu. ft./min.) (from rule 1) 
b. Using oxygen: 
Interval (min.) 
Chamber (or lock) vol. (cu. ft.) 
No. of men hr. Oa X 10 
a. Timing of ventilation; 
1) Use any convenient interval shorter than maximum 
from rule 2. 
2) (Continuous steady-rate ventilation is also satis- 
factory.) 
b. Volume used at each ventilation: 
1) Multiply volume requirement (cu. ft./min.) from rule 
1 by number of minutes since start of last ventilation. 
c. Use predetermined exhaust valve settings to obtain 
required volume of ventilation. (See article 1.6.21 (18), 
(b).) 
9. Tenders 
a. A qualified tender must be in chamber 
1) If patient has had any serious symptom. 
2) Whenever patient is breathing oxygen. 
3) When patient needs unusual observation or care for 
any reason. 
b. Tender must be alert for any change in patient, especially 
during oxygen breathing. 
(See 7, d-f.) 
c. Tender must breathe oxygen if he has been with patient 
throughout TABLE 1 or table 2 
TABLE 1: Breathe oxygen — 
at 40 feet for 30 minutes 
table 2: Breathe oxygen — 
at 30 feet for 1 hour 
d. Tender in chamber only through oxygen breathing part 
of TABLE 1 or 2 gains safety-factor by breathing oxygen for 
30 minutes of last stop, but this is not essential. Tender 
may breathe oxygen during use of TABLE 3 or 4 at 40 feet 
or less. 
e. Anyone entering chamber and leaving before completion 
of treatment must be decompressed according to standard 
diving tables. 
f. Personnel outside must specify and control decompres- 
sion of anyone leaving chamber and must review all deci- 
sions concerning treatment or decompression made by 
personnel (including medical officer) inside chamber. 
11. First Aid 
a. First aid measures may be required in addition to re- 
compression. Do not neglect them. 
b. See table 1-26 and Standard First Aid Training Course, 
NAVPERS 1-0081. 
12. Recompression in the Water 
a. Recompression without a chamber is difficult and 
hazardous. Except in grave emergency, seek nearest 
chamber even if at considerable distance. 
b. If water recompression must be used and diver is 
conscious and able to care for himself: 
1) Use deep sea diving rig if available. 
2) Follow treatment tables as closely as possible. 
3) Maintain constant communication. 
4) Have standby diver ready. 
c. If diver is unconscious or incapacitated, send another 
diver with him to control his valves and otherwise assist 
him. 
d. If lightweight diving outfit or scuba must be used, keep 
at least one diver with patient at all times. Plan carefully 
for shifting rigs or cylinders. Have ample number of 
tenders topside and at intermediate depths. 
e. If depth is inadequate for full treatment according to 
tables: 
1) Take patient to maximum available depth. 
2) Keep him there 30 minutes. 
3) Bring him up according to TABLE 3 if he can tolerate 
exposure. (If patient has been taken beyond 100 feet, 
do not use stops shorter than those of TABLE 2-A.) 
Ventilation of Chamber 
(See art. 1.6.21, par. 18) 
Rule 1. Volume of air required (volume as measured at 
chamber pressure —applies at any depth): 
a. Basic requirement: 
1) Allow 2 cubic feet per minute per man. 
2) Add 2 cubic feet per minute for each man not 
at rest (as tender actively taking care of patient). 
b. When using oxygen; 
Allow 4 cubic feet of air per man breathing oxygen 
if this yields larger figure than basic requirement. 
(Do not add to basic requirement.) 
Figure 8 DECOMPRESSION SICKNESS—PRESELECTION TESTS 
1750-1762 
available, particularly for use with severely 
stricken divers who have had grossly inadequate 
decompression. 
Figure 9 in the present Sourcebook reproduces 
Figure 1 of Goodman and Workman’s mono- 
graph. This figure provides the depth and time 
limits for oxygen breathing in the treatment of 
decompression sickness. 
Rivera (1757) 1963, has conducted an intense, 
thorough analysis of 935 cases of decompression 
sickness among divers. Rivera’s paper is an es- 
sential resource for any investigation of the 
efficacy of various treatment procedures for de- 
compression sickness. Reference may be made 
also to a report by Sebelien (1758) 1954, who 
pointed out that recompression treatment may be 
successful even if initiated more than 24 hours 
after the onset of the condition. A case is pre- 
sented which demonstrates this conclusion. 
Mackay (1754) 1963, has warned against un- 
warranted confidence in the dogmatic applica- 
tion of recompression tables. He feels that the 
treatment of decompression sickness needs re- 
vision and invites attention to the possible de- 
moralizing effect on patients and attendants of 
the chamber environment. The whole process 
of recompression can be very exhausting since 
there are inadequate provisions for restful sleep, 
and part of the arrangements are lacking in 
comfort, etc. 
1750. Fati, S. and R. Pallotta. Osservazioni sulla 
terapia dei barotraumi. Folia med., Napoli, 1961, 44: 1-12. 
1751. Graziani, G. La terapia della malatti dei cassoni. 
Folia med., Napoli, 1958, 41: 801-805. 
1752. Groulard, (n). Decompressimetre “SPIRO-SUB.” 
Marine Nationale, GERS, Toulon. G.E.R.S. Rept. 22, 
January 1962, 4 pp. 
1753. Lanphier, E. H. Treatment: Recompression. 
Erie Cty. med. Bull., 1960, 37: 10-11. 
1754. Mackay, D. E. Comments on therapeutic de- 
compression. pp. 57-65 in: Second symposium on under- 
water physiology. Edited by C. J. Lambertsen and L. J. 
Greenbaum, Jr. National Research Council, Washington, 
D.C. N.R.C. Publication 1181, 1963, 296 pp. 
1755. Marine Nationale. Traitement en caisson des 
accidents de decompression. Marine Nationale, GERS, 
Toulon. Rept. 3/62, G.E.R.S. no. 183, 11 April 1962, 9 pp. 
1756. McDowell, J. and A. D. Amizich. Physical 
therapy in the treatment of decompression sickness with 
spinal involvement. Phys. Ther. Rev., 1960, 40: 737-740. 
1757. Rivera, J. C. Decompression sickness among 
divers: an analysis of 935 cases. U.S. Navy. Naval Station, 
EDU. E.D.U. Res. Rept. 1-63, Prof. F 015-06-02, Task 
3388, 1 February 1963, 37 pp. 
1758. Sebelien, J. Trykkfallsyke hos dykker behandlet 
efter 29 timer. [Decompression sickness in a diver treated 
after 29 hours.] Nord. med., 1954, 52: 1661-1663. 
1759. Shillito, F. H., J. F. Tomashefski and W. F. 
Ashe. The exposure of ambulatory patients to moderate 
altitudes. Aerospace Med., 1963, 34: 850-857. 
1760. U.S. Navy. Treatment, pp. 42-47 in: Diving 
notes. U.S. Navy, Naval Gun Factory, Washington, D.C. 
PRNC, DSDS-6, October 1952, 382 pp. 
1761. U.S. Navy. Treatment of diving accidents and 
diseases, pp. 97-108 in: Curriculum for submarine medical 
officers (Diving medicine). U.S. Navy, BuPers, Washington, 
D.C., NAVPERS 92427, February 1957, 167 pp. 
1762. Wittenborn, A. F. An analytical development 
of a decompression computor. pp. 82-91 in: Second sym- 
posium on underwater physiology. Edited by C. J. Lam- 
bertsen and L. J. Greenbaum, Jr. National Research 
Council, Washington, D.C. N.R.C. Publication 1181, 1963, 
296 pp. 
6. PRESELECTION TESTS 
Physical standards for diving duty were pub- 
lished (1769) in 1956. The following areas are 
listed with limits for each: 1) history of disease, 
2) age, 3) weight, 4) vision, 5) color vision, 6) 
teeth, 7) ears, 8) nose and throat, 9) respira- 
tory system, 10) cardiovascular system, 11) gas- 
trointestinal system, 12) genitourinary system, 
13) skin, 14) temperament, 15) ability to equal- 
ize pressure and 16) sensitivity to oxygen. Can- 
didates for diving training must be able to toler- 
ate pure oxygen at a simulated depth of 60 feet 
for 30 minutes at rest. They must also be able 
to equalize pressure down to 50 pounds. Any of 
the following diseases in the history shall be dis- 
qualifying: 1) tuberculosis, asthma or chronic 
pulmonary disease; 2) chronic or recurrent sinu- 
sitis, otitis media or otitis externa; 3) chronic 
or recurrent orthopedic pathology; 4) chronic or 
recurrent gastrointestinal disorders; 5) chronic 
alcoholism. No candidate shall be accepted with 
a history of syphilis unless there has been ade- 
quate treatment and no signs of activity or or- 
ganic involvement. Candidates beyond the age of 
30 years shall not be considered for initial train- 
ing in diving (the most favorable age being from 
20 to 30 years). All divers upon reaching the age 
of 40 shall be examined in accordance with sub- 
article 15-30 (3) MMD. Diving candidates 
should be rugged individuals without a tendency 
towards overweight. Fat absorbs about five times 
the volume of nitrogen as does lean tissue, and 
because of the low circulatory rate of fatty tis- DISEASES AND ACCIDENTS 
FIGURE 1 
METHOD USED WHEN RELIEF OF SYMPTOMS IS COMPLETE 
WITHIN 10 MINUTES AT 60 FEET 
COMMENCE O2 BREATHING PRIOR TO DESCENT. 
DEPTH-TIME SCHEDULES SHOULD BE FOLLOWED WITH 
CARE 
DEPTH 
(FEET) 
TIME 
(MINUTES) 
BREATHING 
MEDIA 
TOTAL 
ELAPSED 
TIME (MIN.) 
COMPRESSION; RAPID DESCENT IS DESIRABLE, BUT 
DO NOT EXCEED RATE TOLERATED BY PATIENT. DE- 
60 
20 
o2 
20 
SCENT TIME, USUALLY 1-2 MINUTES, IS NOT COUNTED 
AS TIME AT 60 FEET. DO NOT HALT THE DESCENT 
TO VERIFY A REPORT OF SYMPTOM RELIEF. 
60 
5 
AIR 
25 
DECOMPRESSION: ASCENTS ARE CONTINUOUS AT 
UNIFORM 1 F.P.M. DO NOT COMPENSATE FOR 
SLOWING OF THE RATE BY SUBSEQUENT ACCELERA- 
TION. DO COMPENSATE IF THE RATE IS EXCEEDED. 
IF NECESSARY, HALT ASCENT AND HOLD DEPTH 
WHILE VENTILATING THE CHAMBER. 
60 
20 
o2 
45 
60-30 
30 
o2 
75 
30 
5 
AIR 
80 
30 
20 
o2 
100 
30 
5 
AIR 
105 
INSIDE TENDER: TENDER ROUTINELY BREATHES CHAM- 
30-0 
30 
o2 
135 
BER AIR. IF TREATMENT SCHEDULE IS LENGTHENED 
(SEE BELOW), OR IF THE TREATMENT CONSTITUTES 
A REPETITIVE DIVE FOR THE TENDER, HE MUST BREATHE 
O2 FOR THE FINAL 30 MINUTES, FROM 30 FEET TO THE 
SURFACE. 
METHOD USED WHEN RELIEF OF SYMPTOMS IS NOT 
COMPLETE WITHIN 10 MINUTES AT 60 FEET 
60 
20 
o2 
20 
RELIEF OF SYMPTOMS: IF COMPLETENESS OF RELIEF IS 
AT ALL DOUBTFUL AFTER 10 MINUTES O2 BREATHING 
AT 60 FEET USE THE 285 MINUTE SCHEDULE. 
IF SYMPTOMS RECUR, FRESH SYMPTOMS APPEAR, 
OR THE PATIENT'S CONDITION WORSENS, RETURN 
TO 60 FEET AND USE THE 285 MINUTE METHOD. 
IF RELIEF IS NOT COMPLETE AT 60 FEET, PROCEED 
WITH THE 285 MINUTE SCHEDULE, OBSERVING CLOSELY 
FOR ANY CHANGES OF THE PATIENT'S CONDITION, 
OR LENGTHEN THE SCHEDULE (SEE BELOW), OR RE- 
COMPRESS TO 165 FEET AND COMMIT THE PATIENT 
TO U.S.N. TREATMENT TABLE 2A, OR TABLE 4 IF SYMP- 
TOMS ARE NOT RELIEVED WITHIN 30 MINUTES. 
60 
5 
AIR 
25 
60 
20 
o2 
45 
60 
5 
AIR 
50 
60 
20 
o2 
70 
60 
5 
AIR 
75 
60-30 
30 
o2 
105 
30 
15 
AIR 
120 
A MEDICAL OFFICER QUALIFIED IN DIVING, OR THE 
DIVING SUPERVISOR (DIVING OFFICER; MASTER DIVER) 
CAN EXTEND THE 285 MINUTE SCHEDULE WITH A 
FOURTH O2-AIR SEQUENCE (20 MINUTES Oz-5 MINUTES 
AIR) AT 60 FEET, OR A THIRD AIR-O2 SEQUENCE (15 
MINUTES AIR-60 MINUTES O2) AT 30 FEET, OR BOTH. 
30 
60 
o2 
180 
30 
15 
AIR 
195 
30 
60 
o2 
255 
30-0 
30 
o2 
285 
MINIMAL-PRESSURE, OXYGEN RECOMPRESSION TREATMENT OF DECOMPRESSION SICKNESS 
Figure 9 DECOMPRESSION SICKNESS—PRESELECTION TESTS 
1763-1770 
sues the nitrogen may be eliminated from fatty 
tissue very slowly. This acts to increase the possi- 
ble incidence of bends. The candidate should in 
general have no greater than a ten percent varia- 
tion from the standard age-weight-height tables. 
For further physical requirements reference 
should be made to the U.S. Navy Diving Manual 
(1769). 
Special reference may be made, however, to 
the matter of temperament. The special feature 
of diving duties necessitates a careful examina- 
tion and assessment of the candidate’s emotional, 
temperamental and intellectual soundness. Past 
or recurrent symptoms of neuropsychiatric dis- 
order or of an organic disease of the nervous sys- 
tem are disqualifying. History of any form of 
epilepsy, or head injury with sequelae, or per- 
sonality disorder also lead to disqualification. 
Neurotic tendencies, emotional immaturity or 
instability and asocial traits of a sufficient de- 
gree to militate against satisfactory adjustment 
shall all be disqualifying. Stammering or other 
speech impediment which might become mani- 
fest under excitement is also disqualifying. In- 
telligence should be within the normal range. 
Constitutional factors that may be operating in 
decompression sickness have been studied by 
Wise (1770) 1963. In this study 589 divers who 
had never experienced symptoms of decompres- 
sion sickness were compared with 414 treated 
cases of the same to determine if there were any 
difference of sufficient magnitude to be used as 
selection criteria. Among the factors explored 
(age, weight, height and body type) no useful 
differences between the groups could be found. A 
second problem was to determine whether the 
depth of the dive and body type interacted to 
influence the probability of contracting bends. 
These results suggested that the role of adipose 
tissue in the etiology of decompression sickness 
is not as great as has been thought. 
A chapter on the selection and training of op- 
erational personnel by G. F. Bond has appeared 
in Fundamentals of Hyperbaric Medicine, Publi- 
cation No. 1298, National Academy of Sciences, 
National Research Council, Washington, D.C., 
1966 (chapter 14) pp. 144-148. This chapter 
should be perused, even though it does not dis- 
cuss divers, since it does outline psychological 
and physical requirements for chamber personnel 
that are somewhat similar, although perhaps not 
so rigorous. In discussing psychological require- 
ments, Bond asserts that it is generally believed 
that claustrophobic tendencies in overt reactions 
constitute the sole psychological criterion for 
work in hyperbaric chambers. This is not ex- 
actly the case. Although both frank and latent 
claustrophobia are believed to be significant 
factors in personnel selection, it should also be 
noted that motivation, maturity and interper- 
sonal compatibility merit equal consideration. 
Motivation is extremely important since the 
working conditions are relatively harsh with long 
periods of boring inactivity and frustrating phys- 
ical restraints. The professional personnel have 
not quite the problems with motivation that may 
be found in the paramedical personnel of lower 
echelons. Since the crowded conditions of the 
chamber for relatively long periods of time bring 
personnel in close contact, it is essential that 
all team personnel have unusual maturity and 
compatibility. For further discussion of the 
physical requirements, Bond’s chapter should 
be consulted. 
1763. Alessandri, M. and G. Moretti. Traumatolo- 
gia ed infortunistics del gruppo incursori. Ann. Med. 
Nav., 1963, 68: 531-540. 
1764. Davies, W. The medical examination of under- 
water swimmers. Practitioner, 1961, 187: 783-786. 
1765. Jullien, G. Etude des reactions pathologiques 
consecutives a la plongee sous-marine et au travail dans 
I’air comprim£. Arch. Mai. prof., 1956, 17: 288-236. 
1766. Parker, G. W. and R. S. Stonehill. Further 
considerations of the roentgenologic evaluation of flying 
personnel at simulated altitude. Aerospace Med., 1961, 32: 
501-504. 
1767. Parsons, V. A brief review of aviator’s decom- 
pression sickness and the high altitude selection test. J.R. 
nav. med. Serv.. 1958, 44: 2-13. 
1768. Snyder, J. F. and G. J. Duffner. A methodol- 
ogical test of resistance of divers to decompression sick- 
ness. U.S. Navy. EDIT, Naval Weapons Plant, Washington, 
D.C. Project NS 185-005, sub task no. 5, test no. 10, 13 
November 1958, 12 pp. 
1769. U.S. Navy. Physical standards for diving duty, 
pp. 6-8 in: Submarine medicine practice. U.S. Navy, 
BuMed. NAVMED — P 5054, Gov’t. Printing Office, Wash- 
ington, D.C. 1956, 357 pp. 
1770. Wise, D. A. Constitutional factors in decom- 
pression sickness. U.S. Navy. EDU, Naval Station, Washing- 
ton, D.C. Research Rept. 2-63, 26 April 1963, 18 pp. 1771-1776 
DISEASES AND ACCIDENTS 
7. DRUGS AND HYPOTHERMIA IN THE 
TREATMENT OF DECOMPRESSION 
SICKNESS 
The use of drugs and/or hypothermia are not 
considered adequate substitutes for recompres- 
sion in treatment of decompression sickness, how- 
ever, they may be of adjunctive value. 
Barthelemy (1772) 1963, found in experi- 
ments on mice, rats and rabbits that coagulation 
time was altered during rapid decompression. 
There was hypercoagulability in dives to 30 
meters and hypocoagulability at 60 meters. Since 
the use in rabbits of 5 mg. of heparin did not 
adversely affect (and sometimes improved) the 
condition of the animals, human therapy was 
tried. In five accidents—four decompression sick- 
ness and one air embolism—heparin was given 
(50-100 mgm. two times per day). The sub- 
stance never aggravated the condition but usually 
caused improvement. Studies on the action of 
heparin in the treatment of decompression acci- 
dents have also been carried out by Laborit, 
Barthelemy and Perrimond-Trouchet (1776) 
1961. Rabbits were pressurized to 5 Kg./cm.2 for 
one hour with four minutes decompression. 
There were symptoms of bends including para- 
plegia, monoplegia, quadriplegia, dyspnea and 
pain. A control group of animals was also ade- 
quately decompressed to avoid bends. Heparin 
was given in the following doses: 7.5 mg./Kg. 
and 5 mg./Kg. No difference was noted for the 
two dose levels. Heparin was given when the 
symptoms appeared and then recompression was 
carried out. Some rabbits were given heparin 
without recompression; even then survival was 
greater than in non-recompressed, non-heparin- 
ized animals. The authors believe that heparin 
may be of benefit because of its vasodilator effect; 
the hyperemia reducing tissue damage resulting 
from anoxia. 
The reader may refer also to a paper by Frada 
(1774) 1952, in which it is suggested that ni- 
cotinic acid may be of value in the treatment of 
patients with decompression sickness. The ra- 
tionale for its use under these circumstances is 
not given. 
In studies reported by Erde (1773) 1963, seven 
civilian divers with decompression sickness and 
central nervous system symptoms were treated 
with chamber recompression and some with re- 
compression plus hypothermia. Most of the 
dives had been multiple dives with no stage de- 
compression. No diver used a depth gauge, lead 
line or wrist watch. The time which elapsed 
between symptom manifestation and treatment 
ranged from 180 to 300 minutes. Most of the 
divers had cord lesions ranging from the ninth 
thoracic to the second lumbar levels. Bladder 
and bowel functions were impaired in all but 
two divers. Residual motor weakness was seen in 
one or both lower extremities, but was less com- 
mon in the patients treated with hypothermia 
plus recompression. Since part of the sympto- 
matic picture is ascribed to persistent gas foci 
within the central nervous system, a part may 
also be due to edema in these tissues despite re- 
compression. The patients given hypothermia 
plus recompression experienced relatively prompt 
relief even before decompression had been com- 
pleted. This report includes complete case his- 
tories and course of treatment for each of these 
divers. 
1771. Agadzhanian, N. A., M. I. Vakar, A. R. 
Mansurov and A. S. Tsivilashvili. Dekompressionnaia 
tkanevaia emfizema i metody ee preduprezhdeniia. [De- 
compression tissular emphysema and methods of its pre- 
vention.] Vo.-med. Zh., 1958, 12: 45-48. 
1772. Barthelemy, L. Blood coagulation and chem- 
istry during experimental dives and the treatment of 
diving accidents with heparin, pp. 46-56 in: Second 
symposium on underwater physiology. Edited by C. J. 
Lambertsen and L. J. Greenbaum, Jr. National Research 
Council, Washington, D.C. N.R.C. Publication 1181, 1963, 
296 pp. 
1773. Erde, A. Experience with moderate hypothermia 
in the treatment of nervous systems of decompression sick- 
ness. pp. 66-81 in: Second symposium on underwater 
physiology. Edited by C. J. Lambertsen and L. J. Green- 
baum, Jr. National Research Council, Washington, D.C. 
N.R.C. Publication 1181, 1963, 296 pp. 
1774. Frada, G. L’acido nicotinico endovena quale 
terapia di elezionne degli accidenti embolici dei cassonisti. 
Rif. med., 1952, 66: 791-794. 
1775. Hartmann, H. Blutgerinnungsuntersuchungen 
nach Dekompression. Int. Z. angew. Physiol., 1961, 18: 
439-443. 
1776. Laborit, H., L. Barthelemy and R. Perri- 
mond-Trouchet. Action de 1’heparine dans le traitement 
des accidents de decompression. Rev. Agressol., 1961, 2: 
229-235. 
IV. EXPLOSIVE DECOMPRESSION 
A. GENERAL STUDIES 
Although explosive decompression is essen- 
tially an altitude problem, this section has been EXPLOSIVE DECOMPRESSION—HEART AND CIRCULATION 
1777-1784 
included because some of the pathological phe- 
nomena in explosive decompression are related to 
and resemble those pulmonary leisons found in 
escape accidents. Some of the effects of explo- 
sive decompression on animals have been re- 
ported by Grandpierre, Grognot and Violette 
{1779) 1953. In this study unanesthetized cats 
and dogs and anesthetized dogs were explosively 
decompressed from 9,000 to 15,000 meters in 
0.019 seconds using the double caisson techni- 
que. The unanesthetized animals presented no 
problems in comportment, equilibrium or hear- 
ing except that occasionally an older dog showed 
a light intra-auricular hemorrhage. Immediate 
autopsy showed rare, hemorrhagic pulmonary 
suffusions but the heart was normal and the 
gastrointestinal tract was intact. No apparent 
cerebral lesions were present grossly or microscop- 
ically. Anesthetized dogs constantly presented 
auditory hemorrhage with a paracentesis of the 
tympanum. There was thoracic dilatation fol- 
lowed by an inspiratory apnea of short dura- 
tion. There was a sinusal bradycardia but no 
electrocardiographic abnormality. 
1777. Beliaev, N. P. O vzryvnoi dekompressii pri 
razgermetizatsii kabiny. [On explosive decompression dur- 
ing dehermetization of the cabin.] Vo.-med. Zh., 1961, 
5: 72-75. 
1778. Brown, F. W., Ill and R. H. Lee. A bio- 
physical analog for explosive decompression studies in 
animals. U.S. Navy. Mine Defense Laboratory, Panama 
City, Fla. Med. Res. Kept. 3, 1959, 10 pp. 
1779. Grandpierre, R., P. Grognot and F. Violette. 
Some particular effects of explosive decompressions on 
animals. J. Aviat. Med., 1953, 24: 20-22. 
1780. Haber, F. and H. G. Clamann. Physics and 
engineering of rapid decompression. A. General theory of 
rapid decompression. USAF. School of Aviation Medicine, 
Randolph Field, Texas. Project no. 21-1201-0008, Kept, 
no. 3, August 1953, 29 pp. 
1781. Hitchcock, F. A. Physiological and pathologi- 
cal effects of explosive decompression. /. Aviat. Med., 1954, 
25: 578-586. 
1782. Holmstrom, F. M. G. Collapse during rapid 
decompression. /. Aviat. Med., 1958, 29: 91-96. 
1783. Kolder, H. Explosive Uberdruckdekompression. 
Arch. exp. Path. Pharmak., 1954, 233: 486-492. 
1784. Santa Maria, L. J., and H. R. Greider. Gase- 
ous cavity formation in explosively decompressed animals. 
J. Aviat. Med., 1957. 28: 303-308. 
B. HEART AND CIRCULATION 
In experimental animals explosive decompres- 
sion has been shown to cause a fall in systemic 
arterial blood pressure as well as bradycardia. 
Increased intrathoracic pressure with distention 
of lungs, occurring when the rate of decompres- 
sion of the chamber exceeds the rate at which 
the lungs could decompress, is considered to be 
the primary cause of the fall in arterial pressure. 
Reflexes from distended abdominal organs are 
believed to play a contributing part. 
The effects of explosive decompression and 
subsequent exposure to 30 mm. Hg upon the 
hearts of dogs have been reported by Burch, 
Kemph, Vail, Frye and Hitchcock {1785) 1952. 
The explosive decompression of dogs followed by 
exposure to an ambient pressure of 30 mm. 
Hg results in gas in the thoracic cavity with 
dilatation of the thoracic cage and partial col- 
lapse of the lungs. According to the authors 
gas also forms inside the heart in less than two 
minutes following explosive decompression. 
This gas then expands causing cardiac dilatation. 
There is reflex slowing of the heart, mediated 
through the vagus. The effect on the right heart 
occurs first and is more pronounced than on the 
left. The authors believe that the damage to the 
myocardium is greater than could be accounted 
for on the basis of anoxia alone, and therefore 
they concluded that dilatation of the heart caused 
by expanding gases plays an important part in 
producing the effects observed. Hitchcock, Frye 
and Kemph {1786) 1952, found that in these 
animals the mean arterial blood pressure dropped 
within 15 seconds to a value of 60-70 mm. Hg. 
The pulse pressure decreased drastically. Usually 
there was no recovery from the condition until 
recompression. The authors’ results indicate 
that following explosive decompression com- 
plete circulatory arrest usually occurs. In an 
effort to determine the time at which circulatory 
arrest supervened, ten dogs were explosively de- 
compressed to 30 mm. Hg and immediately after 
decompression Diodrast was injected into the 
external jugular vein and angiograms made at 
intervals of two to seven seconds for 25 seconds 
or longer. The circulation through the right 
heart, pulmonary vessels, left heart and the 
aorta could be followed in this manner. Results 
showed that circulatory arrest occurred within 
16 seconds in all dogs and within 10 seconds in 
6 of the 10 animals. Eight of the dogs had gas 
in the heart within 10 seconds and in one other 1785-1795 
DISEASES AND ACCIDENTS 
gas was found in 16 seconds. The Diodrast 
usually went no further than the right heart, al- 
though occasionally it was seen in the pulmonary 
vein or in the aorta and its branches. These 
data indicate that usually circulatory arrest, 
which results from the formation of gas in the 
cardiovascular system, occurs within 16 seconds 
after explosive decompression to 30 mm. Hg. 
Records of arterial blood pressure, however, in- 
dicate that occasionally circulatory arrest does 
not occur until a minute or more after explosive 
decompression. In such cases the circulatory col- 
lapse is probably due to anoxia. 
1785. Burch, B. H., J. P. Kemph, E. G. Vail, S. A. 
Frye and F, A. Hitchcock. Some effects of explosive 
decompression and subsequent exposure to 30 mm. Hg. 
upon the hearts of dogs. J. Aviat. Med., 1952, 23: 159-167. 
1786. Hitchcock, F. A., S, A. Frye and J. P. 
Kemph. Circulatory arrest in dogs following explosive de- 
compression to 30 mm. Hg. Fed. Proc., 1952, 11: 71. 
1787. Rosbaum, D. A. and F. A. Hitchcock. The 
extent and probable cause of cardio-vascular changes due 
to explosive decompression. USAF. WADC, Wright- 
Patterson Air Force Base, Ohio. WADC Tech. Rept. 53-191, 
153-167, December 1953, 228 pp. 
1788. Vail, E. G. Forces produced in the thorax by 
explosive decompression. Fed. Proc., 1952,11: 165. 
1789. Vail, E. G. and F. A. Hitchcock. The tem- 
peratures in the lungs and heart before and after explosive 
decompression. USAF. WADC, Wright-Patterson Air Force 
Base, Ohio. WADC Tech. Rept. 53-191, 168-182, Decem- 
ber 1953, 228 pp. 
C. RESPIRATORY SYSTEM 
The reader is referred to pages 178 and to 
180 of Volume II of this Sourcebook for a still 
current account of the effects of explosive decom- 
pression upon pulmonary function and path- 
ology. The respiratory and pulmonary effects 
depend upon how drastic the explosive changes 
are. A paper by Pryor and Marks (1772) 1954, 
may be cited. The study in question was done to 
show the effects of repeated exposure to rapid 
and explosive decompression, the latter defined 
as decompression of aircraft pressurized at 8,000 
feet in less than one second to 25,000 feet. In this 
case gas in the respiratory tree cannot be expelled 
quickly enough to accommodate the increased 
volume. In the authors’ studies eight normal men 
from 23 to 42 years of age in good health had 
experienced 30 rapid decompressions from 8,000 
to 25,000 feet within a period of one to two-and-a- 
half seconds and explosive decompression (within 
a second) at least five or six times. All had en- 
gaged in positive pressure breathing (50-150 
mm. Hg) which is also considered a potential 
insult to pulmonary tissue. In these subjects 
no evidence of altered pulmonary function could 
be found by any conventional ventilatory studies. 
It was found that total lung capacity, maximum 
breathing capacity, ratio of residual capacity to 
total capacity, index of pulmonary mixing and 
timed vital capacity were all within normal 
limits. 
1790. Luft, U. C. and R. W. Bancroft. Transthoracic 
pressure in man during rapid decompression. USAF. 
Randolph Field, Texas. School of aviation medicine. 
Kept. no. 56-61, August 1956, 13 pp. 
1791. Porton, W. M. Thoracale drukverschijnselen 
bij “explosive decompression.” [Thoracic pressure symp- 
toms in explosive decompression.] Ned. Milit. Geneesk. T., 
1957, 10: 264-274. 
1792. Pryor, W. W. and G. Marks. Evaluation of 
pulmonary function after rapid or explosive decompres- 
sion. /. Amer. med. Ass., 1954, 1956: 1233-1235. 
1793. Schilling, J. A. and R. B. Harvey. Effect of 
simulated altitude and explosive decompression on dogs 
with bilateral partial pulmonary resection. Fed. Proc., 
1954, 13: 129. 
1794. Vail, E. G. Forces produced in the thorax by 
explosive decompression. /. Aviat. Med., 1952, 23: 577-583. 
D. GASTROINTESTINAL SYSTEM 
Vail, Rosenbaum and Hitchcock (1795) 1953, 
carried out roentenographic studies on the effects 
of explosive decompression and exposure to an 
ambient pressure of 30 mm. Hg upon the gastro- 
intestinal tract and upon the gall bladder of 
dogs. These animals exhibited massive dilatation 
of the stomach and intestine resulting from ex- 
pansion of contained gases. The pressure pro- 
duced in the stomach was found to be sufficient 
at times to cause regurgitation of stomach con- 
tents into the esophagus and mouth. On recom- 
pression this material might be aspirated into the 
lungs. There was no swelling or gas formation 
in the gall bladder. 
1795. Vail, E. G., D, A. Rosenbaum and F. A. 
Hitchcock. Roentenogram studies of the effects of ex- 
plosive decompression and exposure to an ambient pres- 
sure of 30 mm. Hg. upon the gastro-intestinal tract and 
the gall bladder. USAF. WADC, Wright-Patterson Air 
Force Base, Ohio. WADC Tech. Rept. 53-191, 111-118, 
December 1953, 228 pp. EXPLOSIVE DECOMPRESSION—TOLERANCE 
1796-1804 
E. LETHAL FACTORS AND 
PATHOLOGICAL LESIONS 
Pulmonary hemorrhage is observed in animals 
exposed suddenly to pressure equivalents of 
50,000 and 80,000 feet. Previous experiments 
have shown that no pulmonary lesions are found 
in animals decompressed to simulated altitudes 
below 35,000 feet. The left lung shows less ex- 
tensive trauma than does the right, and in both 
lungs the apical poles, the posterior surfaces, 
and the thin pulmonary margins appear to be 
the most vulnerable areas. It has been con- 
sidered than anoxic anoxic is of major import- 
ance as a causative factor in death resulting 
from explosive decompression injury in animals 
compressed to an altitude equivalent of 80,000 
feet. It has been found that explosive decom- 
pression of rats to normal atmospheric pressure 
after exposure to positive pressures of 2-20 
atmospheres for varying intervals of time shows 
effects depending upon the severity of the pres- 
sure change. Decompression from two to as 
much as six atmospheres is well tolerated and 
such decompressions may be considered com- 
pletely innocuous in the rat. Decompression after 
a 50 second exposure to 30 atmospheres is invari- 
ably fatal. On the other hand animals will 
survive this pressure change when the time under 
pressure is reduced to ten seconds. Some studies 
lead to the conclusion that sudden increases in 
pulmonary pressure introduced by explosive de- 
compression are of primary etiological signifi- 
cance in producing lesions in animals. 
The pathological effects of explosive decom- 
pression to 30 mm. Hg have been described by 
Cole, Chamberlain, Burch, Kemph and Hitch- 
cock (1796) 1953. Eighteen dogs were explo- 
sively decompressed from 520 down to 30 mm. 
Hg in 0.035 seconds. Six were held at 30 mm. 
Hg for 2.5 minutes and then recompressed to 
ground level in one minute (series I). Twelve 
were recompressed immediately after explosive 
decompression, six in one minute (series II), 
and six at a rate of a free fall (seven minutes; 
series III). Two animals in series I, all six in 
series II and two in series III survived. The con- 
sistent pulmonary lesions observed in animals 
from all of these series were atelectasis, hemor- 
rhage and emphysema. It was found that blood 
occluded the bronchi and bronchioles in areas 
adjacent or proximal to atelectic areas giving 
rise to the suggestion that hemorrhage contributes 
to the maintenance of atelectasis. Hemorrhage 
was consistently found in the heart, intestines, 
stomach, liver, spleen, kidney and brain of dogs 
in all series. Cytological changes included rup- 
ture of the cell walls, extrusion of cytoplasm 
with liberation of nuclei. These changes were 
seen in hepatic and renal cells. There was 
transverse fragmentation of the myocardial fibers 
and hemorrhage as well as separation of myo- 
fibrils and extrusion of cytoplasm at points of 
rupture. These changes were observed in the 
heart of all 18 dogs. There was hemorrhage in 
the middle and inner ears in 17 of the 18 dogs. 
In all animals the tympanic membrane was in- 
tact after the experiment. 
1796. Cole, C. R., D. M. Chamberlain, B. H. 
Burch, J. P. Kemph and F. A. Hitchcock. Pathological 
effects of explosive decompression to 30 mm. Hg. J. eppl. 
Physiol, 1953, 6: 96-104. 
1797. Domenici, F. Lesioni da decompressione es- 
plosiva. Rass. Clin. Scient., 1955, 21: 139-141. 
1798. Cell, C. F., W. M. Hall and F. K. Mostofi. 
Pathologic evaluation of explosive decompression to 65,000 
feet. J. Aviat. Med., 1958, 29: 15-26. 
1799. Grognot, P. and R. Senelar. Etude exp£ri- 
mentale des lesions vasculaires lors de decompressions ex- 
plosives chez le chien. Med a£ro., 1958,13: 49-58. 
1800. Grognot, P. A. and F. Violette. Lesions 
anatomo-pathologiques au niveau du cortex cerebral et du 
poumon de chiens soumis A une decompression explosive 
(9.000 a 15.000 m). Med. aero., 1952, 7; 476-480. 
1801. Kolder, H. Explosive Dekompression auf Un- 
terdruck: Die Folgen der Abnahme des Luftdruckes in 
kurzester Zeit. S.B. dst. Akad. Wiss. Wien, 1956, 165: 357- 
419. 
1802. Kolder, H. Echte explosive Dekompression. 
Int. Z. angeiv. Physiol., 1956, 16: 212-216. 
1803. Kolder, H. and L. Stockinger. Feinstrukturelle 
Veranderungen in der Lunge nach explosiver Dekom- 
pression und Kompression. Arch. exp. Path. Pharmak., 
1957, 231: 23-33. 
1804. Lalli, G. and G. Paolucci. Pyruvic and gluta- 
mic oxalacetic transaminases of the serum of rabbits sub- 
jected to explosive decompression, in relation to the 
anatomical damage. Panminerva med., 1959,1: 338-341. 
F. TOLERANCE 
Close and Ireland (1806) 1961, have stated 
that surgical alterations in airway resistance in 
albino rats and the administration of certain 
drugs to albino rats and guinea pigs may alter 
tolerance and lung pathology upon exposure to 
explosive decompression. Procedures which lower 1805-1814 
DISEASES AND ACCIDENTS 
airway resistance decreased damage and improved 
tolerance, while procedures which raise airway 
resistance increased damage and worsened tol- 
erance. Administration of nor-epinephrine, 
which raises blood pressure, decreases the toler- 
ance to explosive decompression. Perivascular 
hemorrhages of the larger lung vessels were ob- 
served in all fatal decompressions. In death re- 
sulting from lethal doses of nor-epinephrine there 
are exhibited histopathological changes which 
are remarkably similar to those seen in explosive 
decompression. Explosive decompression in the 
guinea pig in conjunction with hypoxic hypoxia 
or the administration of histamine produces 
striking hemorrhagic consolidation in the lungs 
at the capillary level which is atypical of uncom- 
plicated explosive decompression damage. In- 
creased capillary permeability is probably in- 
volved. On the basis of this and other pertinent 
facts the authors hypothesize that major damage 
in severe uncomplicated explosive decompression 
is possibly due to stretching of the pulmonary 
blood vessels in conjunction with increased 
pressure without resulting in their rupture. This 
finding is consistent with the pathological 
changes reported in certain lung traumata in 
man. Efforts to protect human subjects from 
the damaging effects of explosive decompression 
in the form of a partial pressure altitude suit 
have been reported by Hull (1808) 1952. The 
reader is referred to this study. 
1805. Close, P. Tolerance to explosive decompression 
of albino rats in a ‘fetal’ posture. J. appl. Physiol., 1960, 
15: 589-591. 
1806. Close, P. and R. Ireland. Effect of certain vari- 
ations in the physiologic state on tolerance to explosive 
decompression. Aerospace Med., 1961, 52: 1050-1060. 
1807. Hartmann, H. Tierexperimentelle Dekompres- 
sionsversuch. Int. Z. angew. Physiol., 1961, 18: 435^138. 
1808. Hell, W. E. Explosive decompression protection. 
USAF. WADC. Wright-Patterson Air Force Base, Ohio. 
Tech, note WCRD 52-65, September 1952. 
1809. Kolder, H. Die Abhangigkeit der Wirkung einer 
explosiven Dekompression vom absoluten Druck. Pflug. 
Arch. ges. Physiol., 1957, 264: 456-459. 
1810. Kolder, H. Explosive Dekompression im Bereich 
oberhalb 1 Atmosphare. Int. Z. angew. Physiol., 1958, 17: 
120-124. 
1811. Malette, W. G., J. B. Fitzgerald and B. 
Eisenman. Rapid decompression. A protective substance. 
USAF. Aerospace medical center (ATC) School of Aviation 
Medicine, Brooks Air Force Base, Texas. Kept. no. 60-62, 
June 1960. 
1812. Stickney, J. C. and D. W. Northup. Rat LD,*, 
in explosive decompression. Amer. J. Physiol., 1953, 172: 
347-350. 
V. EXPLOSIVE COMPRESSION 
Two papers are included in this section deal- 
ing with rapid compression from one atmosphere 
to high pressures. 
1813. Kolder, H. and F. X. Wohlzongen. Explosive 
Kompression im Bereich oberhalb 1 Atmosphare. Pflug. 
Arch. ges. Physiol., 1957, 265: 348-354. 
1814. Richmond, D. R., M. B. Wetherbe, R. V. 
Taborelli, T. L. Chiffelle and C. S. White. hTe 
biologic response to overpressure. I. Effects on dogs of five 
to ten-second duration overpressures having various times 
of pressure rise. J. Aviat. Med., 1957, 28: 447^160. 
VI. OXYGEN INTOXICATION 
A. EFFECTS OF INCREASED OXYGEN 
TENSION NOT IN EXCESS OF ONE AT- 
MOSPHERE 
1. GENERAL STUDIES 
For a review of the literature on oxygen in- 
toxication the reader should consult the section 
on this subject in both the first and second 
Volumes of this Sourcebook. Since the references 
of the present volume were compiled and num- 
bered, a new monograph has been published by 
the National Academy of Sciences, National Re- 
search Council (Publication No. 1298). This 
monograph entitled Fundamentals of Hyperbaric 
Medicine (1966) was prepared by the Committee 
on Hyperbaric Oxygenation of the National Re- 
search Council. This monograph should be freely 
used by the reader who is interested in oxygen 
toxicity. 
The toxic effects of excess oxygen still remain 
a matter of considerable importance, and the 
mechanism of these toxic effects are not yet 
thoroughly understood. Exposure to oxygen con- 
centrations above 60 percent of one atmosphere 
for sufficient time periods causes toxic effects both 
in animals and in human subjects, and the 
severity of these effects is in proportion to the 
concentration and to the duration of exposure. 
The severity also shows individual variations as 
well as variations from one species to another. 
Under such conditions oxygen has adverse effects 
upon the lungs, the blood and other tissues of 
the body, including also the central nervous sys- 
tem. For example, the administration of 100 
percent oxygen to human beings continuously OXYGEN INTOXICATION AT ATMOSPHERIC PRESSURE—SPECIAL SENSES 
1815-1825 
for 24 hours at normal bamometric pressure 
causes substernal distress in 86 percent of subjects. 
Breathing 75 percent oxygen causes symptoms 
in only 55 percent of subjects and breathing 
50 percent oxygen leads to no symptoms. Ad- 
ministration of 100 percent oxygen for short 
periods, up to 12 hours, is probably safe, but 
when oxygen has to be given for periods beyond 
12 hours it should be reduced to 60 percent un- 
less this is insufficient to saturate the arterial 
blood. If 100 percent oxygen must be given it 
is mandatory that a careful check should be made 
of the symptoms most likely to occur as a result 
of high oxygen tension. 
Papers by Scano (1823,1824, 1825) 1958, com- 
prise a review of oxygen effects. Reference should 
also be made to a report by Elbel, Ormond and 
Close (1815) 1961, on the effects of breathing 
oxygen before and after exercise. Athletes in bet- 
ter than average physical condition were given 
100 percent oxygen during six minutes of rest, air 
during five minutes of treadmill running at eight 
miles per hour and oxygen during 19 minutes 
of recovery. The results were compared with a 
control procedure in which the same subjects 
breathed air throughout. It was found that the 
experimental procedures did not significantly 
facilitate recovery as based upon payment of oxy- 
gen debt, measured by a closed-circuit spiromet- 
ric method. The experimental procedure de- 
pressed the pulse rate during the first two minutes 
of exercise and during the recovery period. It 
also caused the respiratory rate to increase at 
rest, to decrease during the initial part of the 
recovery and to increase during the latter part 
of the recovery. It increased the percentage of 
oxygen saturation of blood hemoglobin as meas- 
ured by an ear oximeter during rest and during 
recovery. Lower oximeter readings were found 
during the latter part of the exercise period. 
For a statement of the effects of oxygen inhala- 
tion upon normal man, a report by Lambertsen 
(1818) 1954, is recommended. The general 
effects of oxygen upon respiration are discussed, 
including, increased respiratory minute volume 
which is followed by pulmonary irritation. 
There is increased sensitivity to normal chemical 
stimuli, for example carbon dioxide; there is 
also cerebral vasoconstriction with carbon 
dioxide accumulation. There is in addition a 
decrease in reduced hemoglobin. The pulse rate 
is lowered as well as cardiac output, because of 
reduced heart rate and stroke volume. Cerebral 
vasoconstriction is apparently due to reduced 
PCOo from oxygen breathing and not due to a 
direct effect of oxygen upon the vessels. 
1815. Elbel, E. R., D. Ormond and D. Close. Some 
effects of breathing oxygen before and after exercise. J. 
appl. Physiol., 1961, 16: 48-52. 
1816. Gell, C. F. Breathing oxygen, pp. 143-161 in: 
Aerospace medicine. Edited by H. G. Armstrong, Williams 
and W’ilkens Co., Baltimore, 1961, 633 pp. 
1817. Jongbloed, J. and H. van Goor. Zuurstof- 
toediening bij sport. [Administration of oxygen to sports- 
men.] Ned. Tijdschr. Geneesk., 1954, 98: 491-497. 
1818. Lambertsen, C. J. Effects of oxygen inhalation 
upon normal man. pp. 55/9 — 55/12 in: Pharmacology in 
medicine. Edited by V. A. Drill, McGraw-Hill Book Co., 
Inc., New York, 1954, 1273 pp. 
1819. Lambertsen, C. J. Physiological effects of oxy- 
gen. pp. 171-187 in: Second symposium on underwater 
physiology. Edited by C. J. Lambertsen and L. J. Green- 
baum, Jr. National Research Council, Washington, D.C. 
N.R.C. Publication 1181, 1963, 296 pp. 
1820. Mullinax, F. P., Jr, and D. E. Beischer. 
Oxygen toxicity in aviation medicine. J. Aviat. Med., 1958, 
29: 660-667. 
1821. Orie, N. G. M., J. J. M. Vegter and W. 
Veeger. Zo genaamde zuurstofintoxicatie. [So-called oxy- 
gen poisoning.] Ned. Tijdschr. Geneesk., 1953, 97: 733-741. 
1822. Pugh, L. G. C. The effects of oxygen on acclima- 
tized men at high altitude. Proc. R. Soc. Med. (Ser. B.), 
1955, 143: 14-17. 
1823. Scano, A. L’iperossia. Riv. Med. aero., 1958, 21: 
88-118. 
1824. Scano, A. L’iperossia. Riv. Med. aero., 1958, 21: 
337-361. 
1825. Scano, A. L’iperossia. Riv. Med. aero., 1958, 21: 
539-566,and 765-799. 
2. EFFECTS ON THE SPECIAL SENSES 
At atmospheric pressure oxygen may have ad- 
verse effects upon the visual system. Noell (1829) 
1962, has stated that with hyperoxia the visual 
cell deteriorates leaving the ganglion and bipolar 
cells preserved. Continued exposure of the rab- 
bit to oxygen at one atmosphere results in severe 
attenuation or dissappearance of the electro- 
retinogram with the b waves most susceptible. 
The electroretinogram (ERG) decline resembled 
an S-shaped survival curve with an average 
latency ranging from 20 minutes at 7 atmospheres 
to 100 minutes at 3 atmospheres. Recovery oc- 
curred unless exposure was extended for several 
hours beyond the occurrence of the first effect. 
The decline of the b wave is delayed if intra- 1826-1829 
DISEASES AND ACCIDENTS 
ocular pressure is continuously increased dur- 
ing exposure to four atmospheres, which results 
in decreased blood flow and provides a protec- 
tion to about one-half an atmosphere. Adrena- 
lectomy also afforded protection by causing a fall 
in tissue oxygen tension. High inspiratory carbon 
dioxide produced comparable ERG abnormality 
but required fifty percent concentration. The 
effect was not accumulative and recovery was 
rapid. If exposure is continued for five to eight 
hours beyond ERG changes, the damage is ir- 
reversible. Young rabbits are found to be more 
susceptible than adult animals. It may be men- 
tioned parenthetically that in the adult man 
exposure to three atmospheres oxygen causes 
progressive failure of peripheral vision with maxi- 
mal constriction at ten degrees and only tem- 
porary impairment of central vision. 
Miller (1827) 1958, has studied the effect of 
breathing 100 percent oxygen upon the visual 
field and upon visual acuity recorded through 
the use of a tangent screen, a perimeter and a 
Clason acuity meter. A control study was made 
by having the subjects breathe air instead of the 
100 percent oxygen during one test run. Each 
of the six subjects was examined with each of 
the three instruments before and after each hour 
of the test run. Analysis of the oxygen data and 
comparison of them with the air data revealed 
no significant depression or constriction of the 
central field and no sector defects; also the size 
of the blind spot remained essentially the same. 
A lack of significant alterations of the more 
peripheral isopters indicated no decreased sensi- 
tivity in this region. Central acuity was un- 
changed and peripheral acuity of the 100 percent 
oxygen test run at both five degrees and ten de- 
grees did not differ significantly from that 
measured during the air-test run. The results 
indicated that vision tested in several regions 
from zero to 60 degrees suffers no apparent dec- 
rement as a result of the breathing of 100 
percent oxygen at atmospheric pressure for a 
period of over four hours. 
1826. Harris, J. G., D. E. Beischer and D. Ever- 
son. The effects of inhalation of 100 per cent oxygen on 
performance of a task involving visual auditory conflict. 
U.S. Navy. NATB, School of Aviation Medicine, Pensacola, 
Fla. Project no. MR005.13-1002, Sub task 11, Kept. no. 3, 
5 October 1960, 20 pp. 
1827. Miller, E. F. Effect of breathing 100 per cent 
oxygen upon visual field and visual acuity. J. Aviat. Med., 
1958, 29: 598-602. 
1828. Noell, W. K. Visual cell effects of high oxygen 
pressures. Fed. Proc., 1955, 14: 107. 
1829. Noell, W. K. Effects of high and low oxygen 
tension on the visual system, pp. 3-18 in: Environmental 
effects on consciousness. Edited by K. E. Schaefer, The 
MacMillan Company, New York, 1962, 146 pp. 
3. EFFECTS ON THE CARDIOVASCULAR 
SYSTEM 
The circulatory effects of oxygen at one atmos- 
phere seem most likely to be caused by suppres- 
sion of tonic activity of peripheral chem©recep- 
tors. There is general agreement in the literature 
that at normal atmospheric pressure the breath- 
ing of 100 percent oxygen results in a slowing 
of the heart, a reduction of respiratory minute 
volume and a decrease in cardiac output. The 
slowing of the heart is considered to be almost 
entirely responsible for the reduction in cardiac 
output. Oxygen also produces changes in the 
circulation of regional vascular beds, thus there 
is constriction of coronary and cerebral vessels 
as the tension of oxygen is increased. This has 
also been observe din the eye as well as in the 
kidney. It is possible that these vasoconstrictor 
effects upon local circulation are due to the direct 
action of oxygen on the smooth muscle of blood 
vessels, and in addition to the possibility of these 
direct effects, central neurological and local 
chemical influences must be considered. 
Bevan and Verity (1835) 1961, have presented 
an analysis of cardiovascular responses to short 
periods of inhalation of oxygen in cats anesthe- 
tized with chloralose. In these animals there was 
an immediate acute fall in arterial blood pressure 
accompanied by varying degrees of bradycardia. 
Following bilateral vagotomy the initial hypoten- 
sion was still present. With inactivation of 
caroticoaortic chemoreceptor regions, no hypoten- 
sion effect was seen, but small, slowly developing 
hypertension was observed originating peripher- 
ally. Barratt-Boyes and Wood (1834) 1958, found 
in normal healthy human subjects that adminis- 
tration of 95 percent oxygen at one atmosphere 
produced a fall in heart rate, with an increase 
in stroke volume but with no systemic change in 
cardiac output under the conditions of the ex- 
periment. Dressier, Slonim, Balchum, Bronfin 
and Ravin (1838) 1952, found a decrease in 
cardiac output during oxygen breathing. Re- OXYGEN INTOXICATION AT ATMOSPHERIC PRESSURE-CARDIOVASCULAR 
duced heart rate was also observed by Grand- 
pierre, Tabusse and Bouverot (1839) 1955. In- 
halation of pure oxygen at one atmosphere pro- 
duced bradycardia in 18 cases out of 20, 
occasionally after 15 minutes, and always after 
an hour. Eighty percent and 60 percent mixtures 
produced comparable bradycardia, but a 40 per- 
cent mixture caused bradycardia in only 50 per- 
cent of the subjects tested. In the anesthetized 
dog bradycardia appeared less often, frequently 
being replaced by tachycardia, even during in- 
halation of pure oxygen, with the EGG changes 
being of the same category as those in man. The 
authors believe it possible to attribute brady- 
cardia in certain cases, above all that produced at 
the very beginning of the inhalation of pure 
oxygen, to an action on the vaso-sensitive zones. 
Late appearance of bradycardia, when the blood 
has been superoxygenated for 15 minutes, does 
not appear to favor this mechanism in human 
beings. It was noted that most of the cardio- 
moderator reflexes were generally diminished in 
the course of the first hours following the inhala- 
tion of pure oxygen. Marshall, Swan, Burchell 
and Wood (1845) 1961, have studied the effect 
of breathing oxygen on pulmonary arterial pres- 
sure and on pulmonary vascular resistance in 
patients with ventricular septal defects. During 
cardiac catheterization pulmonary and systemic 
arterial blood pressure, arterial oxygen satura- 
tion, respiration and heart rate were continously 
recorded during the change from breathing air 
to breathing 95-99.5 percent oxygen for 5-15 
minutes in a series of 31 patients with ventricular 
septal defects. Pulmonary and systemic blood 
flows were also measured. Systemic arterial oxy- 
gen saturation began to increase about five sec- 
onds after the change from breathing air to 
breathing oxygen. Within a few seconds there- 
after the pulmonary arterial pressure and heart 
rate began to decrease. These changes were com- 
plete within three minutes. Pulmonary blood 
flow increased on an average of 32 percent and 
systemic decreased by 15 percent. There was no 
consistent change in pulmonary arterial wedge 
pressure. The average calculated pulmonary re- 
sistance decreased by 36 percent and the systemic 
was increased. These changes were independent 
of pulmonary hypertension, of anesthesia and 
of the patient’s age. 
Oxygen may exert pathological effects upon 
the development of the vascular system, as has 
been shown by Allen (1830) 1961. Fertile white 
Leghorn eggs were exposed to 100 percent oxy- 
gen under very slight positive pressure during 
the first four days of incubation at 37-38°C. 
This exposure resulted in marked changes in the 
development of the vascular system. These were 
demonstrated by failure of development of the 
vitelline circulation, frequent massive hemor- 
rhages in these areas and failure to develop an 
evident heart beat. These changes bear a re- 
markable similarity to the response seen in 
similar embryos exposed to various types of radia- 
tion. It is thus evident that such local concentra- 
tions of oxygen can inhibit the normal develop- 
ment of the vascular system. In a further study 
Allen (1831) 1963, demonstrated that there is 
a critical oxygen-nitrogen ratio for optimal de- 
velopment and maintenance of the vascular sys- 
tem of the chick embryo. Relevant studies by 
Gyllensten (1840) 1959, demonstrated that ex- 
posure of growing young mice to oxygen in- 
fluences postnatal vascularization of the cerebral 
cortex. Thus continuous exposure to concentra- 
tions of oxygen (90-100 percent) for 5, 10, 15, 20 
or 30 days caused a decrease in the relative vas- 
cularization of all laminae of the area striata. 
As has been pointed out by Miles (1847) 1957, 
there is abundant evidence that breathing oxygen 
will lower the threshold for the occurrence of 
syncope, irrespective of its immediate cause, and 
therefore individuals breathing oxygen would be 
more likely to faint than when breathing air. 
To test this theory a simple experiment was de- 
vised that would bring a man breathing air to 
the brink of syncope. The test was carried out 
with 36 young adult men all experienced in the 
use of breathing apparatus. Each man was tested 
with air and with oxygen, one-half having air 
first and the remainder oxygen. All of the tests 
were done at the same time of day (late fore- 
noon) and each man had a rest of 30 minutes 
between tests. Both air and oxygen were sup- 
plied from cylinders into a Douglas bag, no man 
knowing which he was breathing. The subject 
lay horizontally on a tilt table breathing with 
nose clip and mouthpiece from the bag for five 
minutes. This was followed by one minute of 
hyperventilation, on completion of which he was 1830-1853 
DISEASES AND ACCIDENTS 
tilted quickly to the upright position. Men were 
previously instructed in the routine and immedi- 
ately on becoming upright took a final breath 
from the bag, exchanged the mouthpiece for a 
stout rubber pressure tube attached to a mercury 
manometer and blew hard against the pressure, 
with the object of maintaining as high a pressure 
as possible for as long as possible. The mercury 
pressure was recorded every ten seconds and the 
breath holding time noted. Throughout the test 
the subject was kept under observation and upon 
completion he was asked to give an account of his 
sensations. Of the 36 men three became uncon- 
scious on both air and oxygen and a further four 
on oxygen alone. Two had symptoms suggesting 
an approaching syncope on both air and oxygen 
but a further twelve had symptoms on oxygen 
alone. The order of performance of the tests 
did not influence the results and there was little 
difference between the mean pressures held on 
air and oxygen. The mean breath holding time 
was longer however, with oxygen. Less oxygen 
breathing can be shown to lower the threshold of 
syncope. 
1830. Allen, S. C. Response of the developing vascu- 
lar system of the chick embroy to hyperoxia. Fed. Proc., 
1961, 20: 421. 
1831. Allen, S. C. The role of nitrogen in the problem 
of oxygen toxicity. Fed. Proc., 1963, 22: 635. 
1832. Arnould, P., J. Petit and M. Boulange. Effets 
ventilatoires de 1’inhalation d’oxyg£ne et d’azote purs par 
un poumon vasculairement exclu, chez le Chien 
C.R. Soc. Biol., Paris, 1961, 155: 552-555. 
1833. Barratt-Boyes, B. G. and E. H. Wood. 
Hemodynamic response of healthy subjects to exercise in 
the supine position while breathing oxygen. J. appl. 
Physiol., 1957, 11: 129-135. 
1834. Barratt-Boyes, B. G. and E. H. Wood. 
Cardiac output and related measurements and pressure 
values in the right heart and associated vessels, together 
with an analysis of the hemodynamic response to the in- 
halation of high oxygen mixtures in healthy subjects. J. 
Lab. din. Med., 1958, 51: 72-90. 
1835. Bevan, J. A. and M. A. Verity. Cardiovascu- 
lar response to oxygen inhalation in the anesthetized cat. 
J. appl. Physiol., 1961,16: 858-862. 
1836. Cuypers, Y. and E. Evrard. L’influence de la 
circulation sur 1’intoxication par 1’oxygene. Med. airo., 
1957, 12: 59-67. 
1837. Daly, W. J. and S. Bondurant. Effects of 
oxygen breathing on the heart rate, blood pressure, and 
cardiac index of normal men — resting, with active hy- 
peremia, and after atropine. J. din. Invest., 1962, 41: 126- 
132. 
1838. Dressier, S. H., N. B. Slonim, O. J. 
Balchum, G. J. Bronfin and A. Ravin. The effect of 
breathing 100% oxygen on the pulmonary arterial pressure 
in patients with pulmonary tuberculosis and mitral steno- 
sis. J. din. Invest., 1952, 31: 807-814. 
1839. Grandpierre, R., L. Tabusse and P. Bou- 
verot. Modifications du rhythme cardiaque provoqudes 
par I’inhalation d’oxyg6ne. /. Physiol. Path, gen., 1955, 47: 
185-190. 
1840. Gyllensten, L. Influence of oxygen exposure on 
the postnata 1 vascularization of the cerebral cortex in 
mice. Ada Morph, need, scand., 1959, 2: 289-310. 
1841. Harris, A. S., R. W. Olsen, A. Estandia and 
T. J. Ford, Jr. Oxygen administration upon ventricular 
tachycardia and blood pressure in animals with acute 
myocardial infarction. Circ. Res., 1953, 1: 83-86. 
1842. Kilmore, M. A., R. M. Tomasello and H. F. 
Chase. Effect of POa on cerebral blood flow. Fed. Proc., 
1964, 23: 206. 
1843. Lundin, G. Nagra fysiologiska synpunkter pa 
syrgasbehandling. [Physiological aspects of oxygen ther- 
apy.] Svenska Lakartidn., 1953, 50: 1082-1085. 
1844. Manolescu, N., I. Pintilie, V. Teodorescu, 
M. Stoian, S. Schiau, L. Pascalov-Stoenescu, R. 
Stoenescu and G. Arsenescu. Cardiovascular changes 
in aviators during the oxygen pressure breathing test with 
the use of high altitude pressure suit. Stud. Cercet. Filial., 
1960,5; 119-126. 
1845. Marshall, H. W., H. J. C. Swan, H. B. Bur- 
chell and E. H. Wood. Effect of breathing oxygen on 
pulmonary artery pressure and pulmonary vascular resist- 
ance in patients with ventricular septal defect. Circulation, 
1961,25; 241-252. 
1846. Meyer, J. S. and J. Hunter. Polarographic 
study of cortical blood flow in man. J. Neurosurg., 1957, 14: 
382-399. 
1847. Miles, S. Oxygen syncope. Gt. Brit. MRC, 
RNPRC, UPS. Kept. R.N.P. 57/880, U.P.S. 161, January 
1957, 5 pp. 
1848. Morris, J. A., R. W. Smith, R. Beck and 
N. S. Assali. Oxygen effect on the isolated ductus 
arteriosus of the lamb. Fed. Proc., 1963, 22: 343. 
1849. Patterson, J. L., Jr., A. Heyman and T, 
Whatley. Cerebral circulation and metabolism in chronic 
pulmonary emphysema; with observations on the effects of 
inhalation of oxygen. Amer. J. Med., 1952, 12: 382-387. 
1850. Ratschow, M. Untersuchungen zur Wirkung 
des Sauerstoffgases in der Behandlung von Angiopathien. 
Med. Klinik., 1954, 49: 691-693. 
1851. Ross, J., Jr., G. Kaiser and F. Klocke. Studies 
on the role of oxygen tension in the functional hyperemia 
of skeletal muscle. Fed. Proc., 1964, 23: 207. 
1852. Sayen, J. J., W. F. Sheldon, O. Horwitz, 
P. T. Kuo. G. Peirce, H. F. Zinzzer and J. Mead, 
Jr. Studies of coronary disease in the experimental animal. 
II. Polarographic determinations of local oxygen avail- 
ability in the dog’s left ventricle during coronary occlusion 
and pure oxygen breathing. J. din. Invest., 1951, 30: 932- 
940. 
1853. Sharpey-Schafer, E. P. Syncope. Brit. med. J., 
1956, 1: 506-509. OXYGEN INTOXICATION AT ATMOSPHERIC PRESSURE—LYMPH 
1854-1872 
1854. Smith, C. W., P. H. Lehan and J. J. Monks. 
Cardiopulmonary manifestations with high Oa tensions at 
atmospheric pressure. J. appl. Physiol., 1963, 18: 849-853. 
1855. Storstein, O. The effect of pure oxygen breath- 
ing on the circulation in anoxemia. Acta med. scand., 1952, 
269: (suppl.) 185 pp. 
1856. Sugioka, K. and D. A. Davis. Hyperventila- 
tion with oxygen — a possible cause of cerebral hypoxia. 
Anesthesiology, 1960, 21: 135-143. 
1857. Tabusse, L. Le seuil des perturbations orga- 
niques au cours de 1’inhalation d’02 pur. Med. aero., 1954, 
9: 80-81. 
1858. Womack, G. J. Evidence for the cerebral vaso- 
constrictor effects of breathing one hundred per cent oxy- 
gen. Aerospace Med., 1961, 32: 328-332. 
4. EFFECTS ON BLOOD 
In both animals and man exposure to high 
oxygen tension at ambient atmospheric pressure 
for prolonged periods of time results in reduc- 
tion of erythropoietic activity. This has been 
confirmed by Cooperberg and Singer {I860) 
1951, in guinea pigs, and by Gunther, Hodgson, 
Tohe and Quappe {1866) 1951, in rabbits. 
These investigators found that the plasma of 
anemic rabbits maintained free from contact 
with air produced a significantly larger reticu- 
locyte response than that produced by injection 
of plasma of normal animals. These effects were 
produced in receptor rabbits. The plasma of 
anemic rabbits submitted to the action of oxygen 
produced a significantly smaller erythrocyte re- 
sponse in the injected animals than that pro- 
duced by plasma maintained free from contact 
with the air. It is suggested by the authors that 
the action of oxygen on erythropoiesis is medi- 
ated through a humoral mechanism. 
1859. Cole, R. B. and J. M. Bishop. Effect of vary- 
ing inspired 02 tension on alveolar-arterial 02 tension 
difference in man. J. appl. Physiol., 1963, 18: 1043-1048. 
1960. Cooperberg, A. and K. Singer. The reaction 
of the bone marrow to high oxygen tension in normal and 
anemic guinea pigs. J. Lab. din. Med., 1951, 37: 936-947. 
1861. Doll, E., K. Konig and H. Reindell. Das 
Verhalten der arteriellen Sauerstoffspannung und anderer 
arterieller blutgasanalytischer Daten in Ruhe und wah- 
rend korperlicher Belastung. Pfliig. Arch. ges. Physiol., 
1960, 271: 283-295. 
1862. Fleisch, A. and P. C. Frei. De 1’emploi de 
l’oxyg£ne pur dans les des coeurs-poumons 
artificiels. Helv. physiol, acta, 1960,18: 464-466. 
1863. Gibson, Q. H. The kinetics of reactions between 
haemoglobin and gases. Prog. Biophys. biophys. Chem., 
1959, 9: 1-53. 
1864. Gibson, Q. H. and F. J. W. Roughton. The 
kinetics of dissociation of the first oxygen molecule from 
fully saturated oxyhaemoglobin in sheep blood solutions. 
Proc. roy. Soc., 1955,143: 310-342. 
1865. Haab, P., J. Piiper and H. Rahn. Attempt to 
demonstrate the distribution component of the alveolar- 
arterial oxygen pressure difference. J. appl. Physiol., 1960, 
15: 235-240. 
1866. Gunther, B., G. Hodgson, J, Tohe and O. 
Quappe. The inactivation by oxygen of the erythropoietic 
effect of plasma of rabbits rendered anemic by bleeding. 
Acta physiol, lat. amer., 1951, 1: 271-276. 
1867. Heller, M. L. and T. R. Watson, Jr. Arterial 
oxygenation during transition of 100 per cent oxygen to 
air breathing: polarographic Pa0o study. Anesthesiology, 
1961,22: 385-392. 
1868. Hemmingsen, E. and P. F. Scholander. Spe- 
cific transport of oxygen through hemoglobin solutions. 
Why is this transport abolished when opposed by a slight 
back pressure of oxygen? Science, 1960, 132: 1379-1381. 
1869. Hitchcock, F. A., J. F. Atkinson and J. P. 
Kemph. Blool of dogs following controlled breathing of 
air and oxygen. Fed. Proc., 1953, 12: 68. 
1870. Ingvar, D. H., D. W. Lubbers and B. Siesjo. 
Measurement oxygen tension on the surface of the cerebral 
cortex of the cat during hyperoxia and hypoxia. Acta 
physiol, scand., 1960, 48: 373-381. 
1871. Lee, W. L., Jr., P. B. Caldwell, H. S. Schild- 
kraut. Changes of lung volume, diffusion capacity, and 
blood gases in oxygen toxicity in humans. Fed. Proc., 1963, 
22: 395. 
1872. Marx, T. I., W. E. Snyder, A. D. St. John 
and C. E. Moeller. Diffusion of oxygen into a film of 
whole blood. J. appl. Physiol., 1960, 15: 1123-1129. 
5. EFFECTS ON LYMPH 
Said, Davis and Banerjee {1873) 1964, have 
conducted a study on the PGo and Pco,, of pul- 
monary lymph. Right thoracic duct lymph was 
sampled and simultaneously femoral arterial and 
right ventricular blood and alveolar gas sampled 
in six anesthetized dogs. During air breathing 
the PGo of lymph was slightly lower and the 
Pco, slightly higher than in arterial blood. On 
breathing 100 percent oxygen for up to five 
hours lymph PGo increased moderately but re- 
mained appreciably below arterial levels. Agree- 
ment between lymph and arterial blood P0(> was 
restored with the induction of pulmonary edema; 
both fell to a similar level. The findings could be 
explained by 1) a dominant contribution to right 
duct lymph from the gas-exchange area of the 
lung normally or when pulmonary lymph flow 
was enhanced: and 2) by an admixture of hypoxic 
lymph from the non-respiratory part of the lung, DISEASES AND ACCIDENTS 
heart, pleural and peritoneal cavities. If lymph 
reflects tissue tensions, the alveoli may be the only 
tissue that normally operates at high oxygen 
tensions. 
1873. Said, S. I., R. K. Davis and C. M. Banerjee. 
Po2 and PCo2 of pulmonary lymph. Fed. Proc., 1964, 23: 
469. 
6. EFFECTS ON RESPIRATION 
There is a lack of total agreement as to the 
precise effects upon respiration of oxygen or 
hyperoxygenated air at normal barometric pres- 
sures. However, it appears that oxygen adminis- 
tration does cause changes in breathing, although 
these may not be pronounced. Oxygen adminis- 
tration in animals reduces respiratory minute 
volume and this has also been observed in man. 
There is a transient decrease in ventilation on 
administration of oxygen to normal persons at 
sea level, and this gives way within a short time 
to a light stimulation of respiration. Concur- 
rently there is a decrease of the slope of the 
ventilatory response to carbon dioxide inhalation 
so that there may be both stimulation and de- 
pression. Bannister and Cunningham (1876) 
1954, have shown that in all instances addition 
of oxygen to the inspired air increases the time 
required by athletic and non-athletic subjects 
to reach a breaking point when operating on a 
motor-driven treadmill. The performance was 
more improved by 66 percent and by 100 percent 
oxygen than by 33 percent. With 66 percent oxy- 
gen three of the subjects did not reach a break- 
ing point within 23 minutes. The discomfort 
which they had experienced when breathing air 
was replaced by a feeling of positive well-being. 
In contrast when breathing 100 percent oxygen 
they never did feel elation and all reached a 
breaking point within 21 minutes. The de- 
pressant action of 100 percent oxygen when com- 
pared with 66 percent has been discussed by 
the authors. They tentatively suggest that it 
might be due to increases in the cerebral circula- 
tion resulting from the excess of circulating 
carbon dioxide and lactate. Such an increase 
would nullify the protection from the deleterious 
effects of high-pressure oxygen afforded to the 
brain by the cerebral vasoconstriction which oc- 
curs at rest when pure oxygen is breathed. 
Asmussen and Nielsen (1874) 1958, have studied 
the regulation of respiration in heavy work in 
young normal subjects by measuring the arterial 
oxygen tensions and various respiratory func- 
tions in rest and in work when breathing at- 
mospheric air and when breathing air mixtures 
with augmented or lowered oxygen concentra- 
tions. It was found that the arterial P0a in heavy 
work with pronounced hyperventilation (i.e. 
increased ventilation per liter oxygen uptake and 
decreased alveolar PCOo) was of the same magni- 
tude (87 mm. Hg, range 82-94 mm. Hg) as in 
rest and in light work (87 mm. Hg, range 79-96 
mm. Hg) . This value is lower than the reported 
threshold of PGo for the chemoreceptors in ani- 
mals and humans. The breathing of 33 percent 
oxygen diminished the hyperventilation of heavy 
work and increased the arterial Pq2 to 183 mm. 
Hg (range 161-190 mm. Hg.). This value is well 
above the reported threshold P for the chemo- 
receptors. Breathing of 100 percent oxygen fur- 
ther decreased the hyperventilation and increased 
the arterial P0„ to 663 mm. Hg (range 635-685 
mm. Hg). It was concluded by the authors that 
hyperventilation in heavy work cannot be ex- 
plained simply as the result of arterial hypoxia. 
Earlier experiments with sudden changes from 
air breathing to oxygen breathing during work, 
and work experiments with about 12 percent 
oxygen in the inspired air, however, make the 
assumption probable that the chemoreceptor im- 
pulses elicited at the arterial P0„ obtaining in the 
air experiments sensitize the respiratory centre 
towards the work stimulus. Baker and Hitch- 
cock (1875) 1957, have studied the immediate 
effects on respiration in man of inhalation of 100 
percent oxygen at one atmosphere. The ventila- 
tion volume is increased 6.4 percent; carbon 
dioxide 6.5 percent; and respiratory rate 11.5 
percent. With return to normal air there are 
subsequently decreases of 10.5, 11.2 and 7.5 per- 
cent respectively. These effects were attributed 
to a partial loss of the “dual function” of hemo- 
globin. Increased ventilation and carbon dioxide 
output while breathing 100 percent oxygen was 
attributed to stimulation of the medullary 
respiratory center by increased carbon dioxide 
tension and increased hydrogen ion concentra- 
tion. Decreased ventilation and retention of 
carbon dioxide resulted on a return to outdoor 
air from a decreased carbon dioxide tension OXYGEN INTOXICATION AT ATMOSPHERIC PRESSURE—RESPIRATION 
and hydrogen ion concentration. Chapin has 
pointed out that in subjects acclimatized to the 
altitude at Denver, Colorado there is a marked 
depression of ventilation during the first minute 
of oxygen breathing followed by a return toward 
normal ventilation. The magnitude and time 
course of transient respiratory depression by oxy- 
gen administration have also been reported by 
Downes and Lambertsen (1886) 1964. 
The respiratory and cardiovascular effects of 
added external dead space while breathing air 
and oxygen during conditions of rest and exer- 
cise have been reported by Greenbaum (1891) 
1956. During oxygen and air exposures in man 
the respiratory rate, tidal volume and alveolar 
Pcoo were significantly increased with the addi- 
tion of a dead space. With oxygen the increase in 
rate was significantly lower than with air breath- 
ing. Above dead space volumes of 2200 cc. the 
tidal volume and minute volume were greater in 
air than with oxygen, being statistically signifi- 
cant at 3200 cc. of dead space. With exercise, the 
same relationships prevailed, especially at smaller 
dead spaces. There was more subjective discom- 
fort during oxygen than during air exposures. 
With an increase in external dead space the 
systolic and diastolic blood pressures rose ac- 
cordingly. Significant depression of respiratory 
rate produced by breathing oxygen has also been 
observed by Greenbaum (1892) 1960, who ex- 
amined the respiratory effects of breathing oxy- 
gen for 10 minutes at atmospheric pressure in 
both laboratory personnel and trained swim- 
mers. The respiratory rate was depressed from 
14.3 to 11.6 and from 11.6 to 9.6 breaths per 
minute. Respiratory minute volume was reduced 
from 8.3 to 7.2 and from 6.9 to 6.1 liters with 
no significant change in end tidal Poo.,- The 
oxygen consumption of the swimmers was greater 
and the lower oxygen ventilation equivalents 
suggested more efficient respiration in the swim- 
mers. An experiment by Loeschcke (1894) 1953, 
in which 20 persons inhaled 32 percent oxygen in 
120 trials showed a temporary decrease in the 
resting respiratory volume on an average of eight 
percent in the first minute and an average in- 
crease of the alveolar carbon dioxide tension to 
0.44 mm. Hg. Switching back to fresh air led 
to a temporary increase in respiratory volume. 
In studies by Shephard (1897) 1955, oxygen was 
administered by the B.L.B. mask to two normal 
subjects and to 28 cases of congenital heart dis- 
ease, and the effects on respiration were ob- 
served. The normal subjects showed a consistent 
increase in minute volume comparable with 
that previously reported by the observer. Four- 
teen cyanotic patients showed a very similar 
average response to oxygen; the other fourteen 
cyanotic patients tended to have a lesser re- 
sponse but this difference was not statistically 
significant. Initially at least the increase in ven- 
tilation was considered due to a greater tidal 
volume with little change in respiratory rate. 
The alveolar carbon dioxide concentration fell 
steeply during the first 15 minutes of oxygen ad- 
ministration, but there was no consistent further 
change at 30 minutes. This suggested that by the 
latter time a steady level of hyperventilation had 
been reached. The metabolic rate did not change 
with these brief periods of oxygen administra- 
tion, but over a 30 minute period of administra- 
tion a slight increase, perhaps irritative in type, 
was shown by one of the two subjects. According 
to the author the respiratory effects of oxygen are 
best explained by a reduction in chemoreceptor 
activity in association with a local accumulation 
of carbon dioxide in the respiratory center. The 
degree of hyperventilation observed depends on 
the relative magnitude of these two opposing 
effects. 
Ernsting (1888) 1961, has studied the effect 
of breathing high concentrations of oxygen in 
producing a significant decrease in the apparent 
diffusing capacity and the true diffusing capacity 
of the pulmonary membrane. Animals breath- 
ing oxygen at one atmosphere pressure for sev- 
eral days develop vascular engorgement and 
edema of the lungs. Breathing 99 percent oxygen 
at one atmosphere for 24 hours caused substernal 
distress in 30 out of 34 men. The effects on the 
diffusing capacity of the lungs of breathing 100 
percent oxygen for three hours was investigated 
in human subjects. Inhalation of 100 percent 
oxygen also has been shown to cause broncho- 
constriction. Franck, Grandpierre and Arnould 
(1889) 1954, found that artificial respiration 
with 100 percent oxygen in urethane anesthetized 
guinea pigs produced distinct broncho-constric- 
tion as determined by a manometric device. This 1874-1901 
DISEASES AND ACCIDENTS 
increase in bronchial tonus disappeared very 
rapidly after a return to inhalation of air. 
1874. Asmussen, E. and M. Nielsen. Pulmonary ven- 
tilation and effect of oxygen breathing in heavy exercise. 
Acta physiol, scand., 1958, 43: 365-378. 
1875. Baker, S. P. and F. A. Hitchcock. Immediate 
effects of inhalation of 100% oxygen at one atmosphere 
on ventilation volume, carbon dioxide output, oxygen 
consumption and respiratory rate in man. J. appl. Physiol., 
1957,10: 363-366. 
1876. Bannister, R. G. and D. J. C. Cunningham. 
The effects on the respiration and performance during 
exercise of adding oxygen to the inspired air. J. Physiol., 
1954,125: 118-137. 
1877. Barnett, T. B. and R. M. Peters. Studies on 
the mechanism of oxygen-induced hypoventilation. An 
experimental approach. J. din. Invest., 1962, 41: 335-343. 
1878. Bechtel, A. A. Respiratory rate reduction, with 
insufflation of air or oxygen. Fed. Proc., 1953, 12: 12. 
1879. Bryan, A. C., L. G. Bentivoglio, F. Beerel, 
H. McLeish and R. V. Christie. The effect of exercise 
and oxygen breathing on the distribution of ventilation 
and perfusion. Fed. Proc., 1964, 23: 418. 
1880. Chapin, J. L. Ventilatory response to oxygen 
breathing of individuals acclimatized to altitude. /. 
Aviat. Med., 1954, 25: 500-503. 
1881. Collier, C. R. Pulmonary surface activity in 02 
poisoning. Fed. Proc., 1963, 22: 339. 
1882. Cross, K. W. and T. E. Oppe. The effect of 
inhalation of high and low concentrations of oxygen on 
the respiration of the premature infant. /. Physiol., 1952, 
117: 38-55. 
1883. Dale, W. A. and H. Rahn. Ventilation of the 
open lung during unilateral experimental atelectasis. J. 
thorac. Surg., 1955, 29: 458-466. 
1884. Dejours, P,, Y. Labrousse, J. Raynaud, F. 
Girard and A. Teillac. Stimulus de la ventila- 
tion au repos et au cours de 1’exercice masculaire, a basse 
altitude (50 m), chez 1’Homme. Rev. franf. din. biol., 1958, 
3: 105-123. 
1885. Dejours, P., Y. Labrousse, J. Raynaud and 
A. Teillac. Stimulus oxyg&ie ch£mor£flexe de la ventila- 
tion basse altitude (50 m) chez 1’Homme. I. Au repos. 
J. Physiol. Path, gen., 1957, 49: 115-120. 
1886. Downes, J. J. and C. J. Lambertsen. Magni- 
tude and time course of transient respiratory depression 
by 02 at controlled PAC02. Fed. Proc., 1964, 23: 259. 
1887. Ernsting, J. Some effects of oxygen-breathing 
on man. Proc. R. Soc. Med., 1960, 53: 96-98. 
1888. Ernsting, J. The effect of breathing high con- 
centrations of oxygen upon the diffusing capacity of the 
lung in man. J. Physiol, 1961,155: 51P-52P. 
1889. Franck, C., R. Grandpierre and P, Arnould. 
Action de inhalation d’oxyg£ne h 100 p. 100 sur le tonus 
bronchique chez le cobaye. Rev. Path, comp., 1954, 54: 
985-986. 
1890. Froeb, H. F., C. I. Leftwich and H. L. Mot- 
ley. Respiratory acidosis after short periods of oxygen 
breathing in emphysematous patients. Fed. Proc., 1956, 15: 
68. 
1891. Greenbaum, L. J., Jr. The respiratory and 
cardiovascular effects of added external dead space while 
breathing air and oxygen during conditions of rest and 
exercise. M.S. Thesis (Med.), University of Maryland 
Baltimore, 1956, 53 pp. 
1892. Greenbaum, L. J., Jr. Respiratory responses 
of underwater swimmers to oxygen. J. appl. Physiol1960, 
15: 575-578. 
1893. Langdon, D. E. and G. E. Reynolds. Postflight 
respiratory symptoms associated with 100 per cent oxygen 
and g-forces. Aerospace Med., 1961, 52: 713-718. 
1894. Loeschcke, G. C. Spielen fur die Ruheatmung 
des Menschen vom G2-Druck abhangige Erregungen der 
Chemoreceptoren eine Rolle? Pftiig. Arch. ges. Physiol., 
1953. 257; 349-362 
1895. Milic-Emili, G., J. Raynaud and P. Dejours. 
Etude critique d’une method de mise en evidence du 
stimulus oxyg’£ne ventilatoire chez 1’Homme. J. Physiol. 
Path, gtn., 1960, 52: 177-178. 
1896. Perret, C. Hyperoxie et regulation de la venti- 
lation durant 1’exercice musculaire. Helv. physiol, acta, 
1960, 18: 72-97. 
1897. Shephard, R. J. Respiratory responses to the 
inhalation of oxygen at atmospheric pressure in normal 
subjects and in cases of congenital heart disease. J. 
Physiol., 1955,127: 498-514. 
1898. Storstein, O. Virkningen av surstoffanding. 
[Effects of oxygen inhalation.] Nord. med., 1953, 49: 684. 
1899. Stroud, R. C. Combined ventilatory and breath- 
holding evaluation of sensitivity to respiratory gases. J. 
appl. Physiol., 1959, 14: 353-356. 
1900. Swan, H. J. C., H. B. Burchell and E. H. 
Wood. Effect of oxygen on pulmonary vascular resistance 
in patients with pulmonary hypertension associated with 
atrial septal defect. Circulation, 1959, 20: 66-73. 
1901. Zilov, G. N. Gaseous exchange when oxygen is 
inhaled. Bull. exp. Biol. Med., 1959, 48: 926-930. 
7. EFFECTS ON METABOLISM 
There appears to be no consistent and de- 
pendable evidence that breathing oxygen en- 
riched air or pure oxygen at ambient pressures 
causes any change in metabolism, manifested by 
alterations in the exchange of respiratory gases. 
There are, however, a number of metabolic re- 
sponses to high oxygen tension. Thus Hauga- 
ard, Hess and Itskovitz (1911) 1957, studied 
the toxic effect of oxygen on enzyme systems in 
heart muscle. It was found with oxygen at a 
pressure of one atmosphere that there was a 
gradual inhibition of enzyme activity. Cupric 
ions in trace amounts greatly accelerated the toxic 
action of oxygen. The study was carried out on 
glucose and pyruvate oxidation in heart homoge- 
nates. Rueckert and Mueller (1915) 1960, 
showed that high oxygen concentrations have OXYGEN INTOXICATION AT ATMOSPHERIC PRESSURE—METABOLISM 
1902-1917 
powerful growth inhibiting effects on Hela cul- 
tures. Initially there was generalized reduction 
in the rate of cell division and in biosynthesis of 
DNA, RNA and protein, plus a shift of glucose 
metabolism to a completely anaerobic pattern 
and accompanying acceleration of the rate of glu- 
cose utilization. Whalen, Bosch and Dimants 
(1917) 1964, have discussed the limitation of 
oxygen consumption of isolated frog sartorius 
muscle by the P0o. Previous experiments sug- 
gested that the consumption of oxygen by the cell 
is normally limited by the PGo in the cellular 
environment. It was proposed that the energy 
from respiration above a certain basal level was 
converted to heat. To further test this hypothesis 
32 muscles were placed in Ringers-bicarbonate 
solution at 22° or 27.5°C. and exposed to either 
98 percent oxygen or 25 percent oxygen for six 
to seven hours. All gases contained two percent 
carbon dioxide with the balance being nitrogen. 
The Q-O,, of muscles in 98 percent oxygen was 
significantly higher than the Q-Oa of muscles in 
25 percent oxygen. The ability to develop ten- 
sion which was judged by occasional test con- 
tractions, was not impaired in 25 percent oxygen. 
The amount of lactic acid liberated from the 
muscles was small and was independent of the 
PQo. In 16 similar muscles exposed to 25 percent 
oxygen or to 98 percent nitrogen for five to 
seven hours neither the Na22 efflux nor the rest- 
ing membrane potential differed significantly 
from the values obtained from paired muscles 
exposed to 98 percent oxygen for the same 
amount of time. These data are consistent with 
the above hypothesis. Allen (1902) 1962, has 
pointed out that oxygen may not be the only 
gaseous factor in the toxic effects on the develop- 
ing chick embryos of 100 percent oxygen at one 
atmosphere. Fertile hen eggs incubated in an 
atmosphere of 20 percent oxygen with helium 
replacing the nitrogen showed the same retarda- 
tion of development. The addition of 10 percent 
nitrogen is not sufficient to support adequate de- 
velopment of the embryo. Brosemer and Rutter 
(1907) 1961, have conducted experiments which 
indicate that growth of mammalian cells are in- 
hibited in high oxygen tension. This inhibition 
may be reversed by lowering the tension within 
48 hours; after longer periods of incubation irre- 
versible changes including cellular degeneration 
occur. Similar studies have been conducted by 
Cooper, Burt and Wilson (1908) 1958. Exposure 
to increasing oxygen tensions have been shown 
by Plaine (1913) 1955, to increase slightly but sig- 
nificantly the incidence of tumors in Drosophila. 
1902. Allen, S. C. The role of nitrogen in the problem 
of oxygen toxicity. Physiologist, 1962, 4: 2. 
1903. Altschul, R. and I. H. Herman. Influence of 
oxygen inhalation on cholesterol metabolism. Arch. Bio- 
chem., 1954, 51: 308-309. 
1904. Anderson, E. H. The effect of oxygen on muta- 
tion induction by X-rays. Proc. nat. Acad. Sci., Wash., 1951, 
37: 340-349. 
1905. Berloco, N., F. Caspani and C. Stringa. La 
funzione respiratoria durante analazioni di ossigeno puro. 
I. II consume energetico in condizioni di reposo e di 
attivita muscolare. G. ital. Tuberc., 1961, 15: 185-188. 
1906. Berry, L. J. and D. S. Smythe. Effect of pure 
oxygen at reduced pressures on metabolic changes in mice 
living under simulated bio-satellite conditions. USAF. 
School of Aerospace Medicine, Brooks AFB, Texas. Kept, 
no. 62-24, January 1962, 9 pp. 
1907. Brosemer, R. W. and W. J. Rutter. The effect 
of oxygen tension on the growth and metabolism of a 
mammalian cell. Exp. Cell Res., 1961, 25: 101-113. 
1908. Cooper, P. D., A. M. Burt and J. N. Wilson. 
Critical effect of oxygen tension on rate of growth of 
animal cells in continuous suspended culture. Nature, 
Land., 1958, 182: 1508-1509. 
1909. Froese, C. and A. C. Burton. Effect of breath- 
ing 02 on 02 consumption during exposure to cold. Fed. 
Proc., 1957, 16: 42. 
1910. Gray, L. H., A, D, Conger, M. Ebert, S. 
Hornsey and O. C. A, Scott. The concentration of 
oxygen dissolved in tissues at the time of irradiation as a 
factor in radiotherapy. Brit. J. Radiol., 1953, 26: 638-648. 
1911. Haugaard, N., M. E. Hess and H. Itskovitz. 
The toxic action of oxygen on glucose and pyruvate oxida- 
tion in heart homogenates. J. biol. Chem., 1957, 227: 605- 
616. 
1912. Hollaender, A., G. E. Stapleton and F. L. 
Martin. X-ray sensitivity of E. coli as modified by oxygen 
tension. Nature, Lond., 1951,167: 103-104. 
1913. Plaine, H. L. The effect of oxygen and of hydro- 
gen peroxide on the action of a specific gene and on 
tumor induction in Drosophila melanogaster. Genetics, 
1955, 40: 268-280. 
1914. Reusse, U. Der Einfluss von Sauerstoff auf die 
Selektion von S-Zellen aus dissoziierten Kulturen. Z. Hyg. 
InfektKr., 1961, 148: 127-130. 
1915. Rueckert, R. R. and G. C. Mueller. Effect of 
oxygen tension on HeLa cell growth. Cancer Res., 1960, 
20: 944-949. 
1916. Stembera, Z. K. and J. Hodr. Effect of oxygen 
inhalation on the carbohydrate metabolism of parturient 
women during protracted labour. Rev. Czech. Med., 1961, 
7: 227-236. 
1917. Whalen, W. J., P. Bosch and A. Simants. 
Limitation of 02 consumption of isolated frog sartorius 
muscle by the pOz. Fed. Proc., 1964, 23: 518. DISEASES AND ACCIDENTS 
8. EFFECTS ON THE ENDOCRINE GLANDS 
In a study by Bean and Smith (1918) 1953, 
hypophyseal and adrenocortical factors in pul- 
monary damage induced by oxygen at one atmos- 
phere were examined. Hypophysectomized and 
nonhypophysectomized male albino rats were 
continuously exposed to oxygen in concentra- 
tions from 90 to about 98 percent at atmospheric 
pressure and in a chamber from which carbon 
dioxide was continuously absorbed. The non- 
hypophysectomized animals became dyspneic 
and lethargic within 20 hours of exposure and 
rapidly deteriorated. Several succumbed within 
45 hours and all had succumbed or were killed 
in terminal states within 70 hours of exposure. 
The thoraces were filled with clear watery, blood- 
less fluid which clotted firmly on standing. The 
lungs were a deep brownish purple color, of a 
rubbery consistency, devoid of air and sank in 
fixing solution. The massive hydrothorax may 
help explain the decreased vital capacity com- 
monly seen in exposures to oxygen at atmos- 
pheric pressure. In contrast to these findings 
none of the hypophysectomized animals suc- 
cumbed and all were still active but dyspneic 
when killed after 70 hours of exposure. The 
thoraces contained little free fluid. The lungs 
were of essentially normal appearance and all 
were fully air containing. The results confirmed 
the earlier findings of the authors and showed 
how hypophysectomy protects against pulmonary 
damage inflicted by oxygen by eliminating or 
diminishing those principles which released in 
the normal animal augment the susceptibility 
of pulmonary tissues (particularly the vascular 
bed) to the injurious effects of oxygen in high 
concentrations. Corticotropin and cortical hor- 
mones constitute important parts of this aug- 
mentatory mechanism but are not essential to 
the precipitation of injury by oxygen. The pos- 
sibility that increased carbon dioxide is a causa- 
tive factor is raised by the authors. 
Adrenal factors in the toxic action of oxygen 
at atmospheric pressure have also been con- 
sidered by Smith and Bean (1921) 1955. Earlier 
experiments had shown that the adrenals are 
causally related to the toxic effects of oxygen at 
high pressures and that adreno-cortical and 
medullary factors intensified this reaction. The 
same factors appear to enhance the toxic effects 
of oxygen at atmospheric pressure. One experi- 
mental series of 60 rats showed that adrenal- 
ectomy prolonged survival time and diminished 
lung damage induced by oxygen at atmospheric 
pressure. In a second series of 23 rats injection 
of cortisone (2-4 mg./rat/day) for three days 
prior to and during the exposure greatly en- 
hanced lung damage and shortened survival time 
from 71 hours (average) for the non-injected 
controls to 61 hours for the cortisone injected 
animals. In a third series 66 rats subcutaneous 
injections of epinephrine (0.4 mg. at 12 hour 
intervals) enhanced lung damage and shortened 
survival time from 57 hours (average) for the 
controls to 43 for the epinephrinized animals. 
It is concluded by the authors that the protective 
action of hypophysectomy against the toxic ac- 
tion of oxygen at atmospheric pressure is due in 
large measure to the elimination of adreno-corti- 
cal factors, and that adrenalectomy protects by 
eliminating medullary as well as cortical factors, 
each of which when administered by itself 
augments the toxic action (particularly on the 
lungs, as manifest by vascular effects, edema, con- 
gestion and hemorrhage). 
Warshaw, Molomut and Spain (1923) 1952, 
have shown that cortisone increases the suscepti- 
bility of mice to acute pneumonitis induced by 
high oxygen. Pathologic changes appeared ear- 
lier in the lungs of the cotrisone treated animals 
and the mortality rate was accelerated. The 
terminal histologic findings in the lungs of the 
cortisone treated animals and the controls were 
qualitatively similar. It was suggested by the 
authors that cortisone is contraindicated in the 
treatment of acute pulmonary infections. Atten- 
tion was called to the possibility that high oxy- 
gen atmospheres may be deleterious to patients 
receiving cortisone. The participation of hor- 
monal reactions in the mechanism of production 
of pulmonary lesions has been studied in guinea 
pigs by Grandpierre and Grognot (1920) 1954. 
These animals were sustained on pure oxygen 
for seven, eight or nine hours. In controls lesions 
predominated in the lung bases, in the vicinity of 
the bronchi and in the subpleural zones, with 
thickening of the alveolar walls and compression 
of alveolae, swelling of cell nuclei which became 
round and clear, an increase in volume of the OXYGEN INTOXICATION AT ATMOSPHERIC PRESSURE—MITOSIS 
1918-1928 
epithelial cells whose cytoplasm became frothy 
and vaculated, considerable congestion of capil- 
laries with rare hemorrhages. In three series 
ACTH, cortisone and chlorpromazine were ad- 
ministered 30 minutes before the start of the 
experiment. ACTH and cortisone were found to 
aggravate pulmonary lesions with turgescence of 
the nuclei of the capillary endothelium, plas- 
motic leakage into the intercellular spaces which 
produced edema without passage into the lumina 
of the alveolae. However, the lesions in the corti- 
sone animals were distinctly more severe and 
extensive. Chlorpromazine remarkably protected 
the animals against pulmonary damage. These 
data confirm the opinions of Bean and Smith 
on the role of hypophysis and adrenal cortex 
in the mechanism of lesions produced by oxygen 
inhalation; also, they demonstrate the important 
role of the vegetative nervous system. 
Prolonged exposure to moderately increased 
oxygen tension can produce important changes 
in the function and in the tissue structures of a 
great number of biological systems. Gerschman, 
Arguelles and Ibeas (1919) 1962, have studied 
the gonads of young and adult hamsters and 
mice. They were submitted to a partial pressure 
of oxygen of 0.7 atmospheres under controlled 
conditions of temperature, humidity and of 
carbon dioxide content. No changes ranging to 
severe changes in the seminiferous elements were 
observed, depending on the duration of exposure 
(from a few days to a few weeks). Changes were 
seen in the intertubular spaces and in the 
germinal epithelium. 
1918. Bean, J. W. and C. W. Smith. Hypophyseal 
and adrenocortical factors in pulmonary damage induced 
by oxygen at atmospheric pressure. Amer. J. Physiol., 1953, 
172: 169-174. 
1919. Gerschman, R., A. E. Arguelles and D. I. 
Ibeas. Effects of high oxygen tensions on mammalian 
gonads. XXII Inter. Congr. physiol. Sci., Leiden. 1962, 2: 
Abstr. 357. 
1920. Grandpierre, R. and P. Grognot. Sur le 
de production des lesions pulmonaires pro- 
voquees par 1’inhalation d’oxyg£ne pur. J. Physiol. Path, 
gen., 1954, 46: 375-377. 
1921. Smith, C. W. and J. W. Bean. Adrenal factors 
in toxic action of 02 at atmospheric pressure. Fed. Proc., 
1955,14: 140. 
1922. Tiisala, R. Stress reaction to oxygen poisoning 
in newborn, growing, and adult rats. Ann. Paedit. Fenn., 
1959, 5: 59-66. 
1923. Warshaw, L. J., N. Molomut and D. M. 
Spain. Cortisone effect on pneumonitis produced in mice 
by exposure to a high oxygen atmosphere. Proc. Soc. exp. 
Biol., N.Y., 1952, 80: 341-B44. 
9. EFFECTS ON COLD THRESHOLDS 
MacCanon and Resnik (1927) 1963, have 
shown that in a relatively cool environment (22.4 
to 26.5°C.) oxygen breathing increases the cold 
threshold from 90 microcalories/cm.2/sec. to 110 
microcalories/cm.2/sec. A similar change in cold 
threshold was obtained at warm environmental 
temperatures with oxygen inhalation. Similar in- 
formation is given in a paper by MacCanon and 
Resnik (1928) 1963. MacCanon and Eitzman 
(1925) 1961, determined the effects of oxygen 
inhalation on shivering and on thermal and 
metabolic responses to exposure to cold (10°C.) 
in ten healthy male subjects. The results showed 
that the oxygen breathing reduced shivering 
and promoted a feel of greater comfort. The 
ventilatory response to cold was diminished and 
oxygen consumption was significantly lowered 
during the later periods of the cold exposure. 
Carbon dioxide production was reduced and the 
mobilization of large amounts of nitrogen during 
shivering was also noted. Since body tempera- 
tures and their rates of fall were not significantly 
altered by oxygen inhalation, a shift to more 
efficient metabolic heat production seems to 
have been indicated. These results are given in 
more detail by MacCanon and Eitzman (1926) 
1961. 
1924. Cotes, J. E. The role of body temperature in 
controlling ventilation during exercise in one normal sub- 
ject breathing oxygen. /. Physiol., 1955, 129: 554-563. 
1925. MacCanon, D. M. and D. D. Eitzman. Effects 
of oxygen inhalation on responses to cold exposure. Fed. 
Proc., 1961, 20: 213. 
1926. MacCanon, D. M. and D. D. Eitzman. Effects 
of oxygen inhalation on responses to cold exposure. J. 
appl. Physiol., 1961, 16: 627-632. 
1927. MacCanon, D. M. and J. Resnik. Effect of 
oxygen inhalation on cold threshold. Fed. Proc., 1963, 
22: 341. 
1928. MacCanon, D. M. and J. Resnik. Effect of 
oxygen inhalation on cold thresholds. J. appl. Physiol., 
1963,18: 1057-1060. 
10. EFFECTS ON MITOSIS 
The following papers by Malamed (1929, 
1930, 1931) 1954, 1956, 1957, deal with the 
effects of oxygen poisoning on the development 
of frog embryos. Frog legs put under oxygen 1929-1931 
DISEASES AND ACCIDENTS 
lar and endothelial cell layers and accumulation 
of exudate between the basement membrane and 
the alveolar or endothelial cell. It was concluded 
that prolonged stay in concentrated oxygen 
causes alveolar damage probably by increasing 
the transport of blood proteins and blood cells 
through as well as between the endothelial and 
alveolar cells. Experiments conducted by Grog- 
not and Chom6 (1941) 1955, on 102 guinea pigs 
demonstrated that after six hours of exposure to 
pure oxygen at atmospheric pressure there exists 
extensive histological reactions of the lungs, 
lesions consisting primarily of capillary conges- 
tion, minor hemorrhages and changes of the cells 
of the alveolae. These phenomena are reversible. 
The congestion disappears in 24 hours; the cellu- 
lar distention requires a longer period to disap- 
pear. Repetition of oxygen exposure appears to 
be an unimportant aggravating factor, provided 
a free interval of about 24 hours is left between 
each experiment. The authors concluded that 
the pulmonary reactions observed are reversible 
in from 24-48 hours, and they stressed the early 
appearances of these congestive and distentive 
lesions which exist even without any clinical 
manifestations whatsoever after six hours of ex- 
posure to pure oxygen at atmospheric pressure. 
Treciokas (1955) 1959, has found that white 
rats exposed to one atmosphere of oxygen for 38 
hours, or at three atmospheres for 8 hours, show 
mitochondrial changes in the phagocytic alveolar 
cells of the lungs. Further studies of pahtological 
changes produced by breathing oxygen have 
been reported by Schaffner, Lee and Schildkraut 
(1954) 1964. To study the effects on tissues of 
breathing pure oxygen, the rats were exposed 
to one-third, one and three atmospheres of oxy- 
gen for one week, one day and three hours re- 
spectively. On light microscopy pulmonary alveo- 
lar septa were strikingly thickened and aeration 
was greatly reduced. Livers, kidneys and myo- 
cardium looked normal, even with PAS and acid 
phosphatase stains. On electron microscopy the 
livers revealed increased size (partly with and 
partly without changes in density), and numbers 
of hepatocellular mitochondria often crowding 
out the endoplasmic reticulum. There were 
numerous cytolysomes in pericanalicular zones 
containing degenerating mitochondria and large 
pinocytotic vacuoles, usually forming from or 
pressure develop into the normal late blastulae, 
but depending on the dosage of oxygen gastrula- 
tion fails to occur or is abnormal. 
1929. Malamed, S. Influence of oxygen poisoning on 
development of frog embryos. Fed. Proc., 1954,13: 93. 
1930. Malamed, S. Effect of oxygen poisoning on 
gastrulation of frog embryos. Fed. Proc., 1956, 15: 124. 
1931. Malamed, S. Gastrular blockage of frogs’ eggs 
produced by oxygen at atmospheric pressure. Exp. Cell 
Res., 1957,13: 391-394. 
11. PATHOLOGICAL EFFECTS 
Bruns and Shields (1935) 1954, have demon- 
strated hyaline membrane in 75 percent of guinea 
pigs exposed to 98 percent oxygen at sea level 
pressure for 40-100 hours. In these animals that 
survive there is no residual lung damage five 
weeks after exposure. The pathological process 
from breathing oxygen has been examined radio- 
graphically by Ernsting (1938) 1960. In a study 
of the etiology of coughing, chest discomfort 
and difficulty in breathing after flight by pilots 
of RAF fighter aircraft this worker took chest 
radiographs before and after flight in a total of 
42 flights. In 19 radiographs patchy areas of in- 
creased density were present in the lower lung 
fields immediately after landing. The syndrome 
appears peculiar to crew of fighter aircraft and 
appears to depend upon the magnitude and 
duration of applied positive acceleration, on the 
presence or absence of an anti-gravity suit in- 
stallation and on the type of oxygen system used. 
In aircraft where post flight respiratory disturb- 
ances were common the air crew had been sub- 
jected to high positive acceleration and breathed 
100 percent oxygen. The influence of the anti- 
gravity suit on the incidence is not clear. The 
condition appears to be due either to pulmonary 
edema or infarction. Cedergren, Gyllensten and 
Wersall (1936) 1959, studied pulmonary damage 
caused by oxygen poisoning using the electron- 
microscope in mice. A condition resembling 
human neo natal “hyaline membrane disease” 
was produced in adult mice by oxygen exposure 
for four to six days Electromicroscopic studies of 
the damaged pulmonary tissue showed great 
variation. Apparently normal alveolar walls 
were alternating with damaged walls, atelectasis 
and exudate. Scattered injuries to the alveolar 
walls consisted of swelling of the walls, fragmen- 
tation of the basement membrane between alveo- OXYGEN INTOXICATION AT ATMOSPHERIC PRESSURE—PATHOLOGICAL 
1932-1944 
near sinusoidal surfaces. The changes were com- 
parable in all three groups. Previous studies had 
indicated that hepatocellular mitochondrial swel- 
ling, cytolysome formation and vacuolization re- 
sult from hypoxia. In this study pulmonary 
changes account for hypoxia, but in addition 
mitochondrial hypertrophy and/or hyperplasia 
may result from the preceding hyperoxia. Thus 
oxygen, as used in space capsules or in hyperbaric 
chambers, may alter tissues first directly with in- 
creased mitochondrial mass, and secondly in- 
directly, by producing pulmonary changes which 
cause hypoxia. The influence of oxygen exposure 
on brain cells of mice has been studied by 
Gyllensten (1942, 1943) 1959. Newborn mice 
were exposed to concentrated oxygen at atmos- 
pheric pressure during the first 5-30 days after 
birth. Post-natal development of the cerebral 
cortex was studied by measuring the mean 
nuclear diameter and relative amount of inter- 
nuclear material with an integration ocular. The 
study involved the use of control animals. In 
the controls there was a continuous increase of 
nuclear diameter in all laminae of the area striata 
up to the age of 20-30 days, after which a de- 
crease of nuclear size was found. A continuous 
increase of the relative amount of internuclear 
material up to the adult age was observed. After 
ten days of oxygen exposure the average nuclear 
diameter and relative amount of internuclear ma- 
terial exceeded those of control animals in 
laminae II to VI of area striata. The combined 
thickness of laminae II to VI in area striata also 
increased. After 20 days of oxygen exposure 
cortical findings were reversed, that is to say there 
was a decrease of nuclear diameter and amount 
of internuclear material in the area striata, and 
this corresponded to a decrease of cortical thick- 
ness in the area striata. 
Conger and Fairchild (1937) 1952, have re- 
ported that chromosomes have been broken in 
the dry pollen grains and in the microspores of 
the plant Tradescantia by exposure of the cells to 
partial pressures of oxygen greater than that of 
air. The chromosome aberrations produced are 
identical to those caused by ionizing radiations. 
Exposure to 100 percent oxygen for one hour will 
produce as many chromosomal aberrations as 
approximately 1200 r of x-rays; 65 percent oxy- 
gen will produce as much effect as about 350 r. 
The aberrations are not caused by the methods of 
treatment employed, and the reactive is not 
photoactivated. The magnitude of the effect is 
related to the time of exposure and to the partial 
pressure of oxygen, increasing from almost no 
effect in air to a maximum measurable effect at 
100 percent oxygen. As a final example of lesions 
produced by oxygen mention may be made of a 
paper by Gerschman, Nadig, Snell and Nye 
(1939) 1954. In these studies lesions were pro- 
duced in the eyes of newborn mice by continuous 
exposure to 70 percent oxygen for 5-64 days. 
These lesions are suggestive of retrolental fibro- 
plasia in human beings. 
1932. Aikawa, J. K. and P. D. Bruns. Pulmonary 
lesions in experimental oxygen poisoning. Amer. J. Dis. 
Child., 1956, 91: 614-620. 
1933. Ashton, N. Animal experiments in retrolental 
fibroplasia. Trans. Amer. Acad. Ophthal. Oto-laryng., 
1954, 58: 51-54. 
1934. Becker, V. Geweblich gebundener Sauerstoff- 
mangel. Klin. Wschr., 1954, 32: 577-584. 
1935. Bruns, P. D. and L. V. Shields. High oxygen 
and hyaline-like membranes. Amer. J. Obstet. Gynec., 
1954, 67: 1224-1236. 
1936. Cedergren, B., L. Gyllensten and J. Wersall. 
Pulmonary damage caused by oxygen poisoning: An 
electron-microscopic study in mice. Acta paediat., Uppsala, 
1959, 48: 477-494. 
1937. Conger, A. D. and L. M. Fairchild. Breakage 
of chromosomes by oxygen. Proc. nat. Acad. Sci., Wash., 
1952, 38: 289-299. 
1938. Ernsting, J. Some effects of oxygen-breathing 
on man. Proc. R. Soc. Med., 1960, 53: 96-98. 
1939. Gerschman, R., P. W. Nadig, A. C. Snell, 
Jr. and S. W. Nye. Effect of high oxygen concentrations 
on eyes of new born mice. Amer. J. Physiol., 1954, 179: 
115-118. 
1940. Giles, N. H. The oxygen effect on radiation- 
induced chromosome aberrations: breakage-versus-recom- 
bination hypotheses. J. cell. comp. Physiol., 1955, 45: 271- 
284. 
1941. Grognot, P. and J. Chome. Reactions histolo- 
giques precoces du poumon apres inhalation 
pur & la pression (Etude sur 
le cobaye.) Med. aero., 1955, 10: 65-77. 
1942. Gyllensten, L. Influence of oxygen exposure 
on the differentiation of the cerebral cortex in growing 
mice. Acta Morph, neerl. scand., 1959, 2: 311-330. 
1943. Gyllensten, L. Oxygen exposure and brain 
damage. Nature, Lond., 1959, 183: 1068-1069. 
1944. Hemingway, A. and W. L. Williams. Pul- 
monary edema in oxygen poisoning. Proc. Soc. exp. Biol., 
N.Y., 1952.80: 331-334. 1945-1971 
DISEASES AND ACCIDENTS 
1945. Kihlman, B. Studies on the effect of oxygen on 
chromosome breakage induced by 8-ethoxycaffeine. Exp. 
Cell Res., 1955, 8: 404-407. 
1946. Lohr, B. Lungenschaden durch kurzfristige 
Sauerstoffbeatmung. Lang. Arch. klin. Chir., 1958, 289: 
117-127. 
1947. MacHattie, L. and H. Rahn. Survival of mice 
in absence of inert gas. Proc. Soc. exp. Biol., N.Y., 1960, 
104: 772-775. 
1948. Massion, W. Sauerstoff-Intoxikation. Klin. 
Wschr., 1955, 33: 457-457. 
1949. Michel, E. L., R. W. Langevin and C. F. 
Gell. Effect of continuous human exposure to oxygen 
tension of 418 mm Hg for 168 hours. Aerospace Med., 
1960, 31: 138-144. 
1950. Morgan, T. E., Jr., F. Ulvedal, R. G. Cutler 
and B. E. Welch. Effects on man of prolonged exposure 
to oxygen at a total pressure of 190 mm. Hg. Aerospace 
Med., 1963, 34: 589-592. 
1951. Patz, A. Oxygen studies in retrolental fibro- 
plasia. Amer. J. Ophthal., 1953,36: 1511-1522. 
1952. Patz, A. Clinical and experimental studies on 
role of oxygen in retrolental fibroplasia. Trans. Amer. 
Acad. Ophthal. Oto-laryng., 1954, 58: 45-50. 
1953. Patz, A., L. E. Hoeck and E. De la Cruz. 
Studies on the effect of high oxygen administration in 
retrolental fibroplasia. I. Nursery observations. Amer. J. 
Ophthal, 1952, 35: 1248-1253. 
1954. Schaffner, F., W. L. Lee, Jr. and H. S. 
Schildkraut. Hepatic changes after breathing pure oxy- 
gen. Fed. Proc., 1964, 23: 522. 
1955. Treciokas, L. J. The effect of "oxygen poison- 
ing” on the alveolar cell mitochondria as revealed by 
electron microscopy. Aerospace Med., 1959, 30: 674-677. 
1956. Weiss, H. S., R. B. Pilmer, R. A. Wright, 
C. R. Wharton and E. P. Hiatt. Resistance of the 
chick to oxygen toxicity. Fed. Proc., 1964, 23: 522. 
12. THERAPY 
The general references listed below on treat- 
ment are limited since most of the disease states 
referred to do not come under the scope of this 
Sourcebook. The reader is reminded that while 
short periods of oxygen breathing produce no 
demonstrable harm, continuous exposure for long 
periods will lead to severe pulmonary damage. 
On this basis the pulmonary limits of oxygen 
tolerance deserves the most serious attention in 
therapy. 
1957. Bergmann, H., H. Hartl and F. Walker. 
Unsere Erfahrungen mit dem primaren Herzstillstand. 
Wien klin. Wschr., 1955, 67: 451-455. 
1958. Cater, D. B. and I. A. Silver. Quantitative 
measurements of oxygen tension in normal tissues and 
in the tumors of patients before and after radiotherapy. 
Acta radiol, Stockh., 1960, 53: 233-256. 
1959. Dasiuk, N. V. Ingaliatsionnyi metod lecheniia 
kislorodom bol’nykh travamaticheskoi entsefalopatiei. [The 
oxygen inhalation method of treatment of patients with 
traumatic encephalopathies.] Klin. Med., Mask., 1955, 4: 
69-74. 
1960. Di Paolo, J. A. and G. E. Moore. The in- 
fluence of prolonged oxygen change on the formation of 
spontaneous and induced mouse cancer. Cancer Res., 1959, 
19: 1175-1180. 
1961. Henriksen, E. Om Iltinhalation til Patienter 
med svaert Lungeemphysem og Fibrose. [Inhalation of 
oxygen by patient with severe pulmonary emphysema and 
fibrosis.] Ugeskr. Laeg., 1953,115: 496-499. 
1962. Heston, W. E. and A. V. Pratt. Increase in 
induced pulmonary tumors in mice associated with expose 
to high concentrations of oxygen. Proc. Soc. exp. Biol., 
N.Y., 1956, 92: 451-454. 
1963. Hultborn, K. A. and A. Forssberg. Irradiation 
of skin tumors during pure oxygen inhalation. Acta 
radial.. Stockh., 1954, 42: 475-484. 
1964. Judmaier, F. Ergebnisse der Sauerstofftherapie 
bei peripheren Durchblutungsstorungen. Med. Klinik., 
1953, 48: 816-817. 
1965. Knowles, J. H. Diffuse, obstructive emphysema, 
pp. 142-154 in: Respiratory physiology and its clinical 
application. Harvard University Press, Cambridge, Mass. 
1959, 256 pp. 
1966. Krementz, E. T., R. Harlin and L. Knudson. 
The enhancement of chemotherapy by increased tissue 
oxygen tension. Cancer Chemother. Rep., 1960, issue 10: 
125-130. 
1967. Lenhoff, H. M., D. J. D. Nicholas and N. O. 
Kaplan. Effects of oxygen, iron, and molybdenum on 
routes of electron transfer in Pseudomonas fluorescens. 
J. biol. Chem., 1956, 220: 983-995. 
1968. Levine, S. Oxygen in the therapy of cyanide 
poisoning. J. Amer. med. Ass., 1959, 170: 1585. 
1969. Neufeld, O. Oxygen therapy. J. Amer. geriat. 
Soc., 1961, 9: 871-876. 
1970. Small, H. S., G. G. Nahas and E. A. Chas- 
now. Survival of dogs hyperventilated with 100% 02 in 
hypovolemic shock. Fed. Proc., 1963, 22: 640. 
1971. Storstein, O. Surstoffbehandling. [Oxygen ther- 
apy.] Tidsskr. norske Laegeforen., 1952, 72: 426-430. 
B. EFFECTS OF OXYGEN TENSION IN 
EXCESS OF ONE ATMOSPHERE 
1. GENERAL STUDIES 
Breathing oxygen under pressures above 1.0 
atmosphere for a sufficiently long time and at 
sufficiently high pressure eventually leads to the 
development of oxygen toxicity characterized by 
general convulsions. The cause of these convul- 
sions is not yet completely understood in spite 
of considerable investigation in this field. The 
effects of oxygen tension in excess of 1.0 atmos- 
phere are significant not only as they bear upon OXYGEN INTOXICATION ABOVE ONE ATMOSPHERE—GENERAL STUDIES 
the causes, course and treatment and prevention 
of oxygen toxicity, but also because of their 
relevance to hyperbaric oxygenation as a thera- 
peutic modality in certain disease conditions. 
It has been shown that oxygen in high per- 
centages and at ambient pressure acts as a local 
irritant, but oxygen toxicity occurs under high 
pressure in too brief a period for an irritant effect 
to be causative as Lambertsen (1977) 1961, has 
stated. Oxygen poisoning is reversible (except in 
cases of unconsciousness in SCUBA diving) al- 
though sufficiently prolonged breathing of oxy- 
gen at high pressure leads to death of 
experimental animals. Oxygen toxicity, as 
stated, is a function of pressure and duration. 
The safe period for oxygen breathing is reduced 
by immersion and exercise. Tolerance is also re- 
duced by carbon dioxide inhalation. Current 
evidence reveals no carbon dioxide accumulation 
in the brain at the time of oxygen convulsions 
nor any effect on brain tissue slices nor conduc- 
tion in peripheral nerves. The carbon dioxide 
accumulation does, however, cause vasodilatation 
in the brain which increases the effect of oxygen 
and also interacts with it to have an obscure effect 
on the pulmonary toxicity of oxygen. High 
oxygen pressure interferes with oxidative pro- 
cesses especially through inactivation of enzymes 
in which sulfhydryl groups are essential. 
It has been pointed out (1982) 1959, that high 
pressure oxygen poisoning affecting the brain 
and causing convulsions can definitely occur at 
2.0 atmospheres and sometimes at even lower 
pressures. Oxygen poisoning is a concern not 
only in diving, but in its use in decompression 
with helium-oxygen and in the treatment of 
decompression sickness. The latent period to 
the onset of oxygen poisoning is shortened by 
exertion and by excess carbon dioxide, as has 
been stated. Oxygen tolerance has inter- and 
intra-individual variation. Warning symptoms in 
order are: muscular twitching, nausea, abnormali- 
ties of vision and hearing, difficulty in breathing, 
anxiety and confusion, unusual fatigue, inco- 
ordination and convulsions. The convulsions 
are not in themselves dangerous but result in 
tongue chewing, brusing, air embolism (if diver 
is rapidly brought to the surface) and drowning 
(particularly with the use of SCUBA gear). The 
convulsions are usually self-terminating, even if 
the same partial pressure of oxygen is maintained. 
They are followed by a quiet phase of a few 
moments; there are apparently no lasting effects. 
The mechanism of oxygen poisoning, although 
presently obscure, may be considered to be a 
direct effect through interference with enzyme 
systems. For a further general paper on high 
pressure oxygen, including therapeutic potentials 
of hyperbaric oxygenation, a U.S. NRC Report 
(1983) 1963, should be consulted. Oxygen under 
high pressure appears useful when an increased 
gradient of oxygen transfer is required. It can- 
not deal directly with hypoxic anerobic metab- 
olism. There are practical limitations and lung 
damage and convulsions are to be kept in mind. 
There is an approximately two percent incidence 
of convulsions upon breathing oxygen at 2.8 
atmospheres for two hours. Removal of carbon 
dioxide from combination with hemoglobin is 
accelerated by oxygen under high pressure. The 
indications for the use of oxygen under high 
pressure are increasing. (It is perhaps beneficial 
in barbiturate poisoning. It is used as an adjunct 
to radiation therapy in the treatment of malig- 
nant tumors. It has also been utilized in the 
treatment of gas gangrene infections). More 
proof of its true value is needed. Such proof 
must be derived from clinical investigation under 
rigid controls. The oxygen reservoir effect of 
oxygen under high pressure for cardiac surgery 
is likely to be disappointing since the arterial 
P0o is only brought toward normal. Oxygen 
under high pressure may be beneficial as an 
emergency measure in traumatic peripheral 
vascular insufficiency, but could be of doubtful 
benefit in peripheral vascular disease. It is pos- 
sible that oxygen under high pressure has a 
potential application in coronary occlusion. The 
value of oxygen under high pressure in cerebral 
vascular disease may be greatest in the extra- 
cranial form, i.e. carotid arterial obstruction. It 
is said to be of distinct benefit in hemorrhagic 
shock. Carbon monoxide poisoning and acetani- 
lide poisoning have both been treated success- 
fully with oxygen under high pressure. 
The possibility of oxygen toxicity imposes 
serious tactical problems in certain naval maneu- 
vers, for example: underwater demolition team 
swimmers are enabled, through the use of a closed 
circuit breathing apparatus where the oxygen is 1972-1985 
DISEASES AND ACCIDENTS 
recirculated and the carbon dioxide is absorbed, 
to swim underwater to their objective with maxi- 
mum stealth. Not only can they remain under- 
water but also no bubbles reach the surface to 
invite visual detection of their presence. In such 
operations the swimmers can swim for a pro- 
longed period of time without oxygen intoxica- 
tion as long as they do not swim deeper than the 
ten foot depth. If deeper swimming is attempted 
the danger of toxic effects escalates rapidly. For 
example, if a swimmer convulses at depths below 
ten feet the convulsions will not in themselves 
be lethal but he will in all probability lose his 
mouthpiece and drown (quite apart from the fact 
that he is seriously disabled). 
1972. BuBois, A. B. Oxygen toxicity. Anesthesiology, 
1962, 23: 473—477. 
1973. Gerschman, R. Oxygen effects in biological sys- 
tems. XXI Inter. Congr. physiol. Sci., 1959, 21: 222-226. 
1974. Gilbert, D. L., J. Frost, D. Caccamise and 
R. Gerschman. Biological effects of high oxygen tensions 
(motion picture). Fed. Proc., 1957,16: 46. 
1975. Gjone, E. Akutt surstoff-forgiftning. [Acute 
oxygen poisoning.] Nord. med., 1957, 57: 239- 
1976. Lambertsen, C. J. Introduction to seminar on 
oxygen toxicity, pp. 7 in: Proceedings of underwater 
physiology symposium. Edited by L. G. Goff, National Re- 
search Council, Washington, D.C. N.R.C. Publication 377, 
1955,153 pp. 
1977. Lambertsen, C. J. Harmful effects of oxygen, 
nitrogen, carbon dioxide, and carbon monoxide. Oxygen, 
pp. 710-714 in: Medical physiology. Edited by P. Bard, 
C. V. Mosby Company, St. Louis, 1961, 1339 pp. 
1978. Lochner, W. Toxische Wirkung hoher Sauer- 
stoffdrucke auf den Menschen. Dtsch. med. Wschr., 1958, 
83:187-189. 
1979. Pfeifer, K. and W. Bucklitsch. Uber die 
Gefahren des Tauchens mit reinem Sauerstoff. Dtsch. 
Gensundheitwes., 1960,15: 1540-1545. 
1980. Sensing, J. and H. C. Drube. Die Tiefen- 
rausch und andere Gefahren des Tauchens. Dtsch. med. 
Wschr., 1962, 87: 2580-2586. 
1981. U.S. Navy. Oxygen poisoning, pp. 111-114 in: 
Submarine medicine practice. U.S. Navy. BuMed. 
NA VMED — P 5054, Gov’t. Printing Office, Washington, 
D. 1956, 357 pp. 
1982. U.S. Navy. Exygen poisoning, pp. 70-74 in: 
U.S. Navy diving manual. BuShips NAVSHIPS 25-538, 
1959, 433 pp. 
1983. U.S. NRC. Hyperbaric oxygenation: potentiali- 
ties and problems. U.S. NRC, Committee on Hyperbaric 
Oxygenation. Washington, D.C. 1963, 37 pp. 
1984. Watson, S. On oxygen poisoning under water. 
Med.J.Aust., 1961,2; 157-158. 
1985. Anon. Panel-floor discussion of oxygen toxicity, 
pp. 39-49 in: Proceedings of the underwater physiology 
symposium. Edited by L. G. Goff, National Research Coun- 
cil, Washington. D.C. N.R.C. Publication 477, 1955, 153 
pp. 
2. EFFECTS ON THE CENTRAL NERVOUS 
SYSTEM 
Gowdey and Patel {1989) 1962, have studied 
convulsions and other effects induced in conscious 
rats by oxygen under high pressure and have 
examined the effects of repeated exposure to oxy- 
gen. A month after the implantation of elec- 
trodes in the skull each rat was placed in a sling 
and then compressed with oxygen in a small 
chamber (with a carbon dioxide absorber) at 10 
psi per minute to a level of 60 psi (gauge). They 
were maintained at this level until at least three 
convulsions occurred and they were then decom- 
pressed in stages. The frequency of the EEG 
usually decreased and the amplitude increased 
before and immediately after the convulsions. 
Respiratory rate and depth increased; body tem- 
perature was maintained fairly constant. In a 
first series 14 rats were exposed on five successive 
weeks and the time to first convulsions (CT) 
recorded. After an initial rise at the second ex- 
posure the CT fell and was below normal at the 
fifth exposure. Hemoglobin values were above 
controls and extensive lung damage was seen. 
Series II consisted of five groups (10 rats each) 
which were exposed on six successive weeks to 60 
psi (gauge) of oxygen, or air, two percent carbon 
dioxide in oxygen or to normal pressure of oxy- 
gen or of air. The CT was shorter in the carbon 
dioxide group than in the oxygen group; and the 
CT in both groups increased slightly for four 
exposures and then began to fall. No significant 
lung damage could be found. No convulsions 
ocurred at normal pressure. Five rats were ex- 
posed to oxygen at 60 psi (gauge) until respira- 
tion ceased (after some two-and-a-half hours and 
50 convulsions) . Moruzzi (1993) 1954, has 
shown that following breathing of pure oxygen 
at high pressure both cortical and subcortical 
structures show electrical patterns similar to those 
observed during epileptic seizures in man. In the 
unanesthetized cat these patterns resembled those 
observed during the tonic phase of grand mal. 
In the same species under urethane anesthesia 
the same high levels of oxygen pressure produced OXYGEN INTOXICATION ABOVE ONE ATMOSPHERE—NERVOUS SYSTEM 
instead only clonic convulsions. The repetition 
rate of both motor and cortical phenomena is 
clearly increased by sensory stimuli. 
Mantegazzini (1992) 1954, has studied the ef- 
fects of oxygen respiration at high pressure on the 
electrocorticogram as well as on the response of 
the visual cortex to stimuli applied to the optic 
nerve. These studies were done in unanesthe- 
tized rabbits before and after ponto-mesencepha- 
lic section. In intact animals, after 10-30 minutes 
respiration of oxygen at 5.0 to 6.0 atmospheres 
there occurred seizures resembling those of hu- 
man “grand mal” type with typical EEG regis- 
tration. Decompression did not immediately 
interrupt the course of the attack. Section of 
the brain stem at the upper margin of the pons 
did not modify the EEG convulsive picture pro- 
duced by hyperoxia. In the “isolated brain” 
preparations the response of the visual cortex 
to stimulation of the contralateral optic nerve 
was not modified either before or during the 
seizures. High frequency stimulation of the 
optic nerve was incapable of causing seizures and, 
if this was occasionally followed by a spontaneous 
attack, the convulsive activity did not appear 
more in the contralateral visual cortical area than 
in other cortical areas. These latter observations 
indicated to the author that the cerebral cortex 
in the preseizure and interseizure phases is not 
susceptible to the toxic action of oxygen, which 
serves to sustain the hypothesis that hyperoxic 
convulsions are of subcortical origin. 
Perot (1994) 1956, has drawn attention to 
reports describing toxicity of oxygen at high 
pressure on nerve muscle preparations. These 
studies give no direct evidence of functional 
impairment of the nerve per se. In the author’s 
studies frog sciatic and cat ulnar nerves were 
stimulated continuously (20 pulses/second; volt- 
age supramaximal for alpha fibers) in a pressure 
chamber at 13 atmospheres absolute oxygen. 
Changes in action potential amplitude were 
studied. Each nerve’s initial action potential 
amplitude was made the same by amplifier ad- 
justment and conduction block was defined as 
the disappearance of the action potential during 
continuous stimulation with the initial param- 
eters. Complete conduction block occurred in 
all nerves tested. The mean time for the block 
in frog nerves at 13 atmospheres oxygen was 
four-and-a-half hours; in a five percent carbon 
dioxide—95 percent oxygen mixture at 13 at- 
mospheres it was three hours. The block was 
partially reversible on return to room pressure if 
it had not been maintained for more than a few 
minutes. The presence or absence of continuous 
stimulation did not affect the time course of con- 
duction block. Cat nerves maintained in Ty- 
rode’s solution, with no added carbon dioxide 
prior to exposure to oxygen under high pressure, 
were blocked in 13 atmospheres oxygen in 2.25 
hours. Cat nerves maintained in Krebs-Henseleit 
solution equilibrated with five percent carbon 
dioxide and 95 percent oxygen before exposure 
to 0.38 percent carbon dioxide and 99.62 percent 
oxygen at 13 atmospheres (to maintain an ap- 
proximate physiological carbon dioxide tension 
during exposure) were blocked in 50 minutes at 
37°C. Recovery was poor or else not evident. 
The data indicate that oxygen under high pres- 
sure is directly toxic to periphoral nerves, and 
that the mammalian nerve is more susceptible 
than the frog nerve. Kaufman, Owen and Lam- 
bertsen (1990) 1956, have stated that the con- 
vulsions caused by oxygen inhalation at increased 
ambient pressures occur only after a latent period 
free of signs or symptoms of oxygen toxicity. In 
the present investigation the authors explored 
the effect of brief interruptions of oxygen breath- 
ing upon the total duration of oxygen exposure 
required to produce toxicity. Twenty-two control 
guinea pigs were exposed continuously to 100 
percent oxygen at 3.0 atmospheres. At the same 
pressure 22 other guinea pigs breathed 100 per- 
cent oxygen for 30 minutes or 7 percent oxygen 
in nitrogen (equivalent to the PGo of 21 percent 
oxygen at 1.0 atmosphere) for 10 minutes and 
continued this alternation for the duration of the 
experiment. The levels of inspired carbon diox- 
ide did not exceed 0.1 percent for either group. 
In the control guinea pigs exposed continuously 
to 100 percent oxygen, the first animal developed 
toxicity at three hours, while the mean latent 
period for the group was 5.2 hours. The first 
sign of toxicity in the intermittently exposed 
group occurred at 9.6 hours (oxygen time 7.2 
hours), with a mean time for this group of 17.0 
and 12.8 hours respectively. This increased toler- 
ance to 3.0 atmospheres of high oxygen was 
significant and indicates that the rate of recovery 1986-2001 
DISEASES AND ACCIDENTS 
from the central nervous system manifestations 
of oxygen poisoning exceeds the rate of their 
development. In addition to extending oxygen 
tolerance at increased pressure, the alternation 
of high and low P0s allowed elimination of nitro- 
gen during the periods of oxygen breathing and 
prevented the development of ‘bends’ up to 25 
hours total exposure at 3.0 atmospheres pressure. 
1986. Altukhov, G. V. and N. A. Agadzhanian. 
Osobennosti vyrabotki i izmenenii uslovnykh refleksov pri 
dykhanii kislorodom pod povyshennym davleniem. [Pe- 
culiarities of conditioning and changes in conditioned re- 
flexes during breathing of oxygen at increased pressure.] 
Zh. Vyss. Nerv. Deiat. Pavlov, 1959, 9: 865-871. 
1987. Cerchia, M. M. F. and P. Mantegazzini. 
Azione convulsivante dell’ossigeno ad alta pressione in 
alcune specie animali. Ann. Med. Nav. Trap., 1956, 61: 
127-136. 
1988. Gillen, H. W. The role of carbon dioxide in 
hyperoxic convulsions. XXII Inter. Congr. physiol. Sci., 
Leiden. 1962, 2: Abstr. 356. 
1989. Gowdey, C. W. and Y. J. Patel. Effects of 
oxygen under high pressure on normal rats. XXII Inter. 
Congr. physiol. Sci., Leiden. 1962, 2: Abstr. 355. 
1990. Kaufman, 3. D., S. G. Owen and C. J. Lam- 
bertsen. Effects of brief interruptions of pure oxygen 
breathing upon central nervous system tolerance to oxygen. 
Fed. Proc., 1956, 15: 107. 
1991. Mantegazzini, P. Osservazioni elettroencefalo- 
grafiche sugli effetti dell’iperossia nel coniglio. Ann. Med. 
Nav. Trap., 1954, 59: 374-375. 
1992. Mantegazzini, P. Osservazioni elettroencefalo- 
grafiche sugli effetti dell’iperossia nel coniglio. Minerva 
med., 1954, 45: 1332. 
1993. Moruzzi, G. The neural mechanisms of the 
oxygen convulsions. Ann. Med. Nav. Trap., 1954, 59: 369- 
373. 
1994. Perot, P. L., Jr. and S. N. Stein. Conduction 
block in peripheral nerve produced by oxygen at high 
pressure. Fed. Proc., 1956,15: 144. 
1995. Rudin, D. O. and G. Eisenman. Effects of 
oxygen at high pressure on central nervous system axons. 
Fed. Proc., 1952,11: 133. 
1996. Smith, G., D. D. Lawson, S. Renfrew, I. 
Me A. Ledingham and G. R. Sharp. Preservation of 
cerebral cortical activity by breathing oxygen at two 
atmospheres of pressure during cerebral ischemia. Surg. 
Gynec. Obstet., 1961,115: 13-16. 
1997. Sonnenschein, R. R. and S. N. Stein. Elec- 
trical activity of the brain in acute oxygen poisoning. 
EEG din. Neurophysiol., 1953, 5: 521-524. 
1998. Stein, S. N. Neurophysiological effects of oxy- 
gen at high pressure, pp. 20-24 in: Proceedings of the un- 
denvater physiology symposium. Edited by L. G. Goff, 
National Research Council, Washington, D.C. N.R.C. 
Publication 477, 1955, 153 pp. 
1999. Stein, S. N. The neurophysiological effects of 
oxygen under high pressure, pp. 41-46 in: Environmental 
effects on consciousness. Edited by K. E. Schaefer. The 
MacMillan Company, New York, 1962, 146 pp. 
2000. Voino-Yasenetskii, A. V. Otrazhenie evollut- 
sionnykh zakonomernostei v epileptiformnoi reaktsii zhi- 
votnkh na deistvie vysokogo partsial’nogo davleniya kislo- 
roda. [Evolutionary regularities as reflected in the epilepti- 
form reaction of animals to high partial oxygen pressure.] 
The Academy of Sciences of the USSR, Moscow-Leningrad, 
1958, 136 pp. 
3. EFFECTS ON MUSCLE 
Gilbert and Lowenberg (2001) 1963, have ex- 
amined the effects of high oxygen pressure on 
the resting membrane potential of the sartorius 
muscle in the frog. The effect of high oxygen 
pressure on the resting muscle membrane po- 
tential was measured by the use of a microelec- 
trode. From each frog one muscle was subjected 
to an experimental condition and its contralateral 
served as a control. Muscles were immersed in 
solutions buffered with 50 mM. of tris (hydro- 
xymethyl) aminomethane. Control potentials 
were about 90 mV. Thirty minutes after ex- 
posure to 140 atmospheres oxygen for two hours, 
the experimental value was still 98.5 ± 0.8 per- 
cent of its control. However, three hours after 
the oxygen exposure the value was only 90.3 db 
0.95 percent. Exposure to 140 atmospheres of 
nitrogen produced no such effects. When 3.26 
mM. reduced glutathione was added to the 
solutions after exposure to oxygen this decrease 
was inhibited. Immersion of muscles in 1.0 mM. 
of hydrogen peroxide for four hours had no 
influence upon the membrane potential. Similar 
immersion in 50 mM. of hydrogen peroxide did 
decrease the potential to 93.8 ± 0.49 percent of 
its control. 
2001. Gilbert, D. L. and W. E. Lowenberg. Effect 
of high oxygen pressure on the resting membrane potential 
of frog sartorius muscle. Fed. Proc., 1963, 22: 402. 
4. EFFECTS ON HEART AND 
CIRCULATION 
Breathing oxygen at pressures higher than 1.0 
atmosphere causes a reduction of pulse rate and 
diminution of cardiac output. There are also 
changes in the circulation of regional vascular 
beds. Thus, as oxygen tension increases there is 
cerebral and coronary vasoconstriction. Vasocon- 
strictor effects are also found in the human eye, 
in the kidney and possibly in the skin. These OXYGEN INTOXICATION ABOVE ONE ATMOSPHERE—HEART AND CIRCULATION 
effects may be due to a direct action of oxygen 
on vascular smooth muscle and in addition the 
influences of a central increase in carbon dioxide 
as well as neurogenic and chemical factors may 
play a part. If the arterial carbon dioxide is 
maintained constant as oxygen is administered 
to normal human subjects at one atmosphere 
cerebral vasoconstriction is not observed. Thus 
it has been suggested that cerebral vasoconstric- 
tion in normal subjects is caused by arterial hy- 
percapnia that accompanies the respiratory stim- 
ulation produced by oxygen. 
Lambertsen, Rough, Cooper, Emmel, Loe- 
schcke and Schmidt (2006) 1953, found that at 
3.5 atmospheres oxygen inhalation produced a 
55 percent increase in cerebral vascular resistance 
resulting in a 25 percent reduction in the rate 
of blood flow through the brain. When compared 
with oxygen inhalation at 1.0 atmosphere, 
changes were twice as great but not statistically 
different. Dissolved oxygen in arterial blood at 
3.5 atmospheres averaged 6.5 volumes percent, 
but more oxygen was given up to the brain tis- 
sues because of slower cerebral blood flow re- 
sulting in an average internal jugular hemo- 
globin saturation of 89 percent. Removal of 
physically dissolved oxygen as blood passed 
through the brain lowered the PC) by 2000 mm. 
Hg. Partial interference with oxyhemoglobin re- 
duction rendered carbon dioxide transport less ef- 
ficient. This, plus slower flow rate accounted for 
an 8 mm. Hg increase in the A-V PCOo difference 
across the brain. A 5 mm. Hg fall in arterial 
Pc0„ limited venous increase to 3 mm. Hg. This 
is not compatible with a concept of increased 
brain tissue PCOo as contributing to oxygen toxic- 
ity, but rather of reduced exposure of brain tissue 
to toxic levels of oxygen tension by producing 
hyperventilation and cerebral vasoconstriction. 
No alteration in the rate of oxygen consumption 
or the respiratory quotient of the brain could be 
detected at 3.5 or 1.0 atmosphere of inspired oxy- 
gen. In studies reported by Schaefer (2013) 1953, 
twelve trained underwater swimmers swam at 
a speed of about 0.85 knots at the surface and at 
20, 30 and 40 feet depth, while breathing oxygen 
for a period of 93 minutes with rest periods after 
each 15 minutes. The water temperature at the 
surface was 80°F. and the underwater tempera- 
ture was 90°F. The average pulse rate, measured 
at the beginning of rest periods, showed a con- 
sistent decline with continuing exercise at each 
depth, exhibiting the well-known bradycardia 
effect of oxygen, whereas the average respiratory 
rate showed an upward trend. The average pulse 
rate and respiratory rate at the end of swims ter- 
minated because of symptoms were significantly 
higher than those at the end of normally termi- 
nated swims, suggesting that an increased sym- 
pathicotonic activity accompanies symptoms of 
oxygen toxicity. Pulse rate measurements at the 
beginning and end of rest periods made possible 
the demonstration of a sign of predominant para- 
sympathetic activity, namely the fixation of pulse 
rate or nonresponsiveness of pulse rate to 
change from exercise to rest or from rest to exer- 
cise. This sign preceded the development of 
symptoms in 78 percent of the cases and can be 
used by the swimmer as a warning for acute symp- 
toms of oxygen toxicity. Under conditions of 
underwater swimming while breathing oxygen 
dyspnea is the most frequent symptom in con- 
trast to resting conditions at high oxygen ten- 
sion. The dyspnea was usually characterized by 
rapid, shallow breathing and apparent inspira- 
tory inhibition. For a further report on cardiac 
slowing and respiratory rate changes under 
high oxygen pressure in rats, the report by Tay- 
lor (2016) 1958, may be consulted. Whitehorn 
and Bean (2017) 1952, in 18 decerebrate dogs 
also observed a pronounced decrease in heart 
rate as well as a slowing of cardiac conduction 
manifested by a prolonged P-R interval. De- 
creased amplitude of the P wave and increased T 
wave were common. With short exposure these 
effects were largely reversible. With prolonged 
exposure slowed conduction progressed to A-V 
block with suppression or extinction of the P 
wave, accompanied by ventricular extrasystoles 
and nodal rhythms. There was only partial and 
transient recovery, if any. In animals that suc- 
cumbed respiration was arrested before the heart. 
Vagotomy and/or stellatectomy postponed OHP 
changes but did not prevent them. 
Aschan and Wallenius (2003) 1953, have re- 
ported that guinea pigs exposed to oxygen poi- 
soning showed transudation into the tympanic 
cavity, the paranasal sinuses and the pleuroperi- 
cardiac cavity. These transudates had a protein 2002-2022 
DISEASES AND ACCIDENTS 
composition strongly resembling that of serum 
and indicated grave alterations of vascular 
permeability. 
2002. Alifanov, V. N. Changes in the human electro- 
cardiogram on breathing oxygen under pressure and their 
relationship to a compensating pressure applied externally 
to the body (Vector analysis). Bull. exp. Biol. Med., 1961, 
50: 1239-1242. 
2003. Aschan, G. and G. Wallenius. Electrophoretic 
studies of transudates caused by experimental oxygen 
poisoning and oxygen deficiency. Acta Soc. Med., Uppsala, 
1953, 58: 315-320. 
2004. Asmussen, E. and M. Nielsen. The cardiac 
output in rest and work at low and high oxygen pressures. 
Acta physiol, scand., 1955, 35: 73-83. 
2005. Bean, J. W. and H. Wagemaker. Brain blood 
flow, chlorpromazine (Thorazine) and its protective action 
against the toxicity of 02 at high pressure. Amer. J. 
Physiol, 1960, 198: 341-345. 
2006. Lambertsen, C. J., R. H. Kough, D. Y. 
Cooper, G. L. Emmel, H. H. Loeschcke and C. F. 
Schmidt. Oxygen toxicity. Effects in man of oxygen in- 
halation at 1 and 3.5 atmospheres upon blood gas trans- 
port, cerebral circulation and cerebral metabolism. J. appl. 
Physiol, 1953, 5: 471-486. 
2007. Lambertsen, C. J., R. H. Kough, D. Y. 
'"'ooper, G. L. Emmel, H. H. Loeschcke and C. F. 
Schmidt. Comparison of relationship of respiratory mi- 
nute volume to pC02 and pH of arterial and internal 
juglar blood in normal man during hyperventilation pro- 
duced by low concentrations of C02 at 1 atmosphere and 
by Oa at 3.0 atmospheres. J. appl. Physiol, 1953, 5: 803-813. 
2008. Lambertsen, C. J., S. G. Owen, H. Wendel, 
M. W. Stroud, A. A. Lurie, W. Lochner and G. F. 
Clark. Respiratory and cerebral circulatory control dur- 
ing exercise at 2.1 and 2.0 atmospheres inspired p02. J. 
appl Physiol, 1959, 14: 966-982. 
2009. Lambertsen, C. J., M. W. Stround, J. H. 
Ewing and C. Mack. Oxygen toxicity; effects of oxygen 
breathing at increased ambient pressure upon pC02 of 
subcutaneous gas depots in men, dogs, rabbits and cats. 
J. appl. Physiol, 1953, 6: 358-368. 
2010. Marshall, J. R. and C. J. Lambertsen. Inter- 
actions of increased p02 and pC02 effects in producing 
convulsions and death in mice. J. appl. Physiol, 1961, 16: 
1-7. 
2011. Rennie, D. W. and J. R. Pappenheimer. 
Arterial oxygen pressure in dogs breathing oxygen at 2.5 
atmospheres pressure. Proc. Soc. exp. Biol, N.Y., 1958, 99: 
515-517. 
2012. Saltzman, H. A., L. J. Klein, A. Heyman, 
F. M. Mauney, W. W. Smith and I. W. Brown, Jr. 
Hemodynamic and cerebral effects of hyperbaric oxygena- 
tion. Circulation, 1963, 28: 796. 
2013. Schaefer, K. E. Studies of oxygen toxicity: 2. A 
warning sign of acute symptoms of oxygen toxicity. U.S. 
Navy. Submarine Base, New London, Conn. Medical re- 
search laboratory. Project NM 002 015.03.09, 4 August 1953, 
24 pp. 
2014. Schaefer, K. E. Oxygen toxicity studies in un- 
derwater swimming. J. appl. Physiol., 1955-56, 8: 524-531. 
2015. Taylor, D. W. Cardiac function in rats exposed 
to high oxygen pressures. J. Physiol., 1955, 128: 23 P. 
2016. Taylor, D. W. Changes in cardiac and respira- 
tory rates, and in carbon dioxide pressure and pH of 
arterial blood, in anesthetized rats exposed to oxygen 
under high pressures. J. Physiol., 1958, 143: 149-164. 
2017. Whitehorn, W. V. and J. W. Bean. Cardiac 
changes induced by Oz at high pressure, COa and 
low 02, as manifest by the electrocardiogram. Amer. J. 
Physiol., 1952,168: 528-537. 
5. EFFECTS ON THE BLOOD 
Taylor (2022) 1957, has shown that gross 
hemolysis occurs in vitamin E deficient rats ex- 
posed to 5.0 atmospheres of pure oxygen. Pro- 
tection against this hemolysis is given by to- 
copherols in large doses. 
Boerema, Meijne, Brummelkamp, Bouma, 
Mensch, Kamemans, Stem Hanf and Aalderen 
(2018) 1960, have shown in young pigs that the 
hemoglobin level can be lowered to a level of 0.4 
percent by exchanging blood for plasma. In this 
virtually hemoglobin-free state normal physio- 
logic functions are still possible if the animals 
are subjected to oxygen at 3.0 atmospheres in the 
high pressure tank. In such a situation most 
of the oxygen transport uses the mechanism of 
simple solution in the plasma. These animals 
could not live at normal atmospheric pressures 
but recovered uneventfully after re-infusion of 
normal blood. 
2018. Boerema, I., N. G. Meijne, W. H. Brummel- 
kamp, S. Bouma, M. H. Mensch, F. Kamemans, M. 
Stern Hanf and W. Van Aalderen. Life without blood. 
(A study of the influence of high atmospheric pressure 
and hypothermia on dilution of the blood.) J. cardiovasc. 
Surg., 1960,1: 133-146. 
2019. Mengel, C. E., H. E. Kahn and B. D. Horton. 
Studies of the hemolytic effect of in vivo hyperoxia. Clin. 
Res., 1964, 12: 60. 
2020. Mengel, C. E., H. E. Kahn, A. M. Lewis and 
B. D. Horton. Mechanisms of hemolysis induced by 
hyperoxia. Aerospace Med., 1964, 35: 271. 
2021. Mengel, C. E., H. E. Kahn, W. W. Smith 
and B. D. Horton. Effects of in vivo hyperoxia on eryth- 
rocytes. I. Hemolysis in mice exposed to hyperbaric 
oxygenation. Proc. Soc. exp. Biol. Med., 1964,116: 259. 
2022. Taylor, D. W. The effect of high oxygen pres- 
sures on the red cells of vitamin E-deficient and treated 
rats. J. Physiol., 1957, 135: 60P. 
6. EFFECTS ON RESPIRATION 
If oxygen is given to human subjects at sea 
level there is an initial transient reduction in OXYGEN INTOXICATION ABOVE ONE ATMOSPHERE—BLOOD AND TISSUE GAS 2023-2029 
ventilation which is supplanted within approxi- 
mately one minute to a moderate respiratory 
stimulation. Concurrently the slope of the ven- 
tilatory response to carbon dioxide inhalation 
decreases; therefore stimulant and depressant ef- 
fects of oxygen can exist together. It appears that 
the respiratory response to carbon dioxide is 
reduced more by oxygen inhalation at pressures 
of 2.0 and 3.0 atmospheres than at 1.0 atmos- 
phere. In spite of its depressant effects on mech- 
anisms of respiration normal subjects breathing 
oxygen at a pressure of 1.0 atmosphere or more 
show an overall increase in alveolar ventilation. 
This increase appears to be a result of the rise 
in central PCOo and hydrogen ion concentration 
and supervenes when high oxygen pressures inter- 
fere with carbon dioxide transport from the 
tissues. 
Lambertsen, Stroud, Gould, Rough, Ewing 
and Schmidt (2029) 1953, reported that breath- 
ing oxygen at 3.5 atmospheres lowered alveolar 
PCo., 6.7 mm. of Hg and produced an increase in 
respiratory minute volume of about 26 percent 
due to a greater tidal volume with no elevation 
in respiratory rate. There was a slight rise in 
carbon dioxide elimination. Breathing six per- 
cent oxygen (equivalent to 21 percent oxygen at 
sea level) at 3.5 atmospheres lowered the alveolar 
PCOo 1.3 mm. Hg as the only demonstrable effect, 
indicating that respiratory stimulation at in- 
creased ambient pressures is due to the oxygen 
and not to increased density of the inhaled gas. 
Breathing air at 3.5 atmospheres lowered the 
alveolar PCOo 2.5 mm. Hg and produced no other 
significant changes. The relation to oxygen tox- 
icity, the efficiency of alveolar ventilation at in- 
creased ambient pressure and the underlying 
causes of the respiratory stimulation by high in- 
spired oxygen tensions are discussed in this paper. 
The most likely cause of oxygen hyperpnea ap- 
pears to be central accumulation of carbon diox- 
ide resulting from decreased reduction of oxy- 
hemoglobin. 
2023. Albano, G. Fisiologia della respirazione in aria 
compressa. I. La meccanica ventilatoria. Ann. Med. Nav., 
1963, 68: 571-590. 
2024. Bondurant, S. and C. Smith. Effect of oxygen 
intoxication on the surface characteristics of lung extracts. 
Physiologist, 1962,5: 111. 
2025. Bornmann, R. C. The influence of increased 
pressures of oxygen upon the carbon dioxide — ventilation 
response curve. M.S. Thesis (Med.), University of Pennsyl- 
vania, 1963, 52 pp. 
2026. Burke, D. T. On oxygen poisoning under water. 
Med. J. Aust., 1961, 1: 693-694. 
2027. Dickson, J. and R. Bornmann. The degree of 
depression of respiratory reactivity to C02 in man by 1.0, 
2.0 and 3.0 atmospheres inspired P(,2. Fed. Proc., 1964, 23: 
279. 
2028. Lambertsen, C. J. Respiratory and circulatory 
actions of high oxygen pressure, pp. 25-38 in: Proceedings 
of the undenvater physiology symposium. Edited by L. G. 
Goff, National Research Council, Washington, D.C. N.R.C. 
Publication 3T7, 1955, 153 pp. 
2029. Lambertsen, C. J., M. W. Stroud, III, R. A. 
Gould, R. H. Rough, J. H. Ewing and C. F. Schmidt. 
Oxygen toxicity. Respiratory responses of normal men to 
inhalation of 6 and 100 per cent oxygen under 3.5 atmos- 
pheres pressure. J. appl. Physiol., 1953, 5; 487-494. 
7. EFFECTS ON BLOOD AND TISSUE GAS 
TENSIONS 
Breathing oxygen at high atmospheric pres- 
sures results in a rise in blood and tissue oxygen 
tensions. Bahnson and Matthews (2030) 1953, 
studied oxygen poisoning with gas bubble analy- 
sis plus arterial blood studies in rabbits and rats. 
During exposure to 1.0 atmosphere of oxygen 
there was no significant change in tissue oxygen 
and carbon dioxide until there was evidence of 
pulmonary damage and change in arterial gas 
content. At 7.0 atmospheres the carbon dioxide 
rose quickly to approximately 66 mm. Hg and 
was maintained for approximately 12-15 min- 
utes. After 15 minutes the Pc02 rose further. A 
change in the carbon dioxide combining power 
of the blood was demonstrated. According to 
Bean (2032) 1961, shifting from breathing air 
to oxygen at atmospheric pressure in dogs and 
cats caused a well maintained reversible increase 
of available oxygen in the tissues. Subsequent 
compression of the oxygen to as high as 80 psi 
caused a further prompt and more pronounced 
elevation in tissue oxygen which was maintained 
well above the pre-compression value throughout 
the period of exposure (20 to 45 minutes) and 
on to the onset of convulsive seizures. These 
changes were also reversible. Occasionally, in 
prolonged exposures, there was a late very grad- 
ual decline, especially where there was lung dam- 
age. Essentially similar results were obtained by 
using sodium pentobarbital. These experiments 2030-2036 
DISEASES AND ACCIDENTS 
involved continuous polarographic recordings 
from the brains of the animals anesthetized with 
morphine and urethane. These studies are re- 
ported in more detail by Bean (2031) 1961. A 
shift from breathing air to breathing oxygen at 
atmospheric pressure or at 5.0 atmospheres raised 
the availability of oxygen to the brain. Decom- 
pression reversed these effects. The author stated 
that cerebral vasoconstriction which may have 
occurred in oxygen under high pressure was ap- 
parently insufficient to prevent pronounced ele- 
vation of cerebral oxygen or to protect against 
oxygen toxicity. In simultaneous recordings from 
two regions of the brain the occurrence of cyclic 
changes, frequently out of phase, suggested the 
involvement of a reciprocating cerebral vascular 
control mechanism between different regions. Ad- 
dition of carbon dioxide to the OHP to give con- 
centrations of 0.8 to 1.7 percent usually raised the 
oxygen availability and tended to precipitate 
asynchronous cyclic oxygen changes. Apparently 
the vasculature does not necessarily react en 
masse to carbon dioxide. It is suggested that 
jugular venous blood is not a reliable index be- 
cause of wide variations in P0o, PCOo pH in 
circumscribed regions of the brain. Such regions 
may serve to precipitate manifestations of oxygen 
toxicity. Jamieson and Van Den Brenk (2034) 
1963, have measured brain and cerebrospinal 
oxygen tensions in rats breathing air or in var- 
ious high pressures of oxygen. Addition of five 
percent carbon dioxide to the inspired oxygen 
raised the cerebral oxygen tensions when the rats 
were exposed to 2.0 atmospheres or above. Lam- 
bertsen, Ewing, Rough, Gould and Stroud (2035) 
1955-56, found in four human subjects that addi- 
tions of two percent carbon dioxide to oxygen 
inhaled at 3.5 atmospheres caused an average 
increase of internal jugular venous P0„ of nearly 
1000 mm. Hg above the level found during the 
breathing of oxygen alone. The relation of this 
finding to changes in brain P0() and to oxygen 
toxicity are discussed. The authors propose that 
an increased tension of inspired carbon dioxide 
shortens the latent period of oxygen toxicity, 
not by direct action on brain cells, but indirectly 
through a cerebral vasodilatation and the result- 
ing rise in brain P09. The relationships of respira- 
tory minute volume to arterial and internal jug- 
ular venous blood Pco-) and pH during inhala- 
tion of low concentrations of carbon dioxide at 
1.0 atmosphere and oxygen at 3.0 atmospheres 
have been reported by Lambertsen, Rough, 
Cooper, Emmel, Loeschcke and Schmidt (2036) 
1953. During oxygen breathing at 3.0 atmos- 
pheres an average rise of 3 mm. Hg internal 
jugular P00o was accompanied by about a 30 per- 
cent increase in the respiratory minute volume. 
Average results obtained in eight men breathing 
0.0, 2.2, 4.3 and 5.5 percent carbon dioxide in 21 
percent oxygen at 1.0 atmosphere indicate that at 
about two percent inspired carbon dioxide there 
occurs a significant increase in the slope of the 
curves relating respiratory minute volume to 
arterial PCOo or pH and to internal jugular 
venous PCOo or pH. Above this region the re- 
spiratory minute volume versus PCo2 curves are 
essentially linear. The curve relating respiratory 
minute volume to arterial PCOo has a slope of 
1.26 liter/minute/m2/mm. Hg rise in PCOo, while 
the corresponding value for respiratory minute 
volume versus internal jugular Pco2 is 1-76. Ar- 
terial and venous curves therefore converge 
slightly with increasing ventilation, 
2030. Bahnson, H. T. and C. M. Matthews. Blood 
and tissue gases of animals exposed to one and seven 
atmospheres of oxygen and air. Amer. J. Physiol., 1953, 
775; 87-92. 
2031. Bean, J. W. Cerebral Oa in exposures to 02 
at atmospheric and higher pressure, and influence of C02. 
Amer. J. Physiol., 1961, 201: 1192-1198. 
2032. Bean, J. W. Brain P02 in exposures to 02 at 
high pressure (OHP). Fed. Proc., 1961, 20: 100. 
2033. Fuson, R. L., J. P, Boineau, W. W. Smith, 
H. A. Saltzman, M. Spach and I. W. Brown. Oxygen 
transport and acid base responses of cyanotic dogs to hy- 
perbaric oxygenation. Clin. Res., 1964,12: 182. 
2034. Jamieson, D. and H. A. S. Van Den Brenk. 
Measurement of oxygen tensions in cerebral tissues of rats 
exposed to high pressures of oxygen. J. appl. Physiol., 
1963, 18: 869-876. 
2035. Lambertsen, C. J., J. H. Ewing, R. H. 
Kough, R. Gould and M. W. Stroud. Oxygen toxicity. 
Arterial and internal jugular blood gas composition in 
man during inhalation of air, 100% Oa and 2% C02 at 3.5 
atmospheres ambient pressure. J. appl. Physiol., 1955, 8: 
255-263. 
2036. Lambertsen, C. J., R. H. Kough, D. Y. 
Cooper, G. L. Emmel, H. H. Loeschcke and C. F. 
Schmidt. Relationships of respiratory minute volume 
to arterial and internal jugular venous blood pC02 and 
pH during inhalation of low concentrations of CO, at 
one atmosphere and O, at 3.0 atmospheres. Fed. Proc., 
1953,12: 81. OXYGEN INTOXICATION ABOVE ONE ATMOSPHERE—METABOLISM 
2037-2040 
2037. Sonnenschein, R. R., S. N. Stein and P. L. 
Perot, Jr. Oxygen tension of the brain during hyperoxic 
convulsions. Amer. J. Physiol., 1953, 173: 161-163. 
8. EFFECTS ON THE ALIMENTARY TRACT 
Cross {2038) 1954, has studied the effects of 
increased atmospheric pressures and the inhala- 
tion of 95 percent oxygen and helium-oxygen 
mixtures on the viability of the bowel wall and 
the absorption of gas in closed-loop obstructions. 
The rate of diffusion of gas from closed-loop 
obstructions was increased by means of increased 
atmospheric pressure per se. The most satis- 
factory schedule for the absorption of gas from 
closed-loop obstructions in terms of maximal 
absorption in minimal time was the use of 95 
percent oxygen at 2.0 atmospheres pressure for 
six hours. This schedule resulted in the absorp- 
tion of 44.8 percent of the injected air. Oxygen 
intoxication became a significant factor in Cross’ 
studies in those dogs inhaling 95 percent oxygen 
when the pressure was increased above 2.0 at- 
mospheres in a six hour period and when the 
time of exposure extended beyond six hours at 
2.0 atmospheres pressure. Helium-oxygen mix- 
tures were not found to be an effective substitute 
for 95 percent oxygen, because helium diffused 
into the bowel as the nitrogen diffused out, 
thereby partially maintaining the distention of 
the closed loops. The viability of the bowel in 
closed-loop obstructions was well preserved for 
periods up to 92 hours by the use of increased 
atmospheric pressures. 
2038. Cross, F. S. The effect of increased atmospheric 
pressures and the inhalation of 95 per cent oxygen and 
helium-oxygen mixtures on the viability of the bowel wall 
and the absorption of gas in closed-loop obstructions. 
Surgery, 1954, 36: 1001-1026. 
2039. Cross, F. S. and O. H. Wangensteen. The 
effect of increased atmospheric pressures on the viability 
of the bowel wall in the absorption of gas in closed-loop 
obstruction. Surg. Forum, 1953, 4: 111. 
2040. Frittelli, G., E. S. Tank, W. F. Bernhard 
and R. E. Gross. A study of ileus under hyperbaric 
conditions. Surg. Forum, 1963,14: 376. 
9. EFFECTS ON METABOLISM 
For a good review of the toxic effects of oxygen 
on the metabolism of nervous tissue, a chapter 
by Dickens {2045) 1962, should be consulted. 
This excellent paper covers the early literature 
and some recent literature. The reader is re- 
ferred especially to the section on oxygen at 
pressures above one atmosphere, dealing with 
the toxic effect of oxygen on brain tissue and 
respiration. A comparison is given of the sen- 
sitivity of the brain to oxygen under high pres- 
sure with that of other tissues. There is a dis- 
cussion of the possible relationship between oxy- 
gen toxicity and irradiation effects, the effects 
of various hormones, vitamins and autonomic 
drugs on oxygen poisoning, as well as the toxic 
effects of oxygen on isolated enzyme systems and 
the possible role of hydrogen peroxide in oxygen 
poisoning. 
In referring to oxygen toxicity, consideration is 
often given primarily to effects on the nervous 
system and particularly to the development of 
convulsions. However, there may be earlier toxic 
effects in other tissues but the subtle changes in 
metabolism in these tissues may not be so readily 
recognized by behavioral and symptomatic mani- 
festations. Reference has been made to the effect 
that the latent period for convulsion develop- 
ment is shorter than that for enzyme inhibition 
to change metabolism in the test tube. This 
again may suggest that very subtle chemical 
changes can affect the electrical activity of the 
nervous system in its highly organized behavior. 
As Lambertsen has stated {Fundamentals of Hy- 
perbaric Medicine, Publication No. 1298, Na- 
tional Academy of Sciences, National Research 
Council, Washington, D.C., 1966, page 25), the 
effects of oxygen on membranes, not directly 
paralleled by changes in the oxidative metabo- 
lish of cell systems, are responsible for the con- 
vulsions. The discrepancy between in vitro and 
in vivo studies is seen by Lambertsen to be still 
more pronounced when it is recognized that at 
a given elevated ambient PDo the cells of an in 
vitro homogenate are exposed to a rather uni- 
form oxygen tension, whereas while only a very 
small portion of the cells in the brain of an in- 
tact animal are exposed to this high oxygen 
tension. 
As Sullivan and Bean {2057) 1957, have stated, 
the elevation of blood sugar in exposures to 
oxygen at high pressures (OHP) suggests that 
the protection afforded by hypophysectomy and 
adrenalectomy against OHP might be explained 
by an attendant lowering of blood sugar, espe- 
cially since the medullary factor (adrenalin) 
which elevates blood sugar was previously shown 
to enhance the oxygen toxicity as did insulin. DISEASES AND ACCIDENTS 
These authors therefore made an attempt to 
determine what effect preliminary elevation of 
blood sugar would have on the toxicity of oxygen 
under high pressure. Large mature male Sprague- 
Dawley rats were selected in pairs of one test 
and one control. The test rats were injected in- 
traperitoneally with 1 cc. of a 33 percent glucose 
solution; the controls were injected with 1 cc. of 
physiological saline. Blood sugars of test and 
control animals were then determined colori- 
metrically immediately before (and after) their 
exposure to oxygen at 90 pounds pressure for 
about 20 to 40 minutes. They were then decom- 
pressed in stages, sacrificed under pentothal 
anesthesia and the lungs were removed, grossly 
examined and weighed. It was found that in the 
test rats the neuromuscular reactions were more 
delayed in onset, fewer in number, less severe 
and the mortality less than in the controls, as 
was also the lung weight. It would appear to 
the authors therefore that elevation of glucose 
preceding exposure provides some protection 
against OHP and that the initial elevation of 
glucose induced by OHP is a part of a defense 
mechanism operating through the hypothalamus 
and sympathetics which when pushed too far 
becomes a liability, for reasons other than glu- 
cose changes alone. 
In a study on chemical mechanisms in oxygen 
toxicity Thomas and Neptune {2059) 1963, ex- 
amined the production of labeled carbon dioxide 
from labeled glucose using mitochondria from 
rat brain homogenates. The homogenates were 
fortified with DPN+, ATP, hexokinase, KC1 and 
Mg to stimulate maximum carbohydrate metab- 
olism. The experiment was carried out at 0.2, 
1.0 and at 5.0 atmospheres (absolute) and lasted 
30 minutes. Large increases in lactate were seen 
at 5.0 atmospheres, accompanied by large in- 
creases in pyruvate and a slight decrease in glu- 
cose utilization. The production of labeled car- 
bon dioxide was diminished at 5.0 atmospheres. 
The addition of the cofactors CoA and TPP did 
not alter the inhibition by increased oxygen, nor 
did high concentrations of catalase or GSH. The 
authors concluded that oxygen under high pres- 
sure inactivates enzyme systems. Two types may 
be concerned: 1) slow and irreversible inactiva- 
tion of certain enzymes where oxygen acts di- 
rectly on certain protein apoenzymes. This may 
be related to the slowly fatal and irreversible ef- 
fects of oxygen in vivo; 2) rapid and reversible 
inhibition of specific enzyme systems by the action 
of OHP on essential cofactors such as alpha 
lipoic acid related to reversible neurotoxic ef- 
fects in vivo. Oxidation of SH groups are usually 
involved. For a further study of the effect of 
high oxygen tensions upon enzymes a report by 
Haugaard (2054) 1955, should be consulted. The 
effects on phosphatase are described by Becker 
and Sutton (2044) 1963, and a possible method 
of action of oxygen poisoning is presented by 
Gerschman (2047) 1954. The author hypothe- 
sizes that the primary underlying mechanisms of 
oxygen poisoning are similar in principle to 
X-irradiation, viz., possibly formation of oxidiz- 
ing free radicals, OH, OaH and H202. Barron 
(2042) 1955, carried out experiments on the 
rate of oxidation by OHP of certain -SH com- 
pounds and other oxidation-reduction systems 
of biological interest. Nonprotein sulfhydrl 
groups (glutathione, cysteine, coenzyme A) were 
rapidly oxidized by oxygen, the rate being pro- 
portional to the oxygen pressure. The -SH groups 
of yeast alcohol dehydrogenase were also oxidized 
by OHP, and the enzyme activity was inhibited. 
The oxidation of unsaturated fatty acids, of 
hemoglobin and of dihydrodophosphopyridine 
nucleotid was not affected by OHP. The author 
postulated that the harmful effects of oxygen are 
due mainly to the oxidation of the -SH groups 
which are necessary for the cell activities. Gil- 
bert, Gerschman, Ruhm and Price (2055) 1957- 
58, have considered the production of hydrogen 
peroxide in solutions of glutathione exposed to 
oxygen. Gilbert, Gerschman and Fenn (2052) 
1956, have reported on the effects of OHP in in 
vitro systems. Exposure of DNA in the presence 
of reduced glutathione to OHP for about 12 
hours results in a viscosity decrease with a net 
formation of hydrogen peroxide. Further work 
has shown that when 3.26 mM of reduced glu- 
tathione per liter was exposed to 6.0 atmospheres 
for about 14 hours only about one-third was 
oxidized, but at 130 atmospheres oxygen no re- 
duced glutathione was detectable. It was of in- 
terest to the authors to investigate the effects of 
adding various agents which have been used in 
in vivo oxygen toxicity studies, to these in vitro 
systems. Thiourea was found to inhibit the net OXYGEN INTOXICATION ABOVE ONE ATMOSPHERE—METABOLISM 
2041-2058 
formation of hydrogen peroxide in reduced glu- 
tathione solutions exposed to OHP, and also re- 
strained the fall in viscosity produced by OHP 
in the DNA solution containing reduced glu- 
tathione. Thiourea also inhibits the viscosity 
decreases of DNA resulting from X-irradiation. 
In mice thiourea has been reported to protect 
against OHP and X-irradiation. EDTA, a known 
chelating agent, also prevents the fall in viscosity 
of solutions containing DNA and reduced glu- 
tathione when exposed to OHP. EDTA at a 
concentration of 0.3 micromoles/liter prevents 
the oxidation of reduced glutathione exposed to 
OHP, which would strongly indicate that its ac- 
tion is due to removal of trace metals. Yet to 
decrease oxidation of reduced glutathione 3 
millimols/liter diethyldithiocarbamic acid so- 
dium salt, another chelating agent, was necessary. 
The suggestion that some chelating agents may 
be free radical receptors should be given con- 
sideration, according to the authors, in attempt- 
ing to interpret these results. 
Studies by Gerschman, Gilbert and Frost 
(2048) 1958, upon paramecia have shown that 
treatment with cobalt chloride or with man- 
ganese chloride increases the survival times of 
these organisms at 9 atmospheres and decreased 
them at 2 atmospheres oxygen pressure. For an- 
other basic biological paper, a report by Falsetti 
(2046) 1959, may be consulted. This author 
found that oxygen at 8-12 atmospheres (abso- 
lute) depresses the transport of sodium ions 
across the isolated frog skin. The addition of 
8-10 atmospheres of nitrogen without oxygen 
deprivation had no such effect. These observa- 
tions are consistent with the idea that excess 
oxygen interferes with the normal activity of 
oxidative enzymes and inhibits sodium trans- 
port by diminishing the supply of enzymes avail- 
able for the purpose. 
2041. Barker, J., C. E. Quartley and E. R. Turner. 
Studies in the respiratory and carbohydrate metabolism of 
plant tissues. IX. Experimental studies of the influence of 
oxygen at high pressures on the respiration of apples and 
of a “block” in the tricarboxylic acid cycle induced by 
“oxygen poisoning.” Proc. roy. Soc., 1960, 152: 88-108. 
2042. Barron, E. S. G. Oxidation of some oxidation- 
reduction systems by oxygen at high pressures. Arch. Bio- 
chem. Biophys., 1955, 59: 502-510. 
2043. Becker, N. H. and B. F. Galbin. Effect of 
oxygen rich atmospheres on cerebral lipid peroxides. 
Aerospace Med., 1962, 33: 985. 
2044. Becker, N. H. and C. H. Sutton. The his- 
tochemical effects of oxygen at high pressures, pp. 152- 
165 in: Second symposium on underwater physiology. 
Edited by C. J. Lambertsen and L. J. Greenbaum, Jr. 
National Research Council, Washington, D.C. N.R.C. 
Publication 1181, 296 pp. 
2045. Dickens, F. The toxic effect of oxygen on 
nervous tissue, pp. 851-869 in: Neurochemistry. Edited by 
K.A.C. Elliott, I. H. Page and J. H. Quastel. C. C. Thomas, 
Springfield, 1962, 1035 pp. 
2046. Falsetti, H. Effect of oxygen tension on sodium 
transport across isolated frog skin. Proj. Soc. exp. Biol., 
N.Y., 1959, 101: 721-722. 
2047. Gerschman, R. Oxygen poisoning and x-irradia- 
tion: a mechanism in common, pp. 288-291 in Glutathione. 
Edited by S. P. Colowick. Academic Press, Inc., New York, 
1954,341 pp. 
2048. Gerschman, R., D. L. Gilbert and J. N. 
Frost. Sensitivity of Paramecium Caudatum to high oxy- 
gen tensions and its modification by cobalt and manganese 
ions. Amer. J. Physiol., 1958, 192: 572-576. 
2049. Gerschman, R., D. L. Gilbert, S. W. Nye, P. 
Dwyer and W. O. Fenn. Oxygen poisoning and x-ir- 
radiation: a mechanism in common. Science, 1954, 119: 
623-626. 
2050. Gilbert, D. L. The role of pro-oxidants and 
anti-oxidants in oxygen toxicity. Radiat. Res., 1963, 3: 44. 
2051. Gilbert, D. L., R. Gerschman, J. Cohen and 
W. Sherwood. The influence of high oxygen pressures 
on the viscosity of solutions of sodium desoxyribonucleic 
acid and of sodium alginate. J. Amer. chem. Soc., 1957, 79: 
5677. 
2052. Gilbert, D. L., R. Gerschman and W. O. 
Fenn. Effects of high oxygen pressure (HOP) in in vitro 
systems. Fed. Proc., 1956,15: 73. 
2053. Gilbert, D. L., R. Gerschman, K. B. Ruhm 
and W. E. Price. The production of hydrogen peroxide 
by high oxygen pressures. J. gen. Physiol., 1957, 41: 989- 
1003. 
2054. Haugaard, N. Effect of high oxygen tensions 
upon enzymes, pp. 8-12 in: Proceedings of the underwater 
physiology symposium. Edited by L. G. Goff, National Re- 
search Council, Washington, D. C. N.R.C. Publication 377, 
1955, 153 pp. 
2055. Haywood, C., H. C. Hardenberg, Jr. and 
E. N. Harvey. The effect of increased pressures of oxygen 
upon the luminescence of achromobacter fischeri. J. cell, 
comp. Physiol., 1956, 47: 289-293. 
2056. Jamieson, D. and H. A. S. Van Den Brenk. 
Pulmonary damage due to high pressure oxygen breath- 
ing in rats. 2. Changes in dehydrogenase activity of rat 
lung. Aust. J. exp. Biol. med. Sci., 1962, 40: 51-56. 
2057. Sullivan, L. P. and J. W. Bean. Blood glucose 
in exposures to oxygen at high pressures. Fed. Proc., 1957, 
16: 125. 
2058. Tanaka, R., M. Fujimori and R. W. Virtue. 
Oxygen utilization by dogs after administration of potas- 
sium perchlorate, during hypothermia, and at a pressure 
of 2 atmospheres. Anesthesiology, 1961, 22: 20-23. 2059-2061 
DISEASES AND ACCIDENTS 
2059. Thomas, J. J., Jr. and E. M. Neptune, Jr. 
Chemical mechanisms in oxygen toxicity, pp. 139-151 in: 
Second symposium on underwater physiology. Edited by 
C. J. Lambertsen and L. J. Greenbaum, Jr. National Re- 
search Council, Washington, D.C. N.R.C. Publication 
1181, 1963, 296 pp. 
2060. Thomas, J. J., Jr., E. M. Neptune, Jr. and 
H. C. Sudduth. Carbohydrate metabolism in rat brain 
under high oxygen pressure (HOP). XXII Inter. Congr. 
physiol. Sci., Leiden. 1962, 2: Abstr. 354. 
2061. Wood, J. D. and W. J. Watson. Gamma-amino 
butyric acid levels in the brain of rats exposed to oxygen 
at high pressure. Canad. J. Biochem. Physiol., 1963, 41: 
1907. 
10. EFFECTS ON THE ENDOCRINE SYSTEM 
Bean (2062) 1952, and Bean and Johnson 
(2067) 1952, exposed young adult albino rats, 
hypophysectomized and controls, repeatedly to 
oxygen at 70-90 pounds pressure for short pe- 
riods (3 to 20 minutes) once or twice daily for 
several days or weeks. Carbon dioxide was con- 
tinuously removed from the chamber using soda 
lime. The temperature was held at that approxi- 
mately of the room and decompression was such 
as to avoid bubble formation. Although there 
was some individual variation, the data showed 
that hypophysectomy definitely delayed the onset 
and decreased the severity of the acute neuro- 
muscular response and of the convulsive seizures 
induced by oxygen under high pressure (OHP). 
The severity of chronic motor paralysis, com- 
monly induced by repeated exposure to OHP, 
was reduced or completely eliminated. Dyspnea 
was much less severe and the mortality dimin- 
ished. Hypophysectomy provided marked pro- 
tection against pulmonary damage by OHP. 
Lungs of control animals succumbing to OHP 
commonly showed severe damage, hemorrhage, 
congestion and a liver-like appearance in parts 
or all of the lung, which frequently sank in water; 
whereas those of hypophysectomized animals sac- 
rificed under anesthesia were much less severely 
affected, some remaining entirely clear despite 
a much more rigorous exposure to OHP. Low- 
ered metabolism may explain in part the delayed 
onset of acute neuromuscular reactions in the 
hypophysectomized animals, but their greater 
resistance to chronic effects of oxygen poisoning 
such as motor paralysis and lung damage, accord- 
ing to the authors, are not satisfactorily explained 
on this basis. 
OHP if prolonged and repetitive causes cer- 
tain cytological alterations of the adrenal cortex. 
Bean, Baker and Johnson (2065) 1953, found 
that single exposures of short duration to oxygen 
at 5.0 atmospheres induced very little change in 
the adrenals of rats. More prolonged and repeti- 
tive exposures caused distinct changes roughly 
paralleling the increased glandular weight, but 
considerable variation in the magnitude of the 
change was observed. The zona fasciculata was 
thickened, its constituent cells hypertrophied and 
its lipid content reduced. The adrenal cortices of 
those rats exhibiting residual paralyses were af- 
fected most, the outer portion of the zona fasci- 
culata being completely devoid of large lipid 
droplets, although many fine sudanophilic bodies 
remained which probably were mitochondria. 
Lipid depletion and cell hypertrophy were pres- 
ent to a lesser degree in the zona reticularis. The 
zona glomerulosa was not significantly affected. 
The histological picture was characteristic of 
that induced by nonspecific stress and the proce- 
dure used did not reveal any change which might 
be considered peculiar to OHP administration. 
Bean (2063) 1955, has shown that hypophysec- 
tomy, rather than intensifying the adverse re- 
action to OHP, diminished the reaction. The 
number of reactions in hypophysectomized rats 
injected with ACTH was twice as great as those 
that were not injected, and about equal to those 
of unoperated control animals. Corticotropin 
and adrenal cortical hormones augment the pul- 
monary damage inflicted by OHP but are not es- 
sential to the precipitation of injury by oxygen. 
Adrenalin also enhances the toxic effect of OHP, 
particularly of pulmonary damage and of per- 
manent motor disabilities, in both adrenalec- 
tomized and non-operated animals. Pulmonary 
edema and hemorrhage induced by OHP in the 
intact animal are to some degree of nerogenic 
origin, via the hypothalamus and sympathetico- 
adrenal system, including an increased secretion 
of adrenalin and nerve discharge to the thoracic 
visera and to the lungs themselves. Sympathetic 
blocking agents afford some protection against 
OHP. The augmentation of the toxic effects of 
OHP by either endogenous or exogenous carbon 
dioxide is believed to be in large part of central 
origin, possibly within the hypothalamus. Any 
hormone that increases metabolism may augment OXYGEN INTOXICATION ABOVE ONE ATOMSPHERE—BODY TEMPERATURE 
2062-2073 
the toxic reaction via increased oxygen produc- 
tion. Increased metabolism induced by adrenalin 
may entail an increased utilization of cortical hor- 
mones and subsequent release of ACTH, etc. 
Adrenalin may also directly act on the hypothala- 
mus and through the hypophyseal-adrenal sys- 
tem release increased quantities of adreno-cortical 
factors. Such hormones as thyroid and adrenalin 
may act directly on the vascular bed. Oxygen un- 
der high pressure increased capillary permeability 
with hemorrhage, congestion, edema and loss of 
proteins. Repeated exposure of young rats and 
baby chicks to OHP induces permanent motor 
disability, decreased growth, altered higher func- 
tions of the central nervous system and adversely 
affects the visual retina. These studies are also 
discussed by Bean, Johnson and Smith (2068) 
1954. Gerschman and Fenn (2070) 1954, have 
found a decrease in the concentration of ascorbic 
acid in the adrenal glands of rats exposed to 
OHP, and this is taken as evidence that this type 
of stress may cause enhanced secretion of hor- 
mones from the adrenal cortex. Taylor has re- 
ported on effects of high oxygen on adrenalec- 
tomized, treated and untreated rats (2072) 1954. 
Two groups of rats (one unoperated, the other 
bilaterally adrenalectomized) were divided into 
subgroups and treated respectively with DOCA, 
cortisone (1 mg./100 gm. body wg.), thyroid 
(10 mg./lOO gm, body wgt. orally), adrenalin 
(single injection = 0.05 mg./rat subcutaneously) 
and adrenalin in combination with each of the 
other three substances, for seven days prior to 
exposure. Each of these groups also contained 
an untreated group. The animals were exposed 
for 14 days after operation to oxygen at 6.0 at- 
mospheres and convulsion times were determined. 
The effect of adrenalectomy was significant (con- 
vulsion time 53 minutes as compared with 38.3 
minutes, P < 0.0001) . In unoperated rats thy- 
roid reduced the convulsion time (P < 0.01) in 
agreement with previous work. This was not ap- 
parent in operated rats. The only other signifi- 
cant effect (P < 0.05) was the interaction of 
cortisone with the operation; the convulsion time 
being reduced in unoperated and increased in 
operated animals. DOCA treated animals showed 
a rather low convulsion time and a severe degree 
of lung damage, and although the latter was not 
considered significant it was observed that a 
deleterious effect might be concealed by the vari- 
ability of the whole group. Thirty-two adren- 
alectomized rats were also exposed for 50 min- 
utes. Those convulsing were rejected; the rest 
were divided into groups of seven with one being 
treated with DOCA and the other left untreated. 
On re-exposure there was no difference between 
the groups either in convulsion time or in the 
degree of lung damage. 
2062. Bean, J. W. (The hypophysis as a determinant 
in the reaction of the mammal to oxygen at high pressure. 
Amer. J. Physiol, 1952, 170: 508-517. 
2063. Bean, J. W. Hormonal aspects of oxygen toxicity, 
pp. 13-19 in: Proceedings of the underwater physiology 
symposium. Edited by L. G. Goff, National Research Coun- 
cil, Washington, D.C. N.R.C. Publication 377, 1955, 153 pp. 
2064. Bean, J. W. Tris buffer, C02, and sympatho- 
adrenal system in reactions to Oz at high pressure. Amer. 
J. Physiol, 1961, 201: 737-739. 
2065. Bean, J. W., B. L. Baker and P. Johnson. 
Cytological alterations of adrenal cortex induced by 
oxygen at high pressure. Fed. Proc., 1953, 12: 11. 
2066. Bean, J. W. and R. Bauer. Thyroid in pul- 
monary injury induced by 02 in high concentration at 
atmospheric pressure. Proc. Soc. exp. Biol, N.Y., 1952, 81: 
693-694. 
2067. Bean, J. W. and P. Johnson. Hypophyseal 
involvement in response to 02 at high pressure. Fed. Proc., 
1952,11: 9. 
2068. Bean, J. W., P. Johnson and C. W. Smith. 
Adrenocortical and medullary factors in 02 at high pres- 
sure. Fed. Proc., 1954,13: 9. 
2069. Bean, J. W., P. Johnson, C. Smith and R. 
Bauer. Effects of thyroid and insulin on the pulmonary 
reaction to oxygen. Fed. Proc., 1953, 12: 12. 
2070. Gerschman, R. and W. O. Fenn. Ascorbic 
acid content of adrenal glands of rat in oxygen poisoning. 
Amer. J. Physiol, 1954, 176: 6-8. 
2071. Gerschman, R. and P. W. Nadig. Stress and 
oxygen poisoning. Fed. Proc., 1953, 12: 50. 
2072. Taylor, D. W. Effects of high oxygen on 
adrenalectomized, treated and untreated rats. J. Physiol, 
1954, 125: 46-47P. 
2073. Taylor, D. W. Effects of adrenalectomy on 
oxygen poisoning in the rat. J. Phsyiol, 1958, 140: 23-36. 
11. EFFECTS OF BODY TEMPERATURE 
It appears that lowering of body temperature 
has an effective action against high oxygen pres- 
sure toxicity and that this action is mostly be- 
cause of reduced metabolic rate. This has been 
demonstrated by Popovic, Gerschman and Gil- 
bert {2074) 1964, who exposed hibernating 
ground squirrels to 6.0 atmospheres of oxygen. 
These animals survived this condition for 18 
hours. Hypothermic squirrels endured the con- DISEASES AND ACCIDENTS 
2074-2075 
dition for six hours or more and euthermic 
animals endured it for only one-half hour. The 
oxygen consumption was respectively in the pro- 
portion of 1:12:40 (with survival times showing 
an inverse relationship as noted). 
2074. Popovic, V., R. Gerschman and D. L. Gil- 
bert. Effect of high oxygen pressure on ground squirrels 
in hypothermia and hibernation. Amer. J. Physiol., 1964, 
206: 49-50. 
12. EFFECTS ON THE KIDNEYS 
Rennie and Knox {2075) 1962, have observed, 
incidental to other studies, that oxygen breath- 
ing at high ambient pressures reduces renal 
blood flow but not glomerular filtration rate. 
The observations provide evidence for the de- 
pendency of renal oxygen consumption (V0o) 
upon sodium reabsorption rather than upon 
renal blood flow. 
2075. Rennie, D. W. and F. G. Knox. Renal blood 
flow, 02 consumption and sodium reabsorption during 02 
breathing at high ambient pressure. Physiologist, 1962, 5: 
200. 
13. TOLERANCE 
In general it is known that oxygen tolerance at 
rest at 60 feet exceeds the limits for “no de- 
compression” diving at the same depth. No in- 
formation is available regarding resting oxygen 
tolerance between a depth of 60 feet of sea water 
and sea level (where the oxygen tolerance of the 
central nervous system is known to be at least 
24 hours). Exercise reduces the tolerance. Con- 
vulsions may be seen as early as 40 minutes at 
35 feet. One of the great deficiencies of informa- 
tion in mixed gas or oxygen diving is the limit 
of oxygen tolerance while exercising at depths 
between 30 and 20 feet. Some information in- 
dicates that toxic effects do not occur at these 
depths with exposures as long as one and two 
hours respectively. There is as yet no indication 
whether oxygen toxicity can be produced at these 
pressures with normal levels of underwater ac- 
tivity {2090) 1956. 
Taylor {2088) 1953, has pointed out that all 
who have studied the problem of oxygen toxicity 
agree that the metabolic condition of the experi- 
mental animal at the time of exposure bears im- 
portantly on the time of onset of toxic manifesta- 
tions. In an experimental study of the effect of 
vitamin E deficiency on oxygen toxicity, Taylor 
divided 28 rats into two groups each containing 
eight males and 6 females. Both groups were 
from the time of weaning given the same basic 
artificial diet with 20 percent casein and designed 
to contain negligible amounts of vitamin E. 
Animals in the first group were given in addi- 
tion 5 mg. of alpha-tocopheryl acetate orally 
twice weekly. When nine months old all the 
rats were exposed to 5.0 atmospheres of oxygen 
(approximately 98 percent oxygen) for a stand- 
ard period of 50 minutes during the whole of 
which they were under direct observation. In the 
first group convulsions were observed in only 
four animals while all 14 in the second group 
convulsed. In the first group only one animal 
died, but in the second group there was only one 
survivor. Both of these differences are highly 
significant (P < 0.01 and 0.001 respectively). 
Autopsy was performed on all animals to assess 
lung damage which was arbitrarily classified into 
four degrees of severity. First impression seemed 
to indicate greater damage in the deficient an- 
imals, three of which showed damage of the 
most severe grade, as opposed to none in the 
control (second) group, but the overall differ- 
ences were not significant. There was no macro- 
scopic or microscopic liver damage. There seems 
to be no immediate fundamental explanation of 
these results other than such a postulate as en- 
hanced toxicity from some abnormal metabolic 
formation or increase in normal cell metabolism 
in the absence of vitamin E (known to be a tissue 
anti-oxidant). Taylor has also studied the ef- 
fects of methylene blue and glutathione on the 
manifestations of oxygen poisoning in vitamin E 
deficient rats (2089) 1958. As stated above, vita- 
min E deficient rats showed a decreased resistance 
to the effects of oxygen on the central nervous 
system when compared with rats treated with 
alpha-tocopheral acetate. Methylene blue and 
glutathione had smaller but definite protective 
effects. Lung damage was less in rats given 
alpha-tocopherol acetate or glutathione than in 
those given methylene blue or no supplement. 
Survival rates were high in rats maintained on 
alpha-tocopherol acetate and large doses of 
gamma tocopherol. All vitamin E deficient un- 
treated rats exhibited hemolysis in vivo following 
exposure to abnormally high oxygen pressures. 
Tocopherol in any but the smallest doses gave OXYGEN INTOXICATION ABOVE ONE ATMOSPHERE—TOLERANCE 
2076-2085 
complete protection; glutathione gave some pro- 
tection; methylene blue gave no protection (ex- 
cept in four animals exposed to pure oxygen at 
atmospheric pressure). Hemolysis was greater in 
the male than in the female animals. 
In a study of the effect of various substances 
on the survival time of mice exposed to different 
high oxygen tensions, Gerschman, Gilbert and 
Caccamise (2081) 1958, exposed mice to various 
pressures of oxygen up to 10 atmospheres (at 
which level there was a minimum survival time 
of 19 minutes). Cystamine, reduced glutathione 
and thiourea had a dertimental effect at 1 or 1.5 
atmospheres but protected mice at 6.0 atmos- 
pheres. Cystamine and oxidized glutathione did 
not protect at 1.0 atmosphere, but gave protec- 
tion at 6.0 atmospheres of oxygen. DEDTC (di- 
ethyldithiocarbamic acid sodium salt) increased 
the survival time of mice in 6.0 atmospheres of 
oxygen. Trihydroxyphenone antioxidants showed 
some protective effect against oxygen toxicity 
in mice exposed to 6.0 atmospheres of oxygen. 
The results provided by these authors are not 
inconsistent with the notion of a possible com- 
mon mechanism between oxygen poisoning and 
X-irradiation. The action of any given agent was 
found to depend upon the oxygen pressures to 
which the animals were exposed. 
Gerschman, Gilbert, Nye and Fenn (2083) 
1956, have studied the sensitivity of paramecium 
caudatum to oxygen toxicity as influenced by 
cobaltous and manganous ions and hematopor- 
phyrin. Cobaltous chloride was protective at 
5-20 atmospheres but injurious at 1-4 atmos- 
pheres; manganous chloride was protective at 9.0 
atmospheres, but appeared detrimental at 2.0 
atmospheres. Hematoporphyrin was detrimental 
at 9.0 atmospheres. These experiments empha- 
sized the importance of studying the effects of 
given agents at different pressures of oxygen as 
well as at different intensities of radiation. 
In a study of the anticonvulsant threshold of 
carbon dioxide in oxygen under high pressure, 
Chapin (2078) 1955, exposed 68 mice to 5.0 at- 
mospheres of oxygen. All mice receiving only 
oxygen convulsed; all mice receiving less than 
120 mm. PCOo in oxygen convulsed also. Fifty per- 
cent of the mice receiving 120 mm PCOo in oxygen 
convulsed and the rest died without convulsion. 
Only one out of 17 mice receiving more than 
120 mm. PCOo convulsed. Mice receiving oxygen 
diluted with carbon dioxide convulsed sooner 
than mice receiving pure oxygen. The amount 
of shortening of convulsion time did not appear 
to be dependent upon the amount of carbon 
dioxide diluting the oxygen as long as the PCo2 
lay in the range of 27-120 mm. The tension at 
which carbon dioxide becomes anticonvulsant 
appears to be about 120 mm. (16 percent at 1 
atmosphere). 
Walker (2092) 1961, has also examined the 
question of involvement of carbon dioxide in 
the toxicity of oxygen at high pressure. He con- 
cluded that mice adapted to an atmosphere high 
in carbon dioxide (10-20 percent) are more re- 
sistant to the convulsive effects of oxygen at 6.0 
atmospheres pressure than are untreated mice, 
but that long term adaptation to 20 percent car- 
bon dioxide is in itself debilitating and negates 
the positive results. Increased tolerance may be 
essentially increased ability to withstand effects 
of carbon dioxide transport interference. 
2076. Bean, J. W. (Reserpine and reaction to 02 at 
high pressure. Fed. Proc., 1956, 15: 11. 
2077. Cerchia, M. M. F., P. Mantegazzini and 
M. Parma. Epilessia iperossica e farmaci antiepilettici. 
Ann. Med. Nav. Trap., 1956, 61: 244-253. 
2078. Chapin, J. L. Anticonvulsant threshold of C02 
in oxygen under high pressure. Proc. Soc. exp. Biol. N.Y., 
1955, 90: 663-664. 
2079. Galston, A. W. and S. M. Siegel. Antiperoxi- 
dative action of the cobaltous ion and its consequences for 
plant growth. Science, 1954, 120: 1070-1071. 
2080. Gerschman, R. The biological effects of in- 
creased oxygen tension, pp. 171-179 in: Man’s dependence 
on the earthly atmosphere. Edited by K. E. Schaefer. The 
MacMillan Company, New York, 1962, 416 pp. 
2081. Gerschman, R., D. L. Gilbert and D. Cacca- 
mise. Effect of various substances on survival times of mice 
exposed to different high oxygen tension. Amer. J. Physiol., 
1958, 192: 563-571. 
2082. Gerschman, R., D. L. Gilbert, S. W. Nye and 
W. O. Fenn. Role of antioxidants and of glutathione 
in oxygen poisoning. Fed. Proc., 1955,14: 56. 
2083. Gerschman, R., D. L. Gilbert, S. W. Nye 
and W. O. Fenn. Sensitivity of paramecium caudatum 
to oxygen toxicity as influenced by cobaltous and manga- 
nous ions and hematoporphyrin. Fed. Proc., 1956, 15: 72. 
2084. Gilbert, D. L., R. Gerschman and W, O. 
Fenn. Effects of fasting and x-irradiation on oxygen 
poisoning in mice. Amer. J. Physiol., 1955,181: 272-274. 
2085. Gottlieb, S. F, and R. B. Jagodzinski. Role 
of THAM in protecting mice against convulsive episodes 
caused by exposure to oxygen at high pressure. Proc. Soc. 
exp. Biol., N.Y., 1963, 112: 427. 2086-2093 
DISEASES AND ACCIDENTS 
2086. Hempleman, H. V. Effect of pre-exposure to 
carbondioxide upon resistance to acute oxygen poisoning 
in the rat. Gt. Brit. MRC, RNPRC, UPS. Kept. R.N.P. 
56/860, U.P.S. 156, March 1956, 5 pp. 
2087. Kahn, H. E., Jr., C. E. Mengel, W. W. Smith 
and B. D. Herton. Oxygen toxicity and vitamin E. 
Aerospace Med., 1964, 35: 275. 
2088. Taylor, D. W. Effects of vitamin E deficiency 
on oxygen toxicity in the rat. J. Physiol., 1953, 121: 47P- 
48P. 
2089. Taylor, D. W. Effects of tocopherols, methylene 
blue and glutathione on the manifestations of oxygen 
poisoning in vitamin E deficient rats. J. Physiol., 1958, 140: 
37-47. 
2090. U.S. NRC. Oxygen, pp. 5-7 in: Status of research 
in underwater physiology. U.S. NRC-CUW, Kept. 468, 
March 1956, 24 pp. 
2091. Van Den Brenk, H. A. and R. Moore. Effect 
of high oxygen pressure on the protective action of cysta- 
mine and 5-hydroxytryptamine in irradiated rats. Nature 
Lond., 1959, 183: 1530-1531. 
2092. Walker, I. G. The involvement of carbon 
dioxide in the toxicity of oxygen at high pressure. Canad. 
J. Biochem. Physiol., 1961, 39: 1803-1809. 
14. EFFECTS ON PERFORMANCE 
Frankenhaeuser, Graff-Lonnevig and Hesser 
(2093) 1960, tested four women and six men for 
psychomotor performance during exposure to 
oxygen at 3.0 atmospheres as compared to 1.0 
atmosphere. The subjects had tasks including a 
visual choice reaction time (three colored light 
signals to which subjects respond by closing a 
switch) ; a visual simple reaction time (one light 
in response to which the subject closed one 
switch) ; and a mirror drawing (moving a stylus 
along a slit cut out in a metal plate creating 
a star). It was found that there was no systematic 
change in performance level, nor did the per- 
formance deteriorate when the time was increased 
to 30 minutes. The authors state that these tasks 
had proven to be an effective measurement in 
other experiments. Breathing pure oxygen at 3.0 
atmospheres was considered safe up to two hours, 
but at 4.0 or more atmospheres the risk of con- 
vulsions increases rapidly. One subject did con- 
vulse after 17 minutes and yet there was no de- 
terioration in performance prior to the seizure. 
2093. Frankenhaeuser, M., V. Graff-Lonnevig and 
C. M. Hesser. (Psychomotor performance in man as 
affected by high oxygen pressure (3 atmospheres). Acta 
physiol, scnnd. 1960, 50: 1-7. 
15. PATHOLOGICAL EFFECTS 
In laboratory animals severe pulmonary dam- 
age usually results from long exposure to oxygen 
under moderate pressure (Penrod (2098) 1956). 
The extent to which human lungs are damaged 
by similar exposures is not well known. There is 
reason to believe, in small animals at least, that 
lung damage and the central nervous system 
effects produced by oxygen under high pressures 
have separate etiologies. Evidence has been ob- 
tained that the principle factor involved in the 
pulmonary pathology is atelectasis which chiefly 
results from isolation of the areas due to exces- 
sive secretions in the small airways. The processes 
of atelectasis can be delayed or partially reversed 
by a number of procedures such as periodic posi- 
tive pressure insufflation, intermittent exposure 
to an inert gas (such as nitrogen or helium), 
or by induced positive pressure breathing. Pen- 
rod has developed these points further (2099) 
1956, where he has pointed out that when one 
bronchus is cannulated and the other is blocked 
prior to exposure of an animal to oxygen at high 
pressure, the obstructed portion of the lung 
shows massive congestion and complete atelecta- 
sis. The gross appearance is not unlike that 
usually seen in the lungs of laboratory animals 
exposed for long periods to oxygen at high pres- 
sure. They respond, however, as do lungs 
damaged by high oxygen pressure, to tracheal 
insufflation by dramatically regaining their 
original pink healthy color and consistency. The 
author presents reasons for believing that a major 
cause of the pulmonary damage produced by 
high oxygen pressures is simple atelectasis result- 
ing from blockade of the smaller airways with 
resultant absorption of the gases peripheral to the 
obstruction; the process is reversible as can be 
shown by forcibly inflating the collapsed alveo- 
lar areas. The author further believes that the 
hormonal influences on pulmonary damage in 
high oxygen pressures are mediated through an 
influence on the patency of the distal airways. 
For further studies Penrod’s paper (2101) 1958, 
should also be consulted. Jamieson and Van 
Den Brenk (2097) 1962, and Van Den Brenk 
and Jamieson (2103) 1962, have studied pulmo- 
nary damage in rats due to high pressure oxygen 
breathing. Changes in lung weights, histology OXYGEN INTOXICATION ABOVE ONE ATMOSPHERE—PATHOLOGICAL 
and bronchographic appearances are recorded 
in rats subjected to oxygen at 60 psi (gauge). 
Capillary congestion, progressing to alveolar 
exudation and hemorrhage was the earliest ob- 
servable change. The results failed to support a 
postulate that lung damage due to oxygen poison- 
ing is primarily an atelectasis due to bronchial 
obstruction. Positive pressure inflation of the 
lungs immediately post mortem did not reverse 
oxygen damage. Heparinization of rats was also 
without effect upon such damage. Exposure of 
lung tissue in vitro to 100 psi (gauge) of oxygen 
for five hours failed to cause changes similar to 
those observed for lungs exposed in vivo to oxy- 
gen under high pressure. Jamieson and Van 
Den Brenk used the Evans blus dye technique to 
determine increases in capillary permeability in 
the lungs of rats subjected to pure oxygen under 
pressure at 60 psi (gauge). Considerable leakage 
of plasma during OHP was found. Hemoglobin 
in lung tissue was also increased remarkably 
during OHP. Zagorskii {2105) 1960, produced 
oxygen intoxication in five adult cats and dogs by 
breathing oxygen under a higher than ambient 
pressure. Histological analysis of the nervous 
system showed most pronounced changes in the 
cerebellum, in the optic thalami and in the 
caudal spinal cord sections. There were marked 
peripheral changes in the sensory neurones of the 
spinal and cranial sensory ganglia. The character 
of these changes supported the hypothesis that 
tissue hypoxia caused by the angiospastic action 
of increased partial pressure of oxygen in the 
blood is one cause of oxygen poisoning. A study 
by Edstrom and Rockert (2095) 1962, exposed 
rats to oxygen at 6.0 atmospheres daily for about 
eight weeks in one series and for about four 
weeks in a second series. The exposure times 
were so adapted as to give a low incidence of 
convulsions and lung symptoms. The animals 
did not show any evidence of lung damage at 
autopsy. Slight motor symptoms of a paralytic 
nature developed in some rats of the first series 
after about two weeks. Symptoms regressed dur- 
ing continuation of treatment and had disap- 
peared after five weeks. Histological investiga- 
tion of the nervous system after seven to nine 
weeks showed no degeneration. Rats of the sec- 
ond series showed no neurogenic symptoms. His- 
tologically there was an increase in the size of 
the nucleolus of neurons of the stellate ganglion 
and of the adrenal medulla. In both series there 
was a decrease in the weight with thickening 
of the zona fasciculata. 
Pathological processes have been summarized 
by Lambertsen (Fundamentals of Hyperbaric 
Medicine, Publication No. 1298, National Acad- 
emy of Sciences, National Research Council, 
Washington, D.C., 1966, page 29). He points out 
that no specific measures are known to provide 
a rational basis for treating cells damaged by the 
toxic processes. Given severe central nervous sys- 
tem effects and sustained convulsive or neurologi- 
cal damage, these sequelae should be managed 
as other forms of convulsion or central nervous 
system injury. Until more extensive study of the 
general pathology of the central nervous system 
oxygen toxicity has been carried out recommenda- 
tions for other than supportive treatment are 
not likely to be significant. Lambertsen also 
calls attention to damage of the lungs leading 
to diffuse atelectasis, pulmonary edema and 
bronchial pneumonia. Because death results 
from failure of pulmonary gas exchange such 
measures as artificial respiration and prophylactic 
use of antibiotics are only of aid to the less 
seriously injured individual. In selecting the gas 
for lung ventilation, a concentration of oxygen 
not exceeding 60 percent at sea level is the gas 
of choice (because higher tensions of oxygen 
might presumably aggravate the existing pulmo- 
nary condition). Should the lungs of a patient 
have been so severely affected by pulmonary oxy- 
gen poisoning that an anoxemia develops, even 
at inspired oxygen pressures of several atmos- 
pheres, a quandery will exist that will certainly 
end only with the death of the patient. Treat- 
ment by lowering the oxygen pressure will result 
in further anoxemia; treatment of anoxemia with 
oxygen at normal or higher pressures will result 
in further damage. Thus if such mechanical 
approaches of the use of the heart-lung machine 
for extrapulmonary oxygenation are ignored as 
being impractical, no approach to the reversal 
of severe pulmonary damage appears feasible at 
this time. On this basis the pulmonary limits 
of oxygen tolerance deserve the most serious at- 
tention in therapy wih high oxygen pressures, as 
Lambertsen has pointed out. 2094-2105 
DISEASES AND ACCIDENTS 
2094. Beehler, C. C., N. L. Newman, J, F. Culver 
and T. J. Tredici. Retinal detachment in adult dogs 
resulting from oxygen toxicity. Arch. Ophthal., 1964, 71: 
665. 
2095. Edstrom, J. E. and H. Rockert. The effect of 
oxygen at high pressure on the histology of the central 
nervous system and sympathetic and endocrine cells. Acta 
physiol, scand., 1962, 55; 255-263. 
2096. Jamieson, D., K. Ladner and H. A. S. Van 
Den Brenk. Pulmonary damage due to high pressure 
oxygen breathing in rats. Aust. J. exp. Biol. med. Sci., 
1963, 41: 491. 
2097. Jamieson, D. and H. A, S. Van Den Brenk. 
Pulmonary damage due to high pressure oxygen breath- 
ing in rats. 3. Quantitative analysis of fluid changes in 
rat lungs. Aust. J. exp. Biol. med. Sci., 1962, 40: 309-314. 
2098. Penrod, K. E. Pulmonary damage in high 
oxygen pressure. Fed. Proc., 1956, 15: 143. 
2099. Penrod, K. E. Nature of pulmonary damage 
produced by high oxygen pressures. J. appl. Physiol., 1956, 
9: 1-4. 
2100. Penrod, K. E. Factors in oxygen high pressure 
pulmonary damage. Fed. Proc., 1957, 16: 100. 
2101. Penrod, K. E. Lung damage by oxygen using 
differential catheterization. Fed. Proc., 1958, 17: 123. 
2102. Sapov, I. A. O mekhanizme toksicheskogo de- 
istviia kisloroda na legochnuiu tkan’. [On the mechanism 
of the toxic effect of oxygen on pulmonary tissue.] Bull. 
Biol. Med. exp. URSS, 1953, 4: 40-45. 
2103. Van Den Brenk, H. A. S. and D. Jamieson. 
Pulmonary damage due to high pressure oxygen breathing 
in rats. 1. Lung weight, histological and radiological 
studies. Aust. J. exp. Biol. med. Sci., 1962, 40: 37-49. 
2104. Van Den Brenk, H. A. S. and D. Jamieson. 
Potentiation by anesthetics of brain damage due to breath- 
ing high pressure oxygen in mammals. Nature, Land., 
1962,194: 777. 
2105. Zagorskii, IU. M. O morfologicheskikh izmen- 
eniiakh tsentral’noi i nekotorykh otdelov perifericheskoi 
nervnoi sistemy zhivotnykh pri giperoksemii. [Morpho- 
logical changes in the central nervous system and certain 
parts of the peripheral nervous system in hyperoxemic 
animals.] Arkh. Pat., 1960, 22: 27-34. 
16. TREATMENT; GENERAL STUDIES 
The general references on treatment included 
in this section will not be discussed in detail 
since the subject has been covered by Lanphier 
and Brown (Fundamentals of Hyperbaric Medi- 
cine, Publication No. 1298, National Academy of 
Sciences, National Research Council, Washing- 
ton, D.C., 1966, page 33 et seq.), In so far as 
military medicine is concerned oxygen under 
high pressure has a therapeutic value primarily 
in the treatment of carbon monoxide poisoning 
and possibly in the management of air embolism 
to shorten the time at which the victim must be 
repressurized. Lanphier and Brown have pointed 
out that the physiological effects of high pres- 
sure, like those of most abnormal environments, 
are primarily detrimental to man. To use these 
effects for therapeutic advantage means keeping 
the desired action within certain suitable limits 
while avoiding harm from simultaneous effects. 
They have made it clear that our present knowl- 
edge concerning the physiology of high pressure 
is not complete: however, utilizing what is known 
can do much towards placing clinical applica- 
tions of this procedure on a logical and reason- 
ably safe basis. The area of most recent interest 
in high pressure therapy deals with elevation 
of inspiratory oxygen partial pressure as a method 
of overcoming or eliminating various types of 
hypoxia. Although the laws of Dalton and Henry 
supply the physical basis for this application, 
they do not go far by themselves toward provid- 
ing a reasonable physiological rationale. Lan- 
phier and Brown have made it clear that it is 
neither accurate or useful to suggest that elevat- 
ing the inspiratory oxygen pressure by a factor 
of 15 will indeed elevate oxygen pressures by 
the same factor throughout the body. The pic- 
ture is complicated by the properties of hemo- 
globin, by oxygen uptake and blood flow and 
by uncertainties concerning the diffusion of oxy- 
gen from capillaries into the tissue, quite apart 
from the imperfect knowledge of the pathological 
physiology of the diseased states being treated. 
Clinical and experimental studies of strictly con- 
trolled design must be conducted before practical 
indications for hyperbaric therapy can be truly 
defined. Several perplexities and false hopes have 
arisen purely from failure to apply physiological 
knowledge presently available. At this juncture 
perhaps even more important analysis of the 
problem in terms of such knowledge aids in de- 
fining the true areas of uncertainty and offers 
suggestions for critical experiments to cast light 
upon them. Answers to a certain number of 
fundamental questions will go far in enhancing 
our comprehension and our ability to make use- 
ful predictions according to Lanphier and Brown. 
These authors go further to say that the under- 
standing of the potential benefits and limitations 
of oxygen administered under high pressure is 
best sought by considering the stages in the 
process of oxygen transfer, the disordered condi- OXYGEN INTOXICATION ABOVE ONE ATMOSPHERE—TREATMENT 
2106-2108 
tions in each that can result in hypoxia and the 
therapeutic effects that increased oxygen pres- 
sure may cause. 
Lanphier and Brown have offered certain con- 
clusions of a tentative nature which may be gener- 
ally related to proposed therapeutic applications. 
They state that hypoxia of pulmonary origin 
ought to seldom require treatment with oxygen 
under high pressure. However, this application 
provides a quite unique means of handling 
hypoxia caused by continued blood flow through 
unventilated alveoli. In this application, how- 
ever, the tendency of oxygen to produce atelecta- 
sis and overt lung damage may cause a worsen- 
ing of the basic pathological process. Since 
oxygen under high pressure is capable of increas- 
ing the oxygen capacity of the blood the techni- 
que may be applicable for any condition in 
which hemoglobin is inactivated or lost. The 
ability to increase the oxygen content of oxy- 
genated blood provides the only method known 
of offsetting massive venous admixture to obtain 
normal or near-normal arterial values. Never- 
theless the presence of a large right-to-left shunt 
largely eliminates the feasibility of elevating 
arterial oxygen to supranormal levels. Maintain- 
ing significantly higher arterial oxygen content 
does provide an effective way of compensat- 
ing for diminished blood flow in otherwise nor- 
mal vascular beds. This suggests firm indications 
for oxygen at high pressure as a therapeutic 
method in shock and in peripheral vascular 
trauma or disease. Nevertheless our present de- 
fects of knowledge as to the critical levels of 
tissue P09 and the relation to capillary blood 
P0o prevents prediction of the decrement of blood 
flow that can be compensated at practical levels 
of oxygen under high pressure. Lanphier and 
Brown also point out that hyperbaric oxygena- 
tion offers relatively little in extending the dura- 
tion of tissue function or survival in temporary 
complete blood flow cessation. Gains can be 
enhanced by combining oxygen under high pres- 
sure and hypothermia, but may still remain short 
of earlier optimistic predictions. They point out 
further that oxygen under high pressure extends 
the distance of effective oxygen diffusion, but 
this is to such a limited extent that it is not capa- 
ble of handling large regions of ischemia. The 
value of the method in treating myocardial in- 
farction, for example, may best be negligible 
unless there is sufficient collateral circulation re- 
maining or unless effects on the margin of the 
affected region are significant, for example in 
reducing the likelihood of ventricular fibrilla- 
tion. Oxygen under high pressure may be of 
value in stroke only in those forms involving a 
critical reduction of blood flow without actual 
obstruction of end arteries. If there is obstruction 
of a relatively small proportion of the capillaries 
in a particular vascular bed, or with limited in- 
creases in the diffusion pathway of oxygen as in 
tissue edema, Lanphier and Brown feel that 
oxygen under high pressure may be of distinct 
value. In combination with hypothermia oxygen 
under high pressure may be of increasing value 
if reduction of blood flow with hypothermia 
is obviated. The capacity of oxygen under high 
pressure to increase tissue P0.( for such purposes 
as radiation therapy and for the treatment of 
anaerobic infections may be greatly variable de- 
pending in each instance upon the extent of 
remaining local blood flow and on the oxygen 
uptake of tissues in the pathway of the diffusion. 
Finally these authors assert that the levels of 
oxygen under high pressure requisite for signifi- 
cant benefit are such that the oxygen toxicity may 
severely limit the safe time duration of treatment. 
Therefore, the clearest indications of possible 
benefit are in those conditions where the require- 
ment for oxygen under high pressure is of short 
duration and where the basic pathological 
process can be therapeutically reversed or blocked 
during a given exposure. In conditions of longer 
duration, the value of oxygen under high pres- 
sure depends to a great extent upon the possible 
persistence of its beneficial effects in intervals 
between relatively brief periods of repeated treat- 
ment exposure. 
2106. Adams, J. F., I. McA. Ledingham, J. M. 
Jackson and G. Smith. Combined nitrogen mustard and 
hyperbaric oxygen therapy in advanced malignant disease. 
Brit. med. J., 1963, 1: 314-315. 
2107. Allison, M. J., G. Margolis, P. J. Chandler 
and E. Gerszten. Effects of hyperbaric oxygen therapy 
on the development of tuberculosis. Ted. Proc., 1964, 23: 
495. 
2108. Attar, S. M., E. Blair, G. G. Gutierrez, 
W. G. Esmond and R. A. Cowley. Experimental pul- 
monary embolism in dogs treated by hyperbaric oxygena- 
tion. Circulation, 1963, 28: 685. 2109-2141 
DISEASES AND ACCIDENTS 
2109. Back, N. and J. L. Ambrus. Effects of oxygen 
tension on the sensitivity of normal and tumor tissue to 
alkylating agents. J. nat. Cancer Inst., 1963, 30: 17. 
2110. Bernhard, W. F., G. Frittelli, E. S. Tank 
and J. G. Carr. Surgery under hyperbaric oxygenation in 
infants with congenital cardiac disease. Circulation, 1964, 
29 (suppl.): 91. 
2111. Bernhard, W. F. and E. S. Tank. The effect 
of oxygen inhalation at 3.5 atmospheres pressure upon 
infants with cyanotic congenital heart disease. A clinical 
and experimental study. Surgery, 1963, 54: 203. 
2112. Bernhard, W. F., E. S. Tank, G. Frittelli 
and R. E. Gross. Feasibility of hypothermic perfusion 
under hyperbaric conditions in the surgical management 
of infants with cyanotic congenital heart disease. J. thorac. 
Surg., 1963, 46: 651. 
2113. Bernhard, W. F., E. S. Tank, G. Frittelli 
and R. E. Gross. Experimental and clinical cardiovascular 
surgery under hyperbaric conditions. New Engl. Cardio- 
vase. Soc., 1963, 21: 31. 
2114. Boerema, I. and W. H. Brummelkamp. 
Behandeling van anaerobe infecties met inademing van 
zurrstof onder een druk van drie atmosferen. [Treatment of 
anaerobic infections by inhalation of oxygen under a pres- 
sure of 3 atmospheres.] Ned. Tijdschr. Geneesk., 1960, 
104: 2548-2550. 
2115. Boerema, I. and W. H. Brummelkamp. 
Inhalation of oxygen at 2 atmospheres for Clostridium 
welchii infections. Lancet, 1962, 2: 990. 
2116. Boerema, I., J. A. Kroll, N. G. Meijne, B. 
Kroon and J. W. Huiskes. Interventions sous hyperpres- 
sion atmospherique. Un principe auxiliaire dans la de- 
veloppement de la chirurgie intracardiaque. Minerva 
cardioangiol. europ., 1957, 5: 233-244. 
2117. Boerema, I., J. A. Kroll, N. G. Meijne, E. 
Lokin, B. Kroon and J. W. Huiskes. High atmospheric 
pressure as an aid to cardiac surgery. Arch. Chir. Neerl, 
1956, 8: 193-211. 
2118. Boerema, I., N. G. Meijne and D. M. E. 
Vermuelen-Cranch. Observations during operation on 
deeply cyanotic young children breathing oxygen at three 
atmospheres absolute. Surgery, 1962, 52: 796-799. 
2119. Breslau, R. D. and S. I. Schwartz. Protective 
effect of hyperbaric oxygenation during occlusion of the 
thoracic aorta. Surg. Forum, 1963, 14: 267. 
2120. Brown, I. W., Jr. Oxygen therapy at super- 
atmospheric pressure. J. Amer. med. Ass., 1963, 183: 397- 
398. 
2121. Brummelkamp, W. H. De beteknis van de 
toediening van zuurstof onder atmosferische overdruk op 
de behandling van gasflegmone. [The importance of ad- 
ministration of oxygen under atmospheric positive pres- 
sure in the treatment of gas phlegmon.] Ned. Tijdschr. 
Geneesk., 1961, 105: 2430-2432. 
2122. Brummelkamp, W. H., I. Boerema and L. 
Hoogendijk. Treatment of clostridial infections with 
hyperbaric oxygen drenching: a report on 26 cases. 
Lancet, 1963,1: 235-238. 
2123. Brummelkamp, W. H., I. Boerema and L. 
Hoogendijk. Hyperbaric oxygen drenching. Modern Med., 
1963,113-114. 
2124. Brummelkamp, W. H., J. Hoogendijk and 
I. Boerema. Treatment of anaerobic infections (clostridial 
myositis) by drenching the tissues with oxygen under 
high atmospheric pressure. Surgery, 1961, 49: 299-302. 
2125. Cater, D. B., E. L. Schoeniger and D. A. 
Watkinson. Effect on oxygen tension of tumors of 
breathing oxygen at high pressures. Lancet, 1962, 2: 381- 
383. 
2126. Churchill-Davidson, I. The oxygen in radio- 
therapy. J. Obstet. Gynaec., Brit. Emp., 1959, 66: 855. 
2127. Churchill-Davidson, I., C. Sanger and R. H. 
Thomlinson. High-pressure oxygen and radiotherapy. 
Lancet, 1955, 1: 1091-1095. 
2128. Churchill-Davidson, I., C. Sanger and R. H. 
Thomlinson. Oxygenation in radiotherapy. II. Clinical 
application. Brit. J. Radiol., 1957, 30: 406-422. 
2129. Cope, C. The importance of oxygen in the 
treatment of cyanide poisoning. P. Amer. med. Ass., 1961, 
175: 1061-1064. 
2130. Deschner, E. E. and L. H. Gray. Influence of 
oxygen tension on x-ray induced chromosomal damage in 
Ehrlich ascites tumor cells irradiated in vitro and in vivo. 
Radiat. Res., 1959,11: 115. 
2131. Dewey, D. L. Effect of oxygen and nitrous 
oxide on radio-sensitivity of human cells in tissue culture. 
Nature, Land., 1960, 186: 780. 
2132. DuSault, L. A. Effect of oxygen on the response 
of spontaneous tumors in mice to regular therapy. Brit. 
J. Radiol, 1963, 36: 749. 
2133. Eloff, S. J. P., W. H. Brummelkamp and I. 
Boerema. A case of “Ergot foot” treated with hyperbaric 
oxygen drenching. J. thorac. Surg., 1963, 4: 747. 
2134. Evans, W. E., J. C. Darin, E. End and E. H. 
Ellison. The use of hyperbaric oxygen in the treatment 
of endotoxin shock. Surgery, 1964, 56: 184. 
2135. Fenn, W. O., R. Gerschman, D. L. Gilbert, 
D. E. Terwilliger and F. V. Cothran. Mutagenic effects 
of high oxygen tensions on Escherichia coli. Proc. nat. 
Acad. Sci., Wash., 1957, 43: 1027-1032. 
2136. Gottlieb, S. F. The possible use of high pressure 
oxygen in the treatment of leprosy and tuberculosis. Dis. 
Chest, 1963, 44: 215. 
2137. Gottlieb, S. F., N. R. Rose, J. Maurizi and 
E. H. Lanphier. Inhibitory effects of hyperbaric oxy- 
genation on bacteria and fungi. Lancet, 1964, 1: 382. 
2138. Gray, L. H. Oxygenation in radiotherapy. Brit. 
J. Radiol, 1957. 30: 403. 
2139. Gray, L. H. Radiobiologic basis of oxygen as a 
modifying factor in radiation therapy. Amer. J. Roent- 
genol, 1961, 85: 803. 
2140. Hitchcock, C. R., R. H. Harris and J. J. 
Haglin. Hyperbaric oxygenation in cardiac and pulmo- 
nary disease. Dis. Chest, 1963, 44: 622. 
2141. Hopkinson, W. I. and A. G. Towers. Effects 
of hyperbaric oxygen on some common pathogenic bac- 
teria. Lancet, 1963, 2: 1361. OXYGEN INTOXICATION ABOVE ONE ATMOSPHERE—TREATMENT 
2142-2175 
2142. Howard-Flanders, P. Effect of oxygen upon 
radiosensitivity of bacteriophage in the presence of sul- 
phydryal compounds. Nature, Land., 1960, 186: 485. 
2143. Hutchison, J. H., M. M. Kerr, M. F. M. 
McPhail, T. A. Douglas, G. Smith, J. N. Norman 
and E. H. Bates. Studies in the treatment of the pul- 
monary syndrome of the newborn. Lancet, 1962, 2: 465-469. 
2144. Hutchison, W. I. (Hyperbaric oxygen in the 
resuscitation of the newborn. Lancet, 1963, 2: 1019-1022. 
2145. Illingworth, C. Treatment of arterial occlusion 
under oxygen at two-atmospheres pressure. Brit. med. J., 
1962, 2: 1271-1275. 
2146. Ivanov, K. P. Vliianie povyshennykh davlenii 
kisloroda na zhivotnykh, otravlennykh tsianistym kaliem. 
[The influence of increased oxygen pressure on animals 
poisoned by potassium cyanide.] Pharm. & Toxic., 1959, 
22: 468-473. 
2147. Kelley, H. G. and W. G. Pace. Treatment of 
anaerobic infections in mice with hyperpressure oxygen. 
Surg. Forum, 1963,14: 46. 
2148. Koch, A. and D. M. E. Vermeulen-Cranch. 
The use of hyperbaric oxygen following cardiac arrest. 
Brit. J. Anaesth., 1952, 34: 738-740. 
2149. Krementz, E. T. and L. Knudson. The effect 
of increased oxygen tension on the tumoricidal effect of 
nitrogen mustard. Surgery, 1961, 50: 266-273. 
2150. Klopper, P. J., W. H. Brummelkamp and 
J. L. Hoogendijk. Recherches experimentals sur 1’effet 
de 1’oxygenotherapie en hyperpression apres ledature de 
1’artere hepatique. Pr. med., 1962, 70: 1874. 
2151. Kuhn, L. A., H. Kline, M. Wang, T. Yamaki 
and J. H. Jacobson. Hemodynamic effects of hyperbaric 
oxygenation in acute myocardial infarction. Clin. Res., 
1964, 12: 187. 
2152. Leather, R. P. and C. Eckert. Hyperbaric 
oxygenation and mechlorethamine effectiveness. Arch. 
Surg., 1963, 87: 114. 
2153. Ledingham, I. M. Some clinical and experi- 
mental applications of high pressure oxygen. Proc. R. Soc. 
Med., 1963, 56: 999. 
2154. Levy, J. V. and V. Richards. Effect of oxygen 
at high pressure (OHP) on asphyxial survival time of rats. 
Proc. Soc. exp. Biol, 1962, 109: 941-944. 
2155. Libet, B. and B. V. Siegel. Response of a 
virus-induced leukemia in mice to high oxygen tension. 
Cancer Res., 1962, 22: 737-742. 
2156. Marshall, W. W., E. T. Hoppe and F. Stark. 
The effect of ambient oxygen tension on the toxicity and 
therapeutic effect of nitrogen mustard. Arch. Surg., 1963, 
86: 932. 
2157. Maudsley, R. H., W. I. Hopkinson and K. G. 
Williams. Vascular injury treated with high pressure 
oxygen in a mobile chamber. J. Bone Joint Surg., 1963, 
45B: 346-350. 
2158. McAllister, T. A., J. M. Stark, J. M. Nor- 
man and R. M. Ross, nlhibitory effects of hyperbaric 
oxygenation on bacteria and fungi. Lancet, 1963, 2; 104. 
2159. Meijne, N. G. Experimental cardiac surgery 
under high atmospheric pressure. J. thorac. cardiov. Surg., 
1962, 44: 749-753. 
2160. Meijne, N. G., A. B. Bulterijs, S. J. P. 
Eloff and I. Boerema. An experimental investigation 
into the influence of administration of oxygen under in- 
creased atmospheric pressure upon coronary infarction. 
/. thorac. Surg., 1963, 4: 521. 
2161. Meijne, N. G., A. B. Bulterijs, G. Schoe- 
maker and S. J. P. Eloff. Treatment of dogs with 
oxygen under high atmospheric pressure after ligation of 
the descending branch of the left coronary. Dis. Chest, 
1963, 44: 234. 
2162. Meijne, N. G., G. Schoemaker and A. B. 
Bulterijs. The treatment of cerebral gas embolism in a 
high pressure chamber. J. cardiovasc. Surg., 1963, 4: 757. 
2163. Meijne, N. G., G. Schoemaker and A. B. 
Bulterijs. Administration of oxygen under increased 
pressure in cases of low cardiac output caused by injection 
of microspheres of divinylbenzene into the coronary ar- 
teries. J. thorac. Surg., 1964, 47: 664. 
2164. Meijne, N. G., D. M. F. Vermeullen-Cranch, 
M. E. Sluyter, S. J. P. Eloff, L. Schripsema, L. Deen, 
G. Schoemaker and I. Boerema. Experimental cardiac 
surgery under high atmospheric pressure. J. thorac. Surg., 
1962, 44: 749. 
2165. Nuckolls, J. G. and S. Osterhout. The effect 
of hyperbaric oxygen on anaerobic bacteria. Clin. Res., 
1964, 12: 244. 
2166. Panov, A. G. and P. I. Remezov. Effect of 
oxygen under pressure on the course of certain experi- 
mental neurotropic virus infections in white mice. Probl. 
Virol, 1960, 5: 290-296. 
2167. Richards, V., D. Pinto and P. Coombs. 
Studies in suspended animation by hypothermia combined 
with hyperbaric oxygenation. Ann. Surg., 1963, 158: 349. 
2168. Sanger, C. High pressure oxygen and radio- 
therapy. Lancet, 1957, 1: 895. 
2169. Sanger, C., I. Churchill-Davidson and R. H. 
Thomlinson. Anaesthesia for radiotherapy under high- 
pressure oxygen. Brit. J. Anaesth., 1955, 27: 436-446. 
2170. Sanger, C. High pressure oxygen and radiation 
therapy. Amer. J. Roentgenol., 1959, 81: 498-503. 
2171. Seaman, W. B., N. du V. Tapley, C. Sanger, 
H. W. Jacox and H. L. Atkins. Combined high-pressure 
oxygen and radiation therapy in the treatment of human 
cancer. Amer. J. Roentgenol, 1961, 85: 816-821. 
2172. Sharp, G. R., I. McA. Ledingham and J. N. 
Norman. The application of oxygen at 2 atmospheres 
pressure in the treatment of acute anoxia. Anaesthesia, 
1962, 17: 136-144. 
2173. Sluyter, M. E. and N. G. Meijne. A case of 
impaired diffusion capacity for oxygen and cerebral dam- 
age treated with oxygen under high atmospheric pressure. 
Bull Soc. int. Chir., 1962, 21: 161-169. 
2174. Smith, G. and D. D. Lawson. Experimental 
coronary arterial occlusion: Effects of the administration 
of oxygen under pressure. Scot. med. J., 1958, 3: 346-350. 
2175. Smith, G. and D. D. Lawson. The protective 
effect of inhalation of oxygen at two atmospheres absolute 
pressure in acute coronary arterial occlusion. Surg. Gynec. 
Obstet., 1962,114: 320-322. 2176-2192 
DISEASES AND ACCIDENTS 
2176. Smith, G., W. Sillar, J. N. Norman, I. McA. 
Ledingham, E. H. Bates and A. C. Scott. Inhalation 
of oxygen at 2 atmospheres for Clostridium welchii infec- 
tions. Lancet, 1962, 2: 756-757. 
2177. Smith, G., J. Stevens, J. C. Griffiths and I. 
McA. Ledingham. Near-avulsion of foot treated by re- 
placement and subsequent prolonged exposure of patient 
to oxygen at two atmospheres pressure. Lancet, 1961, 2: 
1122-1123. 
2178. Trapp, W. G. The therapeutics of high-pressure 
oxygen. Canad. med. Ass. J., 1963, 88: 356-359. 
2179. Van Den Brenk, H. A. S. and D. Jamieson. 
Studies of the mechanisms of chemical radiation protection 
in vivo. Effect of high pressure oxygen on radio protection 
in vivo and its relationship to oxygen poisoning. Int. J. 
Radiat. Biol., 1961, 4: 379. 
2180. Van Zyl, J. J. W. and P. R. Maartens. High 
pressure oxygen therapy in South Africa. S. Afr. med. J., 
1963, 37: 799. 
2181. Wildermuth, O. Hybaroxic radiation therapy in 
cancer management. Radiology, 1964, 82: 767-777. 
2182. Anon. Tetanus retreats unter pressure, Med. 
World News, 1962, 3: 79. 
2183. Anon, Operating under pressure. Med. World 
News, 1963, 4: 74-82. 
17. TREATMENT: VASCULAR SHOCK 
As in the case of the immediately previous sec- 
tion, so in the present one, the decision has been 
made not to discuss in detail the references in- 
cluded. The principles discussed above apply 
equally, 
2184. Attar, S., W. G. Esmond and R. A. Cowley. 
Hyperbaric oxygenation in vascular collapse. J. thorac. 
cardiov. Surg., 1962, 44: 759-770. 
2185. Blair, E., R. M. Ollodart, G. Henning, S. M. 
Attar, W. G. Esmond and R. A. Cowley. Effect of 
hyperbaric oxygenation (OHP) on bacteremic shock. Cir- 
culation, 1963, 28: 691. 
2186. Burnett, W., R. G. Clark, H. L. Duthie and 
A. N. Smith. The treatment of shock by oxygen under 
pressure. Scot. med. J., 1959, 4: 535-538. 
2187. Elliott, D. E. and D. C. Paton. Effect of 
oxygen pressure on dogs subjected to hemorrhagic hypo- 
tension. Surg. Forum, 1963,14: 5. 
2188. Esmond, W. G., S. Attar and R. A. Cowley. 
Hyperbaric oxygenation in medical and surgical condi- 
tions: Application in experimental vascular collapse. San 
Diego Symposium for Biomedical Engineering, June 19-21, 
1962, pp. 311-325. 
2189. Esmond, W. G., S. Attar and R. A. Cowley. 
Hyperbaric' oxygenation in experimental hemorrhagic 
shock: experimental chamber design and operation. Trans. 
Amer. Soc. artif. intern. Organs, 1962, 8: 384-392. 
2190. Manax, W. M., G. G. Nahas, D. Hassam, 
D. V. Habif and E. M. Papper. Effect of pH control 
and increased Oz delivery on the course of hemorrhagic 
shock. Ann. Surg., 1962, 156: 177. 
2191, Moulton, G, A., W. G. Esmond and M. 
Michaelis. Effect of hyperbaric oxygenation on Noble 
Collip drum shock in the rat. Bull. Univ. Md. Sch. Med., 
1962, 47: 42-44. 
2192. Smith, G., I. M. Ledingham, J. N. Norman, 
T. A. Douglas, E. H. Bates and F. D. Lee. Prolonga- 
tion of the time of “safe” circulatory arrest by preliminary 
hyperbaric oxygenation and body cooling. Surg. Gynec. 
Obstet., 1963, 117: 411. 
18. PRESSURE OXYGENATED SOLUTIONS 
A basic limitation of oxygen use in diving is 
the supervention of convulsions and other toxic 
effects of oxygen when certain depths are ex- 
ceeded. For this reason, the policy has been to 
keep the oxygen partial pressure below 1.6 atmos- 
pheres by dilution with inert gases. As depth is 
increased the oxygen percentage must be dimin- 
ished to maintain non-toxic inspiratory mixtures. 
This precise control of oxygen percentage is 
technically difficult at great depths. In this con- 
nection experimental studies of fluid breathing 
have attracted a certain recent interest. These 
studies have not been extended to man. 
From the references given in this section two 
may be selected for special discussion. Kylstra 
and Lanphier {2196) 1964, ventilated anesthe- 
tized dogs mechanically with bubble-oxygenated 
saline for 50 minutes in a chamber pressurized 
with air at 3.0 atmospheres absolute. With fluid 
ventilation at rates of 4200 ml./minute and 
with an inspiratory P0., below 2200 mm. Hg, 
the arterial oxygen content ranged from 14.7 to 
21.6 volume percent at rates of oxygen uptake 
up to 120 ml./minute in three dogs. The total 
computed dead space for oxygen was less than 
287 ml. Gas exchange during fluid breathing of 
mammals may be impaired as a result of sub- 
normal ventilation due to high airway resistance 
to fluid flow, poor mixing and slow gas diffusion 
in fluid-filled alveoli and uneven distribution of 
inspired fluid. Of these factors, ventilation ap- 
pears to be the most critical. Marked respiratory 
insufficiency and death followed reversion to gas 
breathing. One dog survived seven days after 
having been ventilated with fluid for one hour. 
Pressure-volume diagrams obtained during infla- 
tion of the lungs with air after 50 minutes of 
fluid ventilation suggest marked increases in 
alveolar surface tension. Pegg, Horner and 
Wahrenbrock {2198) 1963, pointed out that 
since the solution of a gas in a liquid is directly NOXIOUS AGENTS—CARBON MONOXIDE 
2193-2205 
proportional to the applied partial pressure, it 
is possible with sufficient pressure to dissolve 
physically an arbitrarily great amount of oxygen 
in a liquid. Saline at 37°C, exposed to oxygen 
at 10 atmospheres absolute will contain in solu- 
tion 20 volumes percent of oxygen. In the 
authors’ experiments 30 etherized and trache- 
otimized rats were tied in lucite frames and 
placed in a pressure chamber breathing an oxy- 
genated saline solution. On immersion the heart 
rate dropped, the irregularity of respiration dur- 
ing the first three minutes gave way to a respira- 
tory rate of 28 per minute (compared with a 
control rate of 69 per minute). As the pressure 
increased the survival time increased. Thus, at 
2.5 atmospheres the survival time was approxi- 
mately five minutes; this rose to 170 and 248 
minutes at 10 atmospheres and dropped to 90 
and 135 minutes at 20 atmospheres. After 30 
minutes the rats were decompressed and the lungs 
drained. Eight rats resumed normal breathing, 
in some, however, in 15 minutes there was a sero- 
sanguinous fluid bubbling from the end of the 
tracheal tube. Respiration was slow and labored; 
the animals became cyanotic and some died 
even though 100 percent gaseous oxygen was 
administered. 
2193. Kylstra, J. A. Breathing fluid. Experientia, 1962, 
18: 68. 
2194. Kylstra, J. A. Survival of mice in saline equili- 
brated with oxygen at high tensions. XXII Inter. Congr. 
physiol. Sci., Leiden, 1962, 2: Obstr. 309. 
2195. Kylstra, J. A. Hyperbaric oxygenation of sub- 
merged mammals. Lancet, 1962, 2: 149. 
2196. Kylstra, J. A. and E. H. Lanphier. Gas 
exchange in fluid-ventilated dogs. Fed. Proc., 1964, 23: 469. 
2197. Pegg, J., T. Horner and E. Wahrenbrock. 
Mammalian respiration of pressure-oxygenated solutions. 
Physiologist, 1962, 5; 194. 
2198. Pegg, J. H., T. L. Horner and E. A. Wahren- 
brock. Breathing of pressure-oxygenated liquids, pp. 
166-170 in: Second symposium on underwater physiology. 
Edited by C. J. Lambertsen and L. J. Greenbaum, Jr. Na- 
tional Research Council, Washington, D.C. N.R.C. Publi- 
cation 1181, 1963, 296 pp. 
VII. NOXIOUS AGENTS 
A. CARBON MONOXIDE 
1. GENERAL STUDIES OF CARBON MON- 
OXIDE POISONING 
The literature on carbon monoxide is large, 
and therefore a selection has had to be made 
of those reports to be considered in this volume. 
Moreover, the knowledge regarding carbon 
monoxide has not changed drastically in the 
last ten years and therefore reference can be 
made to the sections on carbon monoxide in 
volumes I and II of this Sourcebook. 
The reader is particularly referred to a U.S. 
NRC report on the Status of research in under- 
water physiology (2204) 1956, in which the 
toxicity of carbon monoxide is compared at sea 
level and at depth. At sea level the toxicity of 
carbon monoxide is proportional to the amount 
of COHb formed, while at depth a diver may 
tolerate considerably higher ratios of COHb be- 
cause some of the oxygen transport requirements 
are met by oxygen in solution (due to the in- 
creased partial pressure of oxygen at depth). 
However, since the reconversion of COHb to 
oxyhemoglobin is slow he may be in immediate 
difficulty on ascent. 
2199. Bokhoven, C. and H. J. Niessen. Amounts of 
oxides of nitrogen and carbon monoxide in cigarette 
smoke, with and without inhalation. Nature, Land., 1961, 
192, 458-459. 
2200. Brunner, J. and H. Ley. Statistische, differ- 
ential-diagnostische und prognotische Beitrage zum Thema 
der Schlafmittel- und der CO-Vergiftung. Munch, med. 
Wschr., 1961, 103: 301. 
2201. Hill, A. B. Recent statistics of carbon monoxide 
poisoning. Brit. med. J., 1956, 2: 1220-1222. 
2202. Marriott, H. L, Carbon-monoxide poisoning. 
Brit. med. J., 1958, 2: 1591-1592. 
2203. Meigs, J. W. and J. P. W. Hughes. Acute 
carbon monoxide poisoning: and analysis of one hundred 
five cases. Arch, industr. Hyg., 1952, 6: 344-356. 
2204. U.S. NRC. Carbon monoxide, pp. 11-22 in; 
Status of reesarch in underwater physiology. U.S. NRC- 
CUW, Kept. 468, March 1956, 24 pp. 
2205. Zorn, O. and P. D. Kruger. The problem of 
chronic carbon monoxide poisoning. Industr. Med. Surg., 
1960, 29: 580-581. 
2. CARBON MONOXIDE IN SUBMARINES 
AND OTHER NAVAL VESSELS 
Contamination of the atmosphere is still a 
potential problem in fleet type submarines where 
diesel engines are used for propulsion. In such 
vessels operating under strong following winds 
engine exhaust gases may not be carried away 
completely from air intake. The advent of the 
nuclear powered submarines has greatly reduced 
the contamination of the submarine atmosphere 
by carbon monoxide. A case of mass carbon 2206-2211 
DISEASES AND ACCIDENTS 
monoxide poisoning in a submarine has been re- 
ported by Alvis and Tanner (2206) 1952. Men 
engaged in active work were affected first. Head- 
ache was the first symptom noted, and all aboard 
were affected except one. There was nausea 
and vomiting, as well as headache, and the head- 
ache was so severe that sedation was required. 
The carbon monoxide concentration in the air 
was found to be 0.01 percent; the carbon dioxide 
level was at 2 percent. Exposure lasted for ap- 
proximately 10 hours. It was suggested that the 
high carbon dioxide percent did not cause the 
condition but tended to hasten the onset of 
carbon monoxide poisoning symptoms. All 
aboard probably had carboxyhemoglobin satura- 
tions between 10 and 20 percent; several between 
20 and 30 percent, and a few may have had as 
high as 30 to 40 percent saturation. As these 
authors have reported elsewhere (2207) 1952, 
this episode illustrates the danger of such a situa- 
tion developing aboard snorkel equipped sub- 
marines under diesel power. The influence of 
work and an elevated concentration of carbon 
dioxide in the atmosphere in precipitating 
the toxic symptoms of carbon monoxide poison- 
ing are demonstrated in this incident. The reader 
is referred to a statement on acceptable limits of 
concentrations of carbon monoxide in submarines 
(Gt. Brit. MRC., 2209). The maximum per- 
missable level of carbon monoxide in nuclear 
powered submarines is given as 0.005 percent 
(50 parts per million). The following table 
gives maximum times allowable for given 
exposures: 
concentrations of carbon dioxide) a significant 
concentration of carbon monoxide was also 
found. Further testing was done to determine 
the rate of accumulation and diurnal variation, 
if any. Concentrations varying between 50 ppm 
and 100 ppm were present for a period of 12 
days, and concentrations in excess of 100 ppm 
for a period of 4 days. At this point, hopcalite 
canisters were installed in the ventilation system 
and the carbon monoxide concentration was re- 
duced considerably. Carbon monoxide blood 
saturation in men tested dropped rapidly upon 
return to outboard ventilation. However, the 
rate of elimination appeared slower than reported 
by other workers, since after 12 hours on 
weather air, significant saturations were still 
present. It was established that unrestricted 
smoking in a sealed space, such as a submarine 
during prolonged submergence, can give rise 
to toxic concentrations of carbon monoxide. 
Contamination of intake air from any source of 
exhaust gas can cause a carbon monoxide buildup 
(2212, 1956). In certain types of oil lubricated 
high pressure compressors cylinder temperatures 
may become high enough to promote partial 
combustion of the oil. Careful attention to the 
type of compression and maintenance must be 
given to keep the carbon monoxide within al- 
lowable concentrations. 
2206. Alvis, H. J. and C. W. Tanner. Carbon 
monoxide toxicity in submarine operations. Report of a 
case. Arch, industr. Hyg., 1952, 6: 404-406. 
2207. Alvis, H. J. and C. W. Tanner. Carbon 
monoxide toxicity in submarine medicine, a case report. 
U.S. Navy. Submarine Base, New London, Conn. Medical 
research laboratory. Project NM 002 015.03, Kept. no. 8, 
1952. 
2208. Bogatkov, P. I., lu. G. Nefedov and M. I. 
Poletaev. Vydykhaemyi vozdukh kak istochnik zagriaz 
neniia okis’iu ugleroda vozdushnoi sredy germetichnykh 
pomeshchenii. [Expired air as a source of carbon monox- 
ide contamination of the air environment of hermetically 
sealed compartments.] Vo.-med. Zh., 1961, 2: 37-39. 
2209. Gt. Brit. MRC. Statement on acceptable levels 
of concentrations of carbon monoxide in submarines. Gt. 
Brit. MRC. RNPRC, SMS. Kept. S.M.S. 23, 2 pp. 
2210. Nichols, G., Jr. and J. L. Kinsey. Carbon 
monoxide as a habitability factor in prolonged submarine 
submergence. U.S. Navy. Submarine Base, New London. 
Conn. Medical research laboratory. Project NM 002 
015.10.01, Kept. no. 223, 16 April 1953, 10 pp. 
2211. Soegard, H. Risikoen for kulilteforgiftning i 
militaere motorvogne. Risks of carbon monoxide poisoning 
in military vehicles. Militaerlaegen, 1960, 66: 55-60. 
Percent 
pp 10,000 
ppm 
Maximum times 
of exposure 
0.005 
0.5 
50 
indefinite 
0.01 
1 
100 
6 hours 
0.02 
2 
200 
3 hours 
0.04 
4 
400 
U/2 hours 
0.05 
5 
500 
1 hour 
0.10 
10 
1000 
1/2 hour 
0.20 
20 
2000 
14 hour 
Carbon monoxide as a habitability factor in 
prolonged submarine submergence has been 
studied by Nichols and Kinsey (2210) 1953. 
During routine analysis of the air of the sub- 
marine USS Haddock which was used for Opera- 
tion Hideout (the purpose of which was to ascer- 
tain the effect of prolonged exposure to low NOXIOUS AGENTS—CLINICAL, FUNCTIONAL, AND PATHOLOGICAL 
2212. U.S. Navy. Carbon monoxide poisoning, pp. 
173-175 in: Submarine medicine practice. U.S. Navy, 
BuMed. NAVMED — P 5054, Gov’t. Printing Office, Wash- 
ington, D.C., 1956, 357 pp. 
3. CLINICAL PICTURE, FUNCTIONAL 
CHANGES AND PATHOLOGICAL EF- 
FECTS 
As in previous years, carbon monoxide persists 
as a potential hazard in industry and in caisson 
operations, as well as in submarine and diving. 
After prolonged moderate exposure to carbon 
monoxide there may be symptoms of acute in- 
toxication or the symptoms of chronic carbon 
monoxide poisoning may indeed develop without 
any preceding symptoms of acute intoxication. 
There may be headache, lassitude and drowsi- 
ness, insomnia, irritability, memory loss, vertigo, 
tremor and slight confusion. With blood satura- 
tions from 10 to 20 percent there may be slight 
headache. Saturations of 20 to 30 percent may be 
associated with throbbing headaches, while sat- 
urations of 30 to 40 percent may be associated 
with weakness, dizziness, dimness of vision, 
nausea and vomiting. At saturations of 40 to 50 
percent there may be collapse or syncope with 
acceleration of respiratory and pulse rates. 
Cheyne-Stokes respiration may supervene at 50 
to 60 percent saturation and there may be coma 
with intermittent convulsions. Death may occur 
at saturations between 60 and 80 percent. Atten- 
tion may also be called to such symptoms as 
palpitation, precordial pain, dyspnea, colic, at- 
tacks of diarrhea, polyuria, impotence and re- 
duced tolerance for alcohol. There may also 
be attacks of elevated temperature and disturb- 
ances of vision and hearing. Circulatory re- 
sponses of normal and carbon monoxide ac- 
climatized dogs during carbon monoxide 
inhalation have been reported by Lillehei, Wilks 
and Carter (2220) 1954. During inhalation of 
0.5 percent carbon monoxide in air for at least 30 
minutes (sufficient to produce over 50 percent 
carboxyhemoglobin) normal and nembutal 
anesthetized dogs showed: 1) a rise in pulse rate, 
respiratory rate, mean pulmonary arterial pres- 
sure and cardiac output; 2) a relatively smaller 
rise in mean intrapleural pressure; and 3) little 
or no change in mean femoral arterial and left 
atrial pressure. Dogs which had been gradually 
acclimatized to breathing 0.1 percent carbon 
monoxide in air for six to eight hours daily over 
a period of a year were found to have a signifi- 
cantly lower pulse and respiratory rate, a higher 
mean pulmonary arterial pressure, but approxi- 
mately the same mean femoral arterial and in- 
trapleural pressure as normal dogs. Wagemann 
(2230) 1960, has pointed out that in acute carbon 
monoxide intoxication the cochlear and/or 
vestibular apparatus are damaged. It is stated 
that the vestibular disturbances are central in 
type and that they generally recover. The re- 
covery of the damaged hearing on the other 
hand is less certain. Courville (2214) 1957, has 
called attention to demyelination as a delayed 
residual of carbon monoxide asphyxia. Accord- 
ing to Dutra (2215) 1952, the cerebral lesions 
occurring as a residue of carbon monoxide 
poisoning consist essentially of dilatation of 
blood vessels, edema, perivascular hemorrhages, 
degeneration and death of ganglian cells, focal 
demyelination and foci of necrosis. Each of these 
is either directly or indirectly caused by a reduc- 
tion of the supply of oxygen to the brain. 
Garassini and De Santis (2216) 1960, have 
described a case of a 49 year old man who suffered 
acute carbon monoxide poisoning from a wood 
burning stove who presented typical acute symp- 
toms of deep coma, cyanosis of the face and 
extremities and shallow and rapid respiration 
and pulse upon arrival at the hospital. After 
emergence from the coma the patient displayed, 
in addition to pyramidal symptoms, neuritis 
of the right brachial plexus followed by muscular 
atrophy of the regions involved. No cause for 
this, other than the carbon monoxide poisoning, 
could be found. The symptoms relating to the 
brachial plexus improved progressively. Schwarz 
and Muller (2226) 1960, reported the case of a 
21 year old woman suffering from severe carbon 
monoxide poisoning with psycho-pathologic 
manifestations, including disturbance of con- 
sciousness, confusion and amnesia. Five months 
later there were epileptic attacks which con- 
tinued for three years. The epileptic sequelae 
were considered by the authors to be related to 
the original carbon monoxide poisoning. For 
EEC changes in carbon monoxide poisoning, 
reference may be made to papers by Lennox 
and Petersen (2219) 1958, and Takahashi 
(2228) 1961. Electrocardiographic changes have 2213-2235 
DISEASES AND ACCIDENTS 
been described by Bouvrain, Gaultier, Gervais 
and Pasquier {2213) 1960. 
2213. Bouvrain, Y., M. Gaultier, P. Gervais and 
P. Pasquier. (Les accidents carcliaques retards de 1’oxyde 
de carbone. Sem. Hop. Paris, 1960, 36: 3163-3172. 
2214. Courville, C. B. The process of demyelination 
in the central nervous system. IV. Demyelination as a de- 
layed residual of carbon monoxide asphyxia. J. nerv. merit. 
Dis., 1957,125: 534-546. 
2215. Dutra, F. R. Cerebral residua of acute carbon 
monoxide poisoning. Amer. J. clin. Path., 1952, 22: 925- 
935. 
2216. Garassini, G. and G. De Santis. Interessamento 
del sistema nervoso neU’ossicarbonismo acuto: contribute 
clinico. Un caso di paresi del plesso brachiale destro. 
Folia med., Napoli, 1960, 43: 1048-1054. 
2217. Herbich, J. and A. Stacker. Zur chronischen 
Kohlenmonoxydeinwirkung auf das Knockenmark. Wien. 
Z. inn. Med., 1961, 42: 338-340. 
2218. Lambertsen, C. J. Harmful effects of oxygen, 
nitrogen, carbon dioxide, and carbon monoxide. Carbon 
monoxide, pp. 716-719 in: Medical physiology. Edited by 
P. Bard, C. V. Mosby Company, St. Louis, 1961, 1339 pp. 
2219. Lennox, M. A. and P. B. Petersen. Electro- 
encephalographic findings in acute carbon monoxide poi- 
soning. EEG clin. Neurophysiol, 1958, 10: 63-68. 
2220. Lillehei, J. P., S. S. Wilks and E. T. Carter. 
Circulatory responses of normal and of CO-acclimatized 
dogs during CO inhalation. Fed. Proc., 1954, 13: 89. 
2221. Middleton, G. D., D. W. Ashby and F. 
Clark. Delayed and long-lasting electrocardiographic 
changes in carbon-monoxide poisoning. Lancet, 1961, 1: 
12-14. 
2222. Musselman, N. P., W. A. Groff, P. P. Yevich, 
F. T. Wilinski, M. H. Weeks and F. W. Oberst. 
Continuous exposure of laboratory animals to low concen- 
tration of carbon monoxide. Aerospace Med., 1959, 30: 
524-529. 
2223. Paeslack, van V. Diabetes mellitus nach Koh- 
lenoxydvergiftung. Schweiz, med. Wschr., 1961, 91: 946- 
949. 
2224. Rapoport, K. M. O deistvii povyshennogo dav- 
leniia kisloroda pri eksperimental’noi gipolsemii, vyzvan- 
noi otravleniem okis’iu ugleroda. [The effect of increased 
partial hypoxemia induced by carbon monoxide poison- 
ing.] Patol. Fiziol. Eksp., Ter., 1959, 3: 27-32. 
2225. Schollmeyer, von W. and M. Dises. Zur 
Diagnose chronischer und subakuter CO-Vergiftung. 
Dtsch. Gesundheihves., 1961,16: 1403-1407. 
2226. Schwarz, von B. and D. Muller. Symptoma- 
tische Epilepsie nach Kohlenoxydvergiftung. Z. ges. inn. 
Med., 1960, 15: 1104-1112. 
2227. Schwedenberg, T. H. Leukoencephalopathy 
following carbon monoxide asphyxia. /. Neuropath., 1959, 
18: 597-608. 
2228. Takahashi, K. Cardiac disturbances due to CO 
poisoning in experimental animals. I. Electrocardio- 
graphic changes due to CO poisoning and those under the 
influences of fluid infusion. Tohoku J. exp. Med., 1961, 
74: 211-223. 
2229. Takahashi, K. Cardiac disturbances due to CO 
poisoning in experimental animals. II. Changes of the 
heart excitability due to acute CO poisoning. Tohoku J. 
exp. Med., 1961, 74: 225-233. 
2230. Wagemann, W. Das otologische Bild der Koh- 
lenoxydvergiftung. Z. Laryng. Rhinol., 1960, 39: 691-702. 
2231. Wieland, H. Die Beeinflussung der Herzstrom- 
kurve durch Kohlenoxyd. Arztl. Forsch., 1955, 9: 78-87. 
2232. Wilks, S. S. Effects of pure carbon monoxide 
gas injection into the peritoneal cavity of dogs. J. appl. 
Physiol, 1959, 14: 311-312. 
2233. Wilks, S. S. and R. T. Clark, Jr. Carbon 
monoxide determinations in post-mortem tissues as an aid 
in determining physiologic status prior to death. J. appl. 
Physiol, 1959, 14: 313-320. 
2234. Wilks, S. S., J. F. Tomashefski and R. T. 
Clark, Jr. Physiological effects of chronic exposure to 
carbon monoxide. J. appl. Physiol, 1959, 14: 305-310. 
4. MECHANISMS OF CARBON MONOXIDE 
POISONING 
Interference with oxygen transport mechanisms 
in the blood is still regarded as the major action 
of carbon monoxide on the body. It has also 
been pointed out that carbon monoxide has an 
affinity for respiratory enzymes but this point is 
mainly of theoretical concern. Thus Brecken- 
ridge {2236) 1953, has reported on carbon 
monoxide oxidation by cytochrome oxidase in 
muscle; and Fati, Mole and Pecora (2238) 1960, 
have shown that daily carbon monoxide poison- 
ing for three days in rabbits produced a progres- 
sive reduction in erythrocytic phosphoglucomu- 
tase activity which persisted ten days or longer 
after the poisoning. This inhibition, according 
to the authors, must be considered as inde- 
pendent of the oxygen deficiency produced by 
the poisoning, for in control animals kept in an 
atmosphere of nitrogen until the appearance of 
symptoms of asphyxia, no appreciable change in 
phosphoglucomutase activity appeared. The 
reader is referred to a paper on the effect of 
carbon monoxide poisoning in rabbits upon 
oxygen consumption and respiratory rate and 
respiration time in the erythrocytes (Mole 
{2242) 1960) . The author concluded that 
carbon monoxide acts upon the oxygen consump- 
tion of the erythrocytes by slowing down aerobic 
oxidation without reducing the total value. 
2235. Ackerman, E. and R. L. Berger. Reaction of 
oxyhemoglobin with carbon monoxide. Biophys. J., 1963, 
3: 493-505. NOXIOUS AGENTS—UPTAKE AND ELIMINATION 
2236-2244 
2236. Breckenridge, B. Carbon monoxide oxidation 
by cytochrome oxidase in muscle. Amer. J. Physiol., 1953, 
173: 61-69. 
2237. Candura, F., A. Craven and F. Brasca. La 
fibrinolisi nell’ossicarbonismo acuto. Ricerche sperimentali. 
Folia med., Napoli, 1961, 44: 400-408. 
2238. Fati, S., R. Mole and L. Pecora. Gli enzimi 
glicolitici del globulo rosso nell’intossicazione ossicar- 
bonica. Nota III. II comportamento della fosfoglicomutasi 
eritrocitaria nell’ossicarbonismo acuto. Folia med., Napoli, 
1960, 43: 1092-1097. 
2239. Gibson, Q. H. Some observations on the reac- 
tions of two annelid haemoglobins with oxygen and with 
carbon monoxide. Proc. roy. Soc., 1955, 143: 334-342. 
2240. Gibson, Q. H. The direct determination of the 
velocity constant of the reaction Hb4(CO)3+ CO Hb4(CO)4. 
J. Physiol, 1956, 134: 123-134. 
2241. Gwozdz, B., F. M. Spioch and J. S. Dutkie- 
wicz. Untersuchungen iiber den Einfluss des Cytochroms 
C auf die Gewebeatmung von mit Kohlenoxyd vergifteten 
Tieren. Z. Vitam.- Harm.- u. Fermentforsch., 1961, 11: 
282-289. 
2242. Mole, R. II consumo di ossigeno degli eritrociti 
di conigli intossicati acutamente con CO. Boll. Soc. ital. 
Biol, sper., 1960, 36: 973-975. 
2243. Sendroy, J., Jr. and J. D. O’Neal. Relative 
affinity constant for carbon monoxide and oxygen in blood. 
Fed. Proc., 1955, 14: 137. 
5. UPTAKE AND ELIMINATION OF CARBON 
MONOXIDE 
The uptake of carbon monoxide depends first 
of all upon the absorption of the gas by the 
lungs. This has been investigated by Forster, 
Fowler, Bates and VanLingen (2249) 1954, who 
have studied the absorption of carbon monoxide 
by the lungs during breathholding in seven nor- 
mal subjects. The alveolar carbon monoxide 
concentration did not fall exponentially with 
time as had been assumed by previous workers. 
The most likely explantion of this phenomenon 
is that the diffusing capacity per unit gas vol- 
ume varies throughout the lung. The rate of 
uptake of carbon monoxide by the normal hu- 
man erythrocyte and experimentally produced 
spherocytes has been reported by Carlsen and 
Comroe (2247) 1958. The uptake of the gas 
by the erythrocyte involves first of all diffusion 
across the cellular membrane, secondly in- 
traerythrocytic diffusion, and finally chemical 
combination with hemoglobin. The experiments 
suggest that surface area and maximum linear 
distance for intracellular diffusion do not 
measurably retard gas uptake. Shrunken eryth- 
rocytes showed a marked decrease in the rate 
of gas uptake and it is hypothesized that in 
the shrunken cells a change in the orientation 
and concentration of intraerythrocytic hemo- 
globin and/or of the membrane components 
may have impeded gas diffusion. For photo- 
colorimetric determinations of rate of uptake of 
carbon monoxide by human red cell suspensions 
at 37°C. a paper by Forster, Roughton, Kreuzer 
and Briscoe (2257) 1952, should be consulted, 
as should also a study by French and Hall 
(2252) 1954, on the time course of carboxy- 
hemoglobin formation in subjects exposed to 
carbon monoxide for periods of ten to sixteen 
hours, and its modification by intermittent 
breathing of 100 percent oxygen. Joels and Pugh 
(2254) 1958, have developed carbon monoxide 
dissociation curves of human blood which differ 
slightly from the curves published in 1912 by 
Douglas and colleagues. The effect of levels of 
exercise upon pulmonary diffusing capacity by 
steady-state methods using oxygen and carbon 
monoxide in normal subjects has been reported 
by Shepard, Martin, White, Permutt, Varnaus- 
kas and Riley (2258) 1958. Three normal young 
men carried out different levels of treadmill 
exercise with and without hypoxia. Subjects 
were studied at each of four levels of exercise 
producing oxygen uptake between one and two- 
and-half liters per minute and cardiac outputs 
between nine and 22 liters per minute. Diffusing 
capacity for carbon monoxide increased progres- 
sively with increasing exercise in all subjects. 
It was higher during hypoxia than during air- 
breathing at the same level of exercise, as were 
total ventilation, tidal volume and cardiac out- 
put. It appears that this increase in the diffusing 
capacity for carbon monoxide cannot be ex- 
plained solely on the basis of increased affinity 
of hemoglobin for carbon monoxide during 
hypoxia. Diffusing capacity for oxygen did not 
increase significantly with increasing exercise 
after cardiac output had reached 15 liters per 
minute. These data support the belief, based on 
theoretical considerations that the steady-state 
diffusing constant for oxygen and steady 
diffiusion constant for carbon monoxide are not 
related in the same way to the diffusing capacity 
of the lungs. 
2244. Borbely, F. Uber die Existenz der chronischen 
Kohlenoxydvergiftung. Internist, 1961, 2: 265-269. 2245-2263 
DISEASES AND ACCIDENTS 
2245. Burrow, B., A. H. Niden, C. Mittman, R. C. 
Talley and W. R. Barclay. Non-uniform pulmonary 
diffusion as demonstrated by the carbon monoxide equili- 
bration technique: experimental results in man. J. din. 
Invest., 1960, 39: 943-951. 
2246. Carlsen, E. and J. H. Comroe, Jr. Rate of 
CO uptake by normal erythrocytes and by spherocytes. 
Fed. Proc., 1955,14: 25. 
2247. Carlsen, E. and J. H. Comroe, Jr. The rate 
of uptake of carbon monoxide and of nitric oxide by nor- 
mal human erythrocytes and experimentally produced 
spherocytes. J. gen. Physiol, 1958, 42: 83-107. 
2248. Forster, R. E., W. S. Fowler and D. V. 
Bates. Considerations on the uptakes of carbon monoxide 
by the lungs. J. din. Invest., 1954, 33: 1128-1134. 
2249. Forster, R. E., W. S. Fowler, D. V. Bates 
and B. VanLingen. The absorption of carbon monoxide 
by the lungs during breathholding. J. din. Invest., 1954, 
33: 1135-1145. 
2250. Forster, R. E., F. J. W. Roughton, L. 
Gander, W. A. Briscoe and F. Kreuzer. Apparent 
pulmonary diffusing capacity for CO at varying alveolar 02 
tensions. /. appl Physiol, 1957,11: 277-289. 
2251. Forster, R. E., F. J. W. Roughton, F, 
Kreuzer and W. A. Briscoe. Photocolorimetric determi- 
nation of rate of uptake of CO and 02 by reduced human 
red cell suspensions at 37°C. J. appl. Physiol, 1957, 11: 
260-268. 
2252. French, N. and A. L. Hall. The time course 
of carboxyhemoglobin formation in subjects exposed to 
carbon monoxide for periods of ten to sixteen hours, and 
its modification by intermittent breathing of 100% oxy- 
gen. U.S. Navy. School of Aviation Medicine, Pensacola, 
Fla. Res. Kept. NM 001 059.32.01, 6 July 1954, 7 pp. 
2253. Hanson, J. S. and B. S. Tabakin. Steady state 
carbon monoxide diffusing capacity in normal females. 
J. appl Physiol, 1961, 16: 839-841. 
2254. Joels, N. and L. G. C. E. Pugh. The carbon 
monoxide dissociation curve of human blood. J. Physiol, 
1958, 142: 63-77. 
2255. Moore, N. M., T. C. Smith, P. I. Sunahara 
and I. Rankin. A new concept of the physiological 
factors influencing the absorption of CO by the human 
lung. Fed. Proc., 1961, 20: 424. 
2256. Rankin, I., R. S. McNeill and R. E. Forster. 
Influence of increased alveolar CO„ tension on pulmonary 
diffusing capacity for CO in man. J. appl. Physiol, 1960, 
15: 543-549. 
2257. Roughton, F. J. W. The equilibrium between 
carbon monoxide and sheep haemoglobin at very high 
percentage saturations. J. Physiol, 1954, 126: 359-383. 
2258. Shepard, R. H., H. B. Martin, H. A. White, 
S. Permutt, E. Varnauskas and R. L. Riley. Compari- 
son of estimates of pulmonary diffusing capacity by 
steady-state methods using oxygen and carbon monoxide 
in normal subjects at different levels of exercise. Fed. 
Proc., 1958, 17: 147. 
2259. Smith, T. C. and I. Rankin. The effects of 
respiratory maneuvers on the uptake of carbon monoxide 
and calculated diffusing capacity during breathholding. 
Fed. Proc., I960, 19: 382. 
2260. Turino, G. M., M. Brandfonbrener, R. M. 
Goldring and A. P. Fishman. Influence of inspired 
02 tension on pulmonary diffusing capacity for CO. Fed. 
Proc., 1957,16: 129. 
2261. Turino, G. M., E. H. Bergofsky and A. P. 
Fishman. Maximum diffusing capacity of the lung for 
oxygen and carbon monoxide. Fed. Proc., 1958, 17: 164. 
2262. Wald, G. and D, W. Allen. The equilibrium 
between cytochrome oxidase and carbon monoxide. J. 
gen. Physiol, 1957, 40: 593-608. 
2263. Wilks, S. S. Reactions of normal, altitude- 
acclimatized and CO-acclimatized animals to local injec- 
tions of pure carbon monoxide gas. Fed. Proc., 1954, 13: 
165. 
6. TOLERANCE AND ACCLIMATIZATION TO 
CARBON MONOXIDE 
It appears that some acclimatization to carbon 
monoxide may occur without evidence of a 
hematopoietic response. According to Clark and 
Otis (2264) 1952, mice that had been acclima- 
tized to concentrations of carbon monoxide up to 
0.15 percent for 14 days can survive an acute 
exposure to 34,000 feet altitude considerably 
longer than mice unacclimatized to carbon 
monoxide. Mice which have been exposed to 
low oxygen for 14 days can survive in an atmos- 
phere containing 0.25 percent carbon monoxide 
considerably longer than mice unacclimatized to 
low oxygen. The oxygen capacity and hematoc- 
rit in the authors’ experiments increased to 
about the same extent for the mice acclimatized 
to low carbon monoxide and to low oxygen. The 
oxygen capacity increased about 50 percent above 
the controls and the hematocrit 85 percent. The 
carbon dioxide capacity of the plasma was found 
to decrease for the mice acclimatized to low 
oxygen. Mice acclimatized to low carbon 
monoxide showed a higher carbon dioxide 
capacity than unacclimatized mice. In studies 
by Weeks (2265) 1962, dogs, rats and rabbits 
were exposed to 50.9 ppm carbon monoxide 
for three months with carbon dioxide content 
ranging between 600 and 1300 ppm and 
ammonia from 20 to 50 ppm. The carbon 
monoxide content of the blood was 6.4 percent 
saturation of hemoglobin for dogs, 3.0 percent 
for rabbits and 1.6 percent for rats. The dogs 
showed a rise in hemoglobin of 12 percent, in NOXIOUS AGENTS—TREATMENT 
2264-2265 
hematocrit of 9 percent and a possible increase 
in red blood cells, perhaps indicating some ac- 
climatization and giving the only indication of 
a possible metabolic response to 50 ppm carbon 
monoxide. There was a small increase in 
eosinophil count in rats. No significant differ- 
ences between exposed and control animals 
were found in reticulocytes, WBC’s, differentials, 
macroscopic and microscopic examinations of 
organs and tissues respectively, or in behavior 
or activity. After a 24 hour exposure of dogs to 
carbon monoxide the formation of carboxy- 
hemoglobin was 6 percent saturation of hemo- 
globin with 50 ppm of carbon monoxide, 12.6 
percent with 100 ppm, 21 percent with 200 ppm 
and 31 percent with 300 ppm. 
2264. Clark, R. T., Jr. and A. B. Otis. Comparative 
studies on acclimatization of mice to carbon monoxide 
and to low oxygen. Amer. J. Physiol., 1952, 169: 285-294. 
2265. Weeks, M. H. Effects of chronic exposure to low 
concentrations of carbon monoxide, pp. 347-349 in: Man’s 
dependence on the earthly atmosphere. Edited by K. E. 
Schaefer, The MacMillan Company, New York, 1962, 416 
pp. 
7. TREATMENT 
This section will include a selection of reports 
on treatment of carbon monoxide poisoning by 
the use of carbogen, oxygen at ambient pres- 
sures, oxygen at pressures greater than one at- 
mosphere and succinic acid. Douglas, Lawson, 
Ledingham, Norman, Sharp and Smith (2266) 
1961, have carried out experimental studies on 
the use of carbogen in experimental carbon 
monoxide poisoning. Two groups of 10 dogs 
were gassed with carbon monoxide until the 
level of carboxyhemoglobin was 70 percent. Ani- 
mals were then resuscitated using 5 and 7 percent 
carbogen in turn. When a non-return valve was 
placed in a resuscitation circuit no difference 
was found between the efficacy of 5 and 7 per- 
cent carbogen. Thus the choice of a respiratory 
valve which prevents rebreathing when resuscita- 
tion is undertaken in carbon monoxide poison- 
ing is of more importance than the choice of 5 
or 7 percent carbogen mixture. The same authors 
(2267) 1962, found that treatment of carbon 
monoxide poisoning in dogs with pure oxygen at 
two ATA was by far the most efficient. Next 
in order was 5 or 7 percent carbogen. Least 
effective was pure oxygen alone. Lawson, Me- 
Allister and Smith (2271) 1961, also treated 
animals with acute carbon monoxide poisoning 
by oxygen under pressure. Rats and cats were 
exposed to 3 percent carbon monoxide in air and 
showed ataxia after two minutes. The animals 
were unconscious after 3-4 minutes and died in 
5-13 minutes. Animals rendered unconscious 
by 3 percent carbon monoxide could be revived 
with oxygen at a pressure of 15 psi. Simultane- 
ous exposure to 3 percent carbon monoxide 
and oxygen at 15 psi prevented evidence of 
carbon monoxide poisoning. It was suggested 
that oxygen under pressure not only increased 
plasma carriage of oxygen in solution but also 
altered the equilibrium mixture of carboxy- and 
oxyhemoglobin in favor of the latter. Hep- 
arinized human an equine blood exposed to 
coal gas by bubbling for 20 minutes contains 
high levels of carboxyhemoglobin which is liber- 
ated slowly when filmed in air, faster in one at- 
mosphere of oxygen and fastest in two atmos- 
pheres oxygen. Four anesthetized dogs inhaled 
carbon monoxide for one to two hours with 
considerable respiratory depression. Using arti- 
ficial respiration, carbon monoxide was liberated 
most rapidly with oxygen at two atmospheres, 
distinctly slower with oxygen at normal atmos- 
pheric pressure or with carbogen, and least 
rapidly in air alone. Fresh air may be sufficient 
in mild cases of carbon monoxide poisoning, but 
in severe cases the twin aims of immediate ade- 
quate oxygenation of the tissues, and rapid 
elimination of the gas can be carried out most 
effectively using artificial respiration with oxy- 
gen at a pressure of two ATA. The treatment 
of patients with carbon monoxide poisoning with 
oxygen at two atmospheres pressure has been 
described by Smith, Ledingham, Sharp, Norman 
and Bates (2276) 1962. Thirty-two patients 
with coal gas poisoning were admitted to the 
Western Infirmary, Glasgow, during a 12 month 
period. All of these recovered completely. 
Twenty-two of these patients who appeared to be 
severely gassed were treated within 30 minutes 
after exposure in a pressure chamber where they 
breathed oxygen at two ATA through face 
masks. This form of treatment rapidly corrected 
the anoxia and increased the speed at which 
carbon monoxide was removed from the blood 
and tissues. High pressure therapy was believed 2266-2282 
DISEASES AND ACCIDENTS 
by the authors to be particularly beneficial in 
cases complicated by cerebral depression from 
barbiturate overdose or in states of diminished 
cerebral blood flow. Experimental use of succinic 
acid in the treatment of acute carbon monoxide 
poisoning has been described by Gershon, 
Trethewie and Crawford (2268) 1961. This 
substance was injected intraperitoneally into cats 
and guinea pigs comatose from exposure to coal 
gas, producing marked respiratory improvement 
and greatly increased rate of recovery. In dogs 
intravenous administration of succinic acid pro- 
duced an immediate return to a normal level of 
consciousness and reversed electrocardiographic 
changes due to carbon monoxide poisoning. 
2266. Douglas, T. A., D. D. Lawson, I. McA. 
Ledingham, J. N. Norman, G. R. Sharp and G. Smith. 
Carbogen in experimental carbon-monoxide poisoning. 
Brit. med. J., 1961, 5268: 1673-1675. 
2267. Douglas, T. A., D. D. Lawosn, I. McA. 
Ledingham, J. N. Norman, G. R. Sharp and G. Smith. 
Carbon monoxide poisoning: a comparison between the 
efficiencies of oxygen at one atmosphere pressure, of oxy- 
gen at two atmospheres pressure, and of 5% and 7% car- 
bon dioxide in oxygen. Lancet, 1962, 1: 68-69. 
2268. Gersohn, S., E. R. Trethewie and M. Craw- 
ford. The use of succinic acid in the treatment of acute 
carbon monoxide poisoning. Arch. int. Pharmacodyn., 
1961, 134: 16-27. 
2269. Jacobinzer, H. and H. W. Raybin. Carbon 
monoxide poisoning. N.Y. St. J. Med., 1962, 62: 2714-2716. 
2270. Lawson, D., R. A. McAllister and G. Smith. 
The effect of high pressure oxygen in experimental acute 
carbon monoxide poisoning. Scot. med. J., 1959, 4: 327. 
2271. Lawson, D. D., R. A. McAllister and G. 
Smith. Treatment of acute experimental carbon-monoxide 
poisoning with oxygen under pressure. Lancet, 1961, 1: 
800-802. 
2272. Ldyning, Y. Oksygen-overtrykks-behandling ved 
kulloksydforgiftning. [Treatment with oxygen under pres- 
sure in carbon monoxide poisoning.] Tidsskr. norske 
Laegeforen., 1961, 81: 1207-1208. 
2273. Rapport, K. M. O lechenii otravelnii okis’iu 
ugleroda kislorodom pod povyshennym davleniem. [On 
the treatment of carbon monoxide poisoning with oxygen 
under increased pressure.] Vo-med. Zh., 1958, 8: 46-49. 
2274. Sluyter, M. E. The treatment of carbon mon- 
oxide poisoning by administration of oxygen at high at- 
mospheric pressure. Proc. R. Soc. Med., 1963, 56: 1002. 
2275. Sluyter, M. E. and I. Boerema. Treatment of 
carbon monoxide poisoning by administering pressurized 
oxygen. Ned. Tijdschr. Geneesk., 1962, 106: 826-829. 
2276. Smith, G., I. McA. Ledingham, G. R. Sharp, 
J. N. Norman and E. H. Bates. Treatment of coal-gas 
poisoning with oxygen at 2 atmospheres pressure. Lancet, 
1962, 1: 816-819. 
2277. Smith, G. and G. R. Sharp. Treatment of 
carbon-monoxide poisoning with oxygen under pressure. 
Lancet, I960, 2: 905-906. 
2278. Smith, G., G. R. Sharp and I. McA. Leding- 
ham. Treatment of coal gas poisoning in humans by 
oxygen under pressvire. Scot. med. J., 1961, 6: 339. 
2279. Tomashefski, J. F. and C. E. Billings, Jr. 
Carbon monoxide poisoning. The physiologic basis for 
treatment. Ohio St. med. J., 1961, 57: 149-154. 
B. STIBINE 
Antimony hydride (SbH3), known as anti- 
moniuretted hydrogen and later as stibine, was 
discovered by Thomson working in England and 
independently by Pfaff in Germany in 1837. 
Both of these investigators were studying the 
March test for arsenic. 
Since battery grids often contain from 5 to 10 
percent antimony, the production of stibine in 
perceptible quantities during overcharging of 
batteries is a potential hazard in submarines. 
Since the nuclear submarines are not as de- 
pendent on battery power as the older fleet-type 
boats, this hazard has been almost completely 
obviated by the new source for machinery power. 
A more comprehensive review of this subject was 
provided in Volume II of this Sourcebook. 
2280. Doig, A. T. (Arseniuretted hydrogen poisoning 
in tank cleaners. Lancet, 1958, 2: 88-92. 
2281. Gt. Brit. MRC. Hazard from stibine. Gt. Brit. 
MRC, RNPRC, SMS. Kept. S.M.S. 22, 2 pp. 
2282. Sax, N. I., L. J. Goldwater, B. Feiner, M. B. 
Jacobs, J. H. Harley, J. J. Fitzgerald and M. S. 
Dunn. Antimony hydride, p. 454 in: Dangerous properties 
of industrial materials. Reinhold Publishing Corp., New 
York, 1343 pp. 
C. OZONE 
Ozone, according to Von Oettingen {2306), 
is a faintly blue gas when pure and has an odor 
like hay, but when contaminated becomes acrid 
and irritating. The gas causes irritation to the 
respiratory tract, resulting in coughing, frontal 
headache and sometimes nausea. Continued ex- 
posure leads to fatigue, somnolence, disturbed 
sleep, loss of appetite, oppression of the chest, 
vomiting, and later pulmonary edema and even 
death may result. This gas may be present in 
modern submarines (2284), having been pro- 
duced by electrostatic precipatators and other 
arcing electrical equipment on the boat. It there- 
fore presents a hazard. Early reports demon- 
strated that exposure to 0.4 percent ozone killed NOXIOUS AGENTS—OZONE 
animals in one minute. Autopsy revealed severe 
pathological alterations in the lung. In general, 
concentrations of ozone greater than 0.1 ppm 
are toxic, and the lung seems to be the only organ 
affected. Carbon dioxide excretion and oxygen 
uptake by the lung are reduced. Transfusions 
of blood from an ozonized animal did not 
produce symptoms in the transfused animal. 
Subtoxic concentrations of the gas produce 
irritation of the eyes and respiratory tract. Ex- 
posure to 6 ppm for one hour reduced the vital 
capacity to 57.7 percent of normal (5035 and 
2905 cc.) and the residual capacity was in- 
creased by 840 cc. This was explained by partial 
filling of alveolar sacs with edematous fluid 
while swelling of the bronchioles was thought 
to prevent complete opening of the bronchioles 
into the alveoli. Thorp (2305) 1950, has pointed 
out that the toxicity of ozone is greatly enhanced 
by contamination with nitrogen oxides. An 
excellent review of the literature on ozone 
toxicity through 1953 has been published by 
Stokinger (2301) 1954. Patty (2298) 1958, has 
listed the following thresholds for ozone: Thres- 
hold for odor 0.01-0.015 ppm; maximum allow- 
able concentration 0.04 ppm; disorders or 
breathing and reduced oxygen consumption 
0.5-1.0 ppm; inhibition of fungal growth 0.3-1.5 
ppm; headache, respiratory irritation 1-10 ppm; 
lethal to small animals within 2 hours 15-20 
ppm; germicidal for airborne organisms 6500 
ppm. 
According to Mittler, King and Burkhardt 
(2296) 1957, repeated exposure to 2.4 ppm of 
ozone induced some hemorrhage and edema in 
the lungs of rats. Adaptation to ozone is noticed 
after 32 hours of accumulative exposure. Twenty 
percent of 102 mice died after continued ex- 
posure to 2.4 ppm of ozone for 241 hours. 
Chronic exposure to ozone decreased weight gain 
by young rats and concentrations greater than 
1.2 ppm and longer than 7 hours per day 
significantly affected growth of young rats. The 
0.1 ppm value as a maximum allowable concen- 
tration of ozone for an 8 hour workday appears 
reasonable. Mittler, Hedrick, King and Gaynor 
(2294) 1956, have also demonstrated species 
differences in ozone toxicity. The LD50 for a 
three hour exposure of ozone was found to be 21 
ppm for mice, 21.8 ppm for rats, 34.5 ppm for 
cats, 36 ppm for rabbits and 51.7 ppm for guinea 
pigs. Edema occurred in lungs of rats exposed to 
6 ppm for eighteen hours. No damage was 
caused by 24 hour exposure to concentrations of 
less than 3 ppm of ozone. 
Clamann and Bancroft (2285) 1957, have 
called attention to the confusion in the literature 
on the actual toxicity of ozone. With respect to 
the ever increasing importance of ozone for 
industrial purposes and the presence of ozone in 
the upper atmosphere as a possible hazard in 
high altitude conditions, accurate data on the 
physiological effects of ozone are very desirable. 
In animals it was found that for a three hour 
exposure time the LD50 was 12.6 ppm by volume 
for mice, and 25.7 ppm for guinea pigs. Death 
was caused by edema and hemorrhage of the 
lungs. Studies on five human subjects revealed 
great differences in human sensitivity. Irritation 
of the respiratory tract was observed at concen- 
trations as low as 0.6 ppm after 30 minutes. 
Gross changes of respiratory function (reduc- 
tion of vital capacity in more than 50 percent 
and pulmonary edema) occurred after one hour 
at 6 ppm. The soft tissues of the respiratory 
tract seem to be the only tissues of the body at- 
tacked by ozone. The sense of smell is definitely 
affected. An effect on the conjunctiva of the eye 
was neither felt nor observed by inspection. No 
effects upon blood and the circulatory system 
were found. Stokinger, Wagner and Dobrogorski 
(2302) 1957, also found chronic injury as a 
result of repeated inhaltion of ozone at concen- 
trations only 2-3 times greater than currently 
reported in urban areas. The injury is character- 
ized pathologically as chronic bronchitis and 
bronchiolitis. In this condition the terminal 
airways of the lungs were thickened, the air 
passages narrowed, with fibrotic tissue extending 
into the surrounding areas of the lungs with 
consequent emphysema resulting in a lessened 
capacity to move air in and out of the lungs. 
The dog showed none of these deep lung changes 
seen in the smaller animals. Man’s relative posi- 
tion in this range of pulmonary response to ozone 
was judged to be between that of the dog and 
the smaller animals. Griswold, Chambers and 
Motley (2291) 1957, reported the case of one 
author who spent two hours in a chamber ex- 
posed to 2 ppm ozone. Twenty-two hours later 2283-2293 
DISEASES AND ACCIDENTS 
on the following day there was a 13 percent re- 
duction in the total vital capacity with return 
to normal after 22 hours. In studies reported by 
Young and Shaw (2307) 1963, eight normal men 
in twelve experiments breathed air from a breath- 
ing circuit while seated for two hours and then 
breathed air containing 0.6-0.8 ppm of ozone for 
two hours from the same circuit. There was a 
slight reduction of vital capacity from which 
the authors concluded that breathing less than 1 
ppm of ozone for two hours does produce a 
significant but reversible reduction of steady 
state Dlc0 in normal subjects, 
Kleinfeld and Giel (2292) 1956, reported three 
cases of ozone poisoning in welders employing 
a new welding technique. There is difficulty in 
diagnosis in view of a number of clinical condi- 
tions resembling ozone poisoning, such as acute 
pulmonary edema, pulmonary infarction, acute 
myocardial infarction, bronchial asthma, and 
bronchial pneumonia, as well as pulmonary in- 
flammatory conditions due to other toxins such 
as phosgene. The diagnosis of ozone poisoning 
may be suspicious and depend on adequate oc- 
cupational history, familiarity with the toxico- 
logical effects and finding significant amounts of 
ozone in the working environment. In the cases 
reported, the presence of 9.2 ppm of ozone at the 
work site was far in excess of the presently ac- 
cepted threshold limit of 0.1 ppm. Regarding the 
effect of oxygen and carbon dioxide upon the 
acute toxicity of ozone, Mittler, Hedrick and 
Phillips (2295) 1957, found that ozone in oxygen 
was less toxic for mice than ozone in air. The 
oxygen had no influence on toxicity of ozone for 
rats and guinea pigs. Ozone in 2 percent carbon 
dioxide-air mixture was more toxic for guinea 
pigs than ozone in air. The two percent carbon 
dioxide had no significant effect on the toxicity 
of ozone for rats and mice. 
In further studies of ozone toxicity Stokinger, 
Wagner and Wright (2303) 1956, found a strik- 
ing enhancement of toxicity of ozone in rats 
and mice when the animals were exercised in- 
termittently during exposure. Thus an ozone 
concentration of 1 ppm was fatal in six hours 
in these species when accompanied by exercise 
for 15 minutes each hour of exposure. The 
authors found that marked tolerance to ozone 
developed rapidly (within 24 hours) and per- 
sisted for 4-6 weeks. 
Treatment is symptomatic and the condition 
is best dealt with by prevention. Fairchild, 
Murphy and Stokinger (2288) 1959, described 
two distinct but related pathways of protection 
against the lethal effects of ozone and nitrogen 
dioxide: a) simultaneous inhalation of com- 
pounds that furnish -SH or -SS groups or both, 
and b) by injection of thiourea derivatives sev- 
eral days prior to exposure to these oxidant 
gases. The mechanism of a) is believed similar 
to that proposed for the action of radiation pro- 
tective compounds. That of b) involves the 
development of a tolerance initiated by the 
thiourea against the oxidants. A paper by 
Mittler (2297) 1958, also brings out the difficulty 
of therapy. In submarine operations the strategy 
must be to prevent the buildup of toxic levels of 
ozone in the atmosphere. 
2283. Christensen, E. and A. C. Gies.e. Changes in 
absorption spectra of nucleic acids and their derivatives 
following exposure to ozone and ultraviolet radiations. 
Arch. Biochem. Biophys., 1954, 51: 208-216. 
2284. Clamann, H. G. Physical and medical aspects of 
ozone, pp. 143-156 in: Physics and medicine of the atmos- 
phere and space. Edited by O. O. Benson, Jr. and H. 
Strughold, John Wiley and Sons, Inc., New York, 1960, 
645 pp. 
2285. Clamann, H. G. and R. W. Bancroft. Phys- 
iological effects of ozone. Fed. Proc., 1957, 16: 22. 
2286. Davis, I. Microbiologic studies with ozone. 
Quantitative lethality of ozone for escherichia coli. USAF. 
Brooks Air Force Base, Texas. School of Aerospace Medi- 
cine, Kept. no. 61-54, March 1961, 16 pp. 
2287. Diggle, W. M. and J. C. Gage. The toxicity of 
ozone in the presence of oxides of nitrogen. Brit. J. in- 
dustr. Med., 1955, 12: 60-70. 
2288. Faircihld, E. J., II, S. D. Murphy and H. E. 
Stokinger. Protection by sulfur compounds against the 
air pollutants ozone and nitrogen dioxide. Science, 1959, 
130: 861-862. 
2289. Forchheimer, O. L. and H. Taube. Tracer 
studies on the decomposition of ozone in water. J. Amer. 
Chem. Soc., 1954, 76: 2099-2103. 
2290. Giese, A. C., H. L. Leighton and R. Bailey. 
Changes in the absorption spectra of proteins and repre- 
sentative amino acids introduced by ultraviolet radiations 
and ozone. Arch. Biochem. Biophys., 1952, 40: 71-84. 
2291. Griswold, S. S., L. A. Chambers and H. L. 
Motley. Report of a case of exposure to high ozone 
concentrations for two hours. Arch, industr. Hlth., 1957, 
15: 108-110. 
2292. Kleinfeld, M. and C. P. Giel. Clinical manifes- 
tations of ozone poisoning: report of a new source of ex- 
posure. Amer. J. med. Sci., 1956, 231: 638-643. 
2293. Mendenhall, R. M. and H. E. Stokinger. 
Surface active films as a model of lung injury by irritant 
gases. Fed. Proc., 1961, 20: 420. NOXIOUS AGENTS—TOBACCO SMOKE 
2294-2310 
2294. Mittler, S., D. Hedrick, M. King and A. 
Gaynor. Toxicity of ozone. I. Acute toxicity. Industr. 
Med., 1956, 25: 301-306. 
2295. Mittler, S,, D. Hedrick and L. Phillips. 
Toxicity of ozone. II. Effect of oxygen and carbon dioxide 
upon acute toxicity. Industr. Med., 1957, 26: 63-66. 
2296. Mittler, S., M. King and B. Burkhardt. 
Toxicity of ozone. III. Chronic toxicity. Arch, industr. 
Hlth., 1957,15: 191-197. 
2297. Mittler, S. Toxicity of ozone. IV. Silicone aero- 
sols and alcohol vapor therapy in ozone poisoning. Industr. 
Med. Surg., 1958, 27; 43-45. 
2298. Patty, F. A. Ozone, pp. 915-917 in: Industrial 
hygiene and toxicology. Volume II. Edited by F. A. Patty, 
Interscience Publishers, Inc., New York, 1958, 2377 pp. 
2299. Sax, N. I. Ozone, p. 1064 in: Dangerous prop- 
erties of industrial materials. Edited by N. I. Sax, Reinhold 
Publishing Corp., New York, 1963, 1343 pp. 
2300. Spector, W. S. Ozone, p. 346 in: Handook of 
toxicology. Volume I. U.S. National Research Council, 
W. B. Saunders Co., Philadelphia, 1956, 408 pp. 
2301. Stokinger, H. E. Ozone toxicity. A review of 
the literature through 1953. Arch, industr. Hyg., 1954, 9: 
366-383. 
2302. Stokinger, H. E., W. D. Wagner and O. J. 
Dobrogorski. Ozone toxicity studies. III. Chronic injury 
to lungs of animals following exposure at a low level. 
Arch, industr. Hlth., 1957,16: 514-522. 
2303. Stokinger, H. E., W. D. Wagner and P. G. 
Wright. Studies of ozone toxicity. I. Potentiating effects 
of exercise and tolerance development. Arch. ind. Hlth., 
1956,14: 158-162. 
2304. Tamas, A. A. Threshold limit values for hydro- 
carbons and ozones in confined spaces, pp. 343-346 in: 
Man’s dependence on the earthly atmosphere. Edited by 
K. E. Schaefer, The MacMillan Company, New York, 1962, 
416 pp. 
2305. Thorp, C. E. The toxicity of ozone. Industr. 
Med., 1950, 19: 49-57. 
2306. Von Oettingen, W. F. Ozone, pp. 470-471 in: 
Poisoning. A guide to clinical diagnosis and treatment. 
W. B. Saunders Co., Philadelphia, 1958, 627 pp. 
2307. Young, W. A. and D. B. Shaw. Effect of low 
concentrations of ozone on pulmonary function. Fed. 
Proc., 1963, 22: 396. 
D. RADON 
The following papers on radon have been 
included because of the potential hazard in closed 
spaces. However, at present in submarines radon 
is no longer used in luminous paint for dials. 
2308. Martin, E. J. and J. K. W. Ferguson. 
Radon in normal breath. Canad. J. med. Sci., 1952, 30: 
42-47. 
2309. Martin, E. J. and J. K. W. Ferguson. Fluctua- 
tions of breath, radon in subjects seated at rest. Arch, in- 
dustr. Hyg., 1953, 8: 574-581. 
2310. Nussbaum, E. and J. B. Hursh. Radon solu- 
bility in fatty acids and triglycerides. J. phys. Chem., 1958, 
62: 81-84. 
E. TOBACCO SMOKE 
Since smoking is still a virtually universal habit 
and since the use of tobacco does have definite 
morale values, it is not desirable to restrict 
smoking except under certain conditions. Smok- 
ing does add to the carbon monoxide content of 
the air and this should be a limiting factor. The 
papers that follow are selected from the large 
literature on physiological effects of tobacco 
smoking. McGiff (2319) 1963, found in anesthe- 
tized dogs a three to thirty-fold increase in renal 
vascular resistance associated with a marked 
pressor response (range 75 to 150 mm./Hg in- 
crement) . Femoral vascular resistance was only 
moderately increased. The response of the renal 
bed was examined in detail by measuring flows 
from both kidneys, one of which was denervated. 
Denervation did not preclude the increased renal 
vascular resistance. Adrenergic blocking agents 
(e.g. 0.1 mgm./kg. phentolamine) will prevent 
the pressor response or terminate an established 
pressor response concomitantly with restoration 
of renal flows to control levels. Ganglionic block- 
ing agents, reserpine and adrenalectomy will 
prevent both the hypertensive response and the 
increase in renal vascular resistance. Shepherd 
(2324) 1951, found in human subjects that in- 
halation of tobacco smoke at intervals of one 
minute led to a transient decrease in hand blood 
flow at the time of inhalation. Similar decreases 
occurred when inhalations of the same depth 
were carried out with the cigarette unlit. Tran- 
sient decrease in flow was therefore due to the 
physiological effect of the deep breath and was 
not necessarily caused by the pharmacological ac- 
tion of the substance in the tobacco. Apart from 
this decrease in flow on inhalation, the general 
level of hand flow was unaltered during and 
immediately after smoking one cigarette. When 
cigarette smoke was inhaled every 20 seconds, 
more rapidly than normal, the hand blood flow 
steadily decreased during the smoking period. 
When cigarettes were smoked at rates in excess 
of normal there was a resulting decrease in hand 
blood flow that was mainly pharmacological and 
not physiological in origin. In studies carried 
out by Wechsler (2323) 1958, normal subjects 
(17 to 85 years of age) smoked three regular 
sized cigarettes in 10 minutes. No significant 2311-2315 
DISEASES AND ACCIDENTS 
changes in cerebral blood flow, oxygen consump- 
tion, vascular resistance, respiratory quotient or 
blood pH were observed. Electroencephalograms 
were made before, during and for 10 minutes 
after smoking and revealed intermittent flatten- 
ing, lasting for 1-30 seconds. This pattern only 
occurred with puffing on the cigarette. It also 
occurred to a lesser degree in individuals who 
did not inhale and in those subjects smoking fil- 
tered or denicotinized cigarettes. This pattern 
could be an abnormal attention response. Lung 
volumes in smokers and non-smokers have been 
reported by Blackburn, Brozed, Carlson and Tay- 
lor (2311) 1958. The subjects were 222 clinically 
healthy business and professional men aged 
47-57 years. The mean age and relative body 
weight were similar in different categories of 
cigarette smokers and of non-smokers. Vital 
capacity and residual volume were measured with 
the subjects seated. In comparison with the non- 
smokers, all smokers showed smaller vital 
capacity, larger residual volume, smaller total 
lung capacity and larger ratio of residual volume 
to total lung capacity. The relation of lung 
volume to smoking is in the direction to be 
expected if smoking is a repeated source of 
bronchial irritation causing increased airway 
resistance. In 31 subjects who had successfully 
stopped all smoking one or more years prior to 
the experiment, the mean values were not 
significantly different from the category of sub- 
jects who had never smoked. In studies by Nadel 
and Comroe (2320) 1961, a body plethysmograph 
was used to measure the ratio of airway con- 
ductance (reciprocal of airway resistance) to 
thoracic gas volume in a group of healthy sub- 
jects, including 23 non-smokers and 25 smokers. 
The ratio decreased after inhalation of cigarette 
smoke in both groups and the effect was almost 
immediate, lasting about 35 minutes. Krumholz, 
Chevalier and Ross (2315) 1963, carried out an 
investigation designed to study the effect of 
chronic cigarette smoking on some aspects of 
pulmonary physiology and on the ability of 
the individual to handle and repay his oxygen 
debt during and after exercise. Studies were 
carried out in nine smokers and in nine non- 
smokers who were similar in body surface area, 
age and occupation. All smokers had smoked at 
least one pack a day for five years. Every subject 
exercised for five minutes on a bicycle ergometer 
and a mean oxygen uptake of 2.06 L./minute was 
achieved during the fifth minute of work. The 
ratio of the oxygen debt to the total oxygen up- 
take was significantly greater in the smoking 
group than in the non-smokers. Resting breath- 
holding and pulmonary diffusing capacity was 
significantly greater in non-smokers than in 
smokers. In a study by Orma, Karvonen, Keys 
and Brozek (2321) 1958, in a group of male 
subjects aged 20-59 years of age and judged 
“healthy” from clinical and electrocardiographic 
examination, the serum cholesterol was signifi- 
cantly higher while the blood pressure tended 
to be lower in smokers as compared to non- 
smokers. Westfall and Watts (2326) 1963, found 
a significantly higher 24 hour urinary excretion 
of epinephrine in smokers than in non-smokers. 
The difference in nor-epinephrine excretion was 
not significant. In other studies the excretion 
of epinephrine and nor-epinephrine was deter- 
mined at 30 minute intervals before, during and 
after heavy smoking in 15 subjects. The results 
indicated that the epinephrine and total 
catecholamine output increases progressively 
above control levels during periods of heavy 
smoking. Experiments were also carried out in 
which blood samples were obtained from the 
inferior vena cava above and below the adrenal 
glands in patients undergoing cardiac catheriza- 
tion before, during and after smoking one 
cigarette. The results showed an increase in the 
epinephrine levels from the inferior vena cava 
blood from a control value of 1.2 /cgm./L. to a 
value of 3.7 p,gm./L. during smoking. 
2311. Blackburn, H., J. Brozek, W. Carlson and 
H. L. Taylor. Lung volumes in smokers and non-smokers. 
Fed. Proc., 1958,17: 15. 
2312. Brozek, J. and A. Keys. Smoking and body 
composition. Fed. Proc., 1957, 16: 16. 
2313. Haagen-Smit, A. J., M. F. Brunelle and J. 
Kara. Nitrogen oxide content of smoke from different 
types of tobacco. Arch, industr. Filth., 1959, 20: 399-400. 
2314. Kratochvil, C. H., S. S. Wilks and W. A, 
Gerrard, III. Cigarette smoking at altitude. Fed. Proc., 
1957,16: 75. 
2315. Krumholz, R, A., R. B. Chevalier and J. C. 
Ross. Pulmonary diffusing capacity and oxygen debt at 
rest and during exercise in smokers and non-smokers. 
Circulation, 1963, 28: 754. NOXIOUS AGENTS—AIR IONS 
2316-2326 
2316. Levine, R. R., E. W. Pelikan and C. J. 
Kensler. The effect of cigarette smoking on the excretion 
of phenol red. Fed. Proc., 1961, 20: 414. 
2317. Lyons, M. J. and H. Johnston. Chemical in- 
vestigation of the neutral fraction of cigarette smoke tar. 
Brit. J. Cancer, 1957,11: 544-562. 
2318. Maliszewski, T. F. and D. E. Bass. ‘True’ 
and ‘apparent’ thiocyanate in body fluids of smokers and 
nonsmokers. /. appl. Physiol., 1955-56, 8: 289-291. 
2319. McGiff, J. C. Regional flow response to cigarette 
smoking in the dog. Fed. Proc., 1963, 22: 509. 
2320. Nadel, J. A. and J. H. Comroe, Jr. Acute 
effects of inhalation of cigarette smoke on airway conduct- 
ance. J. appl. Physiol, 1961, 16: 713-716. 
2321. Orma, E., M. Karvonen, A. Keys and J. 
Brozek. Cigarette smoking, serum cholesterol and blood 
pressure. Fed. Proc., 1958, 17: 120. 
2322. Osborne, J. S., S. Adamek and M. E. Hobbs. 
Some components of gas phase of cigarette smoke. Analyt. 
Chem., 1956, 28: 211-215. 
2323. Rinfret, A. P. Effect of ionized air and tobacco 
smoke on the adrenal lipid content in rats. Stanf. med. 
Bull, 1953,11: 125. 
2324. Shepherd, J. T. Effect of cigarette-smoking on 
blood flow through the hand. Brit. med. J., 1951, 2: 1007- 
1010. 
2325. Wechsler, R. L. Effects of cigarette smoking 
and intravenous nicotine on the human brain. Fed. Proc., 
1958, 17: 169. 
2326. Westfall, T. C. and D. T. Watts. Catechola- 
mine excretion in smokers and nonsmokers. Fed. Proc., 
1963, 22: 509. 
F. AIR IONS 
It has been suggested that an excess of positive 
air ions may be partly responsible for reduced 
well being and efficiency. A large literature has 
developed in which this possibility is discussed. 
In a study of the effect of gaseous ions on tracheal 
ciliary rate, Krueger and Smith {2347) 1958, 
have pointed out that positive and negative air 
ions have notable effects upon ciliary rate and 
other properties of the mammalian trachea both 
in vitro and in vivo. It seems reasonable, accord- 
ing to the authors, to conclude that these effects 
stem from physiologically significant alterations 
in the state of gases present in the ambient at- 
mosphere and that deliberately produced changes 
in composition of the atmosphere will be re- 
flected in the response of the tracheal tissue. To 
test this assumption experiments were performed 
on rabbits. The experiments demonstrated that 
when administered in unmodified humid air, 
negative ions increase the ciliary rate by about 
200 beats per minute reaching maximum effect 
within 10-20 minutes, while positive air ions 
lower the ciliary rate by about 300 beats per 
minute or abolish ciliary activity altogether 
(reaching maximum effect within 15-20 min- 
utes) . These effects were seen both in tracheas 
of living animals and in extirpated tracheal 
strips. In similar studies Krueger and Smith 
(2343) 1957, carried out experiments to deter- 
mine whether negative ions were beneficial in 
certain cases of hay fever and asthma, while posi- 
tive ions produce nasal obstruction, dryness of 
mucous membranes and headaches. The experi- 
ments were also designed to test whether these 
observations could be correlated with measurable 
changes in pulmonary clearing mechanisms in- 
cluding ciliary rate, rate of mucous flow and 
smooth muscle tone. Ciliary activity became 
slowed and ceased usually in six hours with ex- 
posure of tracheal strips to positive ions. Nega- 
tive ions produced increased ciliary rate. Ex- 
posure to positive ions caused the mucous flow 
to decrease markedly or to cease. Negative ions 
caused an increase in one-half of the experiments 
and no effect in the other half. Positive ions 
routinely caused the membranous posterior wall 
of the trachea to contract. In this condition it 
was possible to elicit peristalsis by stretching 
the tissue laterally. Negative ions completely re- 
versed this effect. On exposure to positive ions 
the tracheal surface assumed a dry, non-glossy 
appearance, whereas negative ions either had no 
effect or caused the appearance of watery fluid. 
Positive ions rendered the cilia particularly 
vulnerable to mechanical trauma. This com- 
pletely disappeared when the tissue was exposed 
to negative ions. All of these studies were carried 
out on rabbit tissue, and the authors point out 
that no theory has yet been developed for the 
action of air ions on the trachea. Krueger and 
Smith (2351) 1962, have concluded that air ions 
are unquestionably physiological mediators, posi- 
tive ions being harmful and negative ions bene- 
ficial. Ion-induced changes in the physiological 
state of the trachea tend to persist. After 72 
hours in a positively ionized environment, mice 
retained the effects for four weeks. Tracheal 
effects attributed to positive ions can be dupli- 
cated by intravenous injection of 5-hydroxytrypta- 
mine and like positive ions, effects can be 
reversed by treatment with negative air ions. DISEASES AND ACCIDENTS 
Therefore, positive air ions appear to be 
“serotonin releasers” and a local accumulation of 
5-hydroxytryptamine is the immediate cause of 
positive ion effects. That negative ion reversal 
of positive ion effects is by increasing the rate of 
5-hydroxytryptamine oxidation is supported by 
the direct action of negative ions on cytochrome 
oxidase and acceleration of the cytochrome-linked 
conversion of succinate to fumarate. Reserpine 
which causes tissue depletion of 5-hydroxytrypta- 
mine, has an effect on the trachea similar to 
negative ions and positive ions have no effect 
on reserpine-treated animals. Iproniazid blocks 
the enzyme responsible for metabolizing 5-hy- 
droxytryptamine and an accumulation of 5-hy- 
droxytryptamine develops. An ipronazid treated 
animal displays tracheal effects resembling those 
produced by positive air ions and resists the 
normal action of negative air ions in reversing 
this effect. A similar report has been given by 
Krueger and Smith (2350) 1960. Nielsen and 
Harper (2361) 1954, have studied the effect of 
ait ions on succinoxidase activity of rat adrenal 
glands. After four hours in positively ionized 
air the succinoxidase content of the rat’s adrenal 
gland was significantly reduced. A similar period 
in negatively ionized air produced slight but in- 
significant rise in succinoxidase activity. By com- 
parison, a single injection of 5 mgm. of ACTH 
produced a moderate rise whereas the same dose 
given twice daily for six days resulted in a 
significant fall in adrenal succinoxidase. Ac- 
cording to Worden (2374) 1954, exposure of 
young adult male hamsters to positive air ion 
concentrations decreased the carbon dioxide 
capacity of the blood whereas exposure to nega- 
tive air ions increased the carbon dioxide capacity 
of blood. In both cases the changes were signifi- 
cantly different from controls. Worden and 
Thompson (2375) 1956, found that the rate of 
proliferation of cultures of pure strain L cells 
(Earle’s) was accelerated under conditions of 
negative ionization and decelerated under condi- 
tions of positive ionization. The nature of these 
effects is compatible with those observed in intact 
animals. Worden (2373) 1953, studied the 
effect of unipolar ionized air on the growth 
of selected organs of the Gold hamster. Ninety- 
two of these animals divided into three groups 
lived in ion controlled or a normal atmosphere 
for 60 or more days of the postnatal development 
period. It was found that an atmosphere with 
an increased concentration of negative ions 
exerted a stimulating influence on the growth 
and ultimate relative weights of certain organs as 
compared with the same organs in control ani- 
mals. An increased concentration of positive 
ions demonstrated no statistically significant 
values. Jordan and Sokoloff (2339) 1959, ex- 
amined the effect of air ionization on maze learn- 
ing in rats. A multiple T-pattern maze with 
escape from water was used on 150 rats of an 
average of three months of age and 150 rats of an 
average of 22 months of age in a study of age 
differences in maze learning. It was found that 
the number of errors and the time scores of the 
group of old rats were about three times and 
two times greater respectively than those of the 
young rat group under normal atmospheric con- 
ditions. Negative air ionization reduced con- 
siderably the number of errors and the time 
scores of the runs of the old rats. The psychologi- 
cal effects of artificially produced air ions in hu- 
man subjects have been examined by McGurk 
(2355) 1959. Ten college age males were sub- 
jected to five hours exposure at specific work 
tasks under two environments: 1) approximately 
8000 negative air ions/cc. or air, and 2) natural 
ion concentration of the test room. Some sub- 
jects also performed two hours of the same work 
in environments of approximately 8000 positive 
ions/cc. of air. There was no statistically signifi- 
cant difference in the mean scores of performance 
in the various conditions. The subjects were 
not able to respond accurately to the question, 
“Was the air ionized today?” when control con- 
ditions prevailed judgments differed from chance 
at the 1 percent level; when positive conditions 
prevailed judgments differed at the 10 percent 
level. Although the findings are tentative there 
was general agreement with previous literature 
that negative ionization environments were as- 
sociated with feelings of well being and that 
positive ionization was associated with irritation, 
depression and fatigue. 
The use of negatively ionized air in the treat- 
ment of burns has been reported by David, Mine- 
hart and Kornblueh (2330) 1960, and by Mine- 
hart, David and Kornblueh (2356) 1958. It 
appears that in a large number of the cases there NOXIOUS AGENTS—AIR IONS 
2327-2358 
is relief of pain, reduction of local infection, de- 
crease in exudation and deoderization of the 
burned area. Accelerated epithelialization has 
also been observed. Kornblueh, Piersol and 
Speicher [2343) 1958, reported relief from hay 
fever symptoms in 123 patients exposed to nega- 
tive ionization. Positive ionization provided 
either no relief or increased distress. The relief 
obtained from negative ionization is said to be 
temporary since the symptoms reappear shortly 
after the individual returns to an environment 
with the normal ion balance. 
2327. Behounek, F. and J. Kletschka. Ionization of 
air in an air-conditioned building. Nature, Lond., 1938, 
142: 956. 
2328. Chase, C. T, and C. H. Willey. A biological 
effect of ionized air. Science, 1935, 82: 157-158. 
2329. Cupcea, S., M. Deleanu and T. Frits. Ex- 
perimentelle Untersuchungen fiber den Einfluss der 
Luftionisation auf pathologische Veranderungen der 
Magenschleimhaut. Acta biol. med., Germ., 1959, 3: 407- 
416. 
2330. David, T. A., J. R, Minehart and I. H. 
Kornblueh Polarized air as an adjunct in the treatment 
of burns. Amer. J. phys. Med., 1960, 39: 111-113. 
2331. Deleanu, M. and T. Frits. Versuche uber die 
Beteiligung des Nervensystems im biologischen Wirkungs- 
mechanismus von ionisierter Luft. Acta biol. med., Germ., 
1961, 6: 103-109. 
2332. Dougherty, J, H., K. E. Schaefer and W. 
Anderson. Interaction of airions and aerosols. Fed. Proc., 
1961, 20: 210. 
2333. Duffner, G. J. Man-made air. Problems and 
limitations. Ann. Otol, etc., St. Louis, 1961, 70: 410^117. 
2334. Edstrom, G. Studies in natural and artificial 
atmospheric electric ions. Acta med. scand., 1935, 61: 1-83. 
2335. Frey, A. H. Human behavior and atmospheric 
ions. Psychol. Rev., 1961, 68: 225-228. 
2336. Golovanova, G. P. and G. S. Gracheva. 
K voprosu o vliianii gidroaeroionizatsii na sostoianie 
zdorov’ia i razvitie detei rannego vozrasta. [On the effect 
of hydroaeroionization on the health status and growth 
of young children.[ Pediatrics, Moscow, 1961, 1: 24-28. 
2337. Herrington, L. P. The influence of ionized air 
upon normal subjects. J. din. Invest., 1935,14: 70-80. 
2338. Hinchcliffe, R. Some aspects of nasal function 
and dysfunction in relation to environmental air. Ann. 
occup. Hyg., 1961, 3: 6-21. 
2339. Jordan, J. and B. Sokoloff. Air ionization, 
age, and maze learning of rats. J. Geront., 1959, 14: 344- 
348. 
2340. Karmen, A., L. Giuffrida and R. L. Bowman. 
Detection by ionization of atmospheric gases during analy- 
sis by gas chromatography. Nature, Lond., 1961, 191: 906- 
907. 
2341. Koiranskii, B. B., L, la. Ukvol’berge, M. V. 
Dmitriev and N. S. Kolodina. O vliianii ionizatsii 
vozdukha na fizicheskuiu rabotosposobnost’. [On the effect 
of ionization of air on physical efficiency.] Gigiena San., 
Moskva, 1961, 7; 29-33. 
2342. Kornblueh, I, H. and J. E. Griffin. Artificial 
air ionization in physical medicine: preliminiary report. 
Amer. J. phys. Med., 1955, 34: 618-631. 
2343. Kornblueh, I. H., G. M. Piersol and F. P. 
Speicher. Relief from pollinosis in negatively ionized 
rooms. Amer. J. phys. Med., 1958, 37: 18-27. 
2344. Krueger, A. P. Some biologic properties of 
gaseous ions. J. Einstein med. Cent., 1960, 8: 79-88. 
2345. Krueger, A. P. and R. F. Smith. Effects of air 
ions on isolated rabbit trachea. Proc. Soc. exp. Biol., N.Y., 
1957, 96: 807-809. 
2346. Krueger, A. P. and R. F. Smith. The effects 
of air ions on the living mammalian trachea. J. gen. 
Physiol, 1958, 42: 69-82. 
2347. Krueger, A. P. and R. F. Smith. Effects of 
gaseous ions on tracheal ciliary rate. Proc. Soc. exp. Biol., 
N.Y., 1958, 98: 412-414. 
2348. Krueger, A. P. and R. F. Smith Parameters 
of gaseous ion effects on the mammalian trachea. J. gen. 
Physiol, 1959, 42: 959-969. 
2349. Krueger, A. P. and R. F. Smith. An enzymatic 
basis for the acceleration of ciliary activity by negative air 
ions. Nature, Lond., 1959, 183: 1332-1333. 
2350. Krueger, A. P. and R. F. Smith. The biologi- 
cal mechanisms of air ion action. I. 5-hydroxytryptamine 
as the endogenous mediator of positive air ion effects on 
the mammalian trachea. J. gen. Physiol, 1960, 43: 533- 
540. 
2351. Krueger, A. P, and R. F. Smith. The phys- 
iological significance of positive and negative ionization 
of the atmosphere, pp. 356-367 in: Man’s dependence on 
the earthly atmosphere. Edited by K. E. Schaefer, The 
MacMillan Company, New York, 1962, 416 pp. 
2352. Krueger, A. P., R. F. Smith and I. G. Go. 
The action of air ions on bacteria. Protective and lethal 
effects on suspensions of staphylococci in droplets. J. gen. 
Physiol, 1957-58, 41: 359-381. 
2353. Laub, J. Uber Schwankungen atmospharischer 
lonen und ihre biologische Wirkung. Bull, schweiz. Akad. 
med. Wiss., 1960, 16: 292-304. 
2354. Martin, T. L. Climate control through ioniza- 
tion. J. Franklin Inst., 1952, 254: 267-280. 
2355. McGurk, F. C. J. Psychological effects of arti- 
ficially produced air ions. Amer. J. phys. Med., 1959, 38: 
136-137. 
2356. Minehart, J. R., T. A. David and I. H. 
Kornblueh. Artificial ionization and the burned patient. 
Med. Sci., 1958,3: 363-367. 
2357. Minehart, J. R., T. A. David, F. J. McGurk 
and I. H. Kornblueh. The effect of artificially ionized 
air on post-operative discomfort. Amer. J. phys. Med., 1961, 
40: 56-62. 
2358. Minkh, A. A. lonizatsiia vozdukha i ee gigieni- 
cheskoe znachenie. [Air ionization and its hygienic import- 
ance.] Thesis (Med.), Moskva, Medgiz, 1958, 187 pp. 2359-2380 
DISEASES AND ACCIDENTS 
2376. Zylberberg, B. and M. H. Loveless. Prelimi- 
nary experiments with ionized air in asthma. J. Allergy, 
I960, 31: 370-374. 
VIII. MOTION SICKNESS 
The subject of motion sickness was covered 
quite fully in Volume II of this Sourcebook. 
Since that time, however, the emergence of the 
nuclear powered boat has made it practical to 
travel submerged for prolonged distances, and 
this has obviated the necessity of running on the 
surface where stormy conditions may prevail. 
Therefore at present, and increasingly in the 
future, motion sickness problems in submarining 
may be considered to be abated. The following 
items have been included primarily for their 
academic interest. The factors which determine 
vulnerability to motion sickness seem to be neuro- 
physiological rather than psychological, although 
psychological factors may play a role. 
2377. Kottenhoff, H. (How efficient are optical inver- 
sion methods with adults to test their motion sickness 
susceptibility? Acta psychol., 1960, 17: 96-99. 
2378. Lindahl, L. E. H. PGR changes and other 
variables related to experimentally induced motion-sick- 
ness. Acta psychol., 1960, 17: 99-111. 
2379. U.S. Navy. Miscellaneous problems, pp. 81-82 
in: U.S. Navy diving manual. BuShips, NAVSHIPS 250- 
538, 1958-1959, 433 pp. 
2380. Wang, S. C. and H. I. Chinn. Experimental 
motion sickness in dogs. Importance of labyrinth and 
vestibular cerebellum. Amer. J. Physiol., 1956,185: 617-623. 
IX. SUBMARINE ESCAPE 
PROCEDURES 
A. BREATH HOLDING 
Breath control is of importance in the correct 
practice of free escape under emergency condi- 
tions or in training. Breath control is also im- 
portant to the SCUBA diver in certain emer- 
gencies such as exhaustion of the breathing gas 
tanks or malfunction of the breathing apparatus. 
Free escape is now the standard practice for in- 
dividualized emergence from disabled subma- 
rines, and since buoyancy is now provided by an 
inflatable life vest, problems of buoyancy and 
ascent are obviated. Correct breath control is 
absolutely essential, the procedure being ex- 
pressed colloquially as “blow and go”. This 
means that the submariner exhales continuously 
throughout the ascent. 
2359. Minkh, A. A. O gigienicheskom znachenii 
ionnogo rezhima vozdukha pomeshchenii. [On the hygienic 
significance of the ionic condition of indoor air.] Gigiena 
San., Moskva, 1960, 1: 78-83. 
2360. Minkh, A. A. Aeroionizatsiia v meditsine. 
[Aeroionization in medicine.] Vest. Akad. Med. Nauk., 
SSSR, 1961, 7: 3-13. 
2361. Nielsen, C. B. and H. A. Harper. Effect of 
air ions on succinoxidase activity of the rat adrenal gland. 
Proc. Soc. exp. Biol., N.Y., 1954, 86: 753-756. 
2362. Okada, Y. The influence of the inhalation of 
ionized air on the living body. Chem. Abstr., 1939, 33: 
5425. 
2363. Portnov, F. G. Aeroionoterapiia bol’nykh 
gipertonicheskoi bolezn’iu. [Aeroionotherapy of patients 
with hypertension.] Thesis (Med.), Akad. Nauk. Latv. 
SSR, Riga, 1960, 270 pp. 
2364. Schaefer, K. E. Airborne condensation droplets, 
ions, as health factors in closed spaces. U.S. Navy. Sub- 
marine Base, New London, Conn. Medical research labora- 
tory. Project NM 24 04 20.05, Kept. no. 1, 20 September 
1959. 
2365. Silverman, D. and I. H. Kornblueh. Effect 
of artificial ionization of the air on the electroencephalo- 
gram; preliminary report. Amer. J. phys. Med., 1957, 36: 
352-358. 
2366. Silverman, D. and I. H. Kornblueh. Ioniza- 
tion and the EEG; a preliminary report. [Summary.] EEG 
din. Neurophysiol., 1957, 9: 180. 
2367. Skorobogatova, A. M. Vliianie ionizirovannogo 
vozdukha na arterial’noe davlenie u zhivotnykh s perekre- 
stnym krovoobraschcheniem pri vagotomii dykhatel’nykh 
putei. [The effect of ionized air on arterial pressure in 
animals with crossed blood circulation in the presence of 
vagotomy of the respiratory tract.] Trud. fiziol. Inst. im. 
I.P. Pavlova, 1959, 8: 411-418. 
2368. Steigerwald, B. J. Air ions. pp. 65-79 in: 
Air pollution. Volume I. Edited by A. C. Stern, Academic 
Press, New York, 1962, 656 pp. 
2369. Vasiliev, L. L. (Teoriia i praktika lecheniia 
ionizirovannym vozdukhom. [Theory and practice of treat- 
ment by ionized air.] Leningrad, LGU, 2nd ed., 1953. 
2370. Vasiliev, L. L. The physiological mechanisms 
of aeroions. Amer. J. phys. Med., I960, 39: 124-128. 
2371. Verzar, F. Physiological and toxicological 
significance of atmospheric condensation nuclei, pp. 350- 
355 in: Man’s dependence on the earthly atmosphere. 
Edited by K. E. Schaefer. The MacMillan Company, New 
York, 1962, 416 pp. 
2372. Winsor, T. and J. C. Beckett. Biologic effects 
of ionized air in man. Amer. J. phys. Med., 1958, 37: 83-89. 
2373. Worden, J. L. The effect of unipolar ionized 
air on the relative weights of selected organs of the golden 
hamster. Sci. Stud., 1953, 15: 71-82. 
2374. Worden, J. L. Effect of air-ion concentration 
and polarity on the carbon dioxide capacity of mammalian 
blood plasma. Fed. Proc., 1954, 13: 168. 
2375. Worden, J. L. and J. R. Thompson. Air-ion 
concentration and the growth of cells in vitro. Anat. Rec., 
1956, 124: 500. SUBMARINE ESCAPE—BREATH HOLDING 
Breath holding is an important skill to escape 
tank instructors who must make free dives from 
the surface of the tank to observe the trainees as 
they perform their maneuvers. For this purpose 
they may have to hold a breath for three or four 
minutes. Skill in breath holding can be acquired 
and the duration of breath holding can be in- 
creased by practice. 
Breath holding is part of the occupational skill 
of pearl and sponge divers and in some parts of 
the world, as in Japan and Korea, this work is 
undertaken by women who maintain a long tradi- 
tion for this kind of activity. 
For a sound review paper on breath holding, 
DuBois (2396) 1955, may be consulted. As 
pointed out in this review, breath holding is im- 
possible with a Pco<) greater than 60 mm. Hg, 
even with a normal P0i) and lung volume. Breath 
holding is also impossible with Pn., less than 30 
mm. Hg (with other factors normal). A Pco„ of 
76 mm. Hg at full inspiratory tidal volume or 37 
mm. Hg at full expiratory volume will terminate 
slow voluntary rebreathing. Just under the sur- 
face of the water, breath holding is impossible 
after the carbon dioxide has risen to 50 mm. Hg 
and the oxygen has fallen to 50 mm. Hg (about 
50 seconds). At 100 feet (4 ATA) 60 mm. Hg 
carbon dioxide can be tolerated because of ade- 
quate oxygen saturation. Breath holding during 
depth changes are calculated on the basis of the 
rate of gas entering the pulmonary blood. This 
is equal to the A-V content difference times blood 
flow and is also dependent on the relationship of 
the rate of change, which equals the rate of 
change of concentration times volume. On ascent 
from 100 feet (I14 minutes), starting with nor- 
mal alveolar air and lung volume (4.7 liters), 
there is a decrease in PC09 which is due to expan- 
sion and to oxygen consumption. There is no rise 
in the alveolar PCOo because expansion just coun- 
teracts the metabolic rise as carbon dioxide is 
brought to the lungs by the venous blood. Dur- 
ing rapid ascent after three minutes breath hold- 
ing at 100 feet there is some danger of the Pc09 
falling to a low level during the last few feet. A 
subject short of breath at 100 feet is actually re- 
lieved by ascent. The rate of ascent should in- 
crease as the rate of carbon dioxide production 
is increased by actively swimming. During de- 
scent to 100 feet at one foot per second, the Pc0,, 
reaches 61 mm. Hg at 20 feet, and at two feet per 
second reaches 69 mm. Hg at 30 feet. The al- 
veolar oxygen is always high, but these levels of 
carbon dioxide are dangerous. As the depth 
increases, the rate of compression is less, and the 
effect of blood flow in taking excess carbon diox- 
ide out of the lungs is greater because of the 
small lung volume. A given amount of carbon 
dioxide taken out of a small lung volume de- 
creases the PCOo to a greater degree. 
Rahn has cited some unpublished data on 
Korean Amas diving to 30 feet in the Yellow Sea. 
These data were derived from his own investiga- 
tions. Gas samples indicated that about 20 sec- 
onds after the beginning of the Ama’s breath 
hold dive the total amount of carbon dioxide in 
her lungs was less than she had at the start of 
her dive, and the alveolar P0o was nearly as high 
as the inspired air at the surface. Of particular 
interest was the alveolar oxygen concentration on 
reaching the surface at the end of a 45-60 second 
dive. Values as low as 3.5 percent were recorded. 
The rapid expansion of the gases during the 
ascent caused the alveolar P0o to fall below the 
mixed venous level and therefore the usual di- 
rection of oxygen transport was reversed. During 
compression the PCOo in arterial blood increases 
above the values of mixed venous Pco„ and re- 
mains elevated. The usual drop in P0f> is pre- 
vented by compression. Therefore at this time 
the PCOo the only important stimulus to respira- 
tion. Subjectively this is the hardest time of 
voluntary apnea. Upon ascent the arterial PCo2 
drops and brings immediate relief, but the Pq2 
falls to very low levels and may drop so rapidly 
that the impairment of consciousness does not 
allow the full effect of the low oxygen drive to 
be experienced. The mental confusion just be- 
fore reaching the surface makes such subjective 
analysis difficult. 
Craig (2387) 1961, has given case reports of 
eight survivors and of five deaths from loss of 
consciousness. All of the victims were considered 
good swimmers and were experienced in under- 
water swimming. All of the survivors hyper- 
ventilated before going under the surface. Seven 
of these had some goal in mind or were in com- 
petition with others. Swimmers usually expe- 
rienced an urge to breathe but there was little 
or no warning before “passing out”. Cerebral DISEASES AND ACCIDENTS 
function was such that the victims were unable 
to take appropriate action to meet the situation. 
The author conducted experiments to attempt to 
explain why a person might lose consciousness 
while swimming under water. Prior hyperventi- 
lation increases breath holding time. During 
voluntary overbreathing PCOo in the blood is 
decreased as well as other carbon dioxide stores. 
During breath holding, plus exercise, metaboli- 
cally produced carbon dioxide raises the Pc0„ in 
the blood. The rate of repletion of stores will 
limit the time at which blood PCOo attains levels 
associated with the overwhelming urge to breathe 
again. In humans the contribution of oxygen 
to the respiratory drive is weak. When the oxy- 
gen consumption is increased, as in the first few 
seconds of exercise, the P0o may decrease to a 
degree incompatible with cerebral function be- 
fore the rise of P00.5 becomes unbearable. Exer- 
cise seems to increase the subject’s tolerance of 
hypercapnia. The PCOo in the alveolae is higher 
at the breaking point when the subject held his 
breath during exercise than when respiration was 
suspended during rest. This displacement of the 
breaking point curve increases the likelihood of 
hypoxia. Loss of consciousness in hypoxia occurs 
with little specific warning. Between the time of 
loss of consciousness and final collapse the sub- 
ject may continue his previous activity. Similar 
data are analyzed in Craig’s paper (2388) pub- 
lished in 1961. 
Bradycardia is a response to apneic diving 
which man shares with many other species. Craig 
(2390) 1963, observed slowing of the heart rate 
during diving in children as well as in adults 
and found that this was as prominent in poor 
swimmers as in those subjects who were familiar 
with the water. The response was independent 
of depth down to 27 meters, but could not be pro- 
duced by simulated dives in a decompression 
chamber. Diving in water implies several maneu- 
vers, some of which were investigated during 
breath holding. It was observed that the tachycar- 
dia produced by breath holding at different val- 
salva pressures was proportional to the increase of 
intrathoracic pressure. At equal pressures the 
tachycardia was less when the subject was in 
water than when in air. Other maneuvers which 
increased venous return at the beginning of the 
breath hold produced a bradycardia during the 
apnea, and conversely when venous return was 
impaired there was a tachycardia. The hypothesis 
is presented that diving bradycardia in man 
might be explainable in terms of already known 
physiological mechanisms. In a study of breath 
holding after exercise, Craig and Cain (2391) 
1957, measured breath holding time after five 
grades of work in a group of 12 men. An average 
of 1.4 seconds elapsed between the signal (given 
without warning) and the cessation of inhala- 
tion. During this time the volume inhaled varied 
with the phase of the breathing cycle in which 
the signal was given. It was greatest when the 
signal was given in the quarter cycles immedi- 
ately before and after the beginning of inspira- 
tion. Since breath holding time was unaffected 
by the phasing of the signal it is thought that 
the volume of the lung was adjusted to enable 
the breath holder to begin with a full lung (full 
in the sense of a full tidal volume characteristic 
of the previous grade of work). The mean breath 
holding time decreased from 25.8 seconds after 
the lowest grade of work to 5.8 seconds after the 
highest. It was proposed that the stimulus to 
breathe at the end of the hold was the same 
after all grades of work. The stimulus was eval- 
uated in terms of a rate of accumulation of a 
chemical stimulating condition proportional to 
the previous respiratory minute volume multi- 
plied by the length of the hold and divided by the 
estimated volume of the lungs during the hold. 
Calculated in this way the value assigned to the 
stimulus varied from 1.0 to 1.3 among the grades 
of previous work. In half of the trials alternating 
gasps and holds were continued after the initial 
hold for a total of 30 seconds. The succeeding 
breath holding times were essentially of the same 
length as the first. The volume of the succeeding 
gasps varied only slightly with the previous grade 
of work. 
Fowler (2400) 1953, has reported an attempt 
to evaluate the mechanical factors which are 
determinants of the breaking point of voluntary 
breath holding. 
Olsen, Fanestil and Scholander (2412) 1962, 
carried out investigations of the effects of breath 
holding on cardiac rate and rhythm in man. 
The subjects held their breath in a wooden 
tank lying prone underwater. The periods of 
apnea were the longest with simple breath hold- SUBMARINE ESCAPE—BREATH HOLDING 
2381-2384 
ing without exercise and without preceding hy- 
perventilation. There was a consequent brady- 
cardia which was not prevented by exercise. Out 
of 64 periods no changes in cardiac rhythm were 
seen in 10 out of 15 periods of simple breath 
holding. The most frequent rhythm change 
was a decrease in the amplitude of the P wave 
without any alteration in the P-Q interval. This 
was usually preceded by an abrupt decrease in 
the rate. The next most common change con- 
sisted of abnormal rhythms arising in the A-V 
node or common bundle of His, sometimes pre- 
ceded by A-V dissociation. This appeared at an 
average heart rate of 54 beats per minute. There 
were idioventricular rhythms and a sinus arrest 
in three subjects at rates of 37, 43 and 30 beats 
per minute. Supraventricular premature beats 
were observed during dives and during recovery. 
Progressive increase in the amplitude of the T 
wave was observed during breath holding. Dur- 
ing recovery there was prompt return to sinus 
rhythm: the return to normal T waves was more 
gradual. Sinus tachycardia and arrhythmia with 
premature beats of atrial nodal or ventricular 
origin were common during the first 30 seconds 
of breathing following the test. The develop- 
ment of bradycardia during underwater swim- 
ming is apparently a prerequisite to safe adapta- 
tion. In a study of effects of apneic underwater 
diving on blood gases, lactate and pressure in 
man, Olsen, Fanestil and Scholander (2413) 
1962, directed five men (32-54 years of age) of 
outstanding diving ability in performing apneic 
underwater dives in a specially fitted tank. A 
forearm was held out of water in some studies; 
in others the head and shoulders were out of 
water. The water temperature ranged from 26 
to 37°C. Exercise dives consisted of pedaling 76 
strokes per minute with 12-23 Kg. weights. The 
divers hyperventilated to extreme degrees of hy- 
pocapnia before submerging, and their arterial 
blood carbon dioxide tensions rarely rose above 
normal levels during a dive. Arterial blood oxy- 
gen content was 15.5 volumes percent or above 
at the end of two 3-minute rest dives and of three 
1.5 minute exercise dives. Blood lactate con- 
centrations increased during the latter half of 
exercise dives and reached peak values after sur- 
facing. An initial rise in blood pressure was 
followed by a drop which was maximal at five 
seconds and then rose and continued to the end 
of the dive. The blood pressure became irreg- 
ular at the end of the dive coinciding with the 
increased muscular activity. A transient rise in 
heart rate coincidental with a fall in blood pres- 
sure was followed by a progressively irregular 
fall in pressure. The rate of blood pressure rise 
was greater during a dive in water of 26°C. than 
with breath holding by the same subject out of 
water. Eisner (2397) 1963, has experimentally 
studied limb blood flow in man during breath 
holding dives. The circulatory responses to div- 
ing in animals are known to include bradycardia 
and general peripheral and visceral ischemia 
with little change in blood pressure. In Eisner’s 
study a search was made for peripheral ischemic 
reactions during diving. Young adult male sub- 
jects were used in experiments in which heart 
rate and calf blood flow were measured in the 
prone position during simple breath holding 
and during dives which consisted of face immer- 
sion in water. Typical apneic periods lasted one 
minute. Limb blood flow was measured plethys- 
mographically using the Whitney gauge method. 
All subjects had bradycardia and decreased calf 
blood flow during dives. Both heart rate and 
blood flow were reduced more with face immer- 
sion than by breath holding alone. The response 
was unrelated to diving experience and it was 
variable, ranging from slight to extreme. A heart 
rate of 12 per minute was recorded in one subject; 
another’s blood flow was undetectable during 
the dive, although he had profuse flow both be- 
fore and after it. Tachycardia and hyperemia 
caused by limb exercise were also reduced by 
diving. 
For further information on breath holding the 
reader is referred to a symposium on this subject 
held at the International Physiological Congress 
in Japan in 1966 and as of this writing still 
unpublished. 
2381. Astrand, P.-O. Breath holding during and 
after muscular exercise. /. appl. Physiol., 1960, 15: 220-224. 
2382. Cain, S. M. Effects of exercise and heat on 
breathholding time. Fed. Proc., 1954,13: 22. 
2383. Cain, S. M. Breaking points of two breath holds 
separated by a single inspiration. Fed. Proc., 1957, 16: 18. 
2384. Cain, S. M. Breaking point of two breath holds 
separated by a single inspiration. J. appl. Physiol., 1957, 
11: 87-90. 2385-2419 
DISEASES AND ACCIDENTS 
2385. Chapin, J. L. Comparison of rebreathing and 
breath holding breaking point curves at 5300 feet. Fed. 
Proc., 1955,14: 27. 
2386. Chapin, J. L. Relationship between lung volume 
and breath-holding breaking point. /. appl. Physiol, 1955- 
56. 8: 88-90. 
2387. Craig, A. B., Jr. Underwater swimming and 
loss of consciousness. J. Amer. med. Ass., 1961,176: 255-258. 
2388. Craig, A. B., Jr. Causes of loss of consciousness 
during underwater swimming. J. appl. Physiol, 1961, 16: 
583-586. 
2389. Craig, A. B., Jr. Regulation of respiration in 
exercise and breath holding. Ann. N.Y. Acad. Sci., 1963, 
109: 901-907. 
2390. Craig, A. B., Jr. Heart rate responses to apneic 
underwater diving and to breath holding in man. J. appl. 
Physiol, 1963,18: 854-862. 
2391. Craig, F. N. and S. M. Cain. Breath holding 
after exercise. /. appl. Physiol, 1957, 10: 19-25. 
2392. Craig, F. N. and E, G. Cummings. Breath 
holding during exercise. Fed. Proc., 1958,17: 30. 
2393. Davis, J. H. Fatal underwater breath holding 
in trained swimmers. J. forensic Sci., 1961, 6: 301-306. 
2394. DuBois, A. B. Alveolar O., and COQ during 
inspiration, expiration and breath holding. Fed. Proc., 
1952,11: 37. 
2395. DuBois, A. B. Alveolar C02 and 02 during 
breath holding. J. appl. Physiol, 1952, 5; 1-12. 
2396. DuBois, A. B. Breath holding, pp. 99-100 in: 
Proceedings of the underwater physiology symposium. 
Edited by L. G. Goff, National Research Council, Wash- 
ington, D.C. N.R.C. Publication 377, 1955, 153 pp. 
2397. Eisner, R. W. Reduced limb blood flow in man 
during breath-holding dives. Fed. Proc., 1963, 22: 179. 
2398. Fabre, H., Y. Linquete and R. Rougier. 
Modifications £lectrocardiographiques a 
1’apnee volontaire avec ou sans effort. J. Physiol. Path, gen., 
1957, 49: 149-150. 
2399. Fink, B. R. and G. G. Nahas. Apneic thres- 
hold and acid-base balance. Ann. N.Y. Acad. Sci., 1963, 
109: 804-814. 
2400. Fowler, W. S. Mechanical factors in breath 
holding. Fed. Proc., 1953,12: 44. 
2401. Gorlin, R., J. H. Knowles and C. F. Storey. 
The Valsalva maneuver as a test of cardiac function; 
pathologic physiology and clinical significance. Amer. J. 
Med., 1957, 22: 197-212. 
2402. Heller, M. L. and T. R. Watson, Jr. Polaro- 
graphic study of arterial oxygenation during apnea in 
many. New Engl. J. Med., 1961, 264: 326-330. 
2403. Holmdahl, M. H. Pulmonary uptake of oxygen, 
acid-base metabolism and circulation'during prolonged 
apnea. Acta chir. scand., Suppl, 1956, 212: 1-128. 
2404. Klocke, F. J. and H. Rahn. Breath holding 
after breathing of oxygen. J. appl. Physiol, 1959, 14: 689- 
693. 
2405. Knowles, J. H., W. Newman and W. O. 
Fenn. Determination of oxygenated, mixed venous blood 
COz tension by a breath-holding method. J. appl. Physiol, 
1960,15: 225-228. 
2406. Lambertsen, C. J. and J. M. Benjamin, Jr. 
Breath-by-breath sampling of end-expiratory gas. J. appl. 
Physiol, 1959, 14: 711-716. 
2407. Lanphier, E. H. and H. Rahn. Gas exchange 
during simulated breath-hold dives. Fed. Proc., 1961, 20: 
424. 
2408. Lee, G. de J., M. B. Matthews and E. P. 
Sharpey-Schafer. The effect of the Valsalva manoeuvre 
on the systemic and pulmonary arterial pressure in man. 
Brit. Heart J., 1954,16: 311-316. 
2409. Mithoefer, J. C. Mechanism of C0o transport 
during breath holding. Fed. Proc., 1958,17: 112. 
2410. Mithoefer, J. C. Mechanism of pulmonary gas 
exchange and C02 transport during breath holding. J. 
appl. Physiol, 1959, 14: 706-710. 
2411. Ogilvie, C. M., R. E. Forster, W. S. Blake- 
more and J. W. Morton. A standardized breath holding 
technique for the clinical measurement of the diffusing 
capacity of the lung for carbon monoxide. /. din. Invest., 
1957, 36: 1-17. 
2412. Olsen, C. R., D. D. Fanestil and P. F. 
Scholander. Some effects of breath holding and apneic 
underwater diving on cardiac rhythm in man. J. appl. 
Physiol, 1962, 17: 461-466. 
2413. Olsen, C. R., D. D. Fanestil and P. F. Scho- 
lander. Some effects of apneic underwater diving on 
blood gases, lactate, and pressure in man. J. appl. Physiol, 
1962,17: 938-942. 
2414. Pappenheimer, J. R. The respiratory dead 
space, pp. 101-111 in: Proceedings of the underwater physi- 
ology symposium. Edited by L. G. Goff, National Research 
Council, Washington, D.C. N.R.C. Publication 377, 1955, 
153 pp. 
2415. Rahn, H. Lessons from breath holding, pp. 
293-302 in: The regulation of human respiration. Edited 
by D. J. C. Cunningham and B. B. Lloyd, F. A. Davis Co., 
Philadelphia, 1963, 591 pp. 
2416. Silvertson, S. E. and W. S. Fowler. Expired 
alveolar carbon dioxide tension. Fed. Proc., 1955, 14: 140. 
2417. Stroud, R. C. Combined ventilatory and breath- 
holding evaluation of sensitivity to respiratory gases. J. 
appl. Physiol, 1959,14: 353-356. 
2418. Weybrew, B. B. and R. P. Youniss. The re- 
lationship of breathholding ability, manifest anxiety, and 
past aquatic experience to performance in the pressure 
chamber and escape training tank. U.S. Navy. Submarine 
Base, New London, Conn. Medical research laboratory. 
Project MR005.14-2100-3, Rept. no. 4, 29 January 1960. 
2419. Anon. Risks of hyperventilation before swim- 
ming under water. Brit. med. ]., 1961, 5239: 1596. 
B. ESCAPE PROCEDURES 
It is strongly suggested that readers refer to 
Volume II of this Sourcebook (pages 251-254) 
for two dramatic accounts of actual escape at- 
tempts. The first disaster occurred off Formosa in 
1944 when the U.S.S. Tang was sunk by its own 
torpedo. The second catastrophe concerns re- SUBMARINE ESCAPE—ESCAPE PROCEDURES 
ports of survivors from the German submarine 
U—1195 sunk in April 1945 in the English chan- 
nel. Both of these reports provide valuable in- 
formation. 
A general discussion of submarine escape and 
free ascent has been given by Miles (2430) 1962. 
To reach the surface the submariner must first 
be compressed to the pressure of the water sur- 
rounding the submarine and then be decom- 
pressed as he rises through the water. It is quite 
impossible for any hatch in a submarine to be 
opened from within until the pressure inside 
has been raised to that outside. Even at a shal- 
low depth of 33 feet the hatches are kept shut 
by a pressure of about 7 tons. A history of sub- 
marine escape is outlined and a report of an 
Admiralty Committee on Submarine Escape 
stated as follows: 1) The major hazard is within 
the submarine prior to ascent. About 75 percent 
of all submarine escape casualties occurred dur- 
ing the period of flooding. 2) During World 
War II as many men made an escape ascent with- 
out breathing apparatus as did with it. 
Escape procedures must fall into two major 
groups; 1) those in which survivors remain at 
atmospheric pressure throughout (as in the sit- 
uation in which the escape bell can be lowered 
from the surface and fastened to the escape hatch 
of the submarine). 2) situations in which the 
pressure in the submarine must be raised to that 
of the surrounding water so as to allow the 
survivors to open the hatch and then make their 
ascent. Both methods are in use today. There 
are of course definite limitations to the use of 
the bell. Direct rescue with the bell depends 
upon the early arrival of highly technical surface 
assistance. A limitation to such methods is that 
frequently much time will elapse before rescue 
ships can reach the area and fasten the bell upon 
the submarine or that the submarine may be in 
a position which makes such an operation diffi- 
cult or impossible. The state of the sea further 
complicates or prevents the above maneuvers. 
With nuclear powered submarines a situation 
may well arise where such a vessel although dis- 
abled and unable to leave the bottom may main- 
tain its domestic services and air purification 
facilities for weeks. This opens up possibilities 
of “unhurried” salvage and improves chances of 
obtaining ideal conditions for the use of the 
rescue chamber. The rescue chamber or bell is 
standard equipment in the U.S. Navy and im- 
mense organization is demanded to maintain it. 
In practice the chamber is carried by rescue 
vessels which have trained and experienced divers 
on board. The pressure equalization method of 
escape depends on the man’s ability to leave the 
submarine on his own. For this it is necessary 
for the pressure within to be raised to that out- 
side before any hatch can be opened. Four stages 
must be considered: 1) within the submarine be- 
fore flooding and pressure equalization is com- 
menced; 2) the period of equalization; 3) the 
ascent and 4) survival on the surface. 
Miles has stated that what happens during the 
pre-flooding period depends upon conditions 
within the hull just after the accident. If there 
has been structural damage and general flood- 
ing, escape of toxic fumes or other immediate 
emergency, escape must be precipitous with the 
object of abandoning the craft as quickly as pos- 
sible. Under other circumstances the damage 
may be isolated and the men alive and secure 
in undamaged compartments. Here considera- 
tion must be given to the number of men, the 
condition of the atmosphere and so on. 
During the period of pressure equalization an 
important hazard may arise from the increase in 
pressure which in turn can produce lethal pres- 
sures of carbon dioxide and other impurities. 
The effects of a continued stay at pressure must 
also be considered. The longer the time of ex- 
posure to pressure the greater will be the danger 
of decompression sickness on ascent. If the 
submarine is deeper than 145 feet there will be 
risk of decompression sickness if air is breathed. 
At 200 feet the safe time for exposure if bends 
are to be avoided is about six minutes, and at 
300 feet it is three minutes. The pressure being 
equalized, the hatches can be opened and no time 
is lost by the men in escaping either from the 
compartment or the chamber. Miles has sug- 
gested that the outflow of air helps to prevent 
an accumulation of carbon dioxide which might 
otherwise bring breath holding to an end and 
at the same time there is sufficient oxygen partial 
pressure to maintain consciousness. The in- 
crease in the rate of air escape can be seen if a 
man is followed up through the water trailed 
by a gentle stream of bubbles, beginning with a 2420-2434 
DISEASES AND ACCIDENTS 
small bubble and ending with a massive one near 
the surface. Miles has also stated that if there 
is no obstruction to this escape of air there is 
no danger in coming up through the water. 
For survival on the surface flotation gear of 
some type is essential. The problems of survival 
on the surface after submarine escape are not yet 
solved altogether, especially in heavy seas and 
cold water. 
2420. Alvis, H. J. Submarine rescue and escape. 
Arch, industr. Hyg., 1952, 6: 293-304. 
2421. Alvis, H. J. Manual of free escape from sub- 
marines. U.S. Navy. Submarine Base, New London, Conn. 
Medical research laboratory. Project NM 002 015.01.02, 10 
January 1952, 11 pp. 
2422. Arborelius, M., Jr. and C. Lundgren. Fri 
uppstigning; kontrollerad uppstigning. [Free ascent; con- 
trolled acent.f Medd. fiyg. Navmed., 1957, 6: 57-60. 
2423. Bond, G. F., R. D. Workman and W. F, 
Mazzone. Deep submarine escape. U.S. Navy. Submarine 
Base, New London, Conn. Medical research laboratory. 
Project MR 005.14-3200-.02, 30 December 1960, 20 pp. 
2424. Crocker, W. E. Principles and technique of 
free ascent in submarine escape. J.R. nav. med. Serv., 1955, 
41: 133-140. 
2425. Guillerm, R. and Badre. Les pos£s 
par le sauvetage des equipages de sous-marins coul£s. Rev. 
Med. nav., 1953, 8: 165-187. 
2426. Jensen, F. G. and W. F. Searle, Jr. Buoyancy 
control of open circuit SCUBA. U.S. Navy. EDU, Naval 
Weapons Plant, Washington, D.C. Project NS 185-005, sub 
task no. 4, test no. 22, 20 February 1957, 9 pp. 
2427. Kinde, L. Realistisk sakovning till sjoss. [Real- 
istic rescue training at sea.] Medd. flyg. Navmed., 1962, 
11: 9-11. 
2428. Kullander, T. Blodtryck, puls och andning efter 
s. k. fri uppstigning. [Blood pressure, pulse and respiration 
after so-called free ascent.] Medd. flyg. Navmed., 1961, 10: 
1-5. 
2429. Lambert, R. J. W. Submarine escape. Proc. R. 
Soc. Med., 1958, 51: 824-827. 
2430. Miles, S. Submarine escape and free ascent, 
pp. 291-308 in: Underwater medicine. J. B. Lippincott Co., 
Philadelphia, 1962, 328 pp. 
2431. Peirano, J. H,, H. J. Alvis and G. J. Duffner. 
Submarine escape training experience. Summary of twenty- 
five-year period, July 1929-December 1954. Arch, industr. 
Hlth., 1959, 20: 106-116. 
2432. Peirano, J. H., H. M. Alvis and G. J. Duff- 
ner. Submarine escape training experience—summary of 
twenty-five year period July 1929 through December 1954. 
U.S. Navy. Submarine Base, New London, Conn. Medical 
research laboratory. Project NM 002 015.08, Rept. no 3, 
12 May 1955. 
2433. Shelford, W. O. Subsunk. The story of sub- 
marine escape. George G. Harrap and Co. Ltd., London, 
1960, 256 pp. 
2434. U.S. Navy. Escape from submarines, pp. 312—330 
in: Submarine medicine practice. U.S. Navy, BuMed. 
NAVMED — P 5054, Gov’t. Printing Office, Washington, 
D.C., 1956, 357 pp. 
C. GAS EMBOLISM 
The potential hazard of gas in the circulation 
is still significant. Of particular concern in this 
section is the mechanism of air embolism oc- 
curring in free escape accidents. Lung damage 
may occur as a result of improper escape and 
ascent from the submarine or following ditching 
of SCUBA gear. Even during proper ascent, the 
existence of lung pathology such as a broncholith, 
may act as a midus for damaging air trapping. 
In all these accidents air is forced under pres- 
sure into the pulmonary circulation through 
ruptures in the alveoli and is admitted to the 
left heart and thence into the systemic circula- 
tion, including the coronary system. 
The central nervous system is almost invariably 
involved (2486), Most frequently the accident 
has been associated with relatively rapid ascent 
without breathing apparatus, as in the free ascent 
method of submarine escape and in emergency 
ascent following failure of SCUBA gear. Emboli- 
zation of the cerebral circulation by bubbles is 
considered the immediate cause of symptoms. 
Victims occasionally show minimal central 
nervous system defects but profound neurologi- 
cal involvement, including unconsciousness and 
convulsions, may be present. If recompression 
is delayed or omitted death is the usual outcome 
in cases which displays severe symptoms. If there 
are any symptoms at all immediate recompres- 
sion is absolutely mandatory. Recompression 
must be carried out in a chamber and not in the 
water. 
Several papers reporting cases of air embolism 
may be cited. Durant and Oppenheimer (2447) 
1957, have given a clear clinical picture of the 
condition. The paper by Durant and Oppen- 
heimer covers air embolism associated with 
thoracic surgical procedures. In these cases the 
onset of the manifestation of arterial air em- 
bolism is usually sudden but in some cases there 
are warning symptoms before the severe features 
become manifest. The patient will often state 
that he “feels funny”, that he is dizzy or that 
he is faint. Rarely, the patient may complain 
first of pain in the head and in some instances SUBMARINE ESCAPE—GAS EMBOLISM 
may express fear of death. These initial features 
of the embolism may come on during a thoracic 
procedure, as stated. Following the early warn- 
ing symptoms there is usually loss of conscious- 
ness, the duration of which is variable. Some 
patients retain consciousness but are disoriented. 
Convulsions occur in somewhat less than half the 
cases and may be localized or general, tonic or 
clonic, or both of the latter in sequence. Local- 
ized neurological manifestations are noted fol- 
lowing return of consciousness, although they 
may appear earlier. These include hemiplegia, 
hemiparesis, hemianesthesia, monoplegia, hemi- 
anopsia, nystagmus and strabismus. Frequently 
these signs disappear within a few hours or days 
but cases have been recorded in which hemipare- 
sis persisted for as long as four months. Blindness 
may occur also, and may be complete even in 
patients who have not temporarily lost conscious- 
ness. This manifestation may persist for several 
days. Pupils are usually dilated, and sometimes 
widely so, but occasionally they are constricted. 
Cyanosis is noted in the majority of instances. 
The respiratory rate is generally slowed, and 
sometimes Cheyne-Stokes breathing is observed. 
Manifestations of peripheral vascular collapse are 
frequent, and may be severe even in those who 
later recover. Following recovery from the acute 
episode, should the patient be so fortunate, pain 
in the chest referred to the precordial or subster- 
nal area, is a frequent complaint and may be 
accompanied by considerable dyspnea. Elec- 
trocardiographic evidence of myocardial infarc- 
tion has been observed. Nausea and vomiting 
may be troublesome complaints and persist for 
hours or days. 
Liebow, Stark, Vogel and Schaefer (2465, 
2466) 1959 and 1960, have presented details of 
two casualties encountered in submarine escape 
training and have considered the role of intrapul- 
monary air trapping in each case. One patient 
survived and the other died. In the fatal case 
a broncholith of tuberculous origin acted as a 
ballvalve within a subsegmental bronchus. In 
the other patient who survived, the mechanism 
of the bronchial obstruction was not apparent, 
but a large bulla was demonstrated roentgeno- 
graphically after decompression. This was al- 
most entirely absorbed within 36 hours after the 
patient’s return to atmospheric pressure. The 
problem of detecting persons potentially pre- 
disposed to involuntary air trapping when breath- 
ing air at supra-atmospheric pressure and 
subjected to the stress of rapid decompression 
is an important one. Individuals with obstruc- 
tive pulmonary emphysema, with significant pul- 
monary calcification (in whom broncholiths may 
exist), or those with evidence of chronic respira- 
tory disease, should be eliminated from sub- 
marine escape training. As shown in the case 
of the second patient, even careful radiographic 
and physiologic studies may fail to demonstrate 
air trapping under ordinary atmospheric pres- 
sure with the methods now available. Again 
it should be stated that facilities for immediate, 
rapid recompression should be available because 
at present this method offers the only means 
of therapy, the efficacy of which has been at- 
tested to under the practical conditions of sub- 
marine escape training. 
For two other papers reporting case studies, 
reference is made to Collins (2440) 1963, and 
Miasnikov and Mashkov (2472) 1961. 
Further references on the treatment of air 
embolism may be cited: Clemedson and Hult- 
man (2438) 1954, have discussed recompression 
of animals subjected to air blast injury. The 
occurrence of air embolism and the cause of 
death in such injuries was studied by these 
authors in anesthetized rabbits exposed to high 
explosive blasts in an open field and in a spe- 
cially constructed detonation chamber. Intra- 
vascular air was found in a fairly high number 
of the animals that died within 15-20 minutes 
after the exposure. Air embolism was rare in 
animals dying later on. By recompressing the 
animals to four atmospheres gage pressure im- 
mediately after the detonation, it was possible 
to reduce considerably the occurrence of intra- 
vascular air bubbles. Peter and Griming (247(7) 
1954, point out that the pathological-anatomical 
findings in arterial air embolism are similar to 
those existing in caisson disease and recommends 
recompression as the treatment procedure. The 
authors reported the use of this treatment in 
guinea pigs in which large arterial emboli had 
been produced. Moretti (2474) 1963, also calls 
attention to immediate recompression, as well as 
placing the patient in a position with the feet 
elevated and the head lower than the rest of DISEASES AND ACCIDENTS 
the body. The patient should be placed on his 
left side. Musgrove and MacQuigg (2475) 1952, 
report the case of severe air embolism success- 
fully treated by turning the patient to the left 
lateral position. 
The prevention of gas embolism in escape by 
any other ascent from depth rests essentially 
upon training of personnel to achieve an effective 
appropriately controlled exhalation of air from 
the lungs during the ascent. Also, careful physi- 
cal examination to rule out so far as possible 
any pulmonary condition that would impede this 
is required. Various investigators have demon- 
strated that binders around the chest and 
abdomen prevent overdistention of the lungs 
and keep the transpulmonic pressure from reach- 
ing a critical value. Schaefer, McNulty and Carey 
(2478) 1957, for example, have conducted such 
studies on dogs. These animals were decom- 
pressed within two minutes during which time 
the trachea was closed from a pressure equiva- 
lent of 100 or 200 feet to sea level. Recordings 
of pressure were taken from the abdominal 
aorta, the inferior cava, the left atrium, the pul- 
monary artery and trachea, the intrapleural space 
and abdominal cavity. All dogs were prepared by 
operation two to four weeks before the experi- 
ments. The pressure gradient between the in- 
tratracheal and intrapleural pressure (trans- 
pulmonic pressure) was found to be the decisive 
factor in producing embolism. The critical level 
of transpulmonic pressure was 60-70 mm. Hg. 
It was found that binders around the chest and 
abdomen did act effectively. However, abdominal 
binders alone failed to give protection against 
air embolism. Similar studies were also reported 
by Schaefer, McNulty, Carey and Liebow (2479) 
1958. When unprotected dogs were decompressed 
from 100 or 200 feet equivalent depth with the 
trachea closed, there developed pulmonary in- 
terstitial emphysema and air embolism, probably 
via the pulmonary veins when intratracheal pres- 
sure reached a critical level of approximately 
80 mm. Hg. The lungs became markedly dis- 
tended by entrapped air expanding as the 
ambient pressure was reduced. The systemic 
aortic pressure fell in consequence of compres- 
sion of the postarterial vessels in the lungs, in- 
dicated by a higher gradient between pulmo- 
nary arterial and left atrial pressures. Interstitial 
emphysema and air embolism could be prevented 
as indicated above, by the application of thoraco- 
abdominal binders, despite a rise in intratracheal 
pressure to levels of 180 mm. Hg or more. The 
effects of the binders were; a) to prevent over- 
distention of the lung as indicated by the small 
difference between the intratracheal and intra- 
pleural pressures; b) to keep at a lower level the 
pressure gradient between the respiratory pass- 
ages and the pulmonary veins and left atrium; 
and c) to maintain the systemic aortic pressure 
in part, at least in consequence of a low trans- 
capillary pressure gradient. These observations 
suggested to the authors the possible utility of 
compressive garments of the "G-suit” type in 
escape procedures. Malhotra and Wright (2469) 
1960, examined the intratracheal pressures at 
which pulmonary barotrauma occurs in five fresh 
cadavers, one unbound, one with abdominal 
binding and three with both chest and abdomen 
bound. Autopsy examination was done subse- 
quently to determine the site and nature of in- 
juries. It was determined that in the unbound 
subject and in the subject with abdominal bind- 
ing the pressure at which trauma occurred was 
approximately the same, namely 80 and 93 mm. 
Hg respectively. On the other hand in those 
whose chest and abdomen were both bound the 
pressures were very much higher, namely 190 mm. 
Hg in two cases, and 133 mm. Hg in the third 
subject. In the unbound cadaver rupture of the 
visceral pleura was seen where basal pleural 
adhesions were present. In the remaining four 
cases pulmonary interstitial emphysema resulted. 
It was concluded by the authors that rupture 
of the lung occurs due to overexpansion and 
that the presence of basal adhesions predisposes 
to this form of trauma. In cadavers the ab- 
dominal binder protects against rupture of the 
basal part of the lung but not against pulmonary 
interstitial emphysema. Binding of both the 
chest and the abdomen was found to be more 
effective. Malhotra and Wright (2470) 1961, 
have reported that arterial air embolism is 
rarely seen in Naval operations, except during 
diving, submarine escape training or during ex- 
plosive decompression. The authors studied the 
effects of decompression of tracheotimized rab- 
bits. The animals were taken to a simulated 
depth of 100 feet of water in a pressure chamber SUBMARINE ESCAPE—GAS EMBOLISM 
2435-2439 
and then decompressed, the trachea being closed 
at a depth of 60 feet until the surface was reached. 
The principal injuries in ten animals were air 
embolism, pneumothorax and interstitial em- 
physema. When pneumothorax was present, the 
quantity of air in blood vessels was smaller or 
absent altogether. Air appeared in the circula- 
tion only after intratracheal pressure was al- 
lowed to return to ambient pressure. Manual 
squeezing of the chest or applying abdominal 
binders prior to clamping the trachea were both 
found to be effective in preventing these injuries 
in a further series of ten rabbits. Squeezing 
the chest reduced the volume of air in the lungs 
nearly to residual. The binder not only reduced 
the initial lung volume by raising the diaphragm 
but also provided support to the lungs during 
decompression. In a few human trials subjects 
ascending from a depth of 100 feet found the 
ascent more comfortable when wearing binders 
than without them. 
A number of experimental studies of air 
embolism may be referred to. Geoghegan and 
Lam (2451) 1953, concluded in dogs that air 
reaching the left heart is capable of causing al- 
most instant death by filling the coronary arteries. 
Air in the cerebral arteries of dogs given respira- 
tion does not result in immediate death but in 
critical amounts does produce severe brain dam- 
age. The presence of air in the coronary arteries 
does not necessarily constitute an irreversible 
lesion, since a high percentage of hearts can be 
completely resuscitated following injection of an 
otherwise fatal dose of air into the left ventricle 
if a high pressure in the coronary arteries is 
maintained to force air through to the venous 
side. Harvey and Schilling (2453) 1954, have 
studied the relationship between lung pressures 
and volumes in traumatic air embolism. The 
purpose of their study was to determine the con- 
ditions at which lung rupture and air embolism 
occur. The unopened thoraces of nembutalized 
dogs were expanded after occluding the trachea 
by reducing the air pressure in the chamber in 
which the dogs were placed to a predetermined 
value (within 2 seconds). The functional re- 
sidual volume was determined previously by 
decompression at the end expiratory position 
with the trachea open to a spirometer. Subse- 
quently measured amounts of air were added to 
the initial volume. The animal was then decom- 
pressed from ground level to 250 mm. Hg with 
closed airways and kept there from 15-20 seconds 
before return to ground level. Tracheal, intra- 
pleural, pulmonary arterial and venous, femoral, 
arterial and chamber pressure were recorded 
using strain gauges. Criteria of lung rupture and 
air embolism used were a fall in tracheal pres- 
sure, reduction of tracheal pressure below control 
values when the chamber was brought back to 
ambient pressure, a change in electrical con- 
ductance between an electrode catheter in the 
pulmonary vein and the tissues, and lung hemor- 
rhage. Control measurements were made by de- 
compressing the dog without tracheal occlusion. 
It was found that lung rupture and air embolism 
first occurred at lung volumes approximately 
three times the functional residual volume. A 
large pressure gradient between the air passages 
and the pulmonary vein was found to develop 
with lung distention. Reference may be also 
made to Fries, Levowitz, Adler, Cook, Karlson 
and Dennis (2450) 1957, who have reported 
studies of experimental cerebral gas embolism. 
Studies of air embolism during decompression 
and its prevention in animals by Malhotra 
(2468) 1959, should also be consulted. Refer- 
ence should also be made to a report by Eiseman, 
Baxter and Prachuabmoh (2448) 1959. These 
authors have drawn attention to surface tension- 
reducing substances in the management of ex- 
perimental coronary air embolism. It was found 
that the introduction of surface tension de- 
pressants into the left ventricle of dogs simultane- 
ously with injection of an otherwise lethal dose 
of air decreased the mortality approximately 50 
percent. 
2435. Adams, R. D. and H. M. Vander Eecken. 
Vascular diseases of the brain. Annu. Rev. med., 1953, 4: 
213-252. 
2436. Baird, R. J., R. T. Miyagishima and C. J. 
Labrosse. Vasodilating action of intra-arterial oxygen 
emboli. Circulation, 1963, 28: 686. 
2437. Bakran, I. Traitement de 1’embolie gazeuse par 
Tether. Lyon chir., 1956, 51: 523-530. 
2438. Clemedson, C.-J. and H. I. Hultman. Air 
embolism and the cause of death in blast injury. Milit. 
Surg., 1954, 114: 424-437. 
2439. Colebatch, H. J. H. and M. A. DeKock. 
Histamine release in embolism of the lung with barium 
sulphate. Fed. Proc., 1963, 22: 282. 2440-2474 
DISEASES AND ACCIDENTS 
2440. Collins, J. J. An unusual case of air embolism 
precipitated by decompression. New Engl. J. Med., 1963, 
266: 595-598. 
2441. Dembowski, V. U. and H. M. Hasse. Zere- 
brale Gasembolie nach einer Sauerstoffinsufflation in die 
Arteria cubitalis. Dtsch. med. Wschr., 1956, 81: 936-937. 
2442. Dick, W. Differentialdiagnose: Die Erkennung 
der arteriellen Embolie. Med. Klinik., 1952, 47: 776-779. 
2443. Donald, D. E. and J. L. Fellows. Physical 
factors relating to gas embolism in blood. J. thorac. 
cardiov. Surg., 1961,42; 110-118. 
2444. Duff, F., A. D. M. Greenfield and R. F. 
Whelan. Vasodilatation produced by experimental ar- 
terial gas embolism in man. Lancet, 1953, 2: 230-234. 
2445. Duff, F., A. D. M. Greenfield and R. F. 
Whelan. Observations on the mechanism of the vasodila- 
tation following arterial gas embolism. Clin. Sci., 1954, 13: 
365-376. 
2446. Duffner, G. J. and J. H. Lawson. Report of 
a submarine escape hood. U.S. Navy. Submarine Base, 
New London, Conn. Medical research laboratory. Project 
NM 002 015. 08, Rept. no. 2, 1952. 
2447. Durant, T. M. and M. J. Oppenheimer. 
Embolism due to air and other gases. Veterans Administra- 
tion, Washington, D.C. Medical Bulletin MB-1, 16 July 
1957, 13 pp. 
2448. Eiseman, B., B. J. Baxter and K. Prachuab- 
moh. Surface tension reducing substances in the manage- 
ment of coronary air embolism. Ann. Surg., 1959, 149: 374- 
380. 
2449. Frantisek, V. Air embolism of the pulmonary 
and systemic circulation following injury at altitude. Riv. 
Med. aero., 1960, 23: 484-488. 
2450. Fries, C. C., B. Levowitz, S. Adler, A. W. 
Cook, K. E. Karlson and C. Dennis. Experimental 
cerebral gas embolism. Ann. Surg., 1957, 145: 461-470. 
2451. Geoghegan, T. and C. R. Lam. The mechanism 
of death from intracardiac air and its reversibility. Ann. 
Surg., 1953, 138: 351-359. 
2452. Hamby, W. B. and R. N. Terry. Air embolism 
in operations done in the sitting position. A report of five 
fatal cases and one of a rescue by a simple maneuver. 
Surgery, 1952, 31: 212-215. 
2453. Harvey, R. B. and J. A. Schilling. Relation- 
ship between lung pressures and volumes and traumatic 
air embolism. Fed. Proc., 1954,13: 68. 
2454. Harveyson, K. B. and B. E. E. Hirschfeld. 
Fatal air embolism resulting from the use of a compressed 
air diving unit. Med. J. Aust., 1956, 43: 658-660. 
2455. Just-Viera, J. O. and G. H. Yeager. Massive 
pulmonary embolism; immediate and late physiologic 
changes. Circulation, 1963, 28: 745. 
2456. Keeley, J. L. The diagnosis and management 
of peripheral arterial embolism. Minn. Med., 1953, 36: 230- 
234 and 262. 
2457. Kinsey, J. L. Air embolism as a result of 
submarine escape training. U.S. Forces med. J., 1954, 5: 
243-255. 
2458. Kinsey, J. L. A neurologic syndrome occurring 
during treatment of air embolism. U.S. Forces med. J., 
1955, 6: 1762-1766. 
2459. Kohn, K. Grundsatzliche Fehlerquellen des mak- 
roskopischen und histologischen Nachweises der Luftem- 
bolie des Herzens und des Gehirns. Verh. dtsch. path. Ges., 
1952, 36: 247-259. 
2460. Kronberger, L. Zur konservativen Therapie 
der arteriellen Embolie. Med. Klinik., 1961, 56: 310-313. 
2461. Lambertsen, C. J. Harmful effects of oxygen, 
nitrogen, carbon dioxide, and carbon monoxide. Air em- 
bolism. pp. 721-724 in: Medical physiology. Edited by P. 
Bard, C. V. Mosby Company, St. Louis, 1961, 1339 pp. 
2462. Lenggenhager, K. Worauf beruht der Schmerz 
bei der arteriellen Embolie? Schweiz, med. Wschr., 1952, 
82: 588-589. 
2463. Leriche, R. Treatment of embolism and throm- 
bosis of the cerebral vessels. Brit. med. J., 1952, 1: 231-235. 
2464. Lesky, E. Aus der Geschichte der Luftembolie. 
Dtsch. med. Wschr., 1961, 86: 448-451. 
2465. Liebow, A. A., J. E. Stark, J. Vogel and 
K. E. Schaefer. Intrapulmonary air trapping in sub- 
marine escape training casualties. U.S. Forces med. J., 
1959, 10: 265-289. 
2466. Liebow, A. A., J. E. Stark, J. Vogel and 
K. E. Schaefer. Intrapulmonary air trapping in sub- 
marine escape training casualties. U.S. Navy. Submarine 
Base, New London, Conn. Medical research laboratory 
Project MR005.14-3100-2, Kept. no. 1, 15 February 1960. 
2467. Lutz, W. Experimentelle Untersuchungen zur 
Behandlung der Luftembolie mit erhohtem Atmospharen- 
druck. Anaesthesist, 1953, 2: 199-201. 
2468. Malhotra, M. S. Air embolism during decom- 
pression and its prevention. Gt. Brit. MRC, RNPRC, UPS. 
Kept. R.N.P. 60J996, U.P.S. 188, December 1959, 7 pp. 
2469. Malhotra, M. S. and H. C. Wright. The effect 
of a raised intrapulmonary pressure on the lungs of fresh 
unchilled bound and unbound cadavers. Gt. Brit. MRC, 
RNPRC, UPS. Rept. R.N.P. 60/997, U.P.S. 189, February 
1960, 5 pp. 
2470. Malhotra, M. S. and H. C. Wright. Arterial 
air embolism during decompression and its prevention. 
Proc. roy. Soc., 1961,154: 418^127. 
2471. Masland, R. L. and M. G. Netsky. The elec- 
troencephalogram in experimental cerebral embolism, pp. 
60-71 in: Cerebral anoxia and the electroencephalogram. 
Edited by J. S. Meyer and H. Gastaut. Charles C. Thomas, 
Springfield, 1961, 617 pp. 
2472. Miasnikov, V. A. and G. V. Mashkov. 
Sluchai vyrazhennoi barotravmy legkikh s arterial’noi gazo- 
voi emboliei. [A case of expressed barotrauma of the 
lungs with arterial gas embolism.] Vo.-med. Zh., 1961, 5: 
77-79. 
2473. Moretti, G. La formazione delle bolle gassose 
nella malattia da decompressione. Ann. Med. Nav., 1962, 
67: 586-607. 
2474. Moretti, G. L’embolia gassosa traumatica. 
Ann. Med. Nav., 1963, 68: 269-284. SUBMARINE ESCAPE—UNDERWATER BLAST INJURIES 
2475-2488 
2475. Musgrove, J. E. and R. E. MacQuigg. Suc- 
cessful treatment of air embolism. /. Amer. med. Ass., 1952, 
150: 28. 
2476. Peter, H. and W. Griming. Uber die Be- 
handlung der arteriellen Luftembolie mit der Uberdruck- 
kammer. Beitr. klin. Chir., 1954, 188: 27-34. 
2477. Philip, R. B. and C. W. Gowdey. Aeroembol- 
ism and specific gravity of fat following exposures to com- 
presed air. Fed. Proc., 1963, 22: 684. 
2478. Schaefer, K. E., W. McNulty and C. Carey. 
Development of air embolism. Fed. Proc., 1957,16: 113. 
2479. Schaefer, K. E., W. P. McNulty, Jr. C. 
Carey and A. A. Liebow. Mechanisms in development 
of interstitial emphysema and air embolism on decom- 
pression from depth. J. appl. Physiol., 1958, 13: 15-29. 
2480. Schubert, W. Uber das Ergebnis einer Reihen- 
und Gruppenuntersuchung an 150 Leichen aur Priifung 
auf arterielle Luftembolien im grossen Kreislauf. Virchows 
Arch., 1952, 322: 472-487. 
2481. Schubert, W. Uber einen makroskopischen 
Nachweis von Luftembolien im Organgewebe durch 
Fixierung im Unterdruckraum in Formalin im Anschluss 
an die Sektion. Virchows Arch., 1952, 322: 494-502. 
2482. Schubert, W. Experimentelle Untersuchungen 
fiber erhohten Gasgehalt im Organgewebe, zugleich ein 
morphologisch-pathologischer Beitrag zur Luftembolie und 
Drucksturzkrankheit. Virchows Arch., 1954, 324: 563-587. 
2483. Stauffer, H. M., T. M. Durant and M. J. 
Oppenheimer. Gas embolism: roentgenologic considera- 
tions, including the experimental use of carbon dioxide 
as an intracardiac contrast material. Radiology, 1956, 66: 
686-692. 
2484. Tagliaferro, A. and G. Zaccone. Sulle sin- 
dromi emboliche periferiche degli arti. Arch. Marag. Pat. 
Clin., 1953, 8: 433^41. 
2485. Taylor, J. D. Post-mortem diagnosis of air 
embolism by radiography. Brit. med. J., 1952,1: 890-893. 
2486. U.S. NRC. Air embolisma nd related problems, 
pp. 18-19 in: Status of research in underwater physiology. 
U.S. NRC-CUW, Kept. 468, March 1956, 24 pp. 
2487. Venrath, H., F. Rotthoff, H. Valentin and 
W. Bolt. Bronchospirographische Untersuchungen bei 
Durchblutungsstorungen im kleinen Kreislauf. Beitr. Klin. 
Tuberk., 1952, 107: 291-294. 
2488. West, J. W., T. Kobayashi, L. Schlesinger, 
F. S. Anderson and S. M. Bannett. Effect of emboliza- 
tion via coronary arterial catheterization on coronary 
blood flow and coronary sinus blood oxygen saturation. 
Fed. Proc., 1956, 15: 198. 
D. UNDERWATER BLAST INJURIES 
The interest in the hazard of underwater blast 
has escalated with the greater use of underwater 
swimmers for underwater demolition work and 
for other military operations in forward areas. 
The interest also extends to survivors of disaster 
at sea during wartime. In waters where detona- 
tion of armed charges, mines, etc. may occur. 
It has been found (2498) that 500 psi is 
sufficient to cause injury to the lungs and intes- 
tines, and over 2000 psi is fatal. The more serious 
initial compression wave produced by violent 
liberation and expansion of gas during the 
detonation is followed by a low pressure wave 
resulting from the subsequent collapse of the 
mass of expanded gas. Injury takes the form of 
shredding of tissues constituting the walls of 
spaces (or nearby tissues) due to differences in 
pressure which develop from differences in rate 
of pressure transmission in non-compressible 
tissues and airspaces. Slow detonation, although 
of longer maximum pressure, lasts longer and 
does more- damage at long range. The incom- 
pressible nature of water causes transmission of 
the blast with greater force than in air. Parts 
of the body out of water are unaffected by an 
underwater blast and submersion protects against 
air or surface blasts. Reflections of pressure 
from a hard bottom add to the damage. The 
added bulk of most protective clothing makes its 
use generally impractical. Some protection is 
offered by floating with the thicker tissues of the 
back between the vulnerable organs and the 
explosion source. Bebb (2489) 1953, has also 
discussed interposing materials between the 
underwater explosive and the body tissue. The 
factors determining the degree of injury in under- 
water blast (2497) are: a) the proximity to 
the blast, b) the size and type of explosion, c) 
the medium through which the force is trans- 
mitted, d) the degree of submersion of the 
diver or person, and e) the protection worn by 
the diver. The chest and abdomen are the most 
common sites of injury. The brain may be dam- 
aged if the head is submerged at the time of 
blast. Bruising and laceration of the skin is not 
seen even though underlying organs may be sev- 
erely damaged. Skeletal injuries are uncommon. 
Clemedson and Hultman (2438) 1954, have 
carried out a study on the occurrence of air 
embolism and the cause of death in blast injury 
in rabbits. This paper has been referred to 
above. In these animals exposure to high ex- 
plosives in air resulted in air embolism as well 
as severe damage to the myocardium. This latter 
was considered due either to the air embolism 
or to mechanical lesions of the heart muscle. 
Clemedson (2493) 1956, has pointed out that 2489-2499 
DISEASES AND ACCIDENTS 
underwater blast pressures of over 200-300 psi 
will cause lung injuries in rabbits. Intestinal 
perforations may also occur under these condi- 
tions. Immersed persons exposed to blast pres- 
sures in excess of 500 psi will sustain lethal 
injuries from ruptures of pulmonary vessels or of 
the intestine. In a study on the relation between 
the duration of a shock wave and the severity 
of the blast injury produced by it, Celander, 
Clemedson, Ericksson and Hultman (2491) 1955, 
found in mice that the longer the duration of 
the shock the more severe was the inflicted in- 
jury. Of the two factors, maximum pressure and 
duration, the first seems most important as far 
as injurious effects are concerned. Of interest 
are Clemedson’s findings (2492) in rabbits that 
there is no correlation between the respiratory 
phase and the lung damage. Exposure to a shock 
wave of long duration causes an expulsion of air 
from the lungs and is seen even if the lungs are 
in maximal expiration. A shock of a short dura- 
tion causes a slight or no expulsion of air. 
The area of protection of personnel against 
underwater explosion is under investigation and 
various protective garments are being studied. 
For example, House, Prenderville, Wilson, Wil- 
son and Bebb (2496) 1955, have investigated 
suits using fiberglass. Kapok and other substances 
have also been studied; these garments have been 
designed for the chest and abdomen and also 
headdresses have been studied to absorb shock. 
One of the main problems in the practical ap- 
plication of such studies is that of designing suits 
that can be worn under ordinary operation and 
also be effective during emergencies. 
2489. Bebb, A. H. Underwater blast. Gt. Brit. MR, 
RNPRC. Kept. R.N.P. 53/772, U.W.B. 33, 1953, 10 pp. 
2490. Brown, F. W. Ill and R. H. Lee. Injury from 
the decompression component of an air-blast wave. Nature, 
1956, 178: 490. 
2491. Celander, H., C.-J. Clemedson, U. A. Erics- 
son and H. I. Hultman. A study on the relation between 
the duration of a shock wave and the severity of the blast 
injury produced by it. Acta physiol, scand., 1955, 33: 14-18. 
2492. Clemedson, C. Correlation between respiratory 
phase and extent of lung damage in air blast injury. J. 
appl. Physiol, 1954, 7: 38-42. 
2493. Clemedson, C.-J. Blast injury. Physiol. Rev., 
1956, 36: 336-354. 
2494. Clemedson, C.-J., L. Deffet, L. Fornaeus, 
R. Rucquoi and P. Van de Wouwer. High speed 
radiographic visualization of a high explosive shock wave 
in muscular tissue. J. appl. Physiol, 1955, 7: 604-608. 
2495. Clemedson, C.-J. and H. Pettersson. Genesis 
of respiratory and circulatory changes in blast injury. 
Amer. J. Physiol, 1953,174: 316-320. 
2496. House, D. G., P. Prenderville, B. D. Wilson, 
S. A. W. Wilson and A. H. Bebb. Protection against 
underwater blast. V. Comparison of steel and fibre glass. 
Gt. Brit. MRC, RNPRC, UWB. Kept. R.N.P. 55/846, 
U.W.B. 42, September 1955, 4 pp. 
2497. U.S. Navy. Underwater blast injuries, pp. 
117-118 in; Submarine medicine practice. U.S. Navy, 
BuMed. NAVMED - P 5054, Gov’t. Printing Office, Wash- 
ington, D.C., 1956, 357 pp. 
2498. U.S. Navy. Underwater explosions, pp. 79-81 
in: U.S. Navy diving manual. BuShips, NAVSHIPS 250- 
538, 1959, 433 pp. 
2499. White, C. S. and D. R. Richmond. Blast 
biology. U.S. Atomic Energy Commisison. Technical In- 
formation Service. Kept. no. TID-5764, September 18, 1959, 
89 pp. 
E. DROWNING 
Most of the fatal casualties among underwater 
swimmers have been due to drowning. The 
papers quoted in this section do not constitute a 
comprehensive collection of the literature on 
drowning as a whole but are representative and 
are chosen because of their particular relevance 
to resuscitation and survival problems. 
Donald (2501) 1955, has distinguished be- 
tween fresh water drowning and salt water drown- 
ing. In the former there is absorption of water 
across the capillary membrane which can be 
estimated by the degree of hemodilution or by 
measuring the levels of blood concentration of 
tracer substances placed in the drowning fluid. 
It has been shown that an amount of water 
equivalent to 60-150 percent of the blood volume 
can enter the circulation within a few minutes. 
The rate of dilution is quite fantastic. The 
hemodilution is followed by hemolysis with a 
concomitant gain in potassium ions; therefore 
the potassium/sodium ratio is increased. This 
disturbance in electrolyte ratios is more danger- 
ous than the overall changes in tonicity. Within 
a few minutes ventricular fibrillation may begin; 
great overloading of the increased blood volume 
also contributes, along with the anoxemia. There 
is also a pulmonary vasoconstriction. After death 
the right ventricle is distended and the left almost 
empty and fully contracted. The reduced blood 
pressure along with the reduced cardiac output 
leads to central nervous system hypoxia and 
finally anoxia. Respiratory failure occurs about 
the same time as the ventricular fibrillation. SUBMARINE ESCAPE—DROWNING 
In salt water drowning there is movement of 
water out of the blood into the lungs with a 
resulting hemoconcentration. There is no 
hemolysis or change in the potassium/sodium 
ratio, and ventricular fibrillation does not oc- 
cur. The heart fails gradually within five to eight 
minutes. If the systolic blood pressure remains 
above 115 mm. Hg, resuscitation is almost always 
successful, even though the diastolic pressure may 
be extremely low. There is evidence of severe 
pulmonary edema with plasma exudation into 
the alveoli of both the salt water and fresh water 
drowned animals. The resultant protein content 
of the lung fluids is partly responsible for the 
tenacious froth encountered in the air passages. 
The stomach may contain very large amounts of 
the drowning fluid owing to reflex swallowing, 
and there may be evidence of the stomach con- 
tents in the air passages due to agonal vomiting. 
Survival is practically nonexistent without resusci- 
tation when the blood pressure has fallen pre- 
cipitously and this is probably due to the ven- 
tricular fibrillation. 
Exercise before drowning seems to lower the 
survival rate. In surviving human beings mild 
pulmonary edema is usually found in the case 
of both salt and fresh water drowning. This is 
thought to be due primarily to anoxic effects and 
central nervous system effects rather than due to 
aspiration of water. There are no signs of renal 
damage. If irreversible circulatory failure has 
occurred artificial respiration cannot succeed. 
If only respiratory failure has occurred, then only 
seconds may remain before circulatory failure 
supervenes. Not a second, literally, can be wasted 
in initiating resuscitating measures. Artificial 
respiration must be started even at the risk of 
other injuries. No time should be wasted in 
clearing airways, loosening clothing, feeling the 
pulse, etc. If someone else is available they can 
handle these duties. Even a small amount of 
air in the first few seconds may accomplish what 
100 percent oxygen and large pulmonary ventila- 
tion may fail to do after 10-20 seconds. Some- 
times a person with medical knowledge may 
constitute a threat in getting a detailed clinical 
examination while artificial pulmonary ventila- 
tion should be going on. 
Selected case reports are given in the following 
papers: Haddy and Disenhouse (2505) 1954, 
discuss a 10 year old girl who had been immersed 
for two to three minutes in fresh water. The 
child was extremely disoriented and agitated and 
showed swimming movements of the extremities, 
hyperventilation and cyanosis. There was bloody 
mucous in the pharynx, but no sign of injury. 
Many fine moist rales were heard throughout 
both lung fields. Fifty percent oxygen was ad- 
ministered first in an oxygen tent and then under 
positive pressure for 20 minute intervals, alter- 
nating with 40 minute intervals at atmospheric 
pressure. After three hours there was a definite 
increase in pulmonary edema; seven hours later 
there was much improvement. On the third day 
the oxygen tent only was used for a few hours 
and then discontinued. There was a continua- 
tion of recovery with no further difficulty after 
the sixth day. Hack (2511) 1959, reported the 
case of a chief returning to a submarine who fell 
on the saddle tank and was immersed in the water 
for 30-60 seconds. He recovered consciousness 
within a few minutes and was taken to the sick 
bay. There he vomited twice. He was very 
excited and would not lie still. The patient could 
not remember anything about the accident. His 
pulse was 80 and there was good volume. There 
was no cyanosis; within the chest numerous 
crepitations were heard all over. The pupils 
were equal and reacted sugglishly to light; the 
knee jerks were also sluggish. The patient was 
discharged to a hospital ashore with possible 
skull fracture, and died 2.5 hours later. The 
lungs on autopsy were congested and waterlogged 
and the cut surfaces exuded fluid. The right 
auricle and ventricle were dilated and contained 
a clot. The stomach contained 450 cc. of green 
fluid mixed with a few food particles. There 
was no evidence of skull fracture; the brain 
exhibited moderate congestion without evidence 
of brain damage. Microscopically there was in- 
tra-alveolar edema and striking congestion of the 
alveolar capillaries. There was moderate desqua- 
mation of the alveolar lining cells, and there 
was shedding of the epithelial layers in the 
bronchioles. The microscopic appearances in the 
bronchi and lungs, particularly the presence of 
such a well-marked reaction in the bronchioles 
occurring so quickly after immersion, reinforce 
the impression that some irritant in addition to 
sea water was inhaled. The water around the DISEASES AND ACCIDENTS 
submarine had a film of oil which may have been 
contaminated by detergent “scum” from the 
ship’s laundry. 
Courville (2500) 1960, has reported the case 
of a patient who survived for 19 days after pro- 
longed immersion. A young man of 21 years of 
age was pulled out of a swimming pool in an 
unconscious state and was resuscitated by a 
rescue squad. He had been practicing breath 
holding and had evidently inhaled some water 
accidentally. He failed to regain consciousness 
after spontaneous respiration and cardiac action 
had been restored. The patient developed a 
typical decorticate state during the survival 
period. The brain showed histological signs of 
cerebral anoxia. Kvittingen and Naess (2513) 
1963, have pointed out that survival after drown- 
ing in fresh water is rare when submersion has 
lasted so long that aspiration of water has led 
to hemolysis and hemoglobinuria and cardiac 
arrest has also occurred. A case is reported of a 
five year old boy who drowned in ice cold water 
having been immersed for 22 minutes. The 
patient was successfully resuscitated by external 
cardiac compression which was carried out for 
two hours before spontaneous cardiac contrac- 
tions were restored. The hemolysis and hemoglo- 
binuria were treated with an exchange trans- 
fusion of 3000 cc. Apart from a brief return to 
consciousness on the tenth day, the boy was 
unconscious for about six weeks. Air encephalo- 
grams taken six weeks after the accident showed 
severe dilatation of all cerebral ventricles. In 
spite of all this the patient recovered with little 
if any neurological and intellectual damage. 
Air encephalograms taken six months after the 
accident showed that diltation of the cerebral 
ventricles had decreased. The authors suggested 
that cooling of the child’s body during treatment 
and as he hung onto the ice had played an im- 
portant part in the successful outcome. 
King and Webster (2512) 1964, have described 
a case of a German seaman, 21 years of age, who 
was painting the side of a ship and fell 20 feet, 
striking first the wharf and then the water. He 
was recovered by a skin diver who rescued him 
from the river bottom in 30 feet of water. Im- 
mersion lasted at least 17 minutes. The patient 
recovered from cardiac arrest and electrolyte 
disturbances but there was absence of gross 
hemolysis or pulmonary edema. The patient 
made a dramatic recovery. Immediate mouth 
to mouth resuscitation was used and the authors 
stress the importance of this and its continuation 
in even apparently hopeless cases. 
Gordon, Raymon and Ivy (2504) 1954, have 
reported drowning phenomena in various species 
of animals. In a large number of animal species 
submersion in fresh water resulted in two general 
types of blood pressure response: a) a precipitous 
fall to zero within one to three minutes, or b) a 
gradual fall to zero during two to five minutes. 
All animals showing the former response had 
simultaneous ventricular fibrillation. All horses, 
cows and pigs showed precipitous blood pressure 
drop with permanent ventricular fibrillation. 
Most of the dogs showed this response but only 
a few of the sheep and goats. Cats, rabbits and 
monkeys all exhibited a gradual fall in blood 
pressure without permanent ventricular fibrilla- 
tion, however, four cats, three monkeys and one 
rabbit had transient episodes of ventricular 
fibrillation with spontaneous recovery. Data 
were also obtained on serum hemoglobin, sodium, 
potassium, calcium and chlorides, before and 
after fresh water submersion. In general the 
hemolysis was greater in those animals of each 
species that exhibited either transient or perma- 
nent ventricular fibrillation. The serum ionic 
determinations revealed a significant rise in 
potassium and decrease in sodium, calcium and 
chlorides, in all species. The mechanism of 
ventricular fibrillation during fresh water drown- 
ing is stated by the authors to be related to; a) 
ionic imbalances resulting from anoxia, hemodi- 
lution, hemolysis and sympatho-adreno-hepatic 
stress; b) increased intravascular clotting; and 
c) animal size. 
Foden, Stemler, Rockhold and Hiestand 
(2503) 1952, have indicated that body tempera- 
ture is a major factor in survival from drown- 
ing. In an investigation of the effect of altering 
the body temperature of mice on survival to 
drowning, a significant linear relationship ap- 
peared when body temperatures were plotted 
against survival time, as measured by the final 
gasp. Various agents, as well as mechanical 
means of chilling, in ice baths and heating with 
infra-red radiation were used to alter internal 
temperatures. Substances which markedly low- SUBMARINE ESCAPE—DROWNING 
2500-2511 
ered temperature always caused an increase in 
survival time. Those which increased tempera- 
ture or metabolic activity caused a decrease in 
survival. The most pronounced increase in sur- 
vival occurred with chilling, previous exposure 
to oxygen, injections of ethyl alcohol, India ink, 
and powdered charcoal. Prolongation to a lesser 
degree was shown by ACTH, cortisone, thiouracil 
and gum acacia. A decrease in survival time fol- 
lowed heating, exposure to cold for 48 hours, 
dinitrophenol and, to a lesser degree, throxin. 
Other substances tested such as cocaine and 
histamine showed no appreciable effect. Exer- 
cise (swimming in water for periods of 15 min- 
utes to one hour) increased survival time by 
over 20 percent. Starvation for 48 hours reduced 
survival time only slightly. All animals were 
males. 
Rath (2316) 1953, has reported a case of a 
15 year old boy exhibiting hemoglobinemia and 
hemoglobinuria following incomplete drowning. 
The patient recovered and four years later 
was still asymptomatic. There was no evidence 
that the hemoglobinemia was caused by a 
mechanism other than intravascular hemolysis 
from fresh water entering the general circula- 
tion. In experimental studies to localize the 
point of entrance into the circulation, a dog was 
anesthetized and 620 cc. of distilled water were 
injected over a period of 95 minutes into the 
trachea with no evidence of hemoglobinuria. 
Nor was there any evidence of hemoglobinuria 
when 1800 cc. were injected over 45 minutes 
in the same dog. When the tracheal cannula 
was tied in place to prevent coughing up water 
and swallowing, 1000 cc. were injected over a 
period of 65 minutes. One hundred and ten cc. 
and 128 cc. of the water had entered the circula- 
tion through the lungs at 20 and 65 minutes re- 
spectively. The degree of hemolysis was less than 
previously reported by others. There was no 
hemoglobin in the urine. The animal expired. 
Redding, Voigt and Safar {2518, 2519) 1960, 
have carried out some studies on dogs in which 
drowning was treated with intermittent positive 
pressure breathing. These dog experiments were 
designed to simulate the condition of human 
victims of submersion who seemed first to develop 
laryngospasm, followed by flooding of the lungs. 
The tracheal tube of lightly anesthetized dogs 
was clamped until the onset of apnea. The 
lungs were then flooded for 30 seconds with 
fresh water or sea water, or apnea was permitted 
to continue for a comparable period without 
flooding. Resuscitation was attempted with in- 
termittent positive pressure breathing utilizing 
room air. All control dogs (obstructive asphyxia 
without flooding) survived. Fresh water drown- 
ing caused mild arterial hypotension, a severe 
rise in venous pressure and bradycardia, followed 
by sudden ventricular fibrillation within 1-4 
minutes in spite of intermittent positive pressure 
breathing. Sea water drowning caused severe 
arterial hypotension, a slight rise in venous 
pressure and bradycardia. Intermittent positive 
pressure breathing led to partial reoxygenation 
and partial restoration of circulation. When in- 
termittent positive pressure breathing was dis- 
continued all dogs started to breathe spontane- 
ously, but within a few minutes developed 
asystole with pulmonary edema. 
2500. Courvilel, C. B. Anoxic changes in the brain 
after prolonged immersion. Report of case with survival 
for nineteen days. Bull. Los Angeles neurol. Soc., 1960, 25: 
165-169. 
2501. Donald, K. W. Drowning. Brit. med. J., 1955, 
2: 155-160. 
2502. Durlacher, S. H., H. C. Freimuth and H. E. 
Swan, Jr. Blood changes in man following death due to 
drowning. Arch. Path., 1953, 56: 454-461. 
2503. Foden, R. H., F. W. Stemler, W. T. Rock- 
hold and W. A. Hiestand. Body temperature a major 
factor in drowing survival. Fed. Proc., 1952, 11: 46. 
2504. Gordon, A. S., F. Raymon and A. C. Ivy. 
Drowning phenomena in various species. Fed. Proc., 1954, 
13: 58. 
2505. Haddy, T. B. and R. B. Disenhouse. Acute 
pulmonary edema due to near-drowning in fresh water. 
J. Pediat., 1954, 44: 656-569. 
2506. Halmagyi, D. F. J. Lung changes and incidents 
of respiratory arrest in rats after aspiration of sea and 
fresh water. J. appl. Physiol., 1961, 16: 41-44. 
2507. Halmagyi, D. F. J. and H. J. H. Colebatch. 
Ventilation and circulation after fluid aspiration. J. appl. 
Physiol, 1961, 16: 35-40. 
2508. Holden, H. S. and J. W. L. Crosfill. The 
significance of foreign bodies in the alveoli of the appar- 
ently drowned. J. forensic Med., 1955, 2: 141-150. 
2509. Horres, A. D., N. D. Exarhos, W. D. Logan 
and G. A. Brecher. Respiratory effects of fluid aspiration. 
Fed. Proc., 1964, 23: 309. 
2510. Hosier, R. M. A manual on cardiac resuscitation. 
C. C. Thomas, Springfield, Illinois, 1954, 183 pp. 
2511. Jack, D. B. Immersion .followed by acute 
pulmonary edema. J. R. nav. med. Serv., 1959, 45: 228-230. 2512-2520 
DISEASES AND ACCIDENTS 
2512. King, R. B. and I. W. Webster. A case of 
recovery from drowning and prolonged anoxia. Med. J. 
Aust., 1964,1: 919-920. 
2513. Kvittingen, T. D. and A. Naess. Recovery 
from drowning in fresh water. Brit. med. J., 1963, 1: 
1315-1317. 
2514. Mautz, F. R. and R. M. Hosier. Resuscitation, 
pp. 564-571 in: Medical physics. O. Glasser, Editor. Year 
Book Publishers, Chicago, 1960, 754 pp. 
2515. Miles, S. Drowning, pp. 200-212 in: Underwater 
medicine. J. B. Lippincott Co., Philadelphia, 1962, 328 pp. 
2516. Rath, C. E. Drowning hemoglobinuria. Blood, 
1953, 8: 1099-1104. 
2517. Redding, J. S., R. A. Cozine and P. Safar. 
Resuscitation after fresh water drowning. Fed. Proc., 1961, 
20: 129. 
2518. Redding, J., G. C. Voigt and P. Safar. 
Drowning treated with intermittent positive pressure 
breathing. J. appl. Physiol., 1960, 15: 849-854. 
2519. Redding, J. S., G. C, Voigt and P. Safar. 
Treatment of sea-water aspiration. J. appl. Physiol., 1960, 
15: 1113-1116. 
2520. Saline, M. and G. L. Baum. The submersion 
syndrome. Ann. intern. Med., 1954, 41: 1134-1138. Protection and Preservation of 
Personnel 
I. GENERAL STUDIES 
The ability to withstand exposure to severe 
stress is never an adequate selection procedure 
for submariners or divers. Superimposed upon 
a realistic and efficient selection program must 
be efforts to protect personnel from intolerable 
stresses by attention to habitability, food and 
water supply, and special equipment and devices. 
In all procedures and plans for protection and 
preservation of personnel, it must be borne in 
mind that the submarine is a fighting ship. The 
effective fighting power of the submarine is the 
primary consideration, and all matters of pro- 
tection and comfort of personnel are important 
in the degree to which they contribute to this. 
2521. Bates, J. H. Recent aspects in the development 
of a closed ecologic system. Aerospace Med., 1961, 32: 12-24. 
2522. Hanan, T. D. and J. Gaito. Performance and 
habitability aspects of extended confinement in sealed 
cabins. Aerospace Med., 1960, 31: 399-406. 
2523. Hauty, G. T. Human performance in the space 
travel environment. Operat. Res., 1958, 10: 89-107. 
2524. Jacobson, S. L. Engineering of the sealed cabin 
atmosphere control system. Aerospace Med., 1960, 31: 
388-398. 
2525. Lambertsen, C. J. From Submarines to satel- 
lites. Circ. Res., 1958, 6: 405-409. 
2526. Lambertsen, C. J. A philosophy of extremes 
for the gaseous environment of manned, closed ecological 
systems, pp. 316-322 in: Proceedings of the manned space 
stations symposium. Los Angeles, Calif., 20-22 April 1960. 
Institute of the Aeronautical Sciences, New York, 1960. 
2527. McConnaughey, W. E. Atmosphere control on 
submarines. Bu. Ships J., 1960, 9: 11-14. 
2528. McConnaughey, W. E. Atmosphere control of 
confined spaces, pp. 390-399 in: Man’s dependence on the 
earthly atmosphere. Edited by K. E. Schaefer. The MacMil- 
lan Company, New York, 1962, 416 pp. 
2529. Miles, S. New problems in submarine habit- 
ability. Ann. occup. Med., 1959, 2: 224-227. 
2530. Reed, W. S. System controls capsule environ- 
ment. Aviat. Week, 1960, 73: 57-60. 
2531. Schaefer, K. E. Selecting a space cabin atmos- 
phere. U.S. Navy. Submarine Base, New London, Conn. 
Medical research laboratory. Project MR005.14-3300.5, 
Rept. no. 3, 19 October 1959. 
2532. Schaefer, K. E. Physiological problems of sub- 
marine and space medicine. U.S. Navy. Submarine Base, 
New London, Conn. Medical research laboratory. Project 
MR005.14-3300-5, Kept. no. 4, 25 January 1960. 
2533. Simons, D. G. and E, R. Archibald. Selection 
of a sealed cabin atmosphere. /. Aviat. Med., 1958, 29: 
350-357. 
2534. Steinkamp, G. R. and W. R. Hawkins. Medi- 
cal experimentation in a sealed cabin simulator, pp. 370- 
376 in: Physics and medicine of the atmosphere and space. 
Edited by O. O. Benson, Jr. and H. Strughold, John Wiley 
and Sons, Inc., New York, 1960, 645 pp. 
2535. U.S. Navy. Minimum habitability standards for 
ships of the U.S. Navy. U.S. Navy. CNO. Ref. OPNAV 
9330.5, Op-42, Ser. 104P42, 4 March 1960, 17 pp. 
2536. U.S. Navy. The intra-Navy committee for sub- 
marine habitability research and development. “Livability” 
presentation. 1 February 1961, 99 pp. 
2537. U.S. Navy. Submarine habitability data book. 
BuShips, NAVSHIPS 250-649-1, 27 April 1961, 136 pp. 
2538. Welch, B. E. Ecological systems, pp. 309-334 in: 
Physiology of man in space. Edited by J. H. U. Brown, 
Academic Press Inc., New York, 1963, 348 pp. 
II. VENTILATION AND AIR 
CONDITIONING 
A. GENERAL STUDIES 
Modern advances in the engineering of sub- 
marines have largely solved many of the most 
harassing problems of conditioning and habit- 
ability. In many ways the atmosphere of the 
modern nuclear-powered submarine is cleaner 
than that in many American cities. The prob- 
lems that still remain in the air conditioning 
of submarines are the removal of trace con- 
taminants and odors from the sanitary tanks. 
The references included in this section will 
permit the reader to follow the course of some 
of these developments. 
2539. Burke, D., G. Hobby and T. A. Gaucher. 
Closed-cycle air purification with algae, pp. 400-411 in: 
Man’s dependence on the earthly atmosphere. Edited by 
K. E. Schaefer, The MacMillan Company, New York, 1962, 
416 pp. 
2540. Kinsey, J. L. Some toxicological hazards in 
submarines. Fed. Proc., 1960, 19: 36-39. 2541-2564 
PROTECTION AND PRESERVATION OF PERSONNEL 
2541. Konikoff, J. J. Algal System challenges en- 
gineers. S.A.E. JI, 1961, 69: 71. 
2542. Leonard, J. M. Algae and submarine habita- 
bility. pp. 153-150 in: The present status of chemical re- 
search. U.S. Navy. Naval Research Laboratory, Washing- 
ton, D.C. NRL Rept. no. 5465, 21 April 1960, 167 pp. 
2543. Marcelli, J. Etude des atmospheres confin£es. 
Probl&nes chimiques et toxicologiques poses par la navi- 
gation sous-marine. Ann. pharm. frang., 1953, 11: 217-222. 
2544. Nuttall, J. B, Toxic hazards in the aviation 
environment. J. Aviat. Med., 1958, 29: 641-649. 
2545. Roth, E. Some theoretic aspects of the use 
of inert gases in sealed cabin environments. USAF. Brooks 
Air Force Base, Texas. School of Aviation Medicine. Aero- 
space medical center (ATC). Rept. 58-152, November 1959, 
18 pp. 
2546. Scano, A. La depurazione dell ’aria nelle cabine 
stagne. SaU’eliminazione chimica e fisica dell’anidride 
carbonica e di altre sostanze prodotte dall’uomo. Riv. Med. 
aero., 1958, 21: 705-714. 
B. PREVENTION OF ATMOSPERIC 
POLLUTION 
Prevention of atmospheric pollution in the 
submarine rests upon meticulous and successful 
screening of all potential atmospheric pollutants 
that may be brought aboard or used by personnel 
or exist as structural parts of equipment. In 
the reference list that follows the reader will find 
a rich source of papers dealing with various 
contaminants, their detection, screening and 
effects on personnel. 
2547. Amdur, M. O. (The physiological response of 
guinea pigs to atmospheric pollutants. Int. J. Air Wat. 
Poll., 1959,1: 170-183. 
2548. Anderson, W. L. Ions in nuclear submarines, 
pp. 160-163 in; The present status of chemical research in 
atmosphere purification and control on nuclear-powered 
submarines. U.S. Navy. Naval Research Laboratory, Wash- 
ington, D.C. NRL Rept. 5465, April 1960, 167 pp. 
2549. Anderson, W. L. Aerosols in nuclear sub- 
marines. pp. 114-120 in: The present status of chemical re- 
search in atmosperepurification and control on nuclear- 
powered submarines. U.S. Navy. Naval Research Labora- 
tory, Washingotn, D.C. NRL Rept. 5630, July 1961, 134 pp. 
2550. Anderson, W. L. and E. A. Ramskill. Aero- 
sols in nuclear submarines, pp. 151-159 in: The present 
status of chemical research in atmosphere purification and 
control on nuclear-powered submarines. U.S. Navy. Naval 
Research Laboratory, Washington, D.C. NRL Rept., 5465, 
April 1960, 167 pp. 
2551. Baldridge, H. D., D. J. Jensen, C. E. Knight, 
T. J. Preziosi and J. R. Tureman. Toxicology of a 
triaryl phosphate oil. III. Human exposure in operational 
use aboard ship. Arch, industr. Hlth., 1959, 20: 258-261. 
2552. Barnes, J. M. Safe levels of hydrogen fluoride 
and hydrogen chloride. Gt. Brit. MRC, RNPRC, SMS. 
Rept. S.M.S. 30, 1 p. 
2553. Boysen, J. E. Toxicology in aviation, pp. 
477-506 in: Aerospace medicine. Edited by H.G. Arm- 
strong, Williams and Wilkens Co., Baltimore, 1961, 633 pp. 
2554. Carhart, H. W. and V. R. Piatt. The present 
status of chemical research in atmosphere purification and 
control on nuclear-powered submarines. U.S. Navy. Naval 
Research Laboratory, Washington, D.C. NRL Kept. 6053, 
December 1963, 65 pp. 
2555. Carhart, H. W. and V. R. Piatt. Chemical 
constituents of nuclear-submarine atmospheres, pp. 53-59 
in: The present status of chemical research in atmosphere 
purification and control on nuclear-powered submarines. 
Edited by H. W. Carhart and V. R. Piatt. U.S. Navy. Naval 
Research Laboratory, Washington, D.C. NRL Rept. 6053, 
December 1963, 65 pp. 
2556. Carpenter, H. M., D. J. Jensen, N. R. Shul- 
man and J. R. Tureman. Toxicology of a triaryl phos- 
phate oil. I. Experimental toxicology. Arch, industr. Hlth., 
1959, 20: 234-252. 
2557. Chalupa, B., J. Synkova and M. Sevcik. The 
assessment of electroencephalographic changes and memory 
disturbances in acute intoxications with industrial poisons. 
Brit. J. industr. Med., 1960, 17: 238-241. 
2558. Dohan, F. C. and E. W. Taylor. Air pollution 
and respiratory disease. A preliminary report. Amer. J. 
med. Sci., 1960, 240: 337-339. 
2559. Field, D. E. Water-thinned paints for sub- 
marine interiors, pp. 106-113 in: The present status of 
chemical research in atmosphere purification and control 
on nuclear-powered submarines. Edited by V. R. Piatt and 
E. A. Ramskill. LT.S. Navy. Naval Research Laboratory, 
Washington, D.C. NRL Rept. 5630, July 1961, 134 pp. 
2560. Field, D. E., M. E. Umstead and A. L. 
Alexander. Water-thinned paints for submarine interiors, 
pp. 73-79 in: The present status of chemical research in 
atmosphere purification and control on nuclear-powered 
submarines. Edited by R. R. Miller and V. R. Piatt. U.S. 
Navy. Naval Research Laboratory, Washington, D.C. NRL 
Rept. 5465, April 1960, 167 pp. 
2561. Gray, E. Le B,, F. M. Patton, S. B. Goldberg 
and E. Kaplan. Toxicity of the oxides of nitrogen. 
II. Acute inhalation toxicity of nitrogen dioxide, red 
fuming nitric acid, and white fuming nitric acid. Arch 
industr. Hyg., 1954, 10: 418-422. 
2562. Kagarise, R. E. Liquid-oxygen contaminants, 
pp. 88-92 in: The present status of chemical research 
in atmosphere purification and control on nuclear-powered 
submarines. Edited by V. R. Piatt and E. A. Ramskill. 
U. Navy. Naval Research Laboratory, Washington, D.C. 
NRL Rept. 5630, July 1961, 134 pp. 
2563. Johnson, J. E. Organic contaminants, sampling 
and analysis, pp. 46-52 in: The present status of chemical 
research in atmosphere purification and control on nu- 
clear-powered submarines. Edited by H. W. Carhart and 
V. R. Piatt. U.S. Navy. Naval Research Laboratory, 
Washington, D.C. NRL Rept. 6053, December 1963, 65 pp. 
2564. Johnson, J. E. and H. W. Carhart. The 
consumption of oxygen by combustibles in submarine 
atmospheres. U.S. Navy. Naval Research Laboratory, 
Washington, D.C. NRL Memo Rept. 882, December 1958, 
16 pp. VENTILATION AND AIR CONDITIONING—ELIMINATION FROM AIR 
2565-2592 
2565. Johnson, J. E., J. G. Christian, D. E. Field, 
C. M, Murphy, Jr., J. E. Smith, F. S. Thomas and 
M. E. Umstead. Investigation of eye irritation in the 
atmosphere of USS Snook (SS(N)592) — trip report. U.S. 
Navy. Naval Research Laboratory, Washington, D.C., NRL 
Memo Rept. 1248, November 1961, 20 pp. 
2566. Kagarise, R. E. and R. A. Saunders. The 
analysis of contaminants in aviators’ breathing oxygen. 
LT.S. Navy. Naval Research Laboratory, Washington, D.C. 
NRL Rept. 5554, October 1960, 20 pp. 
2567. Miller, R. R. and V. R. Piatt. The present 
status of chemical research in atmosphere purification and 
control on nuclear-poivered submarines. U. S. Navy. 
Naval Research Laboratory, Washington, D.C. NRL Rept. 
5465, April 1960, 167 pp. 
2568. Motley, H. L. Detection of early lung function 
changes in industrial exposure. Industr. Med. 1953, 22: 
262-267. 
2569. Motley, H. L., M. Cinta and C. I. Leftwich. 
Effect of Los Angeles smog on lung volume measurements. 
Fed. Proc., 1959, 18: 109. 
2570. Nestler, F. H. M. and W. D. Smith. Sub- 
marin e habitability-atmosphere sampling and analysis. 
U.S. Navy. Naval Research Laboratory, Washington, D.C. 
NRL Memo Rept. 866, October 1958, 19 pp. 
2571. Piatt, V. R. Chemical constituents of submarine 
atmospheres, pp. 15-24 in: The present status of chemical 
research in atmosphere purification and control on nuclear- 
powered submarines. Edited by R. R. Miller and V. R. 
Piatt. U.S. Navy. Naval Research Laboratory, Washington, 
D. NRL Rept. 5465, April 1960, 167 pp. 
2572. Piatt, V. R. and E. A. Ramskill. The present 
status of chemical research in atmosphere purification and 
control on nuclear-powered submarines. U.S. Navy. Naval 
Research Laboratory, Washington, D.C. NRL Rept. 5630, 
July 1961, 134 pp. 
2573. Piatt, V. R., E. A. Ramskill and J. C. White. 
Chemical constituents of submarine atmospheres. U.S. 
Navy. Naval Research Laboratory, Washington, D.C. 
NRL Rept. 5456, January 1960, 14 pp. 
2574. Piatt, V. R. and J. C. White. The present 
status of chemical research in atmosphere purification and 
control on nuclear-powered submarines. U.S. Navy. Naval 
Research Laboratory, Washington, D.C. NRL Rept. 5814, 
August 1962, 97 pp. 
2575. Saunders, R. A. Spectroscopic studies of nuclear 
submarine atmospheres. I. Description and analysis of 
contaminants from Hopcalite. U.S. Navy. Naval Research 
Laboratory, Washington, D.C. NRL Memo Rept. 903, 
February 1959, 9 pp. 
2576. Saunders, R. A. Spectroscopic studies of nuclear 
submarine atmospheres. II. Infrared analysis of major 
gaseous contaminants. U.S. Navy. Naval Research Labora- 
tory, Washington, D.C. NRL Memo Rept. 922, May 1959, 
!0 pp. 
2577. Schaefer, K. E. Experiences with submarine 
atmospheres. J. Aviat. Med., 1959, 30: 350-359. 
2578. Slager, U. T. Toxicology, pp. 307-337 in: 
Space medicine. Prentice-Hall, Inc., Englewood Cliffs, 
N.J., 1962, 388 pp. 
2579. Spector, W. S. Handbook of toxicology. USAF. 
WADC, Wright-Patterson Air Force Base, Dayton, Ohio. 
WADC Tech. Kept. 55-16, April 1955, 408 pp. 
2580. Stern, A. C. Air pollution. Volume I. Aca- 
demic Press, New York, 1962, 656 pp. 
2581. Stokinger, H. E. Toxicologic interactions of 
mixtures of air pollutants. Review of recent developments. 
Int. ]. Air Wat. Poll, 1960, 2: 313-326. 
2582. Umstead, M. E,, J. G. Christian and J. E. 
Johnson. A study of the organic vapors in the atmos- 
phere of the USS Skate. U.S. Navy. Naval Research 
Laboratory, Washington, D.C. NRL Memo Kept. 1057, 
June 1960, 29 pp. 
2583. U.S. Air Force. Toxic hazards in military flying 
and in the aviation industry. Aviation Medicine Sym- 
posium, Wright-Patterson Air Force Base, Dayton, Ohio, 
November 1957, 131 pp. 
2584. U.S. NRC. Advisory Center on Toxicology. 
The toxicology and health hazards of cellulube 220. U.S. 
NRC, Washington, D.C., 1957, 55 pp. 
2585. U.S. NRC. Toxicology Information Center. 
Toxicity evaluation of potentially toxic materials. U.S. 
NRC, Washington, D.C., 30 July 1958, 35 pp. 
2586. U.S. NRC. Advisory Center on Toxicology. 
Report on the carcinogenicity of a group of aromatic 
compounds. U.S. NRC, Washington, D.C., ACT Rept. 23, 
26 January 1959, 60 pp. 
2587. U.S. NRC. Toxicology Information Center. 
Toxicity of chlorothene. U.S. NRC, Washington, D.C., 3 
February 1959, 28 pp. 
2588. U.S. NRC. Committe on Toxicology. Minutes 
of meeting. 10 February 1959. 8 pp. 
C. ELIMINATION OF DUST, GASES, FUMES 
AND ODORS FROM AIR 
Papers pertinent to this subject are included 
in the following list. 
2589. Anderson, W. L. Atmosphere control in con- 
fined spaces. USAF. Wright-Patterson Air Force Base, 
Dayton, Ohio. Air development division. Tech. Rept. 
60-574, August 1960, 4 pp. 
2590. Anderson, W. L. and J. L. Bitner. Aerosols 
in nuclear submarines, pp. 86-92 in: The present status 
of chemical research in atmosphere purification and con- 
trol on nuclear-powered submarines. Edited by V. R. 
Piatt and J. C. White. U.S. Navy. Naval Research Labora- 
tory, Washington, D. C. NRL Rept. 5814, August 1962, 
97 pp. 
2591. Christian, J. G. Catalytic combustion of freons. 
pp. 93-96 in; The present status of chemical research in 
atmosphere purification and control on nuclear-powered 
submarines. Edited by V. R. Piatt and J. C. White. U.S. 
Navy. Naval Research Laboratory, Washington, D.C. NRL 
Rept. 5814, August 1962, 97 pp. 
2592. Christian, J. G. and J. E. Johnson. Catalytic 
combustion of aerosols, pp. 121-126 in: The present status 
of chemical research in atmosphere purification and con- 
trol on nuclear-powered submarines. Edited by V. R. 
Piatt and E. A. Ramskill. U.S. Navy. Naval Research 
Laboratory, Washington, D.C. NRL Rept. 5630, July 1961, 
134 pp. 2593-2605 
PROTECTION AND PRESERVATION OF PERSONNEL 
2593. Johnson, J. E. and A. J. Chiantella. Thermal 
degradation of triaryl phosphates, pp. 127-132 in: The 
present status of chemical research in atmosphere purifica- 
tion and control on nuclear-powered submarines. Edited 
by V. R. Piatt and E. A. Ramskill. U.S. Navy. Naval 
Research Laboratory, Washington, D. C. NRL Rept. 5630, 
July 1961, 134 pp. 
2594. Johnson, J. E. and J. G. Christian. A labora- 
tory study of the efficiency of hopcalite in catalyzing hydro- 
carbon combustion, pp. 67-72 in: The present status of 
chemical research in atmosphere purification and control 
on nuclear-powered submarines. Edited by R. R. Miller 
and V. R. Piatt. U.S. Navy. Naval Research Laboratory, 
Washington, D.C. NRL Rept. 5465, April 1960, 167 pp. 
2595. McConnaughey, W. E. Submarine atmosphere 
control. USAF Wright-Patterson Air Force Base, Dayton, 
Ohio. Air development division. Tech. Rept. 60-574, 
August 1960, 7 pp. 
2596. McConnaughey, W. E., S. B. Crecelius and 
W. N. Crofford, III. Removal of CO from submarine 
atmospheres by amine resins. A feasibility study. U.S. 
Navy. Naval Research Laboratory, Washington, D.C- 
NRL Rept. 5022, November 1957, 24 pp. 
2597. Miller, R. R. Alkali metal peroxy compounds 
in submarine air purification, pp. 113-118 in: The present 
status of chemical research in atmosphere purification and 
control on nuclear-powered submarines. Edited by R. R. 
Miller and V. R. Piatt. U.S. Navy. Naval Research Labora- 
tory, Washington, D.C. NRL Rept. 5465, April 1960, 
167 pp. 
2598. Musick, J. K. and P. Gustafson. Molecular 
sieves for purification of submarine atmospheres, pp. 
101-112 in: The present status of chemical research in at- 
mosphere purification and control on nuclear-powered 
submarines. Edited by R. R. Miller and V. R. Piatt. U.S. 
Navy. Naval Research Laboratory, Washington, D.C. NRL 
Rept. 5465, April 1960, 167 pp. 
2599. Thomas, F. S. The elimination of the oxidiz- 
able contaminants in submarine atmospheres by com- 
bustion. pp. 55-66 in: The present status of chemical 
research in atmosphere purification and control on nu- 
clear-powered submarines. Edited by R. R. Miller and 
V. R. Piatt. U.S. Navy. Naval Research Laboratory, Wash- 
ington, D.C NRL Rept 5465, April 1960, 167 pp. 
2600. Thomas, F. S. hTe CO/Ht) burner, pp. 103- 
105 in: The present status of chemical research in atmos- 
phere purification and control on nuclear-powered sub- 
marines. Edited by V. R. Piatt and E. A. Ramskill. U.S. 
Navy. Naval Research Laboratory, Washington, D.C. 
NRL Rept. 5630, July 1961, 134 pp. 
2601. Tohmas, F. S. The CO/L, burners, pp. 83- 
85 in: The present status of chemical research in atmos- 
phere purification and control on nuclear-powered sub- 
marines. U.S. Navy. Naval Reesarch Laboratory, Wash- 
ington, D.C. NRL Rept. 5814, August 1962, 97 pp. 
D. PHOTOSYNTHETIC GAS PRODUCTION 
AND UTILIZATION 
Algae as a source of oxygen for nuclear sub- 
marines have been considered and this constitutes 
a lively subject of research concern. 
2602. Hannan, P. J. Algae in a photosynthetic gas 
exchanger, pp. 18-28 in: The present status of chemical 
research in atmosphere purification and control on nuclear- 
powered submarines. Edited by V. R. Piatt and E. A. 
Ramskill. U.S. Navy. Naval Research Laboratory, Wash- 
ington, D.C. NRC Kept. 5630, July 1961, 134 pp. 
2602a. Hannan, P. J., C. Patouillet and R. Shuler. 
Studies of oxygen production by mass culture of algae. 
U.S. Navy. Naval Research Laboratory, Washington, D.C. 
NRL Rept. 5689, December 1961, 23 pp. 
2603. Hannan, P. J,, R. L. Shuler and C. Patouillet. 
Algae in a photosynthetic gas exchanger, pp. 21-34 in: 
The present status of chemical research in atmosphere 
purification and control on nuclear-powered submarines. 
Edited by V. R. Piatt and J. C. White. U.S. Navy. Naval 
Research Laboratory, Washington, D.C. NRL Rept. 5814, 
August 1962, 97 pp. 
2604. Hannan, P. J., R. L. Shuler and C. Patouillet. 
Algae as a source of oxygen for nuclear submarines, pp. 
10-24 in: The present status of chemical research in 
atmosphere purification and control on nuclear-powered 
submarines. Edited by H. W. Carhart and V. R. Piatt. 
U.S. Navy. Naval Research Laboratory, Washington, D.C. 
NRL Rept. 6053, December 1963, 65 pp. 
2605. Leonard, J. M. Algae and submarine habi- 
tability — an appraisal. U.S. Navy. Naval Research Labora- 
tory, Washington, D.C. NRL Rept. 5182, August 1958, 8 pp. 
E. CARBON DIOXIDE ABSORPTION 
Only two of the following references will be 
specifically discussed. Duffner (2611) 1957, has 
studied canister design criteria of carbon dioxide 
removal from SCUBA. An empirical set of de- 
sign criteria for a SCUBA carbon dioxide re- 
moval canister were derived from data obtained 
by a review of the pertinent literature. Such a 
device, presuming satisfactory performance for 
180 minutes at 30 feet, and for 30 minutes at 180 
feet, must be capable of absorbing a minimum of 
600 grams of carbon dioxide. It must also re- 
move 75-80 percent of the carbon dioxide from 
a mixture containing 0.5 to 2.0 percent carbon 
dioxide passing through it at a velocity of 55-90 
liters per minute. It must remove 70-75 percent 
of the carbon dioxide from a mixture contain- 
ing 1.0 to 2.5 percent carbon dioxide passing 
through it at a velocity of 125-200 liters per 
minute. The breathing resistance must not ex- 
ceed 1.5 cm. of water per liter per second, and 
the inter-granular space must be at least 3.5 
liters. 
McConnaughey and Crofford (2620) 1956, 
have conducted tests of the Girdler carbon 
dioxide scrubber installed on the USS Nautilus. 
The project was to evaluate suggested changes in VENTILATION AND AIR CONDITIONING—CARBON DIOXIDE ABSORPTION 
2606-2619 
the plant operation. The purpose was to increase 
the capacity above that attainable with the 
specified absorbent solution mixture of 2.5 nor- 
mal diethyleneglycolamine (DEGA) and mehtyl- 
diethanolamine (MDA). Studies were made 
with 4.5 normal monoethanolamine (MEA) at 
1.5 percent carbon dioxide; with 3.5 normal 
diethanolamine (DEA) at 1.5 percent carbon 
dioxide; and with 4.5 normal MEA at 3 percent 
carbon dioxide. It was found that MEA at both 
carbon dioxide concentrations showed an in- 
creased removal rate, the plant capacity at 1.5 
percent carbon dioxide being 10 to 10.5 pounds 
per hour, or about 70 percent greater than that 
obtained in previous dockside runs using the 
DEGA-MDA mixture. The DEA run removed 
around 8 pounds per hour at 1.5 percent carbon 
dioxide. No detectable amine vapor or fogs 
were found in the atmosphere although exces- 
sive losses of amines occurred on the MEA runs. 
This loss is most likely due, according to the 
authors, to leakage rather than to vapor losses 
or to destruction of the amines. 
Since the reference lists for the present 
Volumes were tabulated and serialized, three ex- 
cellent research reports have appeared and are 
referred to in the text. All of these reports 
emerged from U.S. Navy Experimental Diving 
Unit, U.S. Naval Station, Washington Navy 
Yard Annex, Washington, D.C. The first is a 
study by M. W. Goodman on carbon dioxide 
elimination from SCUBA with standard and 
modified canisters of the U.S. Navy closed- 
circuit oxygen rig, (Research Report 1-64, 
Project F-011-06, Task 3380, Test 6) 1 May 
1964, The second report, also by Goodman is 
entitled: Carbon dioxide absorption systems for 
SCUBA. 1) I. Quantitative considerations of 
design and performance of cylindrical canisters, 
(Research Report 3-64, Project F-011-06-03, 
Task 3380, Test 8), 15 February 1965. The 
third of these reports is by M. W. Goodman and 
T. W. James and is entitled: Carbon dioxide 
absorption systems for SCUBA. 2) II. Theory 
and application of a novel, non-cylindrical low 
resistance carbon dioxide absorption canister for 
SCUBA, (Research Report 4-65, Project 
F-011-06-05, Task 11511, Sub-task 4, Report 
No. 2), 15 June 1965. 
2606. Adrian!, J. Disposal of carbon dioxide from 
devices used for inhalational anesthesia. Anesthesiology, 
1960, 21: 742-758. 
2607. Brown, E. S. Voids, pores and total air space 
of carbon dioxide absorbents. Anestehsiology, 1958, 19: 1-6. 
2608. Brown, E. S. Performance of absorbents: con- 
tinuous flow. Anesthesiology, 1959, 20: 41-44. 
2609. Brown, E. S. and J. O. Elam. Practical aspects 
of carbon dioxide absorption. N.Y. St. J. Med., 1955, 
55: 3436-3442. 
2610. Derrick, W. S. and R. C. Smart. Observations 
on the carbon dioxide absorption properties of monoeth- 
anolamine. Anesthesiology, 1957, 18: 551-558. 
2611. Duffner, G. J. Canister design criteria of carbon 
dioxide removal from SCUBA. U.S. Navy. EDU, Naval 
Weapons Plant, Washington, D.C. Project NS 186-200, 
sub task no. 4, test no. 44, 8 March 1957, 12 pp. 
2612. Elam, J. O. Channeling and overpacking in 
carbon dioxide absorbers. Anesthesiology, 1958, 19: 
403-404. 
2613. Gadomski, S. The absorption and removal of 
carbon dioxide in the alkali (sodium) sulfate process, pp. 
129-135 in: The present status of chemical research in 
atmosphere purification and control on nuclear-powered 
submarines. Edited by R. R. Miller and V. R. Piatt. 
U.S. Navy. Naval Research Laboratory, Washington, D.C. 
NRL Kept. 5465, April 1960, 167 pp. 
2614. Gadomski, T. S. The use of versene to improve 
MEA performance, pp. 50-51 in: The present status of 
chemical research in atmosphere purification and control 
on nuclear-powered submarines. Edited by V. R. Piatt 
and E. A. Ramskill. U.S. Navy. Naval Research Labora- 
tory, Washington, D.C. NRL Rept. 5630, July 1961, 
134 pp. 
2615. Gillen, H. W. An evaluation of the use of 
Baralyme in the submarine escape appliance. U.S. Navy. 
Submarine Base, New London, Conn. Medical research 
laboratory. Project NM 002 015.08, Rept. no. 1, 1956. 
2616. Goan, J. C. Alkazid M as a regenerative carbon 
dioxide absorbent, pp. 92-100 in: The present status of 
chemical research in atmosphere purification and control 
on nuclear-powered submarines. Edited by R. R. Miller 
and V. R. Piatt. U.S. Navy. Naval Research Laboratory, 
Washington, D.C. NRL Rept. 5465, April 1960, 167 pp. 
2617. Goan, J. C. Alkazid M. p. 52 in: The present 
status of chemical research in atmosphere purification and 
control on nuclear-powered submarines. Edited by V. R. 
Piatt and E. A. Ramskill. U.S. Navy. Naval Research 
Laboratory, Washington, D.C. NRL Rept. 5630, July 
1961, 134 pp. 
2618. Huseby, H. W. S. and E. J. Michielsen. 
Carbon dioxide absorbent evaluation and canister design. 
U.S. Navy. EDU, Naval Weapons Plant, Washington, D.C. 
Project NS 186-202, sub task no. 2, test no. 14, 6 November 
1959, 33 pp. 
2619. Leonard, J. M. Algae and submarine habit- 
ability. pp. 143-150 in: The present status of chemical 
research in atmosphere purification and control on nuclear- 
powered submarines. Edited by R. R. Miller and V. R. 
Piatt. U.S. Navy. Naval Research Laboratory, Washington, 
D.C., NRL Rept. 5465, April 1960, 167 pp. 2620-2639 
PROTECTION AND PRESERVATION OF PERSONNEL 
2620. McConnaughey, W. E. and W. N. Crofford, 
III. Shipboard tests of carbon dioxide scrubber on USS 
Nautilus (SSN571). U.S. Navy. Naval Research Laboratory, 
Washington, D.C. NRL Memo Rept. 585, April 1956, 28 
pp. 
2621. Miles, G. and J. Adriani. Carbon dioxide 
absorption. Anesth. Analg., 1959, 38: 293-300. 
2622. Miller, R. R. Lithium hydroxide and soda 
lime as CCX absorbents for naval use. pp. 81-87 in: The 
present status of chemical research in atmosphere purifica- 
tion and control on nuclear-powered submarines. Edited 
by R. R. Miller and V. R. Piatt. U.S. Navy. Naval Re- 
search Laboratory, Washington, D.C. NRL Rept. 5465, 
April 1960, 167 pp. 
2623. Miller, R. R. Comparison of carbon dioxide 
removal systems, pp. 31-36 in: The present status of 
chemical research in atmosphere purification and control 
on nuclear-powered submarines. Edited by H. W. Car- 
hart and V. R. Piatt. U.S. Navy. Naval Research Labora- 
tory, Washington, D.C. NRL Rept. 6053, December 1963, 
65 pp. 
2624. Ravner, H. and C. H. Blachly. Studies on 
monoethanolamine (MEA). pp. 45-50 in: The present 
status of chemical research in atmosphere purification and 
control on nuclear-powered submarines. Edited by V. R. 
Piatt and J. C. White. U.S. Navy. Naval Research Labora- 
tory, Washington, D.C. NRL Rept. 5814, August 1962, 
97 pp.) 
2625. Ravner, H. and C. H. Blachly. Monoethanol- 
amine stability studies, pp. 25-30 in: The present status 
of chemical research in atmosphere purification and con- 
trol on nuclear-powered submarines. Edited by H. W. Car- 
hart and V. R. Piatt. U.S. Navy. Naval Research Labora- 
tory, Washington, D.C. NRL Rept. 6053, December 1963, 
65 pp. 
2626. Smith, S. H., Jr. Carbon dioxide scrubbing 
with an alkaline amine solution, pp. 88-91 in: The present 
status of chemical research in atmosphere purification and 
control on nuclear-powered submarines. Edited by R. R. 
Miller and V. R. Piatt. U.S. Navy. Naval Research Labora- 
tory, Washington, D.C. NRL Rept. 5465, April 1960, 
167 pp. 
F. OXYGEN GENERATORS 
For the most part the oxygen supply for mod- 
ern nuclear submarines is derived from liquid 
oxygen sources. Other possible sources of oxy- 
gen supply are discussed in the references listed 
below. 
2627. Bovard, R. M, Oxygen sources for space 
flights. Aerospace Med., 1960, 31: 407-412. 
2628. Christian, J. G. Hopcalite-catalyzed combus- 
tion. pp. 60-64 in: The present status of chemical research 
in atmosphere purification and control on nuclear-powered 
submarines. Edited by H. W. Carhart and V. R. Piatt. 
U.S. Navy. Naval Research Laboratory, Washington, D.C. 
NRL Rept. 6053, December 1963, 65 pp. 
2629. Gadomski, S. T. and A. L. Pitman. The 
sulfate-cycle system, pp. 6-9 in: The present status of 
chemical research in atmosphere purification and control 
on nuclear-powered submarines. Edited by H. W. Carhart 
and V. R. Piatt. U.S. Navy. Naval Research Laboratory, 
Washington, D.C. NRL Kept. 6053, December 1963, 65 pp. 
2630. Miller, R. R. Weight economics of carbon 
dioxide and oxygen equipment for closed spaces, pp. 39-45 
in: The present status of chemical research in atmosphere 
purification and control on nuclear-powered submarines. 
Edited by V. R. Piatt and E. A. Ramskill. U.S. Navy. 
Naval Research Laboratory, Washington, D.C. NRL Rept. 
5630, July 1961, 134 pp. 
2631. Musick, J. K. and P. R. Gustafson. Chlorate 
candles, pp. 29-38 in: The present status of chemical re- 
search in atmosphere purification and control on nuclear- 
powered submarines. Edited by V. R. Piatt and E. A. 
Ramskill. U.S. Navy. Naval Research Laboratory, Wash- 
ington, D.C. NRL Rept. 5630, July 1961, 134 pp. 
2632. Musick, J. K. and P. R. Gustafson. Chlorate 
candles, pp. 35-43 in: The present status of chemical re- 
search in atmosphere purification and control on nuclear- 
powered submarines. Edited by V. R. Piatt and J. C. 
White. U.S. Navy. Naval Research Laboratory, Wash- 
ington, D.C. NRC Rept. 5814, August 1962, 97 pp. 
2633. Pitman, A. L. An electrolytic cell for the pro- 
duction of oxygen and sodium hydroxide, pp. 136-142 in: 
The present status of chemical research in atmosphere 
purification and control on nuclear-powered submarines. 
Edited by R. R. Miller and V. R. Piatt, LT.S. Navy. Naval 
Research Laboratory, Washington, D.C. NRL Rept. 5465, 
April 1960, 167 pp. 
2634. Pitman, A. L. and S. T. Gadomski. Laboratory 
scale operation of the sulfate cycle for carbon dioxide 
removal and oxygen generation. U.S. Navy. Naval Re- 
search Laboratory, Washington, D.C. NRL Rept. 5714, 
January 1962, 12 pp. 
2635. Roach, C. G. and R. W. Roundy. Present status 
of aircraft liquid oxygen breathing systems. J. Aviat. 
Med., 1958, 29: 898-902. 
2636. Roxburgh, H. L. Some physiological require- 
ments of oxygen systems. Proc. roy. Soc., 1954, 143: 17-24. 
2637. Smith, S. H., Jr. Chlorate oxygen candles, 
pp. 119-122 in: The present status of chemical research 
in atmosphere purification and control on nuclear-powered 
submarines. Edited by R. R. Miller and V. R. Piatt. U.S. 
Navy. Naval Research Laboratory, Washington, D.C. 
NRL Rept 5465, April 1960, 167 pp 
2638. White, J. C. Electrolytic generation of oxygen, 
pp. 123-127 in: The present status of chemical research in 
atmosphere purification and control on nuclear-powered 
submarines. Edited by R. R. Miller and V. R. Piatt. 
U.S. Navy. Naval Research Laboratory, Washington, D.C. 
NRL Rept. 5465, April 1960, 167 pp. 
2639. Work, G. W. Electrolytic generation of oxygen 
without the accompanying generation of hydrogen. U.S. 
Navy. Naval Research Laboratory, Washington, D.C. 
NRL Rept. 4775, June 1956, 9 pp. RESUSCITATION 
2640-2647 
2640. Young, J. A., R. C. Clark and K. D. Law- 
rence. Diaphragms for the sulfate-cycle electrolytic cell, 
pp. 16-20 in: The present status of chemical research in 
atmosphere purification and control on nuclear-powered 
submarines. Edited by V. R. Piatt and J. C. White. U.S. 
Navy. Naval Research Laboratory, Washington, D.C. 
NRL Kept. 5814, August 1962, 97 pp 
III. RESUSCITATION 
In a variety of situations in submarine opera- 
tions, diving and in compressed air work the 
need for resuscitation may arise. The following 
list of references has been selected to provide the 
reader with a source of information on this 
subject. 
2641. Elam, J. O., D. G. Greene, E. S. Brown and 
J. A. Clements. Oxygen and carbon dioxide exchange 
and energy cost of expired air resuscitation. /. Amer. 
med. Ass., 1958, 167: 328-334. 
2642. Frumin, M. J., N. A. Bergman and D. A. 
Holaday. Effects of altered expiratory pressures or resist- 
ances upon arterial oxygen saturation during artificial 
respiration. Fed. Proc., 1957, 16: 42. 
2643. Gordon, A. S., C. W. Frye, L. Gittelson, 
M. S. Sadove and E. J. Beattie, Jr. Mouth-to-mouth 
versus manual artificial respiration for children and adults. 
J. Amer. med. Ass., 1958, 167: 320-328. 
2644. Holaday, D. A., J, Israel, E. K. Williams 
and M. J. Frumin. Variations in ventilation blood flow 
ratios during artificial respiration. Fed. Proc., 1957, 16: 
60. 
2645. Ruben, H. E., J. O. Elam, A. M. Ruben and 
D. G. Greene. Investigation of upper airway problems 
in resuscitation. 1. Studies of pharyngeal x-rays and 
performance by laymen. Anesthesiology, 1961, 22: 271-279. 
2646. Safar, P. Ventilatory efficacy of mouth-to-mouth 
artificial respiration. J. Amer. med. Ass., 1958, 167: 335-341. 
2647. Safar, P. Failure of manual artificial respiration. 
Fed. Proc., 1958, 17: 139. Selection and Training of 
Submarine Personnel, Divers and 
Compressed Air Workers 
1. SELECTION 
The purpose of selection procedures is to 
identify predictably those applicants for sub- 
marine and diving duty who will succeed in train- 
ing and perform creditably. As Wise (2676) 
1963, has pointed out with regard to aptitude 
selection standards for the U.S. Navy’s First 
Class Diving Course, the establishment of selec- 
tion standards based on research would in all 
probability reduce the attrition rates currently 
encountered in training. Wise undertook a cor- 
relational analysis of 137 records of recent gradu- 
ates of the diving course as well as failures. This 
analysis was undertaken to determine what tests 
within the Navy’s basic test battery—general 
classification index (GCT), mechanical compre- 
hension test (MECH), arithmetic test (ARI), 
and clerical test (CLER) —could best be utilized 
as predictors of training success. As determined 
by a multiple correlation value of 0.428 the com- 
bination of ARI and MECH provided the best 
result. A combined cut-off score of 80 on these 
tests was suggested as a requirement for entrance 
in the First Class Diver’s Course. As specified 
by the U.S. Navy the selection requirements for 
the Deep Sea Divers School are: a) to volunteer 
for trainng, b) to pass a physical examination, 
c) to be interviewed by a qualified diving officer, 
d) to meet first class swimmer requirements, and 
e) make a test dive in a diving suit. Using these 
selection criteria the school has had an attrition 
rate in 1960-1962 of approximately 20 percent 
among enlisted men. Of this 20 percent approxi- 
mately 52 percent are classified as academic 
failures, 41 percent voluntarily withdrew and the 
remaining 7 percent were medically disqualified. 
For similar comments on submarine personnel 
selection and assessment reference number 2668, 
1956, should be consulted. The interview con- 
stitutes an important part of the selection proce- 
dure and its reliability as a screen and selection 
technique has been studied by several, including 
Crissy and Pashalian (2650) 1952. When con- 
ducted by an experienced submarine officer the 
assessment interview should offer considerable 
information of predictive value. King (2654, 
2656) 1957 and 1959, has published studies on 
correlates of disqualification in the submarine 
service and also prediction of Submarine School 
attrition from the Minnesota Multiphasic Per- 
sonality Inventory. This investigator studied 
differences in the response and test scores of a 
disqualified group and of a qualified group. The 
two groups were found to be differentiated by a 
number of variables. The disqualified subjects 
were inferior in their attendance at the Sub- 
marine School and had a lower final standing. 
They also had a lower Navy GCT (General 
Classification Index) as well as artithmetic and 
clerical scores. The data suggested a significantly 
higher incidence of personality maladjustment 
in the disqualified group. The two groups were 
also characterized by different opinions and feel- 
ings towards the submarine service. King com- 
ments that his studies do not appear to call /or 
changes in current assessment and selection proce- 
dures. Kinsey and Weybrew (2659) 1953, have 
made a descriptive analysis of disqualified sub- 
marine personnel from 1947-1952 with the ob- 
ject of determining the major etiological factors SELECTION 
contributing to disqualification. Although quite 
tentative major conclusions from this investiga- 
tion were that more than half of the reasons for 
disqualification could be defined as motivational, 
the results indicate that some people are disquali- 
fied as a result of an inadequate need or motiva- 
tional pattern as the onset; others are disquali- 
fied from the inability, even though optimally 
motivated at the onset, to reach important goals 
and to maintain optimal motivation. The Navy 
Test Battery, especially the GCT and the com- 
bined GCT and ARI, was believed by Kinsey 
and Weybrew to be doing a fairly effective job 
of screening aptitudinally deficient people from 
the submarine service. The relationship of these 
scores to the criterion of disqualification is prob- 
ably high. The authors feel that patterns of 
neurotic symptoms are useful predictors of dis- 
qualification, but their data were too incomplete 
in this study to estimate the relationship. Useful 
assessment predictors might be found by means 
of dimensioning some one or several of these 
neurotic variables. Finally, several background 
factors—education, time in service, previous 
academic records, and others—were shown to be 
quite possibly related to the criterion, while job 
histories, criminal records, etc. were probably not 
predictive. Kinsey, in a study of psychological 
aspects of the “Nautilus” transpolar cruise, has 
commented on the value and characteristics of 
leadership, as operationally experienced in sub- 
marines. This leadership depends not only upon 
the personality of the leader but upon the varying 
reactions of the group and of the environment 
as a whole. Kinsey comments that selection and 
promotion systems of the U.S. Navy have built-in 
factors which tend to assure sound leadership. 
That the assessment and selection, as well as 
training programs for submarine service, are 
effective, according to the author, is manifested 
by the achievement of the officers and men of the 
“Nautilus”. 
The selection and training of divers and 
underwater swimmers are equally important mat- 
ters. Miles (2661) 1962, comments that most 
professional diving schools have a training attri- 
tion rate of more than 50 percent. Certain 
respiratory characteristics, such as slow and deep 
breathing, as well as capacity for long distance 
running seems to be highly correlated with sue- 
cess in diving training. Mention is also made 
of the correlation between training failure and 
inadequate tempermental adaptation. Motiva- 
tion undoubtedly plays an important role! 
For further studies on predictors of success in 
training in submarine school, papers by Wey- 
brew (2669, 2670, 2674) 1954, 1957 and 1959 
should be consulted. Youniss (2677) 1956, car- 
ried out an investigation of motivation for sub- 
marine duty and its relation to submarine 
school success. Differences in responses to a 
motivational questionnaire were examined be- 
tween various levels of achievement in submarine 
school between Navy rates and between drop-outs 
and graduates. The most significant differences in 
motivation occurred between drop-outs and 
graduates from submarine school, the former 
being characterized by low initial motivation, 
lack of interest and a reduced level of aspiration. 
From these results it appeared that a well de- 
signed motivation questionnaire might provide 
a means of pre-selecting volunteers with adequate 
motivation and other personality characteristics 
typical of those who are later dropped from sub- 
marine school. An interesting paper is that by 
Youniss (2678) 1959, on the relationship of 
tattoos to personal adjustment among enlisted 
submarine school volunteers. A study was made 
to compare enlisted men who had tattoos with 
those who did not in terms of their level of per- 
sonal adjustment, as indicated by scores on a 
personality questionnaire. It was found that men 
with multiple tattoos are less well adjusted than 
those with none or those with a single tattoo. 
Moreover, those who desire to obtain tattoos in 
the future demonstrate less adequate adjustment 
than those who have no intention of being 
tattooed. The results of this study seem to in- 
dicate that there is a psychological significance 
in tattoos and in addition these studies contribute 
to an understanding of a relatively unexplored 
aspect of human behavior. It should not be 
claimed that the behavioral factor of having 
been tattooed is alone sufficient to delineate or 
identify qualities of personality adjustment. 
For a general background study of the occupa- 
tional problems encountered in submarines a 
paper by Alvis (2648) 1957, should be read. 
This article surveys physical and psychological 
screening, as well as special testing of vision and 2648-2660 
SELECTION AND TRAINING OF PERSONNEL 
hearing. In discussing psychological standards 
the author comments that the idea that sub- 
mariners and divers must be the most normal of 
normal men is not correct. For both the occupa- 
tion of submariner and diver one must search out 
special types of men. The identification and de- 
scription of these men has been most difficult 
and remains difficult. In the field of deep sea 
diving it has been possible to proceed by the cull- 
and-reject method because the number of replace- 
ments required were relatively small. Psychome- 
tric testing has generally been quite successful in 
predicting success as defined by completing the 
submarine school course, however, relating this 
successful prediction to later success in the sub- 
marine force in action has been more difficult. 
One of the most interesting methods of establish- 
ing a desirable and an undesirable characteristic 
of submariners has been the method of peer 
rating, in which submariners describe what they 
like about other submariners they regard highly 
and what they dislike about those they regard 
less highly. From the qualities enumerated in 
such inquiries one may partially describe a sub- 
mariner in terms of confidence in his ability, 
recognition of his limitations, dependability and 
willingness to concede the appropriate social 
status to his shipmates. Ideally the submariner is 
a person who does not “freeze up” or “fall apart” 
in crises, and who does not stand aloof from the 
group. These definitions are applicable to 
many men who would not care to the sub- 
mariners. In addition, a submariner must have 
enthusiasm for doing the unusual without its 
being manifested in foolhardy or socially unac- 
ceptable behavior. He must be willing to pit his 
wits against the calculated risk; he must have a 
zest for accomplishment which overrides creature 
comfort, at least at times of duty. From the fore- 
going it is obvious that the recluse, the timid, 
and the slow witted must be diverted to some 
other field of operation and endeavor. 
A general survey of the literature on selection 
leads conclusively to the need for unified and 
more imaginative effort leading to more effective 
pre-selection and screening of submarine ap- 
plicants. A more general and open examination 
of statistics regarding personnel breakdown in 
the nuclear boats would be highly desirable so as 
to determine associations between the present 
selection techniques and performance outcome. 
2648. Alvis, H. J. Submarine medicine—an occupa- 
tional specialty New Engl. J. Med., 1957, 256: 21-25. 
2649. Briggs, D. L., B. Lyon, H. B. Molish and 
R. R. Deen. Selected socio-cultural factors affecting in- 
terpersonal relations as revealed by the Blacky pictures. 
I. Discrimination between “unsuitable” and "normal” 
recruits. U.S. Navy. Submarine Base, New London, Conn. 
Medical research laboratory. Project NM 003 041.52, Kept, 
no. 1, 22 June 1953. 
2650. Crissy, W. J. E. and S. Pashalian. The inter- 
view: III. Aids to the interview —the submarine stereo- 
type. U.S. Navy. Submarine Base, New London, Conn. 
Medical research laboratory. Project NM 002 016.01, Kept, 
no. 3, 20 October 1952. 
2651. Duffner, G. J. Crew selection for submarine 
duty. U.S. Forces med. J., 1954, 5: 1192-1198. 
2652. Eysenck, H. J. A dynamic theory of anxiety 
and hysteria. J. ment. Sci., 1955, 101: 28-51. 
2653. Foster, R. J. and J. G. Carnaghan. Prediction 
of submarine school success through the use of selected 
themes in the Navy thematic apperception test: U.S. Navy. 
Submarine Base, New London, Conn. Medical research 
laboratory. Project NM 003 041.54, Kept. no. 1, 2 May 
1955. 
2654. King, B. T. Some corerlates of disqualification 
in the submarine service. U.S. Navy. Submarine Base, 
New London, Conn. Medical research laboratory. Project 
NM 23 02 20.01, Kept. no. 2, 1957. 
2655. King, B. T. Relationship between submarine 
school performance and scores on the Navy thematic ap- 
perception test. U.S. Navy. Submarine Base, New London, 
Conn. Medical research laboratory. Project NM 23 02 
20.01, Kept. no. 4, 1958. 
2656. King, B. T. Predicting submarine school attri- 
tion from the Minnesota Multiphasic Personality Inven- 
tory. U.S. Navy. Submarine Base, New London, oCnn. 
Medical research laboratory. Kept. no. 313, 20 August 1959, 
25 pp. 
2657. Kinsey, J. L. Psychologic aspects of the “Nauti- 
lus” transpolar cruise. U.S. Forces med. J., 1959, 10: 
451-462. 
2658. Kinsey, J. L. and H. B. Murphree. Claustro- 
phobic reactions to some stresses of the submarine serv- 
ice. U.S. Navy. Submarine Base, New London, Conn. 
Medical research laboratory. Project NM 003 041.53, Kept, 
no. 2, 4 April 1955. 
2659. Kinsey, J. L. and B. B. Weybrew, Etiological 
factors in the disqualification of submarine personnel. 
U.S. Navy. Submarine Base, New London, Conn. Medical 
research laboratory. Project NM 003 041. 13.03, 22 June 
1953, 40 pp. 
2660. McCabe, F. J. The interview: II. Aids to the 
interview — the confidential questionnaire. U.S. Navy. 
Submarine Base, New London, Conn. Medical research 
laboratory. Project N M002 016.01, Rept. no. 2, 15 October 
1952. PERFORMANCE—SUBMARINE OPERATIONS 
2661-2678 
2661. Miles, S. Selection and training of divers and 
underwater swimmers, pp. 244-253 in: Underwater medi- 
cine. J. B. Lippincott Co., Philadelphia, 1962, 328 pp. 
2662. Ninow, E. H. The use of a standard psychiatric 
interview to predict motivation of enlisted men for the 
submarine service. U.S. Navy. Submarine Base, New 
London, Conn. Medical research laboratory. Project MR 
005.14-2100-2, Rept. no. 3, 23 November 1960. 
2663. Pashalian, S. and W. J. E. Crissy. The 
interview: IV. The reliability and validity of the assess- 
ment interview as a screening and selection technique in 
the submarine service. U.S. Navy. Submarine Base, New 
London, Conn. Medical research laboratory. Project NM 
002 016.01, Rept. no. 4, 12 January 1953. 
2664. Pashalian, S., W. J. E. Crissy, A. I. Siegel 
and E. P. Buckley. The interview: I. A. selectively 
abstracted bibliography. U.S. Navy. Submarine Base, New 
London, Conn. Medical research laboratory. Project NM 
002 016.01, Rept. no. 1, 2 June 1952. 
2665. Rioch, D. McK. Experimental aspects of anx- 
iety. Amer. J. Psychiat., 1956, 113: 435-442. 
2666. Schwartz, I. and F. L. Dimmick. Comparison 
of high acuity scores on Snellen and Orthorater tests. U.S. 
Navy. Submarine Base, New London, Conn. Medical 
research laboratory. Project NM 23 01 20.04, Rept. no. 1, 
1958. 
2667. Stuntz, S. E. Current program of research in 
the selection of submarine sonar operations. U.S. Navy. 
Submarine Base, New London, Conn. Medical research 
laboratory. Project NM 003 041.07, Rept. no. 2, 1952. 
2668. U.S. Navy. Submarine personnel selection and 
assessment, pp. 286-296 in: Submarine medicine practice. 
U.S. Navy, BuMed. NAVMED — 5054, Gov’t. Printing 
Office, Washington, D.C., 1956, 357 pp. 
2669. Weybrew, B. B. Predicting success in submarine 
school. U.S. Navy. Submarine Base, New London, Conn. 
Medical research laboratory. Project NM 003 041.53, Rept. 
no. 1, 2 November 1954. 
2670. Weybrew, B. B. An exploratory study de- 
signed to suggest clusters of traits and assessment tests 
related to submariner adjustment. U.S. Navy. Submarine 
Base, New London, Conn. Medical research laboratory. 
Project NM 003 041.54, Rept. no. 3, 1957. 
2671. Weybrew, B. B. The personal inventory barom- 
eter: II. Observe factor analysis with PIB items as a 
validating technique with submarine school criteria. U.S. 
Navy. Submarine Base, New London, Conn. Medical 
research laboratory. Project NM 23 02 20.01, Rept. no. 2, 
6 May 1959. 
2672. Weybrew, B. B. Patterns of reaction to stress 
as revealed by a factor analysis of autonomic change meas- 
ures and behavioral observations. U.S. Navy. Submarine 
Base, New London, Conn. Medical research laboratory. 
Project NM 23 02 20.03, Rept. no. 3, 26 May 1959. 
2673. Weybrew, B. B. and D. J. Alves. Exploratory 
study of the relation of autonomic resiliency to manifest 
anxiety and selected personality traits. U.S. Navy. Sub- 
marine Base, New London, Conn. Medical research labora- 
tory. Project NM 22 02 20.02, Rept. no. 5, 3 March 1959. 
2674. Weybrew, B. B. and H. B. Molish. Ap- 
proaches to the study of motivation of officer candidates 
for submarine service. U.S. Navy. Submarine Base, New 
London, Conn. Medical research laboratory. Project 
MR005.14-2100.2, Kept. no. 2, 16 October 1959. 
2675. Weybrew, B. B. and R. P. Youniss. Personal 
inventory barometer, I. Development of the questionnaire. 
U.S. Navy. Submarine Base, New London, Conn. Medical 
research laboratory. Project NM 23 02 20.01, Kept. no. 1, 
1957. 
2676. Wise, D. A. Aptitude selection standards for 
the U.S. Navy’s first class diving course. U.S. Navy. EDU, 
Naval Station, Washington, D.C. Res. Rept. 3-63, Proj. 
F 011-06-01, Task 3361, 10 June 1963, 8 pp. 
2677. Younis, R. P. An investigation of motivation 
for submarine duty and its relation to submarine school 
success. U.S. Navy. Submarine Base, New London, Conn. 
Medical research laboratory. Project NM 003 041.53.04, 
4 November 1956, 13 pp. 
2678. Youniss, R. P. Relationship of tattoos to 
personal adjustment among enlisted submarine school 
volunteers. U.S. Navy. Submarine Base, New London, 
Conn. Medical research laboratory. Project NM 23 02 
20.01, Rept. no. 7, 17 September 1959. 
II. PERFORMANCE—SUBMARINE 
OPERATIONS 
The period of World War II generated condi- 
tions under which there was obvious opportunity 
to recognize varying degrees of performance 
quality under stress. The patrols of the Polaris 
submarines do impose great stress at the present 
time, nevertheless, the literature on performance 
in submarines has become reduced in the past 
few years. Performance data have been collected 
from various operational activities including the 
simulated submergence, “Operation Hideout” 
carried out at the Submarine Base, New London, 
Connecticut. Among the several reports based 
on this test, one by Eron and Auld (2680) 1954, 
may be cited. This particular study was an at- 
tempt to discover whether the Hideout popula- 
tion was any different from a random sample 
of submarine enlisted personnel, and what the 
effect of confinement aboard a submarine for 
more than 30 days might be on the results of 
the Thematic Apperception Test (TAT) and 
on certain sentence completion tests. By com- 
parison of two items taken from the personal 
history forms of 100 randomly selected sub- 
mariners and of the Hideout group, it was found 
that there was no significant difference between 
the two samples in age of subject or education of 
the father (the latter item being used as an index 2679-2683 
SELECTION AND TRAINING OF PERSONNEL 
of the social status of the family). The two sam- 
ples were significantly different in the formal 
aspect of the stories they told, with the Hideout 
subjects becoming less emotionally involved in 
the task, and in general not cooperating as well 
as the normative subjects. The incomplete sen- 
tences revealed that the motivations of the two 
groups were different: the normative group 
seemed to contain significantly more individuals 
who felt some social responsibility, and signifi- 
cantly fewer individuals who wanted to avoid 
“messy” details. Between the first and second 
testing it was apparent that the subjects became 
increasingly uncooperative, more apathetic, more 
desirous of leaving and showed heightened sexual 
phantasies. Increased references to sickness and 
ill-health were also noted in the completions, as 
well as an increasing concern over whether or not 
they were doing the right thing in relation to 
their peers. For a review and critique of the 
literature on vigilance performance, reports by 
McGrath, Harabedian and Buckner (2683) 1959, 
and Buckner, Harabedian and McGrath (2679) 
1960, and Harabedian, McGrath and Buckner 
(2682) 1960, should be consulted. These papers 
are also concerned with individual differences in 
vigilance performance and the probability of sig- 
nal detection in a vigilance task as a function of 
intersignal interval. Factors in decline of per- 
formance efficiency, especially over periods of 
time, the effects of display characteristics, the 
effects of signal characteristics in general, effects 
of procedural conditions, physiological factors in 
vigilance performance, motivational differences 
and methods of improving performance are all 
discussed. The authors point out the immediate 
need to investigate performance under opera- 
tional conditions, also to examine the reliability 
of individual difference results. The first of these 
papers is especially valuable in that there is an 
annotated bibliography. 
2679. Buckner, D. N., A. Harabedian and J. J. 
McGrath. Human factor problems in antisubmarine 
warfare. Technical Report 2. A study of individual differ- 
ences in vigilance performance. U.S. Navy. Office of 
Naval Research, Washington, D.C. NONR 2649(00) NR 
153-199, January 1963, 44 pp. 
2680. Eron, L. D. and F. Auld, Jr. A study of the 
thematic apperception test stories and sentence completions 
of subjects in Operation Hideout. U.S. Navy. Submarine 
Base. New London, Conn. Medical research laboratory. 
Project NM 002 015.11, Rept. no. 2, 12 February 1954. 
2681. Fraser, D. C. The relation of an environmental 
variable to performance in a prolonged visual task. Quart. 
J. exp. Psychol, 1953, 5: 31-32. 
2682. Harabedian, A., J. A. McGrath and D. N. 
Buckner. Human factor problems in anti-submarine 
warfare. Technical Report 3. The probability of signal 
detection in a vigilance task as a function of intersignal 
interval. U.S. Navy. Officer of Naval Research, Wash- 
ington, D.C, NONR 2649(00) NR 153-199, February 1960, 
30 pp. 
2683. McGrath, J. J., A. Harabedian. and D. N. 
Buckner. Human factors research in anti-submarine 
warfare. Technical Report I. Review and critique of the 
literature on vigilance performance. U.S. Navy. Office 
of Naval Research, Washington, D.C. NONR 2649(00) NR 
153-199, December 1959, 100 pp. 
III. HUMAN FACTORS IN 
ENGINEERING DESIGN 
A number of factors in the environment affect 
vigilance, as Mackworth (2597) 1957, has pointed 
out. Vigilance may be defined as a state of readi- 
ness to detect and respond to certain specific 
small changes occurring at random time inter- 
vals in the environment. The factors in the 
working situation causing loss of vigilance may 
be outlined as follows: a) The frequency of 
the signal. The more frequent the signal the 
more likely it is to be observed, b) The in- 
tersignal interval. Performance is better with 
a regular interval which is probably the most 
important factor in determining whether or not 
there will be a decline in the probability of 
detection as time goes on. c) The length of the 
working period. There is a decrement after a 
half-an-hour, but this depends on a number of 
physical and psychological factors. It would be 
useful to know the shortest rest period effective 
in restoring vigilance, d) Duration of the signal. 
Decrements may occur with short or longer 
duration. One must consider unwanted signals 
also. Research is needed on regularity, frequency 
and similarity to the wanted signal. There are 
also general environmental effects, such as noise, 
heat, isolation and other factors, which can re- 
duce watchfulness. Motivational effects are also 
to be considered. Loss of sleep may produce re- 
duced motivation, and alertness can be sustained 
by motivation through giving the subject a small 
dose of amphetamine sulfate or benzadrine one 
hour before starting the task. The use of em- 
phetamines demands caution. HUMAN FACTORS IN ENGINEERING DESIGN 
2684-2700 
For reports of biasing attention during a vigi- 
lance task, papers by Baker (2684, 2685) 1956, 
1958, may be consulted. Experiments are de- 
scribed in which the subjects were asked to 
search visual displays and report appearance, at 
any location on the display, of a spot of light 
which persisted for one second. On displays with 
or without a rotating radial line, it was found 
that subjects detect fewer such spots of light near 
the periphery of the display. By modifying a 
radar-like display in order to facilitate a changed 
pattern of visual search it was demonstrated that 
more peripheral spots could be detected. Spatial 
factors in check reading of dial groups have been 
considered by Lincoln and Averbach (2696) 
1956. Papers by Broadbent (2687, 2689) 1952, 
1955, may be consulted for studies of responses 
to one of two synchronous messages. Jones may 
be consulted (2694) 1960, for studies of fatigue 
effect in radio operators during a program of 
high intensity long duration flying. The basic 
flying unit was a 15 hour sortie divided into 
five hour watches. The subjects were given a 
set hourly task, their achievement being scored 
as its percentage completion in each hour. The 
experiment was designed to allow examination 
of results in relation to three different time 
scales, namely from hour to hour within a watch, 
from watch to watch within a sortie, and from 
sortie to sortie within the eight day trial. 
Optimum duration of watch for a signaller on 
radio operator duty in flight was found to be 
three hours, a consistent reduction in measured 
activity, associated with subjective deterioration 
becoming manifest after this time. The penalty 
for exceeding this duration tended to increase 
as the sortie progressed. There was a progressive 
decrease in mean level of activity from watch to 
watch throughout the standard sortie, a decline 
which it is contended could be partially offset by 
introducing appropriate rest schedules during 
long flights. Changes from one sortie to the next, 
although statistically significant, were not progres- 
sive. It was suggested by the author that the re- 
sults were masked by beginning and end effects. 
Changes occurring over the three time scales 
mentioned are discrete and must be separately 
measured for useful interpretation of results. 
2684. Baker, C. H. Biasing attention to visual displays 
during a vigilance task. Gt. Brit. MRC, RNPRC, OES. 
Kept. R.N.P. 561876, O.E.S. 291, October 1956, 6 pp. 
2685. Baker, C. H. Attention to visual displays during 
a vigilance task. I. Biasing attention. Brit. J. Psychol., 
1958, 49: 279-288. 
2686. Berest, N. J. Curveille and G. Perdriel. 
Les normes d’aptitude visuelle des lecteurs de scope. Med. 
aero., 1958, 13: 265-270. 
2687. Broadbent, D. E. Listening to one of two syn- 
chronous mesasges. J. exp. Psychol., 1952, 44: 51-55. 
2688. Broadbent, D. E. Classical conditioning and 
human watchkeeping. Psychol. Rev., 1953, 60: 331-339. 
2689. Broadbent, D. E. Successive responses to simul- 
taneous stimuli. Gt. Brit. MRC, RNPRC, OES. Rept. 
R.N.P. 55/837, O.E.S. 260, April 1955, 16 pp. 
2690. Broadbent, D. E. Time to react. Advanc. Sci., 
Land., 1960, 17: 21-25. 
2691. Farnsworth, D. Developments in submarine 
and small vesesl lighting. U.S. Navy. Submarine Base, 
New London, Conn. Medical research department. Project 
NM 002 014. 02.01, 8 September 1952, 6 pp. 
2692. Gibbs, C. B. and M. J. Bilney. Control disturb- 
ances on a tracking task due to operating push buttons 
on the control level. Gt. Brit. MRC, RNPRC, OES. Rept. 
R.N.P. 55/840, O.E.S. 262, April 1955, 5 pp. 
2693. Gt. Brit. MRC, RNPRC, OES. Human fac- 
tors in design and use of naval equipment. Rept. R.N.P. 
60/962, O.E.S. 336, February 1960, 73 pp. 
2694. Jones, G. M. Fatigue effects in radio operators 
during a program of high intensity, long duration, flying. 
Aerospace Med., 1960, 31: 478-484. 
2695. Koopman, B. O. The theory of search. II. 
Target detection. Operat. Res., 1956, 4: 503-513. 
2696. Lincoln, R. S. and E. Averbach. Spatial fac- 
tors in check reading of dial groups. J. appl. Psychol., 
1956, 40: 105-108. 
2697. Mackworth, N. H. Some factors affecting vigi- 
lance. Advanc. Sci., Land., 1957, 13: 389-393. 
2698. Merton, P. A. The accuracy of directing the 
eyes and the hand in the dark. J. Physiol., 1961, 156: 
555-577. 
2699. Squires, P. S. The shape of the normal work 
area. U.S. Navy. Submarine Base, New London, Conn. 
Medical research laboratory. Project NM 002 014.08.10, 
23 July 1956, 3 pp. 
2700. Wilkinson, R. T. Comparison of paced, un- 
paced, irregular and continuous display in watchkeeping. 
Ergonomics, 1961, 4: 259-267. Special Psychological and 
Psychiatric Problems 
(pre-lunch), 4:00 p.m. (pre-supper), and 8:00 
p.m. each day after 30 minutes rest in a supine 
position. Oxygen consumption at 8:00 a.m. was 
significantly lower than at any other hour. The 
noon and 4:00 p.m. values were not different 
from each other, but the 8:00 p.m. value was 
significantly higher than that at any other hour 
in each environment. A major portion of the 
elevation in metabolism during the day was 
associated with the specific dynamic action. Thus 
when men fasted and exercised moderately or 
fasted with no exercise the daily elevation in 
metabolism was present but was significantly 
less than when food was given. Prior moderate 
exercise had little measurable effect on the rest- 
ing oxygen consumption. The same pattern of 
results was observed in each environment. It 
was concluded that the diurnal pattern of oxy- 
gen consumption is little affected by environment 
within the range studied. 
Physiological 24 hour rhythms have been 
studied by Halberg (2705) 1962. The endogen- 
ous circadian adaptive functional organization 
in time affects an animal’s ability to withstand 
environmental damage and has an important 
bearing upon experimental method. Thus Navy 
recruits on “four-on” and “eight-off” schedules 
for two weeks did not show the bimodality of the 
diurnal temperature curve as previously found 
in submarine crews on the same schedule. 
According to Lehmann (2706) 1962, 3:00 a.m. 
is found to be a period of low efficiency in man 
and this is lessened if preceded by a good sleep 
but it is enhanced by fatigue. Like the pulse 
frequency all other hemodynamic factors are 
subject to rhythmical fluctuations over the 24 
hour period. Among mental workers who prefer 
working nights and among night workers in in- 
dustry there is never a reversed rhythm estab- 
I. DUTY AND REST PERIODS 
Adams and Chiles (2701) 1960, designed a 
study to investigate the effect on performance 
of four different work-rest schedules (two hours 
on and two hours off, four hours on and four 
off, six hours on and six off, and eight hours on 
and eight off) followed over a period of 96 
hours. The subject sample consisted of 16 male 
college students with four subjects being as- 
signed to each of the four work-rest period sched- 
ules. Performance was measured by means of a 
battery of psychomotor tasks involving arithmetic 
computation, pattern discrimination, monitoring 
and vigilance. Additional data were obtained 
from information recorded in an experimenter’s 
log book from responses to a subjective ques- 
tionnaire administered at the end of the testing. 
Although the performance tasks failed to differ- 
entiate among the four experimental groups, the 
observational evidence suggested that the subjects 
in the two hour and four hour groups achieved 
a more favorable adjustment than those in the 
other two groups. The selection of optimum 
work-rest periods may be aided by knowledge of 
diurnal variations in physiological processes. For 
example, Buskirk and lampietro (2703) 1956, 
measured diurnal variations in resting metabo- 
lism during several large field studies to ascertain 
reasonable base line values for oxygen consump- 
tion in any given hour and to ascertain the im- 
pact of environment on resting metabolism. 
Eight men were studied for at least ten days in 
each of four climates. Weather conditions ranged 
from hot-dry at Yuma, Arizona to cold-dry at 
Fort Churchill, Manitoba, Canada. The subjects 
subsisted on standardized rations during each 
experiment. Oxygen consumption was routinely 
measured at 8:00 a.m. (pre-breakfast), noon SLEEP DEPRIVATION—PHYSIOLOGICAL EFFECTS 
2701-2708 
lished. It takes four to five days to adjust to a 
new shift in shiftwork. The biological cycles 
represent fluctuations of the neuro-vegetative 
tonus which varies between a predominantly 
ergotropic (sympathicotonic state) and a pre- 
dominantly trophotropic phase (parasympathetic 
state). A gradual change from a 24 to a 20 
hour cycle will not seriously affect physiological 
functions as rapid changes will (i.e. in airline 
pilots and crew). In submarines the primary 
timegivers are replaced by regular and strong 
secondary ones such as 24 hour rhythm in lighting 
and temperature regulation. 
2701. Adams, O. S. and W. D. Chiles. Human 
performance as a function of the work-rest cycle. USAF. 
WADC. Wright-Patterson Air Force Base, Dayton, Ohio. 
WADC Tech. Kept. 60-248, March 1960, 18 pp. 
2702. Aschoff, J. Timegivers of 24-hour physiological 
cycles, pp. 373-380 in: Man’s dependence on the earthly 
atmosphere. Edited by K. E. Schaefer. The MacMillan 
Company, New York, 1962, 416 pp. 
2703. Buskirk, E. R. and P. F. lampietro. Varia- 
tion in resting oxygen consumption throughout the day. 
Fed. Proc., 1956, 15: 28. 
2704. Halberg, F. Physiologic 24-hour periodicity: 
General and procedural considerations with reference to 
the adrenal cycle. Z. Vitam. — Harm. — u. Fermentforsch., 
1959, 10: 225-296. 
2705. Halberg, F. Physiologic 24-hour rhythms: a 
determinant of response to environment agents, pp. 48-96 
in: Man’s dependence on the earthly atmosphere. Edited 
by K. E. Schafer. The MacMillan Company, New York, 
1962, 416 pp. 
2706. Lehmann, G. Effect of environmental factors 
on biological cycles and performance of work. pp. 381-387 
in: Man’s dependence on the earthly atmosphere. Edited 
by K. E. Schaefer. The MacMillan Company, New York, 
1962, 416 pp. 
2707. Solov’eva, L. M. Sutochnaia periodichnost’ 
nekotorykh protesessov obmena veshchestv u rabochikh 
nochnykh smen metropolitena. [Diurnal rhythm of certain 
metabolic processes in subway operators on nightshifts.] 
Vop. Pitan., 1961, 20: 11-15. 
2708. Walker, J. Shift changes and hours of work. 
Occup. Psychol., 1961, 35: 1-9. 
II. SLEEP DEPRIVATION 
A. PHYSIOLOGICAL EFFECTS 
Hasselman, Schaff and Metz (2721) 1960, have 
reported the effects of sleep deprivation on 
urinary excretion of catecholamines in normal 
human subjects. During a night period before 
work adrenaline excretion was significantly 
higher during sleep deprivation than during 
normal sleep, however, the noradrenaline excre- 
tion increase was statistically insignificant. Dur- 
ing the work period catecholamine secretion was 
much higher than during the preperiod night 
session. The increase of catecholamine excretion 
caused by lack of sleep was less evident at high 
temperatures than at low temperatures. Cate- 
cholamine excretion proved significantly lower 
during postperiod sleep than during the work 
period, but remained somewhat higher than the 
preperiod level. In a study of the effect of sleep 
deprivation on plasma 17-hydroxycorticosteriods, 
Murawski and Crabbe (2734) 1960, deprived 
eighteen male college students of sleep for one 
night on two separate occasions. On each oc- 
casion each student was alone. On a third 
occasion students were asked to stay up all night 
in groups of four. Plasma concentrations of 
17-hydroxycorticosteroids at eight o’clock in the 
morning following the nights without sleep were 
four to five micrograms lower than control values 
(significant at the 0.01 level). The noon values 
after sleep deprivation in a solitary setting were 
not significantly different from the corresponding 
values. When subjects stayed up with three 
other people the noon values tended to be higher. 
Urinary 17-hydroxy corticosteroid levels showed 
a decrease following the nights without sleep, 
but this decrease did not reach statistical sig- 
nificance (between the 0.10 and 0.05 levels). 
Sharp, Slorach and Vipond (2743) 1961, have 
concluded that ketosteroid excretory rhythm may 
depend immediately, and ketogenic steroid 
rhythm ultimately, on habit and environment. 
Evidence is presented that ketogenic steroid 
rhythm is dependent upon synchronization of 
pituitary and adrenal responsiveness. During 
reversal of rhythm, adrenocortical activity takes 
place initially in the early evening and night, 
occurring progressively earlier each day until it 
synchronizes with the new time scale. Suzuki 
(2745) 1961, studied the effects of curtailed sleep 
on serum cholesterol and on the blood glu- 
tathione. These effects were studied on five 
healthy medical students who had three or six 
hours sleep in successive four or six days re- 
spectively. The subjects did light mental work 
every day for two hours in the morning and 
for three hours in the afternoon. During four 
days before, and one or three days after insuffi- 
cient sleep, the subjects slept as long as nine 2709-2711 
SPECIAL PSYCHOLOGICAL AND PSYCHIATRIC PROBLEMS 
hours. Daily food intake was generally equal in 
all subjects during the period of nine hours sleep, 
and in addition a light midnight meal was given 
during the period of insufficient sleep. The 
blood for cholesterol analysis was drawn at 8:10 
to 8:20 in the morning; for glutathione it was 
drawn at 8:10 to 8:20 a.m. and at 5:10 to 5:20 
p.m. every day. The serum cholesterol rose re- 
markably before and at the beginning of in- 
sufficient sleep and was correlated with the high 
fat diet. It was slightly lowered or remained al- 
most unchanged in the latter half of the in- 
sufficient sleep. Esterified cholesterol levels rose 
significantly before and in the beginning of in- 
sufficient sleep and there was no significant 
change thereafter. The percentage of ester form 
to total cholesterol showed remarkable rises in 
the beginning of insufficient sleep, and was di- 
versely variable thereafter in each subject. The 
glutatione level of the blood was noticeably 
lowered after three or four days of insufficient 
sleep, but this fall was rapidly restored. The 
results suggested to the authors that the secre- 
tion of adrenocortical hormone was accelerated 
during insufficient sleep. 
In a report on the effects of sleep deprivation 
on body temperatures, Kreider (2726) 1961, has 
stated that although most earlier work reports 
little effect of sleep deprivation on body tem- 
perature, recent studies indicate that deprivation 
results in a lowering of deep body temperature. 
Kreider conducted a study to assess the effects 
of sleep deprivation on diurnal variation of body 
temperature and to determine the effect of 
deprivation on body temperatures during cold 
stress. Eight men went without sleep for periods 
up to 87 hours. Skin temperature and rectal 
temperature were measured periodically at 80°F. 
during 22 hours of the day, while during the 
remaining two hours subjects were exposed at 
60°F. Following sleep deprivation the men slept 
for 8 hours in sleeping bags at 10°F. Control 
measurements were made under identical condi- 
tions without deprivation. During sleep depriva- 
tion there was a consistently lowered rectal tem- 
perature of 0.5-0.70 which persisted throughout 
the succeeding period of sleep. Rectal tem- 
perature at 80°F. and at 60°F. returned to normal 
after one night of sleep. Skin temperature 
changed little under all conditions, except toe 
temperature which decreased at 80°F. but in- 
creased at 60°F. exposure during both wakeful- 
ness and sleep following deprivation. Changes in 
toe temperature were found to be of the same 
direction and magnitude as observed for cold 
acclimatization. Murray, Williams and Lubin 
(2736) 1958, measured body temperature as 
well as ratings of sleepiness and fatigue from 15 
subjects during 98 hours of sleep deprivation. 
Body temperature showed a persisting diurnal 
variation, but also indicated an over-all decrease 
with succeeding hours of sleep deprivation. Self- 
ratings of sleepiness and fatigue and sleepiness 
ratings by fellow subjects and observers, were 
positively intercorrelated as well as positively 
correlated with increasing hours of sleep loss. 
The four ratings and body temperature were 
inversely correlated, even when hours of sleep 
deprivation were partialed out. The subjects 
tended to rate themselves as less sleepy than the 
observers rated them, which was interpreted as 
an adjustment mechanism. It was concluded by 
the authors that the results support Kleitman’s 
hypothesis that reports of sleepiness are in- 
versely related to body temperature. Schaff and 
Marbach (2739) 1960, conducted experiments 
to determine the action on “quantity of sleep” 
of fatigue states of different degrees brought 
about during the preceding day by various com- 
binations of 1) environmental temperature, 2) 
muscular work, 3) sleep deprivation. Spontane- 
ous movements of the sleeper were used as an 
indication of the depth or quantity of sleep. The 
results showed that only sleep deprivation had 
any significant effect upon the quantity of sleep. 
The muscular work level and the environmental 
temperature level did not significantly influence 
spontaneous motility during sleep. Nor was any 
interaction between the three factors shown to be 
significant. The effect of sleep deprivation upon 
the logarithm of the total number of movements 
per night, however, was clearly apparent. 
2709 Armington, J, C. and L. L. Mitnick. Electro- 
encephalogram and sleep deprivation. /. appl. Physiol., 
1959, 14: 247-250. 
2710. Ax, A. and E. D. Luby. Autonomic responses to 
sleep deprivation. Arch. gen. Psychiat., 1961, 4: 55-59. 
2711. Bliss, E. L., L. D. Clark and C. D. West. 
Studies of sleep deprivation — Relationship to schizoph- 
renia. Arch. Neurol. Psychiat., 1959, 81: 348-359. SLEEP DEPRIVATION—PHYSIOLOGICAL EFFECTS 
2712-2746 
2712. Brauchi, J. T. and L. J. West. Sleep depriva- 
tion. J. Amer. med. Ass., 1959, 171: 11-14. 
2713. Billow, K. Respiration and wakefulness in man. 
Acta physiol, scand., 1963, 59: Suppl. 209, 110 pp. 
2714. Coleman, P. D., F. E. Gray and K. Wat- 
anabe. EEG amplitude and reaction time during sleep. 
J. appl Physiol, 1959, 14: 397-400. 
2715. Dement, W. and N. Kleitman. Body motility 
during sleep and dream duration recall. Fed. Proc., 1956, 
15: 46. 
2716. Fel’dman, G. L. Vliianie lisheniia sna na 
elektricheskuiu aktivnost’ i na drugie pokazateli deiatel 
’nosti golovnogo mozga zhivotnykh. [hTe effect of sleep 
deprivation on the electrical activity and on other indica- 
tors of the cerebral activity of animals.] Sechenov J. 
Physiol, 1961, 11: 169-177. 
2717. Halberg, F. Some physiological and clinical 
aspects of 24-hour periodicity. /. Lancet, 1953, 73: 20-32. 
2718. Halberg, F., E. Halberg, C. P. Barnum and 
J. J. Bittner. Physiologic periodicity in human beings 
and mice, the lighting regimen and daily routine, pp. 
803-878 in: Photoperiodism and related phenomena in 
plants and animals. Edited by R. B. Withrow, Association 
for the Advancement of Science, Washington, D.C., 1959, 
903 pp. 
2719. Halberg, F. and R. B. Howard. (24 hour 
periodicity and experimental medicine: examples and 
interpretations. Postgrad. Med., 1958, 24: 349-358. 
2720. Halberg, F., R. E. Peterson and R. H. Silber. 
Phase relations of 24-hour periodicities in blood corti- 
costerone, mitoses in cortical adrenla parenchyma, and 
total body activity. Endocrinology, 1959, 64: 222-230. 
2721. Hasselman, M., G. Schaff and B. Metz. 
Influences respectives du travail, de la temperature ambi- 
ante et de la privation de sommeil sur 1’excretion urinaire 
de catecholamines chez 1’Homme normal. C. R. Soc. Biol, 
Paris, 1960, 154: 197-201. 
2722. Hoffman, B. F., E. E. Suckling, C. McC. 
Brooks, E. H. Koenig, K, S. Coleman and H. J. 
Treumann. Quantitative evaluation of sleep. J. appl. 
Physiol, 1955, 8: 361-368. 
2723. Kaine, H. D., H. S. Seltzer and J. W. Conn. 
Mechanism of diurnal eosinophil rhythm. J. Lab. din. 
Med., 1955, 45: 247-252. 
2724. Kleitman, N. and T. G. Engelmann. Sleep 
characteristics of infants. J. appl. Physiol, 1953, 6: 269-282. 
2725. Koranyi, E. K, and H. E. Lehmann. Experi- 
mental sleep deprivation in schizophrenic patients. Arch, 
gen. Psychiat., 1960, 2: 534-544. 
2726. Kreider, M. B. Effects of sleep deprivation on 
body temperatures. Fed. Proc., 1961, 20: 214. 
2727. Laughlin, H. P. Research in sleep deprivation 
and exhaustion. An invitation to further observation and 
study. Int. Rec. Med., 1953, 166: 305-310. 
2728. Lewis, P. R. and M. C. Lobban. Persistence 
of a 24 hr. pattern of diuresis in human subjects living on 
a 22 hr. day. J Physiol, 1954, 125: 34P-35P. 
2729. Lewis, P. R. and M. C. Lobban. The effects of 
prolonged periods of life on abnormal time routines upon 
excretory rhythms in human subjects. Quart. J. exp. 
Physiol, 1957, 42: 356-371. 
2730. Malmo, R. B. and W. W. Surwillo. Sleep 
deprivation: Changes in performance and physiological 
indicants of activation. Psychol. Monogr., 1960, 74: 1-24. 
2731. Mills, J. N. Changes in alveolar carbon dioxide 
tension by night and during sleep. J. Physiol, 1953, 122: 
66-80. 
2732. Morris, G. O. and M. T. Singer. Sleep dep- 
rivation. Transactional and subjective observations. Arch, 
gen. Psychiat., 1961, 5: 435-461. 
2733. Morris, G. O., H. L. Williams and A. Lubin. 
Misperception and disorientation during sleep deprivation. 
Arch. gen. Psychiat., 1960, 2: 247-254. 
2734. Murawski, B. J. and J. Crabbe. Effect of sleep 
deprivation on plasma 17-hydroxycorticosteroids. J. appl. 
Physiol, 1960, 15: 280-282. 
2735. Murray, E. J. Conflict and repression during 
sleep deprivation. J. abnorm. soc. Psychol, 1959, 59: 
95-101. 
2736. Murray, E. J., H. L. Williams and A. Lubin. 
Body temperature and phychological ratings during sleep 
deprivation. J. exp. Psychol, 1958, 56: 271-273. 
2737. Pepler, R. D. Warmth and lack of sleep: Ac- 
curacy of activity reduced. J. comp, physiol. Psychol, 
1959, 52: 446-450. 
2738. Robin, E. D., R. D. Whaley, C. H. Crump 
and D. M. Travis. (Alveolar gas tensions, pulmonary 
ventilation and blood pH during physiologic sleep in nor- 
mal subjects. /. din. Invest., 1958, 37: 981-989. 
2739. Schaff, G. and G. Marbach. Recherche d’une 
methode devaluation de la quantity de sommeil. I. Influ- 
ence de la privation de sommeil sur differentes expressions 
quantitatives de la motilit£ spontanee du dormeur. C. R. 
Soc. Biol, Paris, 1960, 154: 202-206. 
2740. Scholander, T. Habituation of autonomic re- 
sponse elements under two conditions of alertness. Acta 
physiol, scand., 1960, 50: 259-268. 
2741. Scholander, T. The effects of moderate sleep 
deprivation on the habituation of autonomic response ele- 
ments. Acta physiol, scand., 1961, 51: 325-342. 
2742. Semagin, V. N. O sne liudei v arktike. [On 
the sleep of humans in the Arctic.] Sechenov J. Physiol, 
1961, 47: 950-957. 
2743. Sharp, G. W. G., S. A. Slorach and H. J. 
Vipond. Diurnal rhythms of keto- and ketogenic steroid 
excretion and the adaptation to changes of the activity- 
sleep routine. J. Endocrin., 1961, 22: 377-385. 
2744. Soderberg, U. The effect of blood-bome in- 
fluences of the cerebral cortex in wakefulness and sleep. 
XXII Inter. Congr. Physiol. Sci., Leiden, 1962, Vol. I, Part 
I, pp. 457-463. 
2745. Suzuki, I. Effects of insufficient sleep on serum 
cholesterol and blood reduced glutathione level. J. Sci. 
Labour, 1961, 37: 166-177. 
2746. Tyler, D. B. (Psychological changes during 
experimental sleep deprivation. Dis. nerv. Syst., 1955, 16: 
293-299. 2747-2748 
SPECIAL PSYCHOLOGICAL AND PSYCHIATRIC PROBLEMS 
2747. Ukolova, M. A. Eksperimental ’nyi nevroz, 
vyzvannyi lisheniem sna. [Experimental neurosis produced 
by sleep deprivation.] Bull. Biol. Med. exp. URSS, 1961, 
5; 43-46. 
2748. Walters, R. H. and G. B. Henning. Isolation, 
confinement and related stress situations. Some cautions. 
Aerospace Med., 1961, 32: 431-434. 
B. EFFECTS OF SLEEP DEPRIVATION ON 
PERFORMANCE 
In general sleep deprivation tends to impair 
performance. As Ax, Fordyce, Loovas, Meredith, 
Pirojnikoff, Shmavonian and Wendahl (2749) 
1954, have stated, however, human beings tend 
to compensate psychophysiologically for the 
fatigue of sleep deprivation by increased effort 
or efficiency. The degree of compensation is a 
function of motivation during performance. In 
a study of the effects of sleep loss on performance, 
reported by Wilkinson (2759) 1958, an effort 
was made to define more precisely the task situa- 
tion in which performance is likely to be im- 
paired by moderate sleep loss, that is to say some 
30 hours without sleep. A wide variety of task 
situations was examined in the course of eight 
experiments and in two of them sleep loss pro- 
nounced decline of efficiency. The first of these 
task situations was a 40 minute vigilance situa- 
tion essentially similar to the job of a radar or 
asdic lookout. In performance tasks the effect 
of sleep loss on efficiency did not become appar- 
ent until at least 10 minutes had been spent on 
the task. Individuals differed considerably in 
the degree of effect shown. In a number of short 
tasks lasting less than 10 minutes, no significant 
decline in efficiency was observed after sleep 
loss. These short tasks included tests of learn- 
ing and sorting ability, and tests which allowed 
comparison between tasks having high positive 
or large negative transfer of skill from past train- 
ing. The author’s results seem to suggest that 
only prolonged tasks will be effected by sleep 
loss. It has been shown as a result of the ex- 
periments that if the task situation is, reorganized 
in such a way as to give the subject more in- 
formation of the results of his efforts, the per- 
formance decrement due to sleep loss may be 
substantially removed. In conclusion it appears 
that the less predictable the sleepless operator 
finds the task situation, the greater the penalty 
he suffers for failing to predict it accurately, 
the less likely he is to let his efficiency fall below 
normal levels. Loveland and Singer (2753) 
1959, have concluded that personality structure 
as reffected in projective tests, is unaltered by 
acute sleep deprivation and personality function- 
ing is little changed. Using the Rorschach test 
alone it was possible to predict how well a sub- 
ject would remain efficient in a variety of mental 
and psychomotor tasks during a sleep deprivation 
period, and also whether or not he would hal- 
lucinate. Subjects whose Rorschach showed high 
motivation tended to maintain or raise the 
efficiency levels on re-test. Others showed decre- 
ment. Those subjects who reported hallucina- 
tions were usually those characterized by loosely 
defended, hysteric-like style of adapting and 
those with prominent schizophrenic traits. Love- 
land and Williams (2754) 1963, had 20 experi- 
mental and 20 control subjects (soldiers from 
18 to 45 years of age and of average Army in- 
telligence) add pairs of one-digit numbers for 
three minutes at 8:00 a.m. and at 8:00 p.m. dur- 
ing a three day baseline period, during three 
days of sleep loss and two days of recovery. The 
most marked effect of sleep loss was to lower 
the speed of addition. The speed during the 
afternoon was higher than in the morning and 
this difference tended to increase with sleep loss 
but not significantly. Accuracy was high through- 
out all test sessions with a slight decrease during 
sleep loss. It was not affected by the diurnal 
cycle and did not correlate with oral temperature. 
The correlation of speed of addition and oral 
temperature was considerably higher than that 
of speed and sleep loss. Behavioral changes dur- 
ing sleep loss have been reported by Luby, Froh- 
man, Grisell, Lenzo and Gottlieb (2755) 1960. 
The effect of sleep deprivation upon behavior, 
thinking, motor performance and biological 
energy transfer systems was studied in a single 
subject who remained awake without drugs for 
200 hours. Behavioral changes included irrit- 
ability, paranoid thinking, expansiveness, gran- 
diosity, hypnagogic states, visual hallucinations 
and episodic rages. Defects in thinking and in 
visual motor performance occurred cyclically 
across days of wakefulness with gradual deteriora- 
tion, finally resulting in virtual untestability on 
the ninth day. The effects of sleep deprivation on SLEEP DEPRIVATION—EFFECTS OF DRUGS AND SLEEP 
2749-2767 
social behavior have been reported by Murray, 
Schein, Erikson, Hill and Cohen (2756) 1959. 
During two separate experiments with 72 and 98 
hours of sleep deprivation, observations were 
made of the social, recreational and general be- 
havior of the subjects. Categories included social 
conversation, games, television, reading, hobbies 
and non-participation. The strongest and most 
significant finding was that with sleep deprivation 
the subjects tended to change restlessly from one 
activity to another. Work on hobbies and in 
crafts decreased during the sleep deprivation 
period. Social conversation, of a listless sort, 
showed an over-all increase with sleep depriva- 
tion, although the exact shape of the relation- 
ship cannot be specified. The authors’ results 
were interpreted as indicating that the subjects 
made efforts to maintain wakefulness by avoiding 
situations producing drowsiness. 
It has been confirmed that 30 hours of sleep 
loss can seriously impair performance toward the 
end of a 25 minute task of serial reaction. Par- 
ticularly, the occurrence of gaps or abnormally 
long response delays is greatly increased. This is 
what hoppens when the test is a continuous one; 
when 30 seconds rest pauses were allowed (Wil- 
kinson (2761) 1959) every five minutes the above 
effect of lack of sleep was found to remain un- 
altered. An equal though small and insignificant 
improvement in performance occurred under 
both normal and sleep deprived conditions with 
the rest pauses. 
2749. Ax, A. F., W. Fordyce, I. Loovas, W. Mere- 
dith, L. Pirojnikoff, B. Shmavonian and R. Wendahl. 
Quantitative effects of sleep deprivation. Amer. Psychol., 
1954, 9: 324-325. 
2750. Fisher, S. and I. Rubinstein. Effects of mod- 
erate sleep deprivation on social influence in the autokine- 
tic situation. U.S. Army. WRAIR, Walter Reed Army 
Medical Center, Washington, D.C. WRAIR-63-67, May 
1957, 6 pp. 
2751. Gieseking, C. F., H. L. Williams and A. 
Lubin. The effects of sleep deprivation upon informa- 
tion learning. Amer. Psychol., 1957, 12: 406. 
2752. Goodnow, J. J. and I. Rubinstein. Effect of 
sleep loss on problem-solving behavior. U.S. Army. 
WRAIR, Walter Reed Army Medical Center, Washington, 
D.C. WRAIR-40-57, March 1957, 13 pp. 
2753. Loveland, N. T. and M. T. Singer. Projective 
test assessment of the effects of sleep deprivation. J. proj. 
Tech., 1959, 23: 323-334. 
2754. Loveland, N. T. and H. L. Williams. Adding, 
sleep loss, and body temperature. Percept, motor Skills, 
1963, 16: 923-929. 
2755. Luby, E. D., C. E. Frohman, J, L. Grisell, 
J. E. Lenzo and J. S. Gottlieb. Sleep deprivation; 
effects on behavior, thinking, motor performance, and 
biological energy transfer systems. Psychosom. Med., 1960, 
22: 182-192. 
2756. Murray, E. J., E. H. Schein, K. T. Erikson, 
W. F. Hill and M. Cohen. The effects of sleep depriva- 
tion on social behavior. J. soc. Psychol., 1959, 49: 229-236. 
2757. Pepler, R. D. Warmth and lack of sleep: ac- 
curacy or activity reduced. /. comp, physiol. Psychol., 
1959, 52: 446-450. 
2758. Stennett, R. G. hTe relationsihp of perform- 
ance level to level of arousal. J. exp. Psychol., 1957, 54: 
54-61. 
2759. Wilkinson, R. T. The effects of sleep loss 
on performance. Gt. Brit. MRC, APU, Rept. 523-589, April 
1958, 36 pp. 
2760. Wilkinson, R. T. The effects of loss of sleep 
on performance. Gt. Brit. MRC, RNPRC, OES. Rept. 
R.N.P. 58/913, O.E.S. 313, December 1958, 39 pp. 
2761. Wilkinson, R. T. Rest pauses in a task affected 
by lack of sleep. Ergonomics, 1959, 2: 373-380. 
2762. Wilkinson, R. T. Performance after lack of 
sleep: the influence of incentive, familiarity with the task, 
and individual differences. Gt. Brit. MRC, RNPRC, OES. 
Rept. R.N.P. 60/969, O.E.S. 340, September 1959, 6 pp. 
2763. Wilkinson, R. T. Effects of sleep-deprivation 
on performance and muscle tension, pp. 329-342 in; The 
nature of sleep. Ciba Foundation Symposium, June 1960. 
2764. Wilkinson, R. T. The effect of sleep on visual 
watch-keeping. Quart. J. exp. Psychol., 1960, 12: 36-40. 
2765. Wilkinson, R. T. Interaction of lack of sleep 
with knowledge of results, repeated testing, and indivi- 
dual differences. J. exp. Psychol., 1961, 62: 263-271. 
2766. Wilkinson, R. T. After-effect of loss of sleep 
on visual watch-keeping. Gt. Brit. MRC, RNPRC, OES. 
Rept. O.E.S. 366, July 1961, 6 pp. 
2767. Williams, H. L., A. Lubin and J. J. Good- 
now. Impaired performance with acute sleep loss. 
Psychol. Monogr., 1959, 73: (14); 1-26. 
C. EFFECTS OF DRUGS AND SLEEP 
DEPRIVATION 
Carlson {2768) 1961, found that after 47 and 
71 hours of sleep deprivation there was over- 
estimation in judgment of size of objects. This 
also occurred after 200 mg. of chlorpromazine 
and the administration of placebos. Kornetsky, 
Mirsky, Kessler and Dorff {2769) 1959, have 
tested normal subjects after 44 and 68 hours of 
sleep loss with and without simultaneous ad- 
ministration of dextro-amphetamines. Ten milli- 
grams of the drug were given at 44 hours and 15 
mg. at 68 hours. The authors’ result support the 2768-2794 
SPECIAL PSYCHOLOGICAL AND PSYCHIATRIC PROBLEMS 
conclusions that sleep loss produces a greater de- 
crement in some phychological performances 
than in others; also, measures of performances 
which reflect “lapses” seem to be more affected 
than measures which are relatively insensitive to 
lapses. Dextro-amphetamine returns only the 
least impaired performances to the non-sleep de- 
prived level. Measures of performances sensitive 
to lapses still differs significantly from the non- 
sleep deprived level. 
2768. Carlson, V. R. Effects of sleep deprivation 
and chlorpromazine on size-constancy judgments. Amer. 
J. Psychol, 1961. 74: 552-560. 
2769. Kornetsky, C., A. F. Mirsky, E. K. Kessler 
and J. E. Dorff. The effects of dextroamphetamine 
on behavioral deficits produced by sleep loss in humans. 
J. Pharmacol, 1959, 127: 46-50. 
2770. Laties, V. G. Modification of affect, social 
behavior and performance by sleep deprivation and drugs. 
J. psychiat. Res., 1961, 1: 12-25. 
III. ISOLATION, SENSORY DEPRIVA- 
TION AND CONFINEMENT 
The references that follow represent a selection 
of pertinent papers dealing with problems that 
may be useful to the reader concerned with pro- 
longed isolation and confinement in submarine 
operations. Closely related are the problems 
that may be encountered by the underwater 
swimmer resulting from partial sensory depriva- 
tion. Since there are many unknown variables 
in this important area, a plea is made for well- 
designed and prosecuted research studies of both 
a basic and applied nature. 
2771. Barton, T. C. and B. B. Weybrew. A short 
summary of the findings of the 265 hour, completely sub- 
merged, habitability cruise made by the USS NAUTILUS 
(SSN 571). U.S. Navy. Submarine Base, New London, 
Conn. Medical research laboratory. Project NM 002 
015.14.04, 9 January 1957, 7 pp. 
2772. Bexton, W. H., W. Heron and T. H. Scott. 
Effects of decreased variation in the sensory environment. 
Canad. J. Psychol, 1954, 8: 70-76. 
2773. Byrd, R. E. Alone. G. P. Putnam’s Sons, New 
York, 1938, 296 pp. 
2774. Gerard, H. B. and J. M. Rabbie. Fear, affilia- 
tion and social comparison. Amer. Psychol, 1960, 15: 409. 
2775. Gewirtz, J. L. and D. M. Baer. The effect of 
brief social deprivation on behaviors for a social rein- 
forcer. J. abnorm. soc. Psychol, 1958, 56: 49-56. 
2776. Gewirtz, J. L. and D, M. Baer. Deprivation 
and satiation of social reinforcers as drive conditions. /. 
abnorm. soc. Psychol, 1958, 57: 165-172. 
2777. Hartman, B., R. E. McKenzie and D. E. 
Graveline. An exploratory study of changes in pro- 
ficiency in a hypodynamic environment. USAF. Brooks 
Air Force Base, Texas. School of aviation medicine. July 
1960, 13 pp. 
2778. Heron, W., W. H. Bexton and D. O. Hebb. 
Cognitive effects of a decreased variation in the sensory 
environment. Amer. Psychol., 1953, 8: 366. 
2779. Heron, W., B. K. Doane and T. H. Scott, 
Visual disturbances after prolonged perceptual isolation. 
Canad. J. Psychol, 1956. 10: 13-18. 
2780. Kinsey, J. L. Observations on the habitability 
of submarines in northern waters. U.S. Navy. Submarine 
Base, New London, Conn. Medical research laboratory. 
Project NM 002 015.04.04, 4 April 1952, 10 pp. 
2781. Levy, E. Z., G. E. Ruff and V. H. Thaler. 
Studies in human isolation. /. Amer. med. Ass., 1959, 
169: 236-239. 
2782. Lilly, J. C. Mental effects of reduction of 
ordinary levels of physical stimuli on intact, healthy 
persons. Psychiat. Res. Repts., 1956 5: 1-9. 
2783. Lilly, J, C. The effect of sensory deprivation 
on consciousness, pp. 93-95 in: Environmental effects 
on consciousness. Edited by K. E. Schaefer. The MacMillan 
Company, New York, 1962, 146 pp. 
2784. McKenzie, R. E., B. Hartman and D. E. 
Graveline. An exploratory study of sleep characteristics 
in a hypodynamic environment. USAF. Brooks Air Force 
Base Texas. School of aviation medicine. Rept. 60-68, 
October 1960, 8 pp. 
2785. Ruff, G. E., E. Z. Levy and V. H. Thaler. 
Studies of isolation and confinement. Aerospace Med., 
1959, 30: 599-604. 
2786. Schulte, J. H. The medical aspects of closed 
cabin atmosphere control. Milit. Med., 1961, 126: 40-48. 
2787. Shurley, J. T. Profound experimental sensory 
isolation. Amer. J. Psychiat., 1960, 117: 539-545. 
2788. Solomon, P., P. H. Leiderman, J. Mendelson 
and D. Wexler. Sensory deprivation; a review. Amer. J. 
Psychiat., 1957, 114: 357-363. 
2789. U.S. Navy. U.S.S. Triton, S.S.R.N. 586. First 
submerged circumnavigation. U.S. Gov’t. Printing Office, 
Washington, D.C., 1960, 80 pp. 
2790. Vernon J. and J. Hoffman. Effect of sensory 
deprivation on learning rate in human beings. Science, 
1956, 123: 1074-1075. 
2791. Walters, R. H., W. E. Marshall and J. R. 
Shooter. Anxiety, isolation, and susceptibility to social 
influence. J. Personality, 1960, 28: 518-529. 
2792. Walters, R. H. and M. J. Quinn. The effects 
of social and sensory deprivation on autokinetic judg- 
ments. J. Personality, 1960, 28: 210-219. 
2793. Walters, R. H. and E. Ray. Anxiety, social 
isolation, and reinforcer effectiveness. /. Personality, 1960, 
28: 358-367. 
2794. Wexler, D., J. Mendelson, P. H. Leiderman 
and P. Solomon. Sensory deprivation; a technique for 
studying psychiatric aspects of stress. Arch. Neurol. 
Psychiat., 1958, 79: 225-233. ISOLATION SENSORY DEPRIVATION AND CONFINEMENT 
2795-2798 
2795. Weybrew, B. B. Psychological and psychophysi- 
cal effects of long periods of submergence. I. Analysis of 
data collected during a 265 hour, completely submerged, 
habitability cruise made by the USS NAUTILUS (SSN 
571). U.S. Navy. Submarine Base, New London, Conn. 
Medical research laboratory. Project NM 23 00 00, Task 
23 02 20, 18 February 1957, 43 pp. 
2796. Weybrew, B. B. Bibliography of sensory de- 
privation, isolation and confinement. U.S. Navy. Sub- 
marine Base, New London, Conn. Medical research labora- 
tory. Project MR 005.14-2100.03.04, January 1960, 13 pp. 
2797. Weybrew, B. B., R. A. Elias and J. Vogel. 
Exploratory study of the efficacy of dioctyl sodium sul- 
fosuccinate (Colace) in the control of constipation of sub- 
mariners during a prolonged snorkel cruise. U.S. Navy. 
Submarine Base, New London, Conn. Medical research 
laboratory. Project NM 24 01 20.04.04, 15 December 1958, 
19 pp. 
2798. Anon. Medicine nucleare applicata al sotto- 
marini “Nautilus” e “Seawolf.” Riv. Med. aero., 1958, 21: 
576-582. Special Problems of Scuba Diving 
I. GENERAL STUDIES 
In contrast to the conventional diver connected 
to the surface by means of his air line, the 
SCUBA diver has the advantage of freedom of 
movement and stealth. These attributes allow 
men to perform a variety of tasks which can be 
accomplished by other means only with great 
difficulty if at all. The military use of SCUBA 
has included the penetration of harbor defenses 
and the sinking of large warships, the recon- 
naissance of beachheads, the clearing of under- 
water obstacles before and after assaults and the 
location and disposal of mines. Diving with 
SCUBA is an expanding field of practical en- 
deavor, not only for military purposes, but also 
for use in scientific submarine explorations, 
oceanographic studies and in marine biological 
research activities. 
Since most of the problems encountered in 
SCUBA diving are also experienced in conven- 
tional diving with the hard hat a full discussion 
of these problems will not be presented here. 
These problems have been discussed in the fore- 
going sections. The expanded civilian interest 
in and participation in SCUBA diving has been 
followed by an expanded literature on medical 
problems of shallow water diving. Of especial 
interest are papers by: Duffner (2814), Lanphier 
(2822), Taylor (2884) and reports 2853 and 
2854. 
2799. Alvis, H. J. Sport diving is fun. Amer. J. 
Nurs., 1958, 58: 1001-1003. 
2800. Alvis, H. J. How deep is dangerous. J. occup. 
Med., 1960, 2: 485-490. 
2801. Backer, O. G. Nogle lagelige problemer ved 
sovarnets dykkerskoler. [Some medical problems in diving 
schools of the Danish navy.] Militaerlaegen, 1958, 64: 
62-71. 
2802. Barbot, R. La Plongee libre. Paris 1957, 24 pp. 
2803. British Sub-Aqua Club. Underwater diving 
manual. Charles T. Branford Co., Newton Centre, Mass., 
1961, 240 pp. 
2804. Brou, W. C. Nageurs de combat. Documents du 
Monde, Paris, 1955, 308 pp. 
2805. Burns, W. T. Medical problems of skin diving. 
J. Amer. med. Ass., 1955, 159: 5-9. 
2806. California, State of. SCUBA diving. Personnel, 
safety and trainng. Dept. Fish and Game, Terminal Is- 
land, California, April 1963, 12 pp. 
2807. Carrier, R. B. Dive; the complete book of skin 
diving. Wilfred Funk, Inc., New York, 1955, 294 pp. 
2808. Cayford, J. E. Underwater work. A manual of 
SCUBA commercial, salvage and construction operations. 
Cornell Maritime Press, Cambridge, Maryland, 1959, 217 
pp. 
2809. Colby, C. B. Frogmen. Training, equipment and 
operations of our Navy’s undersea fighters. Coward-Mc- 
Cann, Inc., New York, 1954, 48 pp. 
2810. Cousteau, J. Y. and F. Dumas. The silent 
world. Harper and Brothers, New York, 1953, 266 pp. 
2811. Davis, G. D. Physiological hazards of skin 
diving. Med. J. Aust., 1961, (n) 1035-1038. 
2812. Duffner, G. J. Medical aspects of recent trends 
in diving. Arch, industr. Hlth., 1958, 18: 208-213. 
2813. Duffner, G. J. Medical problems involved in 
underwater compression and decompression. Clin. Symp., 
1958, 10: 99-114. 
2814. Duffner, G. J. Scuba diving injuries. Predispos- 
ing causes and prevention. J. Amer. med. Ass., 1961, 175: 
375-378. 
2815. Empleton, B. E., E. H. Lanphier, J. E. 
Young and L. G. Goff. The new science of skin and 
SCUBA diving. Association Press, New York, 1962, 208 pp. 
2816. Fields, J. A. Skin diving: its physiological 
and laryngological aspects. Arch. Otolaryng., 1958, 68: 
531-541. 
2817. France, GERS. The complete manual of free 
diving. G. P. Putnam’s Sons, New York, 1957, 185 pp, 
2818. Glass, J. Notes on the physics, physiology and 
fascination of deep diving. Med. J. Malaya, 1958, 12: 
622-636. 
2819. Italic, H. De ontwikkeling van het duiken 
bij de koninkijke Marine en de medische aspecten van 
deze ontwikkeling. Ned. Milit. Geneesk. T., 1957, 10: 
362-376. 
2820. Keast, R. W. Can skin diving be made safe? 
Amer. J. Surg., 1959, 98: 506-508. 
2821. Lambertsen, C. J. and L. J. Greenbaum, Jr. 
Second symposium on underwater physiology. National 
Research Council, Washington, D.C. N.R.C. Publication 
1181, 1963, 296 pp. GENERAL STUDIES 
2822-2861 
2822. Lanphier, E. H. Diving medicine. New Engl. 
J. Med., 1957, 256: 120-131. 
2823. Larson, H. E. A history of self-contained diving 
and underwater swimming. National Research Council, 
Washington, D.C. N.R.C. Publication 469, 1959, 50 pp. 
2824. Lundgren, C. H. Kellers dykeriexperiment i 
Brissago, Schweiz, den 27-28 juni 1961. [H. Kelelr’s diving 
experiment in Brissago, Switzerland, 27-28 June 1961.] 
Medd. flyg. Navmed., 1961, 11: 1-5. 
2825. Macintosh, F. C. Medical problems of under- 
water depths. Canad. med. Ass. J., 1961, 85: 424-428. 
2826. Martins, J. K. What’s new in diving medicine. 
G.P., 1956, 14: 91-96. 
2827. Martins, J. K. More on skin diving. G.P., 
1958, 18: 120-123. 
2828. Miles, S. Discussion: underwater emergencies 
in the Royal Navy. Proc. R. Soc. Med., 1958, 51: 821-824. 
2829. Miles, S. C. Physiological problems of deep-sea 
diving. New Scient., 1962, 15: 671-673. 
2830. Mosesson, E. Nagra allmanna och medicinska 
synpunkter pa dykeri i Sverige. [Some general and medi- 
cal problems in diving in' Sweden.] Svenska Lakartidn., 
1961, 58: 1887-1902. 
2831. Moslener, C.-D. Die Gefahren beim Tauchen. 
Med. Mschr., 1960, 14: 653-658. 
2832. Moslener, C.-D. Tauchen mit Verstand. An- 
taus-Verlag, Liibeck. 1961, 127 pp. 
2833. Mosterd, W. L. Stuwkvachtmeting en slagan- 
alyse bij Gertrainde Zwemmeys. Shotanus Jens, Utrecht, 
1961, 245 pp. 
2834. Pecora, L. J. Skin diving: sport, work, and 
danger. Arch, industr. Hlth., 1956, 15: 93-96. 
2835. Pfeifer, K. and W. Bucklitsch. Medizinische 
Probleme des Sporttauchens. Dtsch. Gesundheitwes., 
1960, 15: 1535-1540. 
2836. Presbitero, R. H. Manual de Buceo Deportivo. 
Impreso en Los Talleres, Barbara, Mexico, 39 pp. 
2837. Rowe, B. Medical hazards of skin diving. 
Med. J. Aust., 1961, (n): 1038-1040. 
2838. Russo, E. and F. Arienzo. Influenza del nuoto 
subacqueo sulyla secrezione gastrica e la crasi ematica. 
Folia med., Napoli, 1960, 45: 1117-1128. 
2839. Slark, A. S. Medical aspects of diving. N. Z. 
med. J., 1960, 59: 201-204. 
2840. Slark, A. G. A review of the medical and 
physiological problems of working at high pressure with 
particular reference to diving. J. R. Inst. publ. Hlth., 
1961, 24 : 251-274. 
2841. Specht, H. Effects of increased atmospheric 
pressure on the body. pp. 594—606 in: Industrial hygiene 
and toxicology. Volume I. Edited by F. A. Patty, Inter- 
science Publishers, Inc., New York, 1958, 830 pp. 
2842. Tatarelli, G. Le basi fisiologiche e 1’aspetto 
Ann. Nav. Med., 1960, 65: 173-176. 
2843. Tatarelli, G. Le base fisiologiche e I’aspetto 
sportivo del nuoto di combattimento. Ann. Nav. Med., 
1961, 66: 669-684. 
2844. Taylor, H. J. Underwater swimming and diving. 
Nature Land., 1957, 180; 838-886. 
2845. U.S. Navy. Diving notes. U.S. Navy, Naval 
Gun Factory, Washington, D.C. PRNC, DSDS-6, October 
1952, 382 pp. 
2846. U.S. Navy. The dive. pp. 60-68 in: Submarine 
medicine practice. U.S. Navy, BuMed. NAVMED — P 
5054, Gov’t. Printing Office, Washington, D.C., 1956, 
357 pp. 
2847. U.S. Navy. Safety considerations in the use 
of SCUBA, pp. 155-162 in: Submarine medicine practice. 
U.S. Navy, BuMed. NAVMED — P 5054, Gov’t. Printing 
Office, Washington, D.C., 1956, 357 pp. 
2848. U.S. Navy. Specific medical problems in the 
use of SCUBA, pp. 165-183 in: Submarine medicine prac- 
tice. U.S. Navy, BuMed. NAVMED - P 5054, Gov’t. 
Printing Office, Washington, D.C., 1956, 357 pp. 
2849. U.S. Navy. Physics of diving, pp. 30-35 in: 
Submarine medicine practice. U.S. Navy, BuMed. 
NA VMED — P 5054, Gov’t. Printing Office, Washington, 
D.C., 1956, 357 pp. 
2850. U.S. Navy. SCUBA diving techniques, pp. 25-27 
in: Curriculum for submarine medical officers (Diving 
medicine). U.S. Navy, BuPers, Washington, D.C. 
NAVPERS 92427, February 1957, 167 pp. 
2851. U.S. Navy. Underwater physiology, pp. 47-65 
in: Curriculum for submarine medical officers (Diving 
imedicine). U.S. Navy, BuPers, Washington, D.C. 
NAVPERS 92427, February 1957. 167 pp. 
2852. U.S. Navy. Diving accidents, pp. 79-94 in: 
Curriculum for submarine medical officers (Diving medi- 
cine). U.S. Navy, BuPers Washington, D. C. NAVPERS 
92427, February 1957, 167 pp. 
2853. U.S. Navy. U.S. Navy diving manual. BuShips. 
NAVSHIPS 250-558, 1959, 433 pp. 
2854. U.S. NRC. Report of the cooperative under- 
water swimmer project. U.S. NRC, November 1952, 95 pp. 
2855. Valle, G. D., C. M. Smithline, B. W. Holder- 
ness, A. Stanfield and H. Vetter. Skin and SCUBA 
diving. Sterling Publishing Co., Inc., New York, 1961, 
128 pp. 
2856. Waldron, T. J. and J. Gleeson, The frogmen. 
The story of the wartime underwater operators. Evans 
Brothers Ltd., London, 1950, 191 pp, 
2857. Wilson, G. What the general practitioner should 
know about the emergencies involved in aqualung diving. 
B.C. med. J., 1960, 2: 295-299. 
2858. Yarbrough, O. D. Outline of major problems of 
underwater swimming and self-contained diving, pp. 2-6 
in: Proceedings of the underwater physiology symposium. 
Edited by L. G. Goff, National Research Council, Wash- 
ington, D.C. N.R.C. Publication 577, 1955, 153 pp. 
2859. Anon. Underwater swimming. Bulletin no. 1. 
Library of Congress, Tech. Info. Div., Washington, D.C. 
May 1957, II pp. 
2860. Anon. Underwater swimming. Bulletin no. 2. 
Library of Congress, Tech. Info. Div., Washington, D.C. 
August 1957, 11 pp. 
2861. Anon. Underwater swimming. Bulletin no. 3. 
Library of Congress, Tech. Info. Div., Washington, D.C. 
October 1957, 13 pp. 2862-2886 
SPECIAL PROBLEMS OF SCUBA DIVING 
2862. Anon. Underwater swimming. Bulletin no. 4. 
Library of Congress, Sci. and Tech. Div., Washington, 
D.C. February 1958, 10 pp. 
2863. Anon. Underwater swimming. Bulletin no. 5. 
Library of Congress, Sci. and Tech. Div., Washington, 
D.C. June 1958, 11 pp. 
2864. Anon. Underwater swimming. Bulletin no. 6. 
Library of Congress, Sci. and Tech. Div., Washington, 
D.C. July 1958, 16 pp. 
2865. Anon. Underwater swimming. Bulletin no. 7. 
Library of Congress, Sci. and Tech. Div., Washington, 
D.C. October 1958, 16 pp. 
2866. Anon. Underwater swimming. Bulletin no. 8. 
Library of Congress, Sci. and Tech. Div., Washington, 
DC. December 1958, 12 pp. 
2867. Anon. Underwater swimming. Bulletin no. 9. 
Library of Congress, Sci. and Tech. Div., Washington, 
D.C. January 1959, 17 pp. 
2868. Anon. Underwater swimming. Bulletin no. 10. 
Library of Congres Sci. and Tech. Div., Washington, 
D.C. July 1959, 19 pp. 
2869. Anon. Underwater swimming. Bulletin no. 11. 
Library of Congress. Sci. and Tech. Div., Washington, 
D.C. January 1960, 24 pp. 
2870. Anon. Underwater swimming. Bulletin no. 12. 
Library of Congress, Sci. and Tech. Div., Washington, 
D.C. March 1960, 48 pp. 
2871. Anon. Hazards and medical problems of skin 
and scuba diving. Spectrum, 1960, 8: 156-165. 
2872. Anon. Skin diving and SCUBA. Instructor’s 
guide. Athletic Institute, Chicago, 1961, 83 pp. 
2873. Anon.SCUBA diving. Canad. med. Ass. J., 1961, 
85: 440-441. 
II. NERVOUS SYSTEM 
Many investigators have shown that air at 
raised barometric pressures exerts certain mental 
and psychomotor effects on man such as euphoria, 
confusion, slowed mental activity, motor incoor- 
dination and impairment in performance. Roger, 
Cabarrou and Gastaut (2876) studied the electro- 
encephalogram in 12 well-trained divers who 
were exposed to a pressure of 10 atmospheres 
absolute. Records were taken immediately be- 
fore and during the pressure exposure. There 
was an augmentation of frequency, a decrease in 
amplitude, and the potentials evoked by photic 
stimuli were augmented in amplitude. 
2874. Gillen, H. W. Neurologic problems encountered 
as a result of diving. Neurology, 1955, 5: 723-727. 
2875. Patti, M. and G. TatareHi. Ricerche clinicbe, 
biochimiche, elettrocardiografiche ed elettroenfalografiche 
sugli effetti del nuoto subacqueo ni apnea. Med. Sport., 
1958, 12: 1-12. 
2876. Roger, A., P. Cabarrou and H. Gastaut. EEC 
changes in humans due to changes of the surrounding 
atmospheric pressure. EEC din. Neurophysiol., 1955, 7: 
152. 
III. CARDIOVASCULAR SYSTEM 
Diving animals gradually develop a marked 
bradycardia which in most cases is of sinus origin. 
Pulse rate may decrease and the bradycardia once 
developed persists during physical activity and 
struggle. The bradycardia and shifting blood 
flow, together with the hypoxia and hyper- 
capnia, indicate that submersion has pronounced 
effects upon the cardiovascular system. Scholan- 
der, Hammel, LeMessurier, Hemmingsen and 
Garey (2884) 1961, studied 31 native skin divers 
in Australia. Of these, the blood lactate remained 
normal in five divers, but also showed an acute 
rise in the recovery period. The authors have 
indicated that this asphyxial defense seems well 
developed at birth, and an acute rise of lactic 
acid after the first cry has recently been described 
by other investigators. 
2877. Anagnostous, J. L., K. S. Zakopoulos and 
P. D. White. Circulatory adaptations in spongs fisher- 
men (skin divers). Amer. Heart J., 1957, 53: 835-840. 
2878. Andersen, H. T. Respiratory, circulatory and 
metabolic adjustments to prolonged diving in the Ameri- 
can alligator, alligator mississippiensis. Disesrt. Abstr., 
1961, 22: 1226. 
2879. Eisner, R., D. L. Franklin and R. L. Van 
Citters. Cardiac output during diving in an unrestrained 
sea lion. Circulation, 1963, 28: 716-717. 
2880. Eisner, R. W., T. F. Hornbein and J, 
Wright. Blood flow distribution in diving mammals. 
Fed. Proc., 1964, 23: 111. 
2881. Graveline, D. E. Effects of posture on cardio- 
vascular changes induced by prolonged water immersion. 
USAF. Wright-Patterson AFB, Dayton, Ohio. ASD Tech. 
Kept. no. 61-563, October 1961, 6 pp. 
2882. Johansen, K. Heart activity during experimental 
diving of snakes. Arner. J. Physiol., 1959, 197: 604-606. 
2883. Murdaugh, H. V,, J. C. Sezbury and W. L. 
Mitchell. Electrocardiogram of the diving seal. Circ. 
Res., 1961, 9: 358-361. 
2884. Scholander, P. F., H. T. Hammel, D. H. 
LeMessurier, E. Hemmingsen and W. Garey. Cir- 
culatory adjustment in pearl divers. Fed. Proc., 1961, 20: 
103. 
2885. Scholander, P. F., H. T. Hammel, H. Le- 
Messurier, E. Hemmingsen and W. Garey. Circulatory 
adjustment in pearl divers. J. appl. Physiol., 1962, 17: 
184-190. 
2886. Wilber, C. G. Cardiac responses of alligator 
mississippiensis to diving. Compar. Biochem. Physiol., 
1960, 1: 164-166. 
IV. RESPIRATION 
Deep sea divers recognize a reduced ability to 
hyperventilate at several atmospheres ambient KIDNEY 
2887-2901 
pressure. Since there is a need for deep diving 
operations by the U.S. Navy and the need for 
heavy work during such dives, it is important to 
know the limitations imposed upon the human 
respiratory apparatus. A comparison by Goff 
and Bartlett (2892) in 1957 of the respiratory 
response of trained versus untrained swimmers 
to the exercise involved in underwater swimming 
revealed that end-tidal carbon dioxide levels were 
elevated in the trained swimmers. The breathing 
pattern in the trained swimmers (slow deep 
breaths with long post-inspiratory pauses) might 
have accentuated the large cyclic variation in 
alveolar PCOo accompanying the respiratory cycle 
during exercise, thus resulting in an elevated 
endtidal PCOo without elevated alveolar or arte- 
rial PCOo. The authors suggested that the increase 
in the average alveolar PCOo might have been 
partially the result of a significantly lower oxygen 
ventilation equivalent in the trained swimmers 
as compared to the non-trained subjects. 
Carey, Schaefer and Alvis (2890) in 1956 com- 
pared lung volumes of laboratory personnel with 
those of escape training tank instructors. Vital 
capacities were found to be significantly larger 
in the tank instructors. Longitudinal studies of 
the lung volumes of instructors carried out for a 
period of one year following their assignment to 
an escape training tank exhibited a significant 
increase in total lung capacity, vital capacity, in- 
spiratory reserve and tidal volume. 
Lanphier (2896) 1955, reported abnormal car- 
bon dioxide levels, as measured with an end- 
tidal gas sampler in divers. The levels were ac- 
companied by corresponding abnormalities in 
the acid-base equilibrium. A definite difference 
from the norm appeared to be a characteristic 
in certain divers. Carbon dioxide sensitivity tests 
were also conducted in the same subjects, and 
these tests correlated with the carbon dioxide 
tensions observed in these men under various 
conditions. Although a definite relationship be- 
tween carbon dioxide sensitivity and the phe- 
nomenon in question was noted, the probable 
utility of a standard sensitivity test as a personnel 
selection procedure remains uncertain. 
2887. Andersen, H. T, A note on the composition of 
alveolar air in the diving duck. Acta physiol scand., 
1959, 46: 240-243. 
2888. Belkin, D. A. Importance of aquatic respira- 
tion in the diving ability of turtles. Fed. Proc., 1963, 22: 
635. 
2889. Buhlmann, A. A. La physiologic respiratoire 
au cours de la plongee sous-marine. Schweiz, med. Wschr., 
1961, 91: 747-778. 
2890. Carey, C. R., K. E. Schaefer and H. J. Alvis. 
Effect of skin diving on lung volumes. /. appl. Physiol., 
1955-56, 8: 519-523. 
2891. Carey, C. R., K. E. Schaefer and H. J. Alvis. 
Studies of lung volumes in instructors at the escape train- 
ing tank. U.S. Navy. Submarine Base, New London, Conn. 
Medical research laboratory. Project NM 002 015.12.01, 
26 November 1954, 12 pp. 
2892. Goff, L, G. and R. G. Bartlett, Jr. Elevated 
end-tidal CO., in trained underwater swimmers. J. appl. 
Physiol, 1957, 10: 203-206. 
2893. Goff, L. G., H. F. Brubach and H. Specht. 
Measurements of respiratory responses and work effi- 
ciency of underwater swimmers utilizing improved instru- 
mentation. J. appl. Physiol, 1957, 10: 197-202. 
2894. Hong, S. K., E. Y. Ting and H. Rahn. Lung 
volumes at different depths of submersion. J. appl. 
Physiol, 1960, 15: 550-553. 
2895. Keast, R. W. Respiratory physiology and skin 
diving. J. Amer. med. Ass., 1959, 169: 1419-1423. 
2896. Lanphier, E. H. Nitrogen-oxygen mixture phy- 
siology. Phase 3. End-tidal gas sampling system. Carbon 
dioxide regulation in divers. Carbon dioxide sensitivity 
tests. U.S. Navy. EDU, Naval Weapons Plant, Washington, 
D.C. Proj. NS 185-005, sub task no. 5, test no. 4, 30 August 
1955, 15 pp. 
2897. Lanphier, E. H. Carbon dioxide retention in 
working divers breathing nitrogen-oxygen mixtures at 
depth. Fed. Proc., 1956, 15: 116. 
2898. Miles, S. The problem of hyperventilation in 
divers. Gt. Brit. MRC, RNPRC, UPS. Kept. R.N.P. 
57/889, U.P.S. 165, April 1957, 11 pp. 
2899. Rahn, H. Introduction of respiratory problems 
in diving, pp. 89 in: Proceedings of the underwater phy- 
siology symposium. Edited by L.G. Goff, National Re- 
search Council, Washington, D.C. N.R.C. Publication 577, 
1955, 153 pp. 
2900. Schaefer, K. E. Adaptation to skin diving 
Fed. Proc., 1961, 20: 215. 
2901. Schaefer, K. E., G. Nichols, Jr., R. C. Stroud 
and C. R. Carey. Pulmonary gas exchange and blood 
gas transport during and after skin diving to 90 feet. 
Fed. Proc., 1958, 17: 141. 
V. KIDNEY 
Utilizing complete water immersion. Grave- 
line and Jackson (2902) recorded the diuretic 
response of five human subjects immersed in 
water for six hours. Their results demonstrated 
a lowered specific gravity diuresis which had the 
characteristics of both a water and an osmotic 
diuresis. 2902-2912 
SPECIAL PROBLEMS OF SCUBA DIVING 
2902. Graveline, D. E. and M. M. Jackson. Diuresis 
associated with prolonged water immerson. J. appl. Phy- 
siol., 1962, 17: 519-524. 
VI. OXYGEN CONSUMPTION 
As might be expected the work of moving air 
through the breathing apparatus will be in- 
creased as the ambient pressure is increased. This 
effect is due primarily to the increased density 
of the gas and to the respiratory resistance of 
the specific breathing apparatus. Lanphier 
(2909) in 1954 measured the oxygen require- 
ments of underwater swimmers using SCUBA 
gear, and recorded the influence of speed and 
other factors on swimming efficiency. Oxygen 
consumption was determined at swimming speeds 
between 0.5 and 1.2 knots in 15 subjects. The 
results indicated that efficiency decreased progres- 
sively above 0.8 knots. At this speed the average 
trained swimmer required 1.3 liters of oxygen 
per minute. Individual variations and the in- 
fluence of training and body size were found 
to be considerable. Goff, Frassetto and Specht 
(2907) in 1956 carried out similar experiments 
on underwater swimmers. The average oxygen 
consumption was 1.3 to 1.9 liters per minute at 
average swim rates from 0.7 to 0.9 miles per hour. 
A wide variation in oxygen consumption was ob- 
served. This range was not narrowed when con- 
verted to liters of oxygen per square meter of 
body surface and the authors attributed these 
differences to individual swimming ability. Fre- 
quent subjective symptoms of carbon dioxide 
accumulation in the breathing apparatus were 
reported. 
2903. Andersen, H. T. Depression of metabolism in 
the duck during experimental diving. Acta physiol, scand., 
1959, 46: 234-239. 
2904. Bartlett, R. G., Jr., H. F. Brubach and H. 
Specht. Oxygen cost of forced breathing in the submerged 
resting subject. J. appl. Physiol., 1957, 11: 377-382. 
2905. Donald, K. W. and W. M. Davidson. Oxygen 
uptake of divers and frogmen. J. Physiol., 1952, 117: 38P. 
2906. Donald, K. W. and W. M. Davidson. Oxygen 
uptake of ‘booted’ and ‘fin’ swimming divers. J. appl. 
Physiol, 1954, 7; 31-37. 
2907. Goff, L. G., R. Frassetto and H. Specht, 
Oxygen requirements in underwater swimming. J. appl. 
Physiol, 1956, 9: 219-221. 
2908. Lange-Andersen, K. Energy cost of swimming. 
Acta chir. scand., 1960, Suppl. 253: 169-174. 
2909. Lanphier, E. H. Oxygen consumption in under- 
water swimming. Fed. Proc., 1954, 13: 84. 
2910. U.S. Navy. Oxygen consumption in underwater 
swimming. U.S. Navy. EDU, Naval Station, Washington, 
D.C. Rept. 15-53, I September 1953, 8 pp. 
VII. SPATIAL ORIENTATION 
The exposure of the underwater swimmer to 
water in which the illumination is considerably 
limited may impose on the swimmer a weightless 
environment similar to that experienced by the 
astronaut in space flight. Beckman, Coburn, 
Chambers, DeForest, Augerson and Benson 
(2911) in 1961 immersed seven subjects in water 
up to the neck level for periods of five to 23 
hours and recorded a significant weight loss dur- 
ing the immersion period. This is explained by 
the diuresis which occurred. A decrease in ex- 
piratory reserve volume and in respiratory mi- 
nute volume was also recorded during the im- 
mersion period. 
The ability to orient to the vertical during 
water immersion was investigated by Brown 
(2913) in 1961. The subjects were immersed 
in water at a depth of either 18 or 25 feet and 
then rotated in a tucked position on a rod 
through three, four or five revolutions. Rotation 
was terminated with the head in one of four 
positions: upright, inclined forward, down or 
back. Upon termination of rotation the subjects 
were directed to point in the up direction and 
then to swim to the surface. There were errors 
in direction of initial pointing of as much as 180 
degrees. Errors were greatest with the head down 
or back, and least with the head up or forward. 
Nodding of the head was followed by consistent 
improvement in the direction of pointing. There 
was little indication of any difficulty in swim- 
ming in the upward direction. A greater density 
of the legs as compared to the trunk resulted in 
fairly rapid vertical orientation of the body upon 
release of the rod. The results were interpreted 
to reflect the relative inefficiency of the utricles 
as gravity sensors when the head is in certain 
positions. 
2911. Beckman, E. L., K. R. Coburn, R, M. Cham- 
bers, R. E. DeForest, W. S. Augerson and V. G. 
Benson. Physiologic changes observed in human sub- 
jects during zero G simulation by immerson in water up 
to neck level. Aerospace Med., 1962, 32: 1031-1041. 
2912. Beritoff, J. S. Spatial orientation of man and 
animals. XXII Inter. Congr. Physiol. Sci., Leiden, 1962. 
Vol. I, Part I, p. 3. HAZARDS FROM DANGEROUS FISH AND OTHER MARINE ORGANISMS 
2913-2922 
2913. Brown, J. L. Orientation to the vertical during 
water immerison. Aerospace Med., 1961, 52: 209-217. 
2914. Graveline, D. E. and B. Balke. The phys- 
iologic effects of hypodynamics produced by water im- 
merison. U.S.A.F. Brooks AFB, eTxas. School of Aviation 
Medicine. Kept. 60-88, September 1960, 11 pp. 
2915. Graveline, D. E., B. Balke, R. E. McKenzie 
and B. Hartman. Psychobiologic effects of water-immer- 
sion-induced hypodynamics. Aerospace Med., 1961, 32: 
387-400. 
2916. Graybiel, A. and B. Clark. Symptoms resulting 
from prolonged immerison in water: The problem of 
zero G asthenia. Aerospace Med., 1961, 32: 181-196. 
2917. Hartman, B., R. E. McKenzie and D. E. 
Graveline. An exploratory study of changes in proficiency 
in a hypodynamic environment. USAF. Brooks AFB, 
Texas. School of Aviation Medicine. Rept. 60-72, July 
1960, IS pp. 
2918. Margaria, R. Wide range acceleration inves- 
tigations in man and animals. Riv. Med. aero., 1958, 21: 
655-690. 
2919. McKenzie, R. E., B. Hartman and D. E. 
Graveline. An exploratory study of sleep characteristics 
in a hypodynamic environment. USAF. Brooks AFB, Texas. 
School of Aviation Medicine. Rept. 60-68, October 1960, 
8 pp. 
2920. Reynolds, S. R. M. Sensory deprivation, weight- 
lessness and anti-gravity mechanisms. Aerospace Med., 
1961,32: 1061-1067. 
2921. Schock, G. J. D. A study of animal reflexes 
during exposure to subgravity and weightlessness. Aero- 
space Med., 1961,32: 336-340. 
2922. Wood, E. H., E. F. Lindberg, C. F. Code and 
E. J. Baldes. Effect of partial immersion in water on 
response of healthy men to headward acceleration. J. appl. 
Physiol, 1963, 18: 1171-1179. 
VIII. HAZARDS FROM DANGEROUS 
FISH AND OTHER MARINE 
ORGANISMS 
Swimming in tropical waters exposes the un- 
derwater swimmer to marine life which on many 
occasions inflicts wounds or stings which can be 
as serious as the results of shark attack. For a 
general review of problems related to dangerous 
fish and other marine organisms the reader 
should consult reports of Halstead (2934) 1959, 
Keegan and Macfarlane (2939) 1963, Miles 
(2942) 1962, Ravina and Ravina (2945) 1959, 
and by the U.S. Navy (2953) 1956. 
Among the marine animals that produce 
wounds the most generally feared are sharks. 
There are more than 225 species of sharks, but 
only a score or more are believed to attack 
men. It is difficult to make specific statements 
concerning the actual risk of attacks by sharks 
since as a whole the experience of divers in- 
dicates that the risk is almost negligible but the 
possibilities exist. Danger of shark attacks is 
greatest in tropical and sub-tropical seas. Par- 
ticularly dangerous areas are Queensland, Aus- 
tralia and South Africa. Most attacks have oc- 
curred when the temperature of the water was 
greater than 70°F., however, sharks feed at all 
hours and particularly at night. Sharks are at- 
tracted by blood, carrion, flashing of light, 
colored materials, thrashing about, explosions or 
unusual noises. When they are hunting in packs 
and food or blood is present sharks become 
highly excited and may radically alter their usual 
habits. It is at times like this that the greatest 
danger is encountered and that “shark repellents” 
are useless. Sharks will frequently single out an 
individual in a crowd and will ignore others 
who may attempt to rescue him; several men to- 
gether, however, are in a better position to ward 
off sharks than is a lone swimmer. It has been 
demonstrated that if the individual is not 
wounded the shark may leave if he remains 
perfectly still. 
Generally dark colored equipment and cloth- 
ing are preferred to light colored articles. The 
use of explosives can easily be expected to at- 
tract sharks in large numbers. The fatality rate 
from actual shark attack has been estimated at 
more than 80 percent. Bites are severe. Death 
is due to massive bleeding and shock. Gilbert 
(2933) 1960, has stated that attempts to wound 
the shark are usually useless and may even ag- 
gravate the situation, but if such action appears 
necessary, hit the shark on the snout, eyes or 
gills. It may be necessary to actually shove the 
shark away with the use of a “shark billy”—a 
large stick carried for this purpose—or with some 
other object. For additional references on shark 
attack papers by Miles (2942) 1962, Coppleson 
(2928) 1958, Gilbert (2932) 1960 ,and Tester 
(2952) 1958, should be consulted. Poisonous 
scorpion fish can be found in all tropical and tem- 
perate seas. One of the most dangerous species 
under this classification is the stonefish (Synan- 
ceja horrida). This species carries venomous 
spines on the back and about the tail. Wiener 
(2954) 1958, has stated that both local and gen- 
eral effects may follow the sting of a stonefish. 
The local effects are pain, swelling, paralysis and 2923-2937 
SPECIAL PROBLEMS OF SCUBA DIVING 
loss of sensation of the injured limb. The general 
effects include repeated syncope, impairment of 
all sensations, involvement of respiration and 
coma. Abscess formation, necrosis and gangrene 
not uncommonly complicate the local effects of a 
sting and delay convalescence. Dyspnea and gen- 
eral weakness may last for several months after 
a sting. The author recommends that a tourni- 
quet be applied immediately and this should be 
followed by scrubbing of the wound with water, 
incision and suction. The wound area should 
be infiltrated with a solution of one grain of erne- 
tin hydrochloride per millilitre. Alternatively, 
and when the use of emetin is contraindicated, 
0.1 to 0.5 millilitre of a five percent solution of 
potassium permanganate may be used. Prophy- 
lactic injections of penicillin and immunization 
against tetanus are required in severe cases of 
injury. 
When stonefish venom is administered intra- 
venously, rabbits (Austin, Carincros sand Mc- 
Callum (2925)) show hypotension, respiratory 
distress and muscular paralysis. Experimental 
evidence indicates that the systemic effects are 
due to the powerful myotoxic properties of the 
venom which produce cardiac paralysis and con- 
duction block in involuntary and skeletal muscle. 
The authors suggest that this conduction block 
is due to a slow depolarization of the muscle and 
that the cause of death is due to paralysis of the 
diaphragm. 
There are many varieties of rays and many 
of them are venomous. The exact nature of the 
venom apparatus varies from species to species, 
but it usually consists of a spine covered by a 
skin-like sheath. The spine is located on the 
upper side of the tail and a variable distance 
from the base of the tail. Stingrays are gen- 
erally found lying on the bottom in shallow 
water; they are usually well-camouflaged and 
are often partly covered by sand. The main 
danger to a swimmer or diver is that of stepping 
on one. When stepped on the ray strikes upward 
with its tail and drives the spine deeply into the 
foot or leg. The venom produces severe pain 
and if present in large quantities can cause gen- 
eralized effects. For a report of an unusual injury 
to the liver by a barbed stingray a paper by Cad- 
zow (2926) 1960, should be consulted. 
A difficult condition to diagnose is the der- 
matitis produced by marine parasites, sea urchins 
and seaweed. For general references on the sub- 
ject papers by the following should be consulted: 
Arnold (2923) 1958, Arnold and Bonnet (2924) 
1950, Chu (2927) 1952, Cort (2929) 1950, Hut- 
ton (2937) 1960, Leigh (2940 and 2941) 1953 
and 1955, Moschella (2943) 1951, Rocha and 
Fraga (2946) 1962, Sams (2947) 1949, Strauss 
(2949) 1956, Stunkard and Hinchhliffe (2950) 
1952, Zinn (2955) 1954, and Temine and Coulier 
(2951) 1961. 
2923. Arnold, H. L., Jr. Sea weed dermatitis appar- 
ently caused by a marine alga. Proc. Hawaii. Acad. Sci., 
1958-59,(n): 18-19. 
2924. Arnold, H. L., Jr. and D. B. Bonnet. “Swim- 
mers’ itch”: its first appearance in Hawaii. Proc. Hawaii. 
Acad. Sci., 1949-50, 25: 4. 
2925. Austin, L., K. D. Cairncross and I. A. N. 
McCallum. Some pharmacological actions of the venom 
of the stonefish “Synanceja horrida.” Arch. int. Pharma- 
codyn., 1961, 131: 339-347. 
2926. Cadzow, W. H. Puncture wound of the liver 
by stingray spines. Med. J. Aust., 1960, 1: 936-937. 
2927. Chu, G. W. T. C. First report of the presence 
of a dermatitis-producing marine larval schistosome in 
Hawaii. Science, 1952, 115: 151-153. 
2928. Coppleson, V. M. Shark attack. Angus and 
Robertson Ltd., Sidney, 1958, 266 pp. 
2929. Cort, W. W. Studies on schistosome dermatitis. 
XI. Status of knowledge after more than twenty years. 
Amer. J. Hyg., 1950, 52: 251-307. 
2930. Flecker, H. Injuries from stone fish. Med. J. 
Aust., 1956, 2: 371-373. 
2931. Fleisher, J. H., P. J. Killos and C. S. 
Harrison. Effects of puffer poison on neuromuscular 
transmission. U.S. Army. Army Chemical Center, Mary- 
land. Chemical Research and Development Laboratories. 
Tech. Kept. CRDLR 3046, December 1960, 26 pp. 
2932. Gilbert, P. W. The shark research panel. 
AIRS Bull., 1960, 10: 19-20. 
2933. Gilbert, P. W., L. P. Schultz and S. Springer, 
Shark attacks during 1959. Science, 1960, 132: 323-326. 
2934. Halstead, B. W. Dangerous marine animals. 
Cornell Maritime Press, Cambridge, Maryland. 1959, 146 
pp. 
2935. Helfrich, P. A study of the possible relation- 
ship between radioactivity and toxicity in fishes from the 
Central Pacific. LT.S. Atomic Energy Commission. Techni- 
cal Information Service, Rept. TID-5748, May 1960, 16 pp. 
2936. Helfrich, P. and A. H. Banner. Hallucinatory 
mullet poisoning: A preliminary report. J. trop. Med. Hyg., 
1960, 63: 86-89. 
2937. Hutton, R. F. Marine dermatosis. Arch. Derm., 
1960, 82: 951-956. UNDERWATER BREATHING APPARATUS 
2938-2969 
2938. Jiiptner, H. Verletzungen durch Steinfische 
(Synanceja trachynis). Z. Tropenmed. u. Parasit., 1960, 11: 
475-477. 
2939. Keegan, H. L. and W. V. Macfarlane. 
Venomous and poisonous animals and noxious plants of 
the Pacific region. Pergamon Press Inc., New York, 1963, 
456 pp. 
2940. Leigh, W. H. Cercaria huttoni, sp. Nov., a 
dermatitis-producing schistosome larva from the marine 
snail, Haminoea antillarum guadalupensis Sowerby. J. 
Parasit., 1953, 39: 625-629. 
2941. Leigh, W. H. The morphology of Gigantobil- 
harzia huttoni (Leigh, 1953) an avian schistosome with 
marine dermatitis-producing larvae. J. Parasit., 1955, 41: 
262-269. 
2942. Miles, S. Marin e animals, pp. 309-321 in: 
Underwater medicine. J. B. Lippincott Co., Philadelphia, 
1962, 328 pp. 
2943. Moschella, L. Further clinical observations on 
seabather’s eruption. Arch. Derm., 1951, 64 : 55-56. 
2944. Phelephs, D. R. Stone-fish poisoning. Med. J. 
Aust., 1960, 1: 293-294. 
2945. Ravina, A. and J. H. Ravina, Dangers des 
animaux aquatiques veneneux ou porteurs de germes 
pathogenes. Pr. med., 1959, 67: 1591-1593. 
2946. Rocha, G. and S. Fraga. Sea urchin granu- 
loma of the skin. Arch. Derm., 1962, 85: 406-408. 
2947. Sams, W. M. Seabather’s eruption. Arch. 
Derm. Syph., 1949, 60: 227-237. 
2948. Saunders, P. R. Sting by a veonmous lionfish. 
U,S. Forces med. J., 1960, 11: 224-227. 
2949. Strauss, J. S. Seabather’s eruption. Arch. 
Derm., 1956, 75: 293-295. 
2950. Stunkard, H. W. and M. C. Hinchliffe. The 
morphology and life-history of Microbilharzia variglandis 
(Miller and Northup, 1926) Stunkard and Hinchliffe, 1951, 
avian bloodflukes whose larvae cause “swimmer’s itch’’ of 
ocean beaches. J. Parasit., 1952, 38: 248-265. 
2951. Temine, P. and L. Coulier. Les accidents 
cutanes causes par les bains dans 1’eau de mer. Marseille 
med., 1961, 98: 687-697. 
2952. Tester, A. L. Fatal shark attack, Oahu, Hawaii, 
December 13, 1958. Pacif. Sci., 1960,14: 181-184. 
2953. U.S. Navy. Marine life. pp. 177-180 in: Sub- 
marine medicine practice. U.S. Navy, BuMed. NAVMED — 
P 5054, Gov’t. Printing Office, Washington, D.C., 1956, 357 
pp. 
2954. Wiener, S. Stone-fish sting and its treatment. 
Med. J. Aust., 1958, 2: 219-222. 
2955. Zinn, D. J. Pruritus produced by the zooea 
larvae of one of the porcelain crabs. J. Parasit., 1954, 40: 
233-234. 
IX. UNDERWATER BREATHING 
APPARATUS 
The references given below constitute a gen- 
eral literature source for a discussion of problems 
encountered in the design, testing and operation 
of underwater breathing apparatus. 
2956. Alvis, H. J. Theoretical consideration of the 
use of the air-filled submarine escape appliance from great 
depths. U.S. Navy. Submarine Base, New London, Conn. 
Medical research laboratory. Project NM 002 015.08.01, 27 
January 1952, 16 pp. 
2957. Alvis, H. J. Hazards of diving with self-con- 
tained underwater breathing apparatus. Industr. Med. 
Surg., 1958, 27: 389-392. 
2958. Dwyer, J. V. Semi-closed circuit mixed-gas 
injection SCUBA. U.S. Navy, EDU, Naval Weapons Plant, 
Washington, D.C. Project NS 186-202, subtask no. 2, test 
no. 9, 24 August 1955, 12 pp. 
2959. Dwyer, J. V. Mixed gas sections for U.S. Navy 
diving manual (proposed). U.S. Navy. EDU, Naval Weap- 
ons Plant, Washington, D.C. Project NS 185-005, subtask 
no. 5, test no. 1, 6 January 1956, 8 pp. 
2960. Fischer, W. F., C. J. Leyden and W. F. 
Searle, Jr. The design of an adjustable breathing bag 
exhaust valve for closed and semi-closed circuit SCUBA. 
U.S. Navy. EDU, Naval Weapons Plant, Washington, D.C. 
Part I of Project NS 186-202, subtask no. 2, test no. 11, 
5 March 1958, 9 pp. 
2961. Funderburk, L. R., Jr. Construction and eval- 
uation of effective dead space comparator. U.S. Navy. EDU, 
Naval Weapons Plant, Wahsington, D.C. Project NS 185- 
005, subtask no. 4, test no. 24, 15 January 1957, 13 pp. 
2962. Greene, J. L. and H. A. Brandenburg. (Design 
and test of diver’s non-return valve. U.S. Navy. EDU, 
Naval Station, Washington, D.C. Res. Kept. 2-62, Proj, 
NS 185-005, subtask 3, Test 11, 15 October 1962, 11 pp. 
2963. Hahn, W. A. and C. J. Lambertsen. On using 
self-contained underwater breathing apparatus. U.S. NRC, 
Washington, D.C., Publication 274, January 1952, 19 pp. 
2964. Hall, F. G. and F. Zechman, Jr. Respiratory 
effects of increased air flow resistance in dogs. Proc. Soc. 
exp. Biol., N.Y., 1957, 96: 329-332. 
2965. Hutchinson, J. C. D. Sanitary plumbing for 
the submarine escape immersion suit. Gt. Brit. MRC, 
RNPRC. Kept. R.N.P. 56/865, O.E.S. 429, C.P. 25, 1956, 
9 pp. 
2966. Ingberg, B. Nagot om riskerna vid dykning 
med andningsapparat. [Remarks on the hazards of diving 
while wearing a breathing apparatus.] Svenska Lakartidn., 
1960, 57: 1351-1359. 
2967. Janney, G. M. Evaluation of a new, positive 
displacement mechanical respirator for use in the testing 
of breathing apparatus. U.S. Navy. EDU, Naval Weapons 
Plant, Washington, D.C. Project NS 185-005, subtask 4, 
test no. 1, 29 August 1960, 11 pp. 
2968. Janney, G. M. and W. F. Searle, Jr. Mechani- 
cal respirator techniques in the evaluation of SCUBA. 
U.S. Navy. EDU, Naval Weapons Plant, Washington, D.C. 
Project NS 185-005, sub task no. 4, test no. 47, 30 June 
1958, 22 pp. 
2969. Leyden, C. J. Breathing resistance in SCUBA 
components. U.S. Navy. EDU, Naval Gun Factory, Wash- 
ington, D.C. Res. Rept. 4-57, Proj. NS 185-005, subtask 4, 
test no. 20, 17 September 1956, 19 pp. 2970-2984 
SPECIAL PROBLEMS OF SCUBA DIVING 
2970. Mackay, R. S. Some principles of self-contained 
underwater breathing apparatus. Science, 1958, 128: 1001- 
1002. 
2971. Mahoney, G. H. Florikan helium-oxygen gas 
mixing methods. U.S. Navy. EDU, Naval Weapons Plant, 
Washington, D.C. Res. Rept. 2-58, Proj. NS 186-201, 16 
August 1957, 6 pp. 
2972. Marshall, R., E. H. Lanphier and A. B. 
DuBois. Resistance to breathing in normal subjects 
during simulated dives. J. appl. Physiol, 1956, 9: 5-10. 
2973. Michel, E. L. and H. S. Sharma. Determina- 
tion of effective dead air space of aviators respiratory 
equipment by physiologic measurement. Aerospace Med., 
1959, 30: 280-286. 
2974. Miles, G. G. and N. T. Martin. Factors influ- 
encing the elimination of nitrogen using semiclosed in- 
halers. Anesthesiology, 1956, 17: 213-221. 
2975. Rickert, F. J. Surface supply conversion. U.S. 
Navy. EDU, Naval Weapons Plant, Washington, D.C. 
Project NS 185-005, subtask no. 4, test no. 26, 28 Septem- 
ber 1956, 7 pp. 
2976. Roberts, F. M. Basic SCUBA. Self-contained 
underwater breathing apparatus. D. Van Nostrand Com- 
pany, Inc., Princeton, New Jersey, 1960, 386 pp. 
2977. Searle, W. F., Jr. and J. Wheat. A considera- 
tion of the use of activated alumina in a modified 3000 
psi air separator for the removal of hydrocarbon carryover 
in divers’ high pressure air systems. U.S. Navy. EDU, 
Naval Weapons Plant, Washington, D.C. Res. Rept. 3-58, 
23 October 1957, 11 pp. 
2978. Specht, H., L. G. Goff, H. F. Brubach and 
R. G. Bartlett, Jr. Work efficiency and respiratory 
response of trained underwater swimmers using a modified 
self-contained underwater breathing apparatus. J. appl. 
Physiol, 1957,10: 376-382. 
2979. St. Louis, F. G. The Momsen lung. Submarine 
escape appliance. Med. Tech. Bull., 1954, 5: 242-244. 
2980. U.S. Navy. Diver’s equipment, pp. 14-24 in; 
Submarine medicine practice. U.S. Navy, BuMed. 
NA VMED — P 5054, Gov’t. Printing Office, Washington, 
D.C., 1956, 357 pp. 
2981. U.S. Navy. Types of self-contained underwater 
breathing apparatus, pp. 134-145 in: Submarine medicine 
practice. U.S. Navy, BuMed. NAVMED — P 5054, Gov’t. 
Printing Office, Washington, D.C., 1956, 357 pp. 
2982. U.S, Navy. Selection and training for the use 
of self-contained underwater breathing apparatus, pp. 148- 
151 in: Submarine medicine practice. U.S. Navy, BuMed. 
NA VMED — P 5054, Gov’t. Printing Office, Washington, 
D.C., 1956, 357 pp. 
2983. U.S. NRC. Suits for underwater swimmers, 
pp. 36-55 in: Report of the cooperative underwater swim- 
mer project. U.S. NRC, November 1952, 95 pp. 
2984. Yaglou, C. P. and V. F. Borum. The suit- 
ability of submarine compressed air for use in the sub- 
marine escape appliance. U.S. Navy. Submarine Base, New 
London, Conn. Medical research laboratory. Project NM 
002 015.08, Kept. no. 2, 30 March 1953. Key to Abbreviations of Journals 
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Acta biol. med.. Germ. Acta Biologica 
et Medica Germanica. Berlin. 
Acta cardiol., Brux. Acta cardiologica. 
Bruxelles. 
Acta chir. orthop. traum. Cech. Acta 
Chirurgiae Orthopaedicae et Trau- 
matologiae Cechoslovaca. Praha. 
Acta chir. scand. Acta chirurgica 
Scandinavica. Stockholm. 
Acta endocr., Copenhagen. Acta en- 
docrinologica. Copenhagen. 
Acta med. hung. Acta medica Acad- 
emiae scientiarum hungaricae. 
Budapest. 
Acta med. scand. Acta medica Scan- 
dinavica. Stockholm. 
Acta morph, neerl.-scand. Acta mor- 
phologica Neerlando-Scandinavica. 
Utrecht. 
Acta oto-laryng., Stockh. Acta oto- 
laryngologica. Stockholm. 
Acta paediatr., Stockh. Acta paedi- 
atrica. Stockholm, Uppsala. 
Acta path, microbial, scand. Acta 
pathologica et microbiologica Scan- 
dinavica. Kjobenhavn. 
Acta physiol, lat. amer. Acta physi- 
ologica Latino Americana. Buenos 
Aires. 
Acta physiol, pharm. need. Acta 
physiologica et pharmacologica 
Neerlandica. Amsterdam. 
Acta physiol, scand. Acta physiologica 
Scandinavica. Stockholm. 
Acta psychiat., Kbh. (see Acta Psy- 
chiat. scand.). 
Acta psychiat. scand. Acta psychiat- 
rica Scandinavica. Kjobenhavn. 
Acta psychol., Hague. Acta psycho- 
logica. Hague. 
Acta radiol., Stockh. Acta radiologica. 
Stockholm. 
Acta Soc. Med., Uppsala. Acta So- 
cietatis medicorum Upsaliensis. 
Uppsala. 
Advanc. Sci., Land. Advancement of 
Science. London. 
Aeromed. Acta. Aeromedica Acta. 
Soesterberg. 
Aerospace Med. Aerospace Medicine. 
Washington. 
Arztl. Forsch. Arztliche Forschung. 
Bad Worishafen. 
Arztl. Wschr. Arztliche Wochen- 
schrift. Berlin. 
A.I.B.S. Bull. American Institute of 
Biological Sciences. Washington. 
Air Univ. Quart. Rev. Air University 
Quarterly Review. Montgomery, 
Washington. 
Amer. chem. Soc. J. (see J. Amer. 
chem. Soc.). 
Amer. Col. Surg., din Conf. (see Surg. 
Forum). 
Amer. Heart J. American Heart Jour- 
nal. St. Louis. 
Amer. ind. Hyg. Ass. J. American In- 
dustrial Hygiene Association Jour- 
nal. Chicago. 
Amer. J. Bot. American Journal of 
Botany. Lancaster, Pa. 
Amer. J. Dis. Child. American Jour- 
nal of Diseases of Children. Chi- 
cago. 
Amer. J. Cardiol. American Journal 
of Cardiology. New York. 
Amer. J. din. Path. American Jour- 
nal of Clinical Pathology. Balti- 
more. 
Amer. J. Hyg. American Journal of 
Hygiene. Baltimore. 
Amer. J. Med. American Journal of 
Medicine. New York. 
Amer. J. med. Sci. American Journal 
of the Medical Sciences. Philadel- 
phia. 
Amer. J. med. Tech. American Jour- 
of Medical Technology. Detroit. 
Amer. J. Nurs. American Journal of 
Nursing. Philadelphia. 
Amer. J. Obstet. Gynec. American 
Journal of Obstetrics and Gynecol- 
ogy. St. Louis. 
Amer. J. Ophthal. American Journal 
of Ophthalmology. St. Louis. 
Amer. J. Optom. American Journal 
of Optometry. Minneapolis. 
Amer. J. Path. American Journal of 
Pathology. Boston. 
Amer. J. phys. Med. American Jour- 
nal of Physical Medicine. Balti- 
more. 
Amer. J. Physiol. American Journal 
of Physiology. Boston. 
Amer. J. Psychiat. American Journal 
of Psychiatry. Baltimore. 
Amer. J. Psychol. American Journal 
of Psychology. Worcester. 
Amer. J. Roentgenol. American 
Journal of Roentgenology (Radium 
Therapy and Nuclear Medicine). 
New York. 
Amer. J. Surg. American Journal of 
Surgery. New York. 
Amer. Psychol. American Psycholo- 
gist. Lancaster, Pa. 
Amer. Rev. resp. Dis. American Re- 
view of Respiratory Diseases. Balti- 
more. 
Anaesthesia. Anaesthesia. London. 
Anaesthesist. Anaesthesist. Berlin. 
Analyt. Chem. Analytical Chemistry. 
Easton, Pa. 
Anat. Rec. Anatomical Record. Phil- 
adelphia. 
Anesth. Analg. Anesth£sie et anal- 
gesic. Paris. 
Anesth. Analg. curr. Res. Anesthesia 
and Analgesia Current Researches. 
Elmira, N.Y. 
Anesthesiology. Anesthesiology. Lan- 
caster, Pa. 
Ann. Chir. Gyn. Fenn. Annales chir- 
urgiae et gynaecologiae Fenniae. 
Helsinki. 
Ann. intern. Med. Annals of Inter- 
nal Medicine. Ann Arbor. 
Ann. Med. nav. trop. Annali di me- 
dicina navale e tropicale. Roma. Ann—Can 
JOURNAL ABBREVIATIONS 
Ann. N.Y. Acad. Sci. Annals of the 
New York Academy of Sciences. 
New York. 
Ann. occup. Hyg. Annals of Occu- 
pational Hygiene. London. 
Ann. Otol., etc., St. Louis. Annals of 
Otology, Rhinology and Laryngol- 
ogy. St. Louis. 
Aim. Paedit. Penn. Annales paedia- 
triae Fenniae. Helsinki. 
Ann. pharm. fratif. Annales pharma- 
ceutiques francaises. Paris. 
Ann. Surg. Annals of Surgery. Phil- 
adelphia, London. 
Annu. Rev. Med. Annual Review7 of 
Medicine. Stanford University. 
Palo Alto. 
Annu. Rev. Physiol. Annual Review 
of Physiology. Stanford University. 
Palo Alto. 
Appl. Ther. Applied Therapeutics. 
Toronto. 
Arch. Biochem. Archives of Biochem- 
istry and Biophysics. New York. 
Arch. bras. Cardiol. Archives brasi- 
leiros de cardiologia. Sao Paulo. 
Arch. Chir. Need. Archivum chirurgi- 
cum Neerlandicum. Arnhem. 
Arch. Derm. Archives of Dermatol- 
ogy. New York. 
Arch, envir. Hlth. Archives of En- 
vironmental Health. Chicago. 
Arch. exp. Path. Pharmak. Naunyn- 
Schmiedebergs Archiv fiir experi- 
mentelle Pathologic und Pharma- 
kologie. Leipzig. 
Arch. gen. Psychiat. Archives of Gen- 
eral Psychiatry. Chicago. 
Arch. Gewerbepath. (see Int. Arch. 
Gewerbepath.). 
Arch, industr. Hlth. Hyg. (see Arch, 
envir. Hlth). 
Arch. int. Pharmacodyn. Archives In- 
ternationales de pharmacodynamic 
et de therapie. Bruxelles-Paris, 
Gand. 
Arch. int. Physiol. Archives Interna- 
tionales de physiologic et de bio- 
chimie. Li6ge, Paris. 
Arch, intern. Med. Archives of In- 
ternal Medicine. Chicago. 
Arch. Mai. prof. Archives des mala- 
dies professionelles de medecine du 
travail et de s£curite sociale. Paris. 
Arch. E. Maragliano. Archivio E. 
Maragliano di patologia e clinica. 
Genova. 
Arch. Neurol. Archives of Neurol- 
ogy. Chicago. 
Arch. Ophthal. Archives of Ophthal- 
mology. New York. 
Arch. Otolaryng. Archives of Otolar- 
yngology. Chicago. 
Arch. Path. Archives of Pathology. 
Chicago. 
Arch. phys. Med. Archives of Physical 
Medicine and Rehabilitation. Oma- 
ha. 
Arch. phys. Ther. Archiv fiir Physi- 
kalische Therapie, Balneologie und 
Klimatologie. Leipzig. 
Arch. Surg. Archives of Surgery. Chi- 
cago. 
Arch. Toxikol. Archiv fiir Toxikolo- 
gie. Berlin. 
Arkh. Pat. Arkhiv Patologii. Moskva. 
Aust. J. exp. Biol. med. Sci. Austral- 
ian Journal of Experimental Biol- 
ogy and Medical Science. Adelaide. 
Aviat. Week. Aviation Week. New 
York. 
B.C. med. J. British Columbia Medi- 
cal Journal. Vancouver. 
Beitr. klin. Chir. Beitrage zur klinis- 
chen Chirurgie. Tubingen. 
Beitr. Klin. Tuherk. Beitrage zur 
Klinik der Tuberkulose und Spezi- 
fischen Tuberkuloseforschung. 
W urzburg. 
Beitr. path. Anat. Beitrage zur patho- 
logischen Anatomic und zur allge- 
meinen Pathologic. Jena. 
Beitr. SilikosForsch. Beitrage zur 
Silikose-Forschung. Bochum. 
Biofizika. Biopzika. Moskva. 
Biol. Bull., Wood’s Hole. Biological 
Bulletin. Marine Biological Labor- 
atory. Wood’s Hole, Mass. 
Biophys. J. Biophysical Journal. New 
York. 
Biul. Inst. Med. morsk. Gdansk. 
Biuletyn Instytutu medycyny mor- 
skiej w Gddnsku. Warszawa. 
Biul. Eksp. Biol. Med. (see Bull. Biol. 
Med. exp. URSS). 
Blood. Blood. The Journal of Hema- 
tology. New York. 
Boll. Soc. ital. Biol. sper. Bollettino 
della Societa italiana di biologia 
sperimcntale. Napoli. 
Brit. Heart J. British Heart Journal. 
London. 
Brit. J. Anaesth. British Journal of 
Anaesthesia. Manchester. 
Brit. J. Cancer. British Journal of 
Cancer. London. 
Brit. J. industr. Med. British Journal 
of Industrial Medicine. London. 
Brit. J. Pharmacol. British Journal of 
Pharmacology and Chemotherapy. 
London. 
Brit. J. Psychiat. British Journal of 
Psychiatry. London. 
Brit. J. Psychol. British Journal of 
Psychology. Cambridge. 
Brit. J. Radiol. British Journal of 
Radiology. London. 
Brit. J. Surg. British Journal of Sur- 
gery. Bristol. 
Brit. tned. Bull. British Medical Bul- 
letin. London. 
Brit. med. J. British Medical Journal. 
London. 
Brookhaven Syrnp. Biol. Brookhaven 
Symposia in Biology. Upton, N.Y. 
Bull. Acad. nat. Med. Bulletin de 
I’Acad&nie nationale de mMecine. 
Paris. 
Bull. Biol. Med. exp. URSS. Byulle- 
ten’ eksperimental’ noi biologii i 
meditsiny. Moskva. 
Bull. exp. Biol. Med. Bulletin of Ex- 
perimental Biology and Medicine, 
U.S.S.R. New York. (Eng. trans. 
of Bull. Biol. Med. exp. URSS). 
Bull Inst, morsk. Med. Gdansk, (see 
Biul. Inst. Med. morsk. Gdansk). 
Bull. Los Angeles neurol. Soc. Bulle- 
tin of the Los Angeles Neurological 
Society. Los Angeles. 
Bull. math. Biophys. Bulletin of 
Mathematical Biophysics. Chicago. 
Bull, schweiz. Akad. med. Wt'55. Bul- 
letin der Schweizerischen Akademie 
der medizinischen Wissenschaften. 
Basel. 
Bull. Soc. int. Chir. Bulletin de la 
Society Internationale de chirurgie. 
Bruxelles. 
Bull. Univ. Md. Sch. Med. Bulletin. 
Maryland University School of 
Medicine and College of Physicians 
and Surgeons. Baltimore. 
Bur. Ships J. Bureau of Ships Jour- 
nal. Washington. 
Canad. Anaesth. Soc. J. Canadian 
Anaesthetists’ Society Journal. To- 
ronto. 
Canad. J. Biochem. Canadian Journal 
of Biochemistry. Ottawa. 
Canad. J. Med. Sci. (see Canad. J. 
Biochem., Canad. J. Physiol. Phar- 
macol.). 
Canad. J. Physiol. Pharmacol. Cana- 
dian Journal of Physiology and 
Pharmacology. Ottawa. JOURNAL ABBREVIATIONS 
Can—J. Car 
Canad. J. Psychol. Canadian Journal 
of Psychology. Toronto. 
Canad. med. Ass. J. Canadian Medi- 
cal Association Journal, Toronto. 
Cancer Chemother. Rep. Cancer 
Chemotherapy Reports. (National 
Cancer Inst.) Bethesda. 
Cancer Res. Cancer Research. Balti- 
more. 
Chem. Abstr. Chemical Abstracts. 
Easton, Pa. 
Circulation. Circulation. Journal of 
the American Heart Association. 
New York. 
Circulation Res. Circulation Re- 
search. New York. 
Clin. Chem. Clinical Chemistry. Bal- 
timore, New York. 
Clin. Res. Clinical Research. Ameri- 
can Federation for Clinical Re- 
search, New York. 
Clin. Sci. Clinical Science, incorporat- 
ing Heart. London. 
Clin. Symp. Clinical Symposia. (CIBA) 
Summit, N.J. 
Compar. Biochem. Physiol. Compara- 
tive Biochemistry and Physiology. 
London. 
C. R. Soc. Biol., Paris. Compte rendu 
des stances de la de biologic- 
Paris. 
Curr. Res. Anesth. (see Anesth. 
Analg. curr. Res.). 
Dis. Chest. Diseases of the Chest. El 
Paso, Texas. 
Dis. nerv. Syst. Diseases of the Nerv- 
ous System. Chicago. 
Dissert. Abstr. Dissertation Abstracts. 
Ann Arbor. 
Dtsch. Gesundheitwes. Das deutsche 
Gesundheitswesen. Berlin. 
Dtsch. med. J. Deutsches medizinis- 
che Journal. Berlin. 
Dtsch. med. Wschr. Deutsche medi- 
zinische Wochenschrift. Leipzig. 
Dtsch. Versuchanst. Luftf. Deutsche 
Versuchsanstalt fiir Luftfahrt e.v. — 
Miilheim (Ruhr). Koln. 
Duodecim. Duodecim. Kirjoituksia 
laaketieteen ja laakarin toiminnan 
aloilta. Helsinki. 
EEG din. Neurophysiol. Electroen- 
cephalography and Clinical Neuro- 
physiology. Montreal. 
Endocrinology. Endocrinology. Glen- 
dale, Calif. 
Ergonomics. Ergonomics. London. 
Erie Cty. med. Bull. Bulletin of the 
Medical Society, County of Erie, 
Buffalo. 
Exp. Cell Res. Experimental Cell Re- 
search. New York. 
Exp. Neurol. Experimental Neurol- 
ogy. New York, London. 
Experientia. Experientia. Basel. 
Farbe. Farbe. Goettingen. 
Farmakol. Toksik. Farmakologiia i 
Toksikologiia. Moskva. 
Fed. Proc. Federation Proceedings 
(American Societies for Experi- 
mental Biology). Washington. 
Fertil. Steril. Fertility and Sterility. 
New York. 
Fiziol. Zh. SSSR Sechenov. Fiziologi- 
cheskii zhurnal SSSR im. I.M. Sech- 
enov. Leningrad. 
Folia med., Napoli. Folia medica. 
Napoli. 
Folia psychiat. neur., jap. Folia psy- 
chiatrica et neurologica japonica. 
Okayama. 
Fortschr. Rdntgenstr. Fortschritte aut 
dem Gebiete der Rontgenstrahlen 
und der Nuklearmedizin. Stuttgart. 
France med. France m&iicale. Paris. 
Genetics. Genetics. Princeton. 
GERS. Groupe d’Etudes et de Re- 
cherches Sous-Marines. 
Gigiena Sanit. Gigiena i sanitariya. 
Leningrad, Moskva. 
G. ital. Tuberc. Giornale italiano 
della tubercolosi. 
G.P. G.P. American Academy of 
General Practice. Kansas City. 
Harvey Lect. Harvey Lectures. Phil- 
adelphia and London. 
Hefte z. Unfallheilk. Hefte zur Un- 
fallheilkunde. Leipzig. 
Helv. physiol, acta. Helvetica physi- 
ologica et pharmacologica acta. 
Basel. 
IEEE Trans med. Electr. IEEE Trans- 
actions on Bio-Medical Electronics. 
New York. 
Industr. Med. Surg. Industrial Medi- 
'cine & Surgery. Chicago. 
Int. Arch. Gewerbepath. Internation- 
ales Archiv fiir Gewerbepathologie 
und Gewerbehygiene. Berlin. 
Internist. Internist. Berlin, Gottin- 
gen. 
Int. J. Air Wat. Poll. International 
Journal of Air and Water Pollu- 
tion. London. 
Int. J. Radiat. Biol. International 
Journal of Radiation Biology and 
related Studies in Physics, Chem- 
istry and Medicine. London. 
XXI Int. physiol. Congr. XXI Inter- 
national Physiological Congress. 
Leiden. 
XXII Int. physiol. Congr. XXII In- 
ternational Physiological Congress. 
Leiden. 
Int. Rec. Med. International Record 
of Medicine and General Practice 
Clinics. New York, Washington. 
Int. Z. angew. Physiol. Internationale 
Zeitschrift fiir angewandte Physiol- 
ogic einschliesslich Arbeitsphysiol- 
ogie. Berlin. 
/. abnorm. soc. Psychol. Journal of 
Abnormal and Social Psychology. 
Boston. 
J. acoust. Soc. Amer. Journal of the 
Acoustical Society of America. 
Menasha, Wis. 
/. Albert Einstein med. Cent. Journal 
of the Albert Einstein Medical 
Center. Philadelphia. 
J. Allergy. Journal of Allergy. St. 
Louis. 
J. Amer. chem. Soc. Journal of the 
American Chemical Society. Easton, 
Pa. 
J. Amer. geriat. Soc. Journal of the 
American Geriatrics Society. Balti- 
more, Chicago. 
J. Amer. med. Ass. Journal of the 
American Medical Association. Chi- 
cago. 
J. Amer. osteop. Ass. Journal of the 
American Osteopathic Association. 
Chattanooga, Tenn. 
Jap. J. med. Progr. Japanese Journal 
of Medical Progress. Nankodo. 
Jap. J. Physiol. Japanese Journal of 
Physiology. Nagoya. 
J. appl. Phys. Journal of Applied 
Physics. Lancaster, Pa. 
J. appl. Physiol. Journal of Applied 
Physiology. Washington. 
J. appl. Psychol. Journal of Applied 
Psychology. Worcester, Mass. 
,/. Aviat. Med. (see Aerospace Med.). 
J. biol. Chem. Journal of Biological 
Chemistry. Baltimore. 
J. Bone Jt. Surg. Journal of Bone and 
Joint Surgery. Boston. 
J. cardiovasc. Surg. Journal of Cardio- 
vascular Surgery. Torino. J. Cell—Med. Serv 
JOURNAL ABBREVIATIONS 
J. cell. comp. Physiol. Journal of 
Cellular and Comparative Physiol- 
ogy. Philadelphia. 
J. Chromatogr. Journal of Chroma- 
tography. Amsterdam, London. 
J. din. Endocrin. Journal of Clinical 
Endocrinology and Metabolism, 
Springfield, 111. 
J. din. exp. Psychopath. Journal of 
Clinical and Experimental Psycho- 
pathology and Quarterly Review 
of Psychiatry and Neurology. New 
York, Washington. 
J. din. Invest. Journal of Clinical In- 
vestigation. Baltimore. 
J. comp, physiol. Psychol. Journal of 
Comparative and Physiological 
Psychology. Baltimore. 
J. comp. Psychol, (see J. comp, phys- 
iol. Psychol). 
J. Endocrin. Journal of Endocrinol- 
ogy. Oxford, Cambridge. 
J. environ. Sci. Journal of Environ- 
mental Sciences. Illinois. 
J. exp. Med. Journal of Experimental 
Medicine. New York. 
J. exp. Psychol. Journal of Experi- 
mental Psychology. Princeton. 
J. Fla. med. Ass. Journal of the Flor- 
ida Medical Association. Jackson- 
ville. 
J. forens. Med. Journal of Ferensic 
Medicine. Cape Town. 
J. forens. Sci. Journal of Forensic 
Sciences. Mundelein, Illinois. 
J. Franklin Inst. Journal of the 
Franklin Institute. Phialdelphia. 
J. gen. Physiol. Journal of General 
Physiology. Baltimore, New York. 
J. Geront. Journal of Gerontology. 
Springfield, 111. 
J. Hered, Journal of Heredity. Wash- 
ington. 
J. int. Coll. Surg. Journal of the In- 
ternational College of Surgeons. 
Chicago. 
J. Kans. med. Soc. Journal of the 
Kansas Medical Society. Columbus. 
J. Lab. din. Med. Journal of Labora- 
tory and Clinical Medicine. St. 
Louis, Mo. 
J. Lancet. Journal-Lancet. Minneap- 
olis, Minn. 
J. ment. Sci. (see Brit. J. Psychiat). 
J. Mich. med. Soc. Journal of the 
Michigan State Medical Society. 
Detroit. 
J. Mt, Sinai Hosp. Journal of the 
Mount Sinai Hospital. New York. 
J. nat. Cancer Inst. Journal of the Na- 
tional Cancer Institute. Washing- 
ton. 
J. nerv. ment. Dis. Journal of Nervous 
and Mental Diseases. New York. 
J. Neurochem. Journal of Neuro- 
chemistry. London, New York. 
J. Neuropath, din. Neurol. Journal 
of Neuropathology and Clinical 
Neurology. Chicago. 
J. Neuropath, exp. Neurol. Journal 
of Neuropathology and Experi- 
mental Neurology. Baltimore. 
J. Neurophysiol. Journal of Neuro- 
physiology. Springfield, 111. 
J. Neuropsychiat. Journal of Neuro- 
psychiatry. Chicago. 
/. Neurosurg. Journal of Neurosur- 
gery. Springfield, III. 
J. Obstet. Gynaec., Brit. Commonw. 
Journal of Obstetrics and Gynaecol- 
ogy of the British Commonwealth. 
London. 
J. occup. Med. Journal of Occupa- 
tional Medicine. Chicago. 
J. opt. Soc. Amer. Journal of the Op- 
tical Society of America. Philadel- 
phia. 
J. Parasit. Journal of Parasitology. 
Lancaster, Pa. 
J. Pediat. Journal of Pediatrics. St. 
Louis, Mo. 
J. Personality. Journal of Personality. 
Durham, N.C. 
J. Pahrmacol. Journal of Pharmacol- 
ogy and Experimental Therapeu- 
tics. Baltimore. 
J. phys. Chem., Ithaca. Journal of 
Physical (and Colloid) Chemistry. 
Ithaca, N.Y. 
J. Physiol., Lond. Journal of Physiol- 
ogy. London and Cambridge. 
J. Physiol., Paris. Journal de physi- 
ologic. Paris. 
J. Physiol. Path. gen. (see J. Physiol., 
Paris). 
J. project. Tech. Journal of Projective 
Techniques. Glendale, Calif. 
J. psychiat. Res. Journal of Psychi- 
atric Research. London. 
J. R. Inst. publ. Tilth. Hyg. Journal 
of the Royal Institute of Public 
Health and Hygiene. London. 
/. R. nav. med. Serv. Journal of the 
Royal Naval Medical Service. Lon- 
don. 
J. Sci. Labour. Journal of the Science 
of Labour. Tokyo. 
J. soc. Psychol. Journal of Social Psy- 
chology. Worcester, Mass. 
J. Speech Dis. Journal of Speech and 
Hearing Disorders. Columbus, O. 
J. thorac. cardiovasc. Surg. Journal of 
Thoracic and Cardiovascular Sur- 
gery. St. Louis, Mo. 
/. thorac. Surg. (see J. thorac. cardi- 
ovasc. Surg.). 
J. trap. Med. Hyg. Journal of Tropi- 
cal Medicine and Hygiene. London. 
Klin. Med., Mosk. Klinicheskaya Me- 
ditsina. Moskva. 
Klin. Wschr. Klinische Wochen- 
schrift. Berlin. 
Konink. Ned. Akad. Wetenschap. 
Koninkliske Nederlandse Akademie 
van Wetenschappen. Amsterdam. 
Lab. Invest. Laboratory Investiga- 
tion. International Academy of 
Pathology. New York. 
Lancet. Lancet. London. 
Lang. Arch. klin. Chir. Langenbecks 
Archiv fiir klinische Chirurgie. 
Berlin. 
Laryngoscope, St. Louis. Laryngo- 
scope. St. Louis. 
Life Sci. Life of Science. Krakow. 
Lyon chir. Lyon Chirurgical. Lyon. 
Maroc mdd. Maroc medical. Casa- 
blanca. 
Marseille med. Marseille medical. 
Marseille. 
Med. aero. Medicine 
Paris. 
Med. Arts Sci. Medical Arts and 
Sciences. Washington. 
Medd. flyg. o. navmed. Namnd. Medi- 
delanden fran Flyg- och Navalmedi- 
canska Namnden. Stockholm. 
Med. Exp. Medicina Experimentalis. 
Basel, New York. 
Medicine, Baltimore. Medicine. Balti- 
more. 
Medizinische. (see Med. Welt, Stuttg.). 
Med. J. Aust. Medical Journal of 
Australia. Sydney. 
Med. J. Malaya. Medical Journal of 
Malaya. Singapore. 
Med. Klinik. Medizinische Klink. 
Herline, Wien. 
Med. d. Lavorc>. Medicina del lavoro. 
Milano. 
Med. Mschr., Stuttg. Medizinische 
Monatsschrift. Stuttgart. 
Med. Sci. Medical Sciences. Series 7, 
Progress in Nuclear Energy. Lon- 
don. 
Med. Serv. J., Can. Medical Services 
Journal, Canada. Ottawa. JOURNAL ABBREVIATIONS 
Med.—Rev. 
Med. Sport. Medicina sportiva. To- 
rino. 
Med. Tech. Bull. Medical Techni- 
cians Bulletin. Washington. 
Med. Welt, Stuttg. Medizinische Welt. 
Stuttgart. 
Med. World, Land. Medical World. 
London. 
Med. World Netvs. Medical World 
News. New York. 
Milit. Med. Military Medicine. Wash- 
ington. 
Milit. med. J. Military Medical Jour- 
nal (Eng. trans. of Vo.-med. Zh.) 
Washington. 
Milit. Surg. (see Milit. Med.). 
Militaerlaegen. Militaerlaegen. Kjob- 
enhavn. 
Minerva cardioangiol. Minerva car- 
dioangiologica. Torino. 
Minerva fisioter. Minerva fisiotera- 
pica. Torino. 
Minerva med., Roma. Minerva me- 
dica. Roma. 
Minn. Med. Minnesota Medicine. St. 
Paul. 
Modern Med., Minneap. Modern 
edicine. Minneapolis. 
Mschr. Unfallheilk. VersichMed. 
Monatsschrift fixr Unfallheilkunde 
und Versicherungsmedizin. Berlin- 
Wilmersdorf. 
Munch, med. Wschr. Miinchener me- 
dizinische Wochenschrift. Miin- 
chen. 
Nature, Lond. Nature. London. 
Nature, Paris. Nature. Paris. 
Naunyn-Schmiedebergs Arch. exp. 
Path. Pharmak. (see Arch. exp. 
Path. Pharmak). 
N.C. med. J. North Carolina Medical 
Journal. Winston-Salem. 
Ned. milit.-geneesk. Tijdschr. Neder- 
lands militair geneeskundig tijd- 
schrift. 
Ned. Tijdschr. Geneesk. Nederlandsch 
tijdschrift voor geneeskunde. Am- 
sterdam. 
Neurology, Minneap. Neurology. 
Minneapolis. 
Nevropat. i Psikh. Nevropatologiya 
i psikhiatriya. Moskva. 
New Engl, cardiovasc. Soc. New Eng- 
land Cardiovascular Society. 
New Engl. J. Med. New England 
Journal of Medicine. Boston. 
New Scient. New Scientist. London. 
Nisshin Igaku. (see Jap. J. med. 
Progr.). 
Nord. med. Nordisk Medicin. Stock- 
holm. 
N.Y. St. J. Med. New York State 
Journal of Medicine. New York. 
N.Z. med. J. New Zealand Medical 
Journal. Wellington. 
Occup. Psychol. Occupational Psy- 
chology. London. 
Ohio St. med. J. Ohio State Medical 
Journal. Columbus. 
Operat. Res. Operations Research So- 
ciety of America. Baltimore, Be- 
thesda. 
Pacif. Sci. Pacific Science. Honolulu. 
Panminerva med. Panminerva me- 
dica. Torina. 
Patol. Fiziol. eksp. Terap. Patologi- 
cheskaya fiziologiya i eksperimental’ 
noya terapiya. Moskva. 
Path. Biol. Pathologic et biologic. 
Paris. 
Pediatrics, Springfield. Pediatrics. 
Springfield, 111. 
Pediatriya. Pediatriya. Moskva. 
Percept. Mot. Skills. Perceptual and 
Motor Skills. Louisville. 
Pfliig. Arch. ges. Physiol. Pfliigers 
Archiv fur die gesamte Physiologic 
des Menschen und der Tiere. Bonn. 
Pharmacol. Rev. Pharmacological Re- 
views. Baltimore. 
Pharm. ir Toxic. (see Farmakol. 
Toksik.). 
Physiologist, Wash. Physiologist. 
Washington. 
Physiol. Rev. Physiological Reviews. 
Baltimore. 
Phys. Med. Biol. Physics in Medicine 
and Biology. London. 
Phys. Ther. Rev. (see Physical Ther- 
apy). New York. 
Postgrad. Med. Postgraduate Medi- 
cine. Milwaukee. 
Practitioner. Practitioner. London. 
Pr. med. Presse m&iicale. Paris. 
Probl. Virol. Problems of Virology. 
New York, London. (Eng. trans. of 
Voprosy virusologii. Moskva). 
Proc. Hawaii. Acad. Sci. Proceedings. 
Hawaiian Academy of Science. 
Honolulu. 
Proc. Mayo Clin. Proceedings of Staff 
Meetings of the Mayo Clinic. 
Rochester, Minn. 
Proc. nat. Acad. Sci., Wash. Proceed- 
ings of the National Academy of 
Sciences of the United States of 
America. Washington. 
Proc. roy. Soc. Proceedings of the 
Royal Society. London. 
Proc. R. Soc. Med. Proceedings of 
the R. Society of Medicine. London. 
Proc. Soc. exp. Biol., N. F. Proceed- 
ings of the Society for Experimental 
Biology and Medicine. New York. 
Prog. Biophys. biophys. Chem. Prog- 
ress in Biophysics and Biophysical 
Chemistry. London. 
Psychiat. et Neurol, jap. Psychiatria 
et neurologia japonica. Tokyo. 
Psychiat. Quart. Psychiatric Quart- 
erly. Albany, Utica. 
Psychiat. Res. Repts. Psychiatric Re- 
search Reports. Washington. 
Psychol. Monogr. Psychological Mon- 
ographs. Lancaster, Pa. Washing- 
ton. 
Psychol. Rev. Psychological Review. 
Lancaster, Pa. 
Psychosom. Med. Psychosomatic Med- 
icine. Washington, Philadelphia. 
Quart. J. exp. Physiol. Quarterly 
Journal of Experimental Physiol- 
ogy. London. 
Quart. J. exp. Psychol. Quarterly 
Journal of Experimental Psy- 
chology. Cambridge. 
Radiat. Res. Radiation Research. New 
York. 
Radiology. Radiology. St. Paul. 
Rass. clin-scient. 1st. biochim. ital. 
Rassegna clinico-scientifica dell ’Is- 
tituto biochimico italiano. Milano. 
Rev. Agressol. Revue d’Agressologie. 
Paris. 
Rev. Cps. Sante Armees. Revue des 
Corps de santd des armees, terre, 
mer, air. Paris. 
Rev. Cps. Sante milit. (see Rev. Cps. 
SantS Armees). 
Rev. Czech. Med. Review of Czecho- 
slovak Medicine. Prague. 
Rev. Frang. din. biol. Revue fran- 
d’etudes cliniques et biologi- 
ques. Paris. 
Rev. Laryng., Paris. Revue de laryn- 
gologie, d’otologie et de rhinologie. 
Paris. 
Rev. med. Aero, Rio de J. Revista 
m&iica de aeronAutica. Rio de 
Janeiro. 
Rev. Med. nav. (see Cps. Sante 
Armees). 
Rev. Path. comp. Revue de path- 
ologic generate et de physiologic 
clinique. Paris. Rev. Soc.—Z Vit 
JOURNAL ABBREVIATIONS 
Rev. Soc. argent. Biol. Revista de la 
Sociedad argentina de biologia. 
Buenos Aires. 
Rif. med. Riforma medica. Napoli. 
Riv. Infort. Rivista degli infortuni e 
delle malattie professionali. Roma. 
Riv. Med. aero. Rivista di medicina 
aeronautica e spaziale. Roma. 
S.A.E. J. S.A.E. Journal. Society of 
Automotive Engineers. New York. 
S. Afr. med. J. South African Medi- 
cal Journal. Cape Town. 
S.B. ost. Akad. Wiss., Wien. Sitzungs- 
berichte der Osterreichischen Aka- 
demie der Wissenschaften. Wien. 
Scand. J. din. Lab. Invest. Scandi- 
navian Journal of Clinical and 
Laboratory Investigation. Oslo. 
Schweiz, med. Wschr. Schweizerische 
medizinische Wochenschrift. Basel. 
Sci. Amer. Scientific American. New 
York. 
Science. Science. New York. 
Sci., III. Science Illustrated. 
Sci. Stud. Science Studies. 
Scot. med. J. Scottish Medical Jour- 
nal. Edinburgh, Glasgow. 
Sechenov. J. Physiol. USSR. Sechenov 
Physiological Journal of the USSR. 
New York, London. English trans. 
of Fiziol. Zh. SSSR Sechenov. 
Sem. Hop. Paris. Semaine des hopi- 
taux de Paris. Paris. 
Spectrum. Spectrum; an Oxford jour- 
nal of Science. Oxford. 
Stanf. med. Bull. Stanford Medical 
Bulletin. San Francisco, Palo Alto. 
Stud. Cercet. Fiziol. Studii si cercetari 
de fiziologie. Bucuresti. 
Surgery. Surgery. St. Louis. 
Surg. Forum. Surgical Forum. Ameri- 
can College of Surgeons. Phila- 
delphia, Chicago. 
Surg. Gynec. Obstet. Surgery, Gyne- 
cology and Obstetrics. Chicago. 
Svenska Lakartidn. Svenska Lakar- 
tidningen. Stockholm. 
Tidsskr. norske Lcegeforen. Tids- 
skrift tor den Norske laegeforening. 
Kristiana, Kjobenhavn. 
Tohoku J. exp. Med. Tohoku Jour- 
nal of Experimental Medicine. 
Sendai. 
Trans. Amer. Acad. Ophthal. Oto- 
laryng. Transactions, American 
Academy of Ophthalomology and 
Otolaryngology. St. Louis. 
Trans. Amer. neural. Ass. Transac- 
tions of the American Neurological 
Association. New York. 
Trans. Amer. Otol. Soc. Transactions 
of the American Otological Society. 
Boston. 
Trans. Amer. Soc. artif. intern. Or- 
gans. Transactions. American 
Society for Artificial Internal 
Organs. Washington. 
Trans. Ass. Amer. Phycns. Transac- 
tions of the Association of Ameri- 
can Physicians. Philadelphia. 
Trans, ophthal. Soc. U.K. Transac- 
tions of the Ophthalmological 
Society of the United Kingdom. 
London. 
Tri-St. med. J. Tri-State Medical 
Journal. Shreveport. 
Tr. Leningr. sanit.-gig. med. Inst. 
Trudy Leningradskogo sanitarno- 
gigienicheskogo meditsinskogo in- 
stituta. Leningrad. 
Trud. Inst, fiziol. I. P. Pavlova. Trudy 
Instituta fiziologii imeni I. P. Pav- 
lova. Akademiya nauk SSSR. Mosk- 
va. 
Ugeskr. Lceg. Ugeskrift for Laeger. 
Kjobenhavn. 
Univ. Mich. med. Bull. University of 
Michigan Medical Bulletin. Ann 
Arbor. 
U.S. Forces med. J. United States 
Armed Forces Medical Journal. 
Washington. 
Verb, dtsch. Ges. KreislForsch. Var- 
handlungen der Deutschen Gesell- 
schaft fiir Kreislaugfforschung. 
Dresden, Darmstadt. 
Verh. dtsch. Ges. Path. Verhandlun- 
gen der Deutschen Gesellschaft 
fiir Pathologic. Stuttgart. 
Vestn. Akad. med. Nauk., SSSR. 
Vestnik Akademii meditsinskikh 
nauk SSSR. Moskva. 
Vestn. Roentg. Radiol. Vestnik roent- 
genologii i radiologii. Leningrad, 
Moskva. 
Vestn. Otorhino.laryng., Leningr. 
Vestnik oto-rino-laringologii. Len- 
ingrad, Moskva. 
Virchows Arch. Virchows Archiv fur 
pathologische Anatomic und Phy- 
siologic und fiir klinische Medizin. 
Berlin. 
Vo.-med. Zh. (see Milit. med. J.). 
Vop. Pitan. Voprosy pitaniya. 
Wien. klin. Wschr. Wiener klinische 
Wochenschrift. Wien. 
Wien. med. Wschr. Wiener medizin- 
ische Wochenschrift. Wien. 
Wien Z. inn. Med. Wiener Zeitschrift 
fiir innere Medizin und ihre Grenz- 
gebiete. Wien. 
Wschr. Unfallheilk. Wochenschrift 
Unfallheilkunde. 
Zbl. allg. Path. Anat. Zentralblatt fiir 
allgemeine Pathologic und path- 
ologische Anatomic. Jena. 
Zbl. ArbMed. ArbSchutz. Zentral- 
blatt fur Arbeitsmedizin und Ar- 
beitsschutz. Darmstadt. 
Z. ges. inn. Med. Zeitschrift fiir die 
gesamte innere Medizin und ihre 
Grenzgebiete. Leipzig. 
Zh. Nevropat. Psikh. Korsakov, (see 
Nevropat. i Psikh.). 
Zh. Vyss. nerv. Deyat. I. P. Pavlova. 
Zhurnal vysshei deyatel’nosti nerv- 
noi imeni I. P. Pavlova. Moskva. 
Z. Hyg. InfektKr. Zeitschrift fiir 
Hygiene und Infektions-krankhei- 
ten. Leipzig, Berlin. 
Z. KreisForsch. Zeitschrift fiir Krei- 
slaufforschung. Dresden, Darmstadt. 
Z. Laryng. Rhinol. Zeitschrift fiir 
Laryngologie, Rhinologie, Otologic 
und ihre Grenzgebiete. Wurzburg. 
Z. Orthopad. Zeitschrift fiir Ortho- 
padie und ihre Grenzgebiete. Stutt- 
gart. 
Z. Tropenmed. u. Parasit. Zeitschrift 
fiir Tropenmedizin und Parasito- 
logic. Stuttgart. 
Z. Vitam.-Horm.-u. Fermentforsch. 
Zeitschrift fiir Vitamin-, Hormon- 
und Fermentforschung. Wien. Index of Authors 
Reference is given to serial numbers 
Aalderen, W. van, 2018 
Abaev, D. V.. 1563 
Abugattas, R., 595 
Ackerman, E., 95, 1472, 2235 
Adamek, S., 2322 
Adams, J. A., 1410 
Adams, J. F„ 2106 
Adams, O. S., 2701 
Adams, R. D., 2435 
Adams, T., 1344 
Adams, W. E., 198 
Ades, H. W.. 1469 
Adler, S„ 2450 
Adolph, E. F„ 540 
Adrian, F. E., 880, 902 
Adriani, J„ 2606, 2621 
Affeldt, J. E.. 62 
Agadzhanian, N. A., 1563, 
1771, 1986 
Aikawa, J. K., 1932 
Alanis, J., 354, 355 
Alano, J., 301 
Albano, G., 1698, 2023 
Albaum, H. G., 491, 748 
Albers, C., 986 
Albretsen, C. S., 1614 
Alessandri, M., 1763 
Alexander, A. L., 2560 
Alexander, J. D., 356 
Alexander, J. K., 946, 987, 
988 
Alexander, S. C., 303, 974 
Alifanov, V. N., 593, 2002 
Allen, D. W., 2262 
Allen, S. C., 1830,1831, 1902 
Allen, T. H„ 34, 277, 278 
Allison, M. J., 2107 
Altland, P. D., 446, 594, 728, 
780 
Altman, P. L., 787 
Altschul, R., 447, 1903 
Altukhov, G. V., 1986 
Alves, D. J., 2673 
Alvis, H. J., 1. 2. 788, 2206, 
2207, 2420. 2421, 2431, 
2432, 2648, 2799, 2800, 
2890, 2891, 2956. 2957 
Alzamora, V., 595 
Alzate, R., 288 
Amassian, V. E., 296 
Ambrus, J. L., 2109 
Amdur, M. O., 2547 
Amizich, A. D., 1756 
Amorim, I. de., 236 
Amyes, E. W., 352 
Anagnostou, J. L., 2877 
Andersen, D. C., 672 
Andersen, H. T., 508, 2878, 
2887, 2903, 
Andersen, K. L., 1306, 1312, 
2904 
Andersen, N., 1746 
Andersen, O. S., 35 
Anderson, E. H., 1904 
Anderson, F. S., 2488 
Anderson, L. L., 657 
Anderson, S. F., 113 
Anderson, WL, 2332 
Anderson, W. H., 874 
Anderson, W. L., 2548, 2549, 
2550, 2589, 2590 
Andreae, R. L., 910 
Andresen, D., 184 
Andrews, P. W., 880, 902 
Andrus, S. B., 691 
Ankeney, J. L., 943 
Annegers, J., 1164 
Anthony, A., 1470, 1471, 
1472, 1473 
Appaix, A., 1546 
Arborelius, M., Jr., 353, 
2422 
Arce, R., 746 
Archibald, E. R., 759, 760, 
2533 
Arden, G. B., 1411 
Arends, R. L., 947 
Arguelles, A. E., 1919 
Arias-Stella, J., 596, 597 
Arienzo, F., 2838 
Arion, M., 1419 
Armington, J. C., 2709 
Armstrong, E. D., 1077, 1163 
Amett, E. L., 1291 
Arnold, H. L., Jr., 2923. 
2924 
Arnold J E., 291, 1484 
Arnould, P., 1832, 1889 
Arsenescu, G., 1844 
Arthurs, R. G. S., 802 
Aschan, G., 521, 2003 
Aschoff, J., 2702 
Ashby, D. W., 2221 
Ashe, W. F„ 1287, 1759 
Ashton, N„ 1933 
Asmussen, E., 467, 989, 990, 
1874, 2004 
Assali, N. S., 1848 
Astaldi, G., 624 
Aston, F. R., 1615 
Astrand, I., 599 
Astrand, P. O., 598, 599, 
658, 2381 
Astrom, A., 991 
Astrup, P., 36, 141 
Asvall, J. E., 492 
Atkins, H. L„ 2171 
Atkinson, J. F., 1869 
Attar, S. M., 2108, 2184, 
2185, 2188, 2189 
Auge, G., 1711 
Augerson, W. S., 2911 
Auld, F., Jr., 2680 
Austin, L., 2925 
Averbach, E., 2696 
Aver’ianov, V. A., 254, 1564 
Averill, W., 57 
Avery, M. E., 992, 1166 
Aviado, D. M., 354, 355, 375, 
416 
Avis, F. R„ 565 
Awad, O., 37 
Ax, A. F., 2710, 2749 
Aykut, R., 699 
Ayres, S. M., 104 
Babcock, S., 1473 
Bacharach, B., 803 
Back, N., 2109 
Backer, O. G., 2801 
Bader, M. E., 843 
Bader, R. A., 843 
Badger, D. W.. 761 
Badr£, (n) 13, 2425 
Baer, D. M., 2775, 2776 
Baer, R. F.. 151 
Bagley, W. P., 1474 
Bahnson, H. T., 2030 
Bailey, R., 2290 
Baillarge, J„ 1656 
Bainton, C. R., 1052 
Baird, B., 600, 601, 703 
Baird, R. J., 2436 
Bakan, P., 1398 
Baker, B. L., 2065 
Baker, C. H., 2684, 2685 
Baker, L. E., 38 
Baker, S. P., 1875 
Bakran, I., 2437 
Balchum, O. J., 1838 
Baldes, E. J., 1245, 2922 
Baldridge, H. D„ 2551 
Balint, P„ 541 
Balke, B., 185, 255, 726, 727, 
732, 744, 749, 1154, 2914. 
2915 
Ball, J. M., 102 
Ballard, F. B„ 513 
Banchero, N., 602, 614, 619 
Bancroft, R. W., 751 1790, 
2285 
Banerjee, C. M., 130, 1873 
Banks, H. S.. 659 
Banner, A. H., 2936 
Bannett, S. M., 2488 
Bannister, R. G., 1876 
Barach, A. L., 493 
Baratz, R. A., 1125 
Barbashova, Z. I., 552 
Barbot, R., 2802 
Barbour, A., 1126 
Barclay, W. R., 2245 
Barcroft, H., 1110 
Bark, J., 305 
Barker, E. S., 1083, 1102, 
1132 
Barker, J. N., 448, 2041 
Barlow, C. F., 977 Bar—Bro 
INDEX OF AUTHORS 
Barltrop, D., 1258 
Barnard, E. E. P., 1420 
Barnes, J. M.. 2552 
Barnett, T. B., 189, 1877 
Barnum, C. P., 2718 
Barnwell, G., 81 
Barratt-Boyes, B. G., 1833, 
1834 
Barre, N., 301 
Barron, C. I., 366, 432 
Barron, D. H„ 449, 643 
Barron, E. S. G., 2042 
Barron, K. D., 557 
Barry, J. Q„ 632, 635, 636, 
637 , 704, 707 
Bartel, A. H., 653 
Bartels, H„ 445, 804 
Barth, C., 908 
Bartha&ny, L.. 237, 1729, 
1772, 1776 
Barthelemy, P. V., 250 
Bartlett, R. G., Jr., 186, 187, 
188, 728, 729, 2892, 2905, 
2978 
Bartlett, W., 677 
Barton, B., 861 
Barton, T. C., 2771 
Basnayake, V., 1110 
Bass, D. E., 206, 1259, 1315, 
1316, 2318 
Bassi, M., 494 
Bates, D. V., 190, 2248, 2249 
Bates, E. H„ 2143, 2176, 
2192, 2276 
Bates, J. H., 2521 
Battaglia F C., 449 
Battey, L. L., 925 
Battilana, G., 595 
Batts, A. A., 712 
Bauer, R„ 2066, 2069 
Baugh, B. L., 439 
Baum, G. L., 2520 
Baumberger, J. P., 106 
Baumgartner, G., 297 
Baxter, B. J., 2448 
Bayless, A. E., 1254 
Bayliss, R. I. S., 522 
Bean, J. W., 1114, 1918, 
1921. 2005, 2017, 2031, 
2032, 2057, 2062, 2063, 
2064, 2065, 2066. 2067, 
2068, 2069, 2076 
Beard, E. F., 356 
Beattie, E, J.. Jr., 902, 2643 
Beavers, W. R., 1292 
Bebb, A. H.. 2489, 2496 
Bechtel, A. A., 1878 
Bechtel, P., 39 
Beck, E. M., 1324 
Beck, R., 1848 
Beck, W., 204 
Becker, E. L., 717, 744 
Becker, N. H., 555, 556, 557, 
2043, 2044 
Becker, V., 1934 
Beckett, J. C., 2372 
Becklake, M. R.. 214 
Beckman, E. L., 1362, 2911 
Bedell, G. N., 993 
Beecher, H. K., 1089 
Beehler, C. C., 2094 
Beerel, F„ 1879 
Behar, M. G., 303 
Behnke, A. R., 3, 279, 280. 
1195, 1565, 1566, 1631, 
1637, 1699 
Behounek, F., 2327 
Behrend, R. C., 576 
Beil, R. G., 1240 
Beischer, D. E., 495, 1820, 
1826 
Belding, H. S., 1260, 1267, 
1281 
Beliaev, N. P., 1777 
Belkin, D. A., 2888 
Bell, F. C., 1341 
Bellville, J. W., 298. 994, 
995 
Benjamin, J. M., Jr., 2406 
Bennett, P. B„ 1196, 1197, 
1198, 1199, 1200. 1201, 
1202, 1203, 1204, 1205 
Bensch, K., 1166 
Benson, C. O., Jr., 256 
Benson, V. G., 2911 
Bentivoglio, L. G., 1879 
Benzinger, T. H., 1278 
Berest, N., 1686 
Berger, L., 1086 
Berger, R. L., 95, 2235 
Bergman, N. A., 40, 2642 
Bergmann, H., 1957 
Bergofsky, E. H., 357, 2261 
Beritoff, J. S., 2912 
Berlin, N. I., 625, 634, 723, 
724 
Berloco, N., 1905 
Bernardelli, E., 624 
Berne, R. M., 358 
Bemelli-Zazzera, A., 494 
Bernhard, W. F„ 2040, 2110, 
2111, 2142, 2113 
Bernstein, L., 41 
Bernstein, W., 1064 
Bernthal, T., 550, 881 
Berry, C. A., 1567, 1595, 
1596, 1616, 1657 
Berry, F„ 1478 
Berry, L. J., 1906 
Bertoin, R., 1524 
Bertrand, M., 1525 
Besse, F„ 1687, 1700 
Bevan, J. A., 1835 
Bexton, W. H., 2772, 2778 
Bhatia, B., 736 
Bickerman, H. A., 493 
Biddulph, C., 520 
Bierman, H. R., 275 
Biersteker, P. A., 339, 340 
Billings, C. E., Jr., 578, 2279 
Bilney, M. J., 2692 
Binder, T., 595 
Bing, R. J., 404, 513 
Birzis, L., 533 
Bishop, B., 251 
Bishop. J. M., 42, 359, 1859 
Bitner, J. L., 43, 2590 
Bittner, J. J., 2718 
Blachly, C. H., 2624, 2625 
Black, J. E., 360, 882 
Blackburn, H., 2311 
Blair, D. A., 883 
Blair, E., 265, 2108, 2185 
Blake, W. D., 542 
Blakemore, W. S., 44, 61, 
2411 
Blanc, P., 1547 
Blanchard, A. J., 4 
Blanchard, C. L., 1498 
Blank, M.. 948 
Blatteis, C. M., 530 
Blimet, T., 997 
Bliss, E. L., 2711 
Blount, S. G., Jr., 657 
Boba, A., 468 
Bobrov, N. I., 1293 
Boerema, I., 176, 2018, 2114. 
2115, 2116, 2117, 2118, 
2122, 2123 2124, 2133, 
2160. 2164, 2275 
Bogaard, J. M., 472 
Bogardus, G. M., 1148 
Bogatkov, P. I., 2208 
Boineau, J. P„ 2033 , 
Bokhoven, C., 2199 
Bokonjic, N., 299 
Bolt, W., 2487 
Bond, G. F., 239, 996, 1182, 
2423 
Bondurant, S., 1837, 2024 
Boniface, K. J., 884 
Bonnet, D. B., 2924 
Bonnet, J. D., 191 
Bonvallet, M., 303, 577 
Boodro, F., 1580 
Boothby, W. M., 256, 1050 
Booyens, J., 1284 
F., 2244 
Bordes, R., 1547 
Bor£us, L. O., 1605 
Borison, H. L„ 859 
Born, G. V. R., 300 
Bornmann, R. C., 2025, 2027 
Bortin, L., 924 
Borum, V. F., 2984 
Bosch. P., 1917 
Bostem, F., 309, 310, 311 
Botwin, A., 879 
Bouchard, R. H., 1491 
Bouhuys, A., 257 
Boulange, M., 1832 
Bouraa, S., 2018 
Bour, H., 997 
Bourdillon, T. D., 750 
Bouroncle, J., 595 
Bouvrain, Y.. 2213 
Bouverot, P., 1839 
Bovard, R. M., 2627 
Bowman, R. L., 2340 
Boysen, J. E., 2553 
Brackett, N. C., Jr., 953 
Bradley, A. F., 138, 139 
Bradley, R. D., 998 
Bradley, S. E., 542, 543, 897 
Bradshaw, M., 1489 
Brain, W. R., 1568 
Bramati, C., 450 
Brandenburg, H. A., 2962 
Brandfonbrener, M., 2260 
Brandi, G., 45 
Branscomb, V., 469 
Branscome, W., 1133 
Brasca, F., 2237 
Brassfield, C. F., 805 
Brauchi, J. T., 2712 
Brauer, R. W., 496 
Braunwald, E., 390, 1234 
Bray, A. P., 46 
Brazeau, P„ 1127, 1128 
Brebbia, D. R., 1294 
Brecher, G. A., 2509 
Breckenridge, B., 2236 
Brennan, B. B., 702, 777 
Breslau, R. C., 2119 
Brestkin, A. P., 258, 1701 
Brewer, H. E., 864 
Briantseva, R. G., 1617 
Brick, H., 806 
Brierley, J. B., 558 
Briggs, D. L., 2649 
Brindley, G. S., 1376 
Brinley, F. J., Jr., 320 
Briscoe, W. A., 68, 259, 264, 
1241, 2250, 2251 
Brismar, J., 47 
Broadbent, D. E., 1422, 1423, 
1503, 1504, 1505, 1506, 
1507, 1508, 1509, 2687, 
2688, 2689, 2690 
Broch, O. J., 48 INDEX OF AUTHORS 
Bro—Cob 
Brodie, D. A., 878 
Brodie, H. R„ 497 
Brodovsky, D., 999 
Brodsky, W. A., 1134 
Bromberger-Barnea, B., 460 
Bronfin, G. J., 1838 
Brooks, C. J„ 292 
Brooks, C. McC„ 2722 
Brooks, R. A., 781 
Brosemer, R. W., 1907 
Brou, W. C„ 2804 
Brouha, L., 1337 
Brouillette, J. H„ 295, 876 
Broussolle, B., 1532 
Brown, A. L., Jr.. 713, 1295 
Brown, A. M., 407, 608 
Brown, E. A., 949 
Brown, E. B„ Jr., 885, 886, 
887, 889, 907, 921, 950, 
951, 961, 1028, 1051, 1105, 
1106, 1152 
Brown, E. S., 1018, 1019, 
2607, 2608, 2609, 2641 
Brown, F. W., Ill, 1778, 
2490 
Brown, H. W„ 854 
Brown, I. W., Jr., 2012, 
2033, 2120 
Brown, J. L., 2913 
Brown, J. M., 884 
Brozek, J„ 283, 2311, 2312, 
2321 
Brubach, H. F„ 186, 1363, 
2893, 2905, 2978 
Brummelkamp, W. H., 2018, 
2114, 2115, 2121, 2122, 
2123, 2124, 2133, 2150 
Brun, C„ 1230 
Brunelle, M. F., 2313 
Bruner, H„ 705 
Brunner, J., 2200 
Bruns, P. D„ 1932, 1935 
Bruzzi, B„ 1526, 1658 
Bryan, A. C„ 152, 1879 
Biicherl, E. S., 888, 1000 
Buchtal, F., 299 
Buck, R„ 1580 
Buckley, E. P., 2664 
Buckley, J. J., 49, 889, 921, 
1051 
Buckley, J. P., 603 
Bucklitsch, W., 1569, 1979, 
2835 
Buckner, D. N., 2679, 2682, 
2683 
Budde, H., 445 
Buettner, K. J. K„ 192 
Bugard, P„ 1475 
Biihlmann, A. A„ 240, 2889 
Bull, G. M., 1126 
Bullard, R. W.. 531, 532, 
807, 808, 835, 1124, 1296 
Bulle, P. H.. 354, 355 
Bulow, K„ 2713 
Bulterijs, A. B., 2160, 2161, 
2162, 2163 
Bunce, P. L., 457 
Bunje, H. W„ 725 
Burch, B. H„ 1785, 1796 
Burch, G. E., 926 
Burchell, H. B„ 361, 1845, 
1900 
Burke, D„ 2539 
Burke, D. T„ 2026 
Burkhardt, B., 2296 
Burnell, J. M„ 1148, 1149 
Burnett, W., 2186 
Burnett, W. A„ 1206 
Burns, W„ 1460, 1516 
Burns, W. T„ 2805 
Burr, H. S., 809 
Burrows, B., 2245 
Burt, A. M„ 1908 
Burtles, R., 46 
Burton, A. C., 1261, 1297, 
1298, 1303, 1304, 1307, 
1909 
Busby, D. E.. 1215 
Buscaino, V. M., 1597, 1649 
Buskirk, E. R„ 206, 281, 
1268, 1294, 1315, 1320, 
1321, 1338, 2703 
Busnengo, E., 362, 604, 1476 
Busse, E. W., 810 
Butler, R. A., 290 
Byon, K., 499 
Byrd, R. E., 2773 
Byrne, J. S., 198 
Cabarrou, P., 2876 
Caccamise, D., 1974, 2081 
Caccuri, S., 1598 
Cadzow, W. H., 2926 
Cahn, J., 301 
Cain, S. M., 350. 689, 2382, 
2383, 2384, 2391 
Cairncross, K. D., 2925 
Caldwell, P. B., 1871 
Callaghan, P. B.. 952 
Calma, I., 302 
Cambruzzi, S., 121 
Cameron, G., 503 
Campbell, E. J. M„ 50, 127 
Campbell, F. W„ 605 
Campbell, G. S., 811 
Campbell, P. A„ 1527, 1528 
Gander, L„ 260, 2250 
Candura, F., 2237 
Canepa, A., 616 
Cannon, P., 1299 
Cappon, D., 802 
Carey, C. R., 812, 813, 862, 
863, 864, 971, 1069, 1141, 
1161, 1162, 2478, 2479, 
2890. 2891. 2901 
Carhart, H. W., 160, 2554, 
2555, 2564 
Carlsen, E., 2246, 2247 
Carlson, L. D., 1300 
Carlson, V. R., 2768 
Carlson, W., 2311 
Carlton, P. L., 1353 
Carman, C. T., 845 
Carnaghan, J. G., 2653 
Carpenter, F. G., 814, 815, 
1167, 1168, 1169, 1170, 
1171 
Carpenter, H. M.. 1164, 2556 
Carr, J. G., 2110 
Carrasquer, G., 1134 
Carrier, R. B., 2807 
Carruthers, C., 1561 
Carter, E. T., 193, 578, 626, 
627, 1262, 2220 
Carter, N. W., 1129 
Carter, R. L., 193 
Caspani, F., 1905 
Cassin, S., 498 
Castaneda, A., 1082 
Castillo, C. A., 51 
Cater, D. B., 52, 53, 54, 55, 
1958, 2125 
Cavert, H. M., 923 
Cayford, J. E., 2808 
Cedergren, B., 1936 
Celander, H., 2491 
Celander, O., 1110 
Cerchia, M. M. F„ 1570, 
1987, 2077 
Cerletti, A., 354, 355 
Chaffee, R., 1335 
Chalazonitis, N., 816 
Chalupa, B„ 2557 
Chamberlain, D. M., 1796 
Chambers, L. A., 2291 
Chambers, R. A., 572 
Chambers, R. M., 2911 
Chandler, P. J., 2107 
Channin, E., 1246 
Chapin, J. L., 677, 817, 1001, 
1002, 1153, 1155, 1880, 
2078, 2385, 2386 
Chapman, C. B., 146 
Chappell, M. N„ 828 
Charlton, G., 56 
Chase, C. T., 2328 
Chase, H. F., 323, 549, 1034, 
1842 
Chase, P. E., 303 
Chasnow, E. A., 1970 
Chassaing, H., 336 
Chaudhuri, S. N„ 1107 
Chavez, R., 616, 758 
Chen, H. C„ 1111 
Cheng, T. O., 225 
Chernjack, R. M., 999, 1003 
Chernick, V., 992 
Chevalier, R. B., 2315 
Chiantella, A. J., 2593 
Chiffelle, T. L., 1814 
Chiles, W. D., 2701 
Chilton, A. B., 1004 
Chinard, F. P., 261 
Chinn, H. I.. 491, 560, 748, 
2380 
Chiodi, H., 438, 486, 621, 
660, 661, 662 
Choral, J„ 1941 
Chossegros, H., 1529 
Christensen, E. H., 470, 
2283 
Christensson, B„ 129 
Christian, J. G., 2565, 2582. 
2591, 2592, 2594, 2628 
Christie, R. V., 1879 
Chu, G. W. T. C., 2927 
Ch’un, C., 1207 
Churchill-Davidson, I., 2126, 
2127, 2128, 2169 
Cieplinski, E. W., 57 
Cincotti, J. J., 468 
Cinquemani, N., 293 
Cinta, M., 2569 
Claff, C. L., 134 
Clamann, H. G., 1571, 1780, 
2284, 2285 
Clark, B., 2916 
Clark, F„ 2221 
Clerk, G. F„ 2008 
Clark. J. K., 1083, 1102, 
1132 
Clark, L. C., Tr„ 58, 59, 60, 
108 
Clark, L. D„ 2711 
Clark, R. C., 2640 
Clark, R. G., 2186 
Clark, R. J., 757 
Clark, R. T„ Jr., 185 , 591, 
627, 751, 2233, 2234, 2264 
Clark, W. C., 688 
Clarke, R. S. J., 1356 
Clauss, R. H„ 391 
Clemedson, C. J., 975, 976, 
2438, 2491, 2492, 2493, 
2494, 2495 
Clements, J. A., 2641 
Close, D., 1815 
Close, P., 1424, 1805, 1806 
Clowes, G. H. A., Jr., 890 
Cobb, S., 1039 Cob—D ob 
INDEX OF AUTHORS 
Cobbold, A. F., 1110 
Coblentz, A., 275 
Coburn, K. R., 1659, 2911 
Cobum, R. F., 61 
Cockett, A. T. K., 1625 
Code, C. F., 2922 
Cohen, B. H„ 1449 
Cohen, G., 201, 392 
Cohen, J. J., 953, 2051 
Cohen, M., 2756 
Cohen, M. I., 818 
Cohen, P. J., 303 
Colby, C. B„ 2809 
Colby, R., 1104 
Cole, C. R., 1796 
Cole, M. B., 128 
Cole, R. B„ 1859 
Colebatch, H. J. H., 2439, 
2507 
Colehour, J. K., 628 
Coleman, K. S., 2722 
Coleman, P. D., 1477, 1482, 
2714 
Coles, R. R. A., 1443, 1530 
Colicchio, G., 1641 
Collier, C. R„ 62, 86, 1005, 
1881 
Collings, W. D„ 228 
Collins, J. J., 2440 
Collins, K. J., 1266 
Collins, W. F„ 1176 
Colombo, G., 121 
Colquhoun, W. P., 1399 
Commoner, B., 194 
Comroe, J. H., Jr., 891, 
2246, 2247, 2320 
Conger, A. D., 1910, 1937 
Conley, J. J., 1555 
Conn, H. L., Jr., 271, 436 
Conn, J. W., 2723 
Connolly, K., 1384 
Contopoulos, A. N., 629 
Converse, J. G., 1039 
Cook, A. W., 2450 
Cook, C. D., 270 
Cook, G. A., 1172, 1173 
Cook, S. F., 601, 703, 730, 
1174, 1175, 1191, 1242, 
1243, 1248, 1253, 1256 
Cooke, R. E., 1081 
Coombs, P., 2167 
Cooper, D. Y., 196, 935, 
1006, 2006, 2007, 2036 
Cooper, E. A., 195 
Cooper, P. D., 1908 
Cooperberg, A., 1860 
Cope, C., 2129 
Coppleson, V. M., 2928 
Corcoran, P. J., 63 
Cormack, R. S., 547, 1007 
Cornell, W. P., 1235, 1236 
Cornish, E. R., Jr., 798, 864, 
1069 
Cort, W. W., 2929 
Cotes, J. E., 663, 1618, 1924 
Cothran, F. V., 2135 
Coughlin, F. R., Jr., 1081 
Coulier, L., 2951 
Coulson, C. K., 591 
Cournand, A., 68, 235, 364, 
365, 387, 388, 390, 391, 
399, 900, 1022 
Courville, C. B., 304, 559, 
2214, 2500 
Cousteau, J. Y., 2810 
Covino, B. G.. 224, 1292 
Cowley, R. A., 2108, 2184, 
2185, 2188, 2189 
Cox, J. R„ Jr., 1461 
Cox, L. M., 943 
Cozine, R. A., 2517 
Crabbe, J., 2734 
Craig, A. B„ Jr., 2387, 2388, 
2389, 2390 
Craig, F. N., 1008, 2391, 
2392 
Craig, P. H., 1317 
Craveri, A., 2237 
Crawford, D. G., 385 
Crawford, M., 2268 
Crecelius, S. B., 2596 
Creese, R., 347 
Creutzfeldt, O., 297, 305 
Criscuolo, D., 520, 591 
Crise, J. R„ 807, 808 
Crissy, W. J. E., 2650, 2663, 
2664 
Crocker, W. E„ 1702, 1703, 
1710, 1730, 2424 
Crofford, W. N., Ill, 2596, 
2620 
Crone, C„ 1230 
Cropp, G., 891 
Crosfill, J. W. L., 2508 
Crosier, J. L., 130, 131 
Cross, A. V. C., 1200, 1201 
Cross, B. A., 1112 
Cross, C. E., 366, 432 
Cross, F. S., 1244, 2038, 2039 
Cross, K. W., 1009, 1882 
Crump, C. H., 858, 2738 
Crumpton, C. W., 51 
Cruz, J., 602, 614, 619 
Csanda, E., 415 
Cullen, S. C.. 271, 1223, 
1224, 1228 
Cullumbine, H., 690 
Culver, J. F., 2094 
Culver W. E., 1301 
Cummings, E. G. 2392 
Cunningham, D. J. C., 547, 
1007, 1010, 1046, 1110, 
1876 
Cupcea, S., 2329 
Curley, F. J., 565 
Currie, J. C. M., 1130 
Curveille, J., 2686 
Cushing, I. E., 146 
Cuthbertson, E. M., 607 
Cutler, R. G., 1950 
Cuypers, Y., 1836 
Dahl, H., 48 
Dahlberg-Parron, R., 819 
Dahnke, J., 64 
Dale, T., 1660 
Dale, W. A., 1883 
Daly, M. de B„ 367, 368. 
369, 471, 1011, 1012 
Daly, W. J., 1837 
Damaschke, K., 132 
Danforth, W. H., 513 
Danhof, I. E., 197, 686, 688 
Danielson, G. K., 61 
Darin, J. C., 2134 
Darling, R. C„ 731, 1572 
Dasiuk, N. V., 1959 
David. T. A., 2330, 2356, 
2357 
Davidsen, H. G., 1230 
Davidson, J. K., 1661 
Davidson, W. M., 1704, 
2906, 2907 
Davies, W., 1764 
Davis, A. L., 1061 
Davis, D. A., 1856 
Davis, G. D., 2811 
Davis, H., 286 
Davis, H. S., 1176 
Davis, I., 2286 
Davis, J. H„ 2393 
Davis, J. M., 1020 
Davis, R. C., 1478 
Davis, R. K., 130, 131, 1873 
Davis, T. R. A., 1341 
Day, B. L., 1247 
Day, S. B., 1082 
Dawes. G. S., 300 
DeAk, P., 1662 
Deatherage, B. H., 286 
De Bersaques, J., 370 
DeBias, D. A., 706 
Deen, L„ 2164 
Deen, R. R., 2649 
Defares, J. G., 353, 472, 
1013, 1014 
Deffet, L., 2494 
DeForest, R. E., 2911 
De Groot, S. G., 1412, 1413 
Dejours, P., 372, 373, 606, 
664, 665, 1015, 1016, 1884, 
1885, 1895 
DeKock, M. A., 2439 
De la Cruz, E., 1953 
de Langen, C. D., 349 
Deleanu, M., 2329, 2331 
Delgado, J. M. R., 813 
Dell, P., 306, 577 
Delp, M„ 1632 
Dembowski, V. U., 2441 
Demeester, G., 466 
Dement, W., 2715 
Demorest, H. L., 49 
Dempsey, M. E., 65 
Dennis, C., 2450 
Denny-Brown, D., 374 
Depocas, F., 1342, 1345 
Derrick, W. S., 2610 
De Santis, G., 2216 
Deschner, E. E., 2130 
Des Granges, M., 1705 1706 
Des Marais, A., 1313 
D6vai, J., 1662 
Devilla, L., 1532 
De Vita, C., 1531 
Dewey, A. W., Jr., 1573, 
1574 
Dewey, D. L., 2131 
Diamond, J., 892 
Dick, W., 2442 
Dickens, F., 2045 
Dickinson, C. J., 1017 
Dickinson, J., 269 
Dickson, J., 2027 
Didonna, P., 1688 
Diggle, W. M., 2287 
Diji, A., 893, 894, 895 
Dil, A., 375 
Dill, D. B., 630, 732 
Dillon, W. H., 1176 
Dimants, A., 1917 
Dimmick, F. L., 1373, 1377, 
1385, 1414, 1416, 2666 
Dingledine, W. S., 930 
Di Paolo, J. A., 1960 
Di Pasquale, E. L., 376 
Disenhouse, R. B., 2505 
Dishoeck, H. A. E., van, 
1455 
Disse, M., 2225 
Dixit, P. K.. 66 
Dixon, W. J., 1283 
Dmitriev, M V., 2341 
Doane, B. K.. 2779 
Dobbins, R. F„ 5 
Dobeln, W., von, 1619 
Doberneck, R. C., 1082 
Dobkin, A. B., 889 
Dobrogorski, O. J., 2302 INDEX OF AUTHORS 
Dod—For 
Dodge, J. M., 1412, 1413 
Doebbler, G. F.( 1187 
Doerr, V., 651 
Dohan, F. C., 2558 
Doig, A. T., 2280 
Dolce, R. G., 212 
Dolk, R. W.. 113 
Doll, E., 1861 
Domenici, F., 1797 
Dominguez, A. M., 560 
Donald, D. E„ 2443 
Donald. K. W., 6, 474, 475, 
548, 1575, 1742, 2501, 
2906, 2907 
Donaldson, R. T., 578 
Donevan, R., 190 
Donnell, A. M„ Jr., 1620 
Dorff, J. E., 2769 
Doring, J., 499 
Dorman, P. J., 1131 
Domhost, A. C., 67 
Dossett, A. N., 1202, 1203 
Dougherty, J. H., 2332 
Douglas, T. A., 2143, 2192, 
2266, 2267 
Douglass, E., 802 
Dowdle, E. B„ 1087 
Downes, J. J., 1886 
Downey, V. M., 1623 
Downing, S. E., 820 
Doyle, J. T., 377 
Drabkin, D. L., 44, 82, 457 
Draper, W. B., 810, 947 
Dreisbach, R. H., 502 
Dressier, S. H„ 1838 
Dripps, R. D., 918, 935 
Drube, H. C., 245. 246, 1980 
Dublin, W. B„ 1245 
Dubois, A. B., 1972, 2394, 
2395, 2396, 2972 
Duckworth, M. W., 752 
Duff, F„ 2444, 2445 
Duff, I. F„ 25 
Duffner, G. J., 262, 1689. 
1712, 1731, 1732, 1768, 
2333, 2431, 2432, 2446, 
2611, 2651, 2812, 2813, 
2814 
Duke. H. N., 378, 379, 380. 
381 
Dumas, F., 2810 
Dunn, J. E., II, 689 
Dunn, M. S., 2282 
Dunseath, W. J. R., 631 
Durant, T. M„ 2447, 2483 
Durfee, W. K., 382 
Durlacher, S. H., 2502 
DuSault, L. A„ 2132 
Duspiva, F„ 561, 562 
Duthie, H. L., 2186 
Dutkiewicz, J. S., 2241 
Dutra, F. R., 2215 
Dutton, R. E„ Jr., 460, 992 
Dwyer, J. V., 1707, 2958, 
2959 
Dwyer, P., 2049 
Dyer, J., 612, 613 
Dzierzynski, M., 896 
Dzinovic, S., 292 
Eagan, C. J., 1302 
Earle, R. H„ 198 
Eaton, W. J., 1718 
Ebersole, J. H„ 7, 8, 9, 10, 
11 
Eberstadt, P., 334 
Ebert, M„ 1177, 1910 
Echevarria, M., 612, 613 
Eckert, C„ 2152 
Eckstein, J. W., 383 
Edholm, O. G., 221, 222, 
1297 
Edstrom, G., 2334 
Edstrom, J. E., 2095 
Edstrom, R. F. S., 563 
Edwards, A. W. T., 406 
Edwards, L. D., 603 
Edwards, M., 1303, 1304 
Edwards, M. W„ Jr., 1080 
Edwards, S., 108 
Egbert, L. D„ 935 
Egdahl, R. H., 1305 
Ehmer, R. H.. 1449, 1493 
Eichelberger, L., 420 
Eicher, M., 110 
Eiseman, B., 482, 1095, 1811, 
2448 
Eisenberg, R. M., 1100 
Eisenman, G., 1995 
Eitzman, D. D„ 1925, 1926 
Elam, J. O., 1018, 1019, 
2609, 2612, 2641, 2645 
Elbel, E. R., 1815 
Eldridge, F. L„ 526, 1020 
Elias, R. A., 2797 
Elkinton, I. R„ 1083, 1102, 
1132 
Elliott, A., 12 
Elliott, D. E„ 2187 
Ellis, J. P., 749 
Ellis, M. M., 512 
Ellison, E. H., 2134 
Eloff, S. J. P„ 2133. 2160, 
2161, 2164 
Eisner R. W„ 1300, 2397, 
2879, 2880 
Emery, E. W., 177 
Emmel, G. L., 1006, 2006, 
2007, 2036 
Empleton, B. E., 2815 
End, E„ 2134 
Endo, S., 322 
Engel, A. K., 141 
Engelmann, T. G., 2724 
Enns, T., 261 
Enson, Y., 68 
Epstein, F. H., 1093, 1133 
Epstein, R. M., 201, 897 
Erde, A., 1773 
Ericsson, U. A., 2491 
Erikson, H., 1306 
Erikson, K. T., 2756 
Erlij, D., 334 
Ernsting, J., 199, 451, 579, 
1887, 1888, 1938 
Eron, L. D., 2680 
Esmond, W. G., 2108, 2184, 
2185, 2188, 2189, 2191 
Essex, H. E., 563 
Estandia, A., 1841 
Etsten, B., 1143 
Ettre, L. S., 57 
Evans, B. M„ 1126 
Evans, H. M., 629 
Evans, J. R., 500 
Evans, M., 1364 
Evans, R., 198 
Evans, W. E„ 2134 
Everson, D., 1826 
Evrard, E., 1836 
Ewing, J. H., 856, 1073, 
2009, 2029. 2035 
Exarhos, N. D„ 2509 
Eysenck, H. J., 2652 
Eyzaguirre, C„ 384 
Fabre, H., 2398 
Fabricant, N. D., 1556 
Fabricius, J., 1230 
Failla, E., 308 
Fairchild, E. J., II, 2288 
Fairchild, H. M., 385 
Fairchild, L. M., 1937 
Falbriard, A., 1146, 1147 
Falsetti, H., 2046 
Fanestil, D. D., 2412, 2413 
Fangman, J., 443 
Farhi, L. E., 69 
Farnsworth, D„ 1378, 1379, 
1380, 1381, 1382, 1384, 
1391, 1396, 2691 
Farr, A. F., 62 
Farrar, C. B., 537 
Fati, S., 1750. 2238 
Fatt, I., 70 
Faucett, R. E., 1425 
Faulconer, A., Jr., 71, 318 
Fay, T., 348, 821 
Featherstone, R. M., 263, 
271, 272, 1178, 1194, 1225, 
1226, 1228 
Feinberg, H., 386, 898, 899 
Feiner, B. 2282 
Fekete, A., 541 
Feldman, G. L„ 2716 
Fellows, J. L., 2443 
Feltman, J. A., 435 
Felts, J. M., 1343, 1350 
Fend, V., 979 
Fenn, W. O., 427, 954, 1084, 
1190, 1208, 2049, 2052, 
2070, 2082, 2083, 2084, 
2135, 2405 
Ferguson, F. P., 631, 632, 
635, 636, 637, 652, 704, 
707, 711, 718, 719, 720 
Ferguson, J. K. W.. 2308, 
2309 
Ferguson, R. W., 925 
Fernandez, C., 287, 288, 290 
Fernandez, F. O., 650 
Fernandez, L., 769 
Fernandez-Guardiola, A., 
309, 310, 311, 333 
Ferris, B. G., Jr., 200 
Field, D. E., 2559, 2560, 
2565 
Field, J., 371, 473 
Fields, J. A., 2816 
Fierer, E., 1064 
Filley, G. F., 72, 476 
Fillios, L. C., 691 
Fimiani, R., 1641 
Fink, B. R„ 1029, 2399 
Finkelstein, B., 580 
Fischer, W. F., 2960 
Fischgold, H., 307, 312 
Fisher, S., 2750 
Fishman, A. P„ 357, 365. 
387, 388, 390, 392, 900, 
1022, 2260, 2261 
Fitzgerald, J. B., 1095, 1625, 
1811 
Fitzgerald, J. J., 2282 
Fitzgerald, R. S., 437 
Fitzmaurice, J. A., 73 
Flandrois, R.. 1015, 1016 
Flecker, H., 2930 
Fleisch, A., 1862 
Fleisher, J. H„ 2931 
Flinn, D. E., 1621 
Floris, V., 308 
Flottes, L.. 1532 
Fliickiger, E., 733 
Foden, R. H., 2503 
Foldi, M., 393 
Folk, G. E., 1263 
Fooks, G., 1414 
Forbes, S., 701 
Forchheimer, O. L., 2289 
Ford, A., 1408 For—Gre 
INDEX OF AUTHORS 
Ford, T. J., Jr., 1841 
Fordyce, W., 2749 
Fornaeus, L., 2494 
Forno, C., 89 
Forssander, C. A., 901 
Forssberg, A., 1963 
Forster, R. E., II, 44, 61, 123, 
927. 1021, 2248, 2249, 
2250, 2251, 2256, 2411 
Foster, R. J., 2653 
Fowler, W. S., 2248, 2249, 
2400, 2416 
Fox, R. H., 222, 1264 
Frada, G.. 1774 
Fraga, S., 2946 
Francheteau, M. G., 389 
Franck, C., 316, 1889 
Franke, D., 74 
Frankel, J., 1179 
Franken, F. H., 561 
Frankenhaeuser, M., 2093 
Franklin. D. L., 2879 
Franklin, W., 1249 
Frantisek, V., 2449 
Fraser, D. C., 2681 
Frassetto, R., 2908 
Frayser, R., 265 
Frederickson, E. L., 822 
Freed berg, A. S., 396 
Freeman, F. H., 954 
Freeman, G., 929 
Fregley, M. J., 226 
Frei, P. C„ 1862 
Freimuth, H. C., 2502 
Fremont-Smith, K., 1148 
French, G., 922 
French, J. D.. 1254 
French, L. A., 826 
French, N., 2252 
Frey, A. H.. 2335 
Freygang, W. H., 906 
Friedland, C. K., 904 
Friehoff, F., 75 
Fries, C. C., 2450 
Frits, T„ 2329, 2331 
Frittelli, G., 2040, 2110, 
2112, 2113 
Fritts, H. W., Jr., 235, 390, 
391, 399, 900, 1022, 1061 
Froeb, H. F.. 1023, 1890 
Froese, G., 1307, 1909 
Frohman, C. E., 2755 
Fromm, G. H., 305. 581 
Frost, J. N., 1974, 2048 
Frumin, J. J., 201 
Frumin, M. J., 40, 343, 897, 
2642, 2644 
Friind, R., 1663 
Fry, D. L., 1188 
Frye, C. W., 2643 
Frye, S. A., 1785, 1786 
Fryers, G. R., 633, 634, 723 
Fuhrman, F. A., 1308 
Fujimori, M., 2058 
Fuleihan, F. J. D., 460 
Fullington, F„ 1300 
Fumagalli, G., 459 
Funderburk, L. R., Jr., 2961 
Furlong, N. B., 1085 
Furuhashi, M., 1627 
Fuson, R. L., 2033 
Gabourel, J. D., 282 
Gadomski, S. T., 2613, 2614, 
2629, 2634 
Gage, J. C., 2287 
Gaito, J., 2522 
Galbin, B. F„ 2043 
Gallo, D. I., 1024 
Galston, A. W„ 2079 
Gambino, S. R., 76 
Gamboa, R., 602, 612. 613, 
614, 619 
Gandel’sman, A. B., 553 
Garassini, G., 2216 
Gardner, M. D., 878 
Garey. W., 2884, 2885 
Garwood, V. P., 1484 
Gastaut, H., 309, 310, 311, 
312, 313, 2876 
Gastaut, Y., 313 
Gaucher, T. A., 2539 
Gaultier, M., 2213 
Gay, E., 72 
Gaynor, A., 2294 
Geber, W. F., 507 
Gedye, J. L., 579 
Gee, J. B. L., 547, 1007 
Geiger, J. W., 507 
Gelfan, S., 314, 315 
Gelfand, R., 915, 974, 980, 
1038 
Cell, C. F., 1798, 1816, 1949 
Gellhorn, E„ 823, 824. 825, 
826 
Genkin, A. M., 501 
Geoghegan, T., 2451 
George, M., 651 
Gerard, H. B., 2774 
Gerlach, E., 502 
Gerola, A., 386, 898, 899 
Gerrard, W. A., Ill, 2314 
Gerschman, R., 1919, 1939, 
1973, 1974, 2047, 2048, 
2049, 2051. 2052, 2053, 
2070, 2071, 2074, 2080, 
2081, 2082, 2083, 2084, 
2135 
Gershberg, H., 1324 
Gershfeld, N. L., 1519 
Gershon, S., 2268 
Gerst, E. C., 523 
Gerszten, E., 2107 
Gertz, K. H., 1048, 1094 
Gervais, P., 2213 
Gewirtz, J. L., 2775, 2776 
Ghinnozzi, G. P., 642 
Gibbs, C. B., 2692 
Gibson, J. F., Jr., 787 
Gibson, Q. H., 452, 1863, 
1864, 2239. 2240 
Gibson. W., 309, 310, 311 
Giebisch, G., 1086 
Giel, C. P., 2292 
Giese, A. C., 2283, 2290 
Gieseking, C. F., 2751 
Gilbert, D. L., 1974, 2001, 
2048, 2049, 2050, 2051, 
2052, 2053, 2074, 2081, 
2082, 2083, 2084, 2135 
Gilbert, P. W., 2932, 2933 
Giles, N. H., 1940 
Gilfillan, R. S., 607 
Gill, M. B., 680 
Gill, P. K., 827 
Gillen, H. W., 1988, 2615, 
2874 
Gilman, A., 1127, 1128 
Gilmore, H. R., 1025 
Girard, F., 606, 664, 665, 
1884 
Girling, F., 230, 620 
Gisselsson, L., 289 
Gittelson, L., 2643 
Giuffrida, L., 2340 
Gjone, E., 1975 
Glaser, E. M., 1309 
Glass, A., 1204, 1205 
Glass, J., 2818 
Gleeson, J., 2856 
Gleichmann, U., 77, 78, 79, 
80 
Glorig, A., 1426 
Glover, W. E., 883 
Go, I. G., 2352 
Goan, J. C., 2616, 2617 
Goddard, D. H„ 789 
Godfrey, M„ 225 
Goff, L. G., 1363, 2815, 
2892, 2893, 2908, 2978 
Gold, A. J., 635, 636, 637, 
704 
Goldbaum, L. R., 560 
Goldberg, H. D., 828 
Goldberg, M. A., 977 
Goldberg, R. I., 1580 
Goldberg, S. B., 2561 
Goldblatt, H., 503 
Goldensohn, E. S., 810 
Golding, F. C., 1599 
Goldman, R. F., 1294, 1315, 
1316 
Goldring, R. M., 392, 2260 
Goldsmith, R., 1264 
Goldstein, A., 273 
Goldstein, M. H., Jr., 1480 
Goldwater, L. J., 2282 
Golovanova, G. P., 2336 
Goluboff, B., 924 
Gomori, G., 1548 
Gomori, P., 393, 541 
Gong, J. K., 753 
Goodale, W. T„ 505 
Goodman, M. W., 81, 1037 
Goodman, R. D., 352 
Goodnow, J. J., 2752, 2767 
Goor, H., van. 231, 1817 
Gordon, A. S., 880, 902, 
2504, 2643 
Gordy, E., 82 
Gorlin, R., 394, 395, 411, 
412, 2401 
Gosselin, R. E., 282 
Gotoh, F., 83, 109, 903 
Gott, V. L„ 504 
Gottlieb, J. S., 2755 
Gottlieb, S. F., 2085, 2136, 
2137 
Gould, R. A., 2029, 2035 
Gowdey, C. W., 1989, 2477 
Gracheva, G. S., 2336 
Gracheva, R. P., 553 
Graff-Lonnevig, V., 2093 
Graham, G. C., 595 
Gramenitskii, P. M., 254 
Gramer, L., 84 
Grandjean, E., 582 
Grandpierre, R., 316, 1779, 
1839, 1889, 1920 
Granger, D., 60 
Grant, W. C., 453 
Grap6, B., 1246 
Graveline, D. E., 1365, 2777, 
2784, 2881, 2902, 2914, 
2915, 2917, 2919 
Gray, E., Le B., 754, 2561 
Gray, F. E., 2714 
Gray, G. W., 692 
Gray, J. S„ 1026, 1054 
Gray, L. H., 1910, 2130, 
2138, 2139 
Graybiel, A., 1469, 2916 
Graziani, G., 1751 
Greaves, M. S., 968 
Green, J., 517 
Green, J. A., 693 
Green, J. H., 1017 
Green, R., 1247 
Greenbaum, L. J., Jr., 1891, 
1892, 2821 INDEX OF AUTHORS 
Gre—Hin 
Greene, D. G., 2641, 2645 
Greene, J. L., 2962 
Greenfield, A. D. M., 894, 
895, 2444, 2445 
Gregoire, F., 476 
Gregoire, R. C., 1250 
Greider, H. R., 1784 
Grenell, R. G., 317 
Gribble, M. de G.. 1650 
Griffin. J. E., 2342 
Griffin. W. O., Jr., 1082 
Griffiths, J. C., 179. 2177 
Griffiths, P., 1599 
Griffo, Z. J., 400, 479 
Grisell, J. L., 2755 
Griswold, R. L., 710 
Griswold, S. S., 2291 
Grodins, F. S., 1026, 1054 
Groff, W. A., 2222 
Grognot, P. A., 1779, 1799, 
1800, 1920, 1941 
Gronqvist, Y. K. J., 318 
Gross, E. E., Jr., 1465 
Gross, E. G., 263, 272, 1223, 
1224, 1228 
Gross, R. E., 2040,2112, 2113 
Groulard, (n) 1752 
Grover, R. F., 694 
Grunbaum, B. W., 710 
Griming, W., 2476 
Guerritore, D., 570 
Guillerm, R„ 13. 1532, 1533, 
2425 
Guitard, J., 1664 
Gunther, B., 1866 
Gustafson, A., 129 
Gustafson, P. R., 2598, 2631, 
2632 
Gutierrez, E., 613 
Gutierrez, G. G., 2108 
Guyton, A. C., 363, 385 
Guz, A., 396 
Gwozdz, B., 2241 
Gyarfas, K., 829 
Gyllensten, L., 1840, 1936, 
1942, 1943 
Haab, P. E., 85, 480, 1865 
Haagen-Smit, A. J., 2313 
Haarstad, J., 48 
Haber, F., 1780 
Habif, D. V., 897, 2190 
Hackel, D. B., 505 
Hackney, J. D., 86 
Haddy, t! B„ 2505 
Hafkenschiel, J. H., 904 
Hager, D., 420 
Hager, H., 564 
Haggerty, J., 1580 
Haglin, J. J., 2140 
Hahn, N., 956 
Hahn, W. A., 2963 
Hain, R. F., 571 
Haines, H. L., 1435, 1436, 
1437, 1438, 1439 
Haist, R. E., 1310 
Hal berg, E., 2718 
Halberg, F., 2704, 2705, 
2717, 2718, 2719, 2720 
Halbouty, M. R., 1600, 1622 
Hale, H. B., 524, 638, 714, 
715, 716, 751 
Hall, A. L., 202. 1642, 2252 
Hall, F. G.. 203, 234, 551, 
639, 666, 667, 905, 1027, 
1063, 2964 
Hall, H. T.. 178 
Hall, J. F., Jr., 1265, 1311 
Hall, P., 1037 
Hall, P. W., Ill, 397 
Hall, W. M„ 1798 
Halmagyi, D. F. J., 2506, 
2507 
Halsey, R. M„ 1383 
Halstead, B. W„ 2934 
Halstead, J. R., 560 
Hamburger, R. J., 454 
Hamby, W. B„ 2452 
Hamilton, L. H., 1125, 1314 
Hamilton, R. W., Jr., 1028 
Hamilton, W. F., 409 
Hammel, H. T., 1351. 2884, 
2885 
Hammond, W. H., 222 
Hamolsky, M. W.. 1113 
Hanks, E. C., 1029 
Hanna, C. H., 721 
Hanna, T. D., 2522 
Hannan, P. J., 2602, 2602a, 
2603, 2604 
Hanninen, P. T., 1643 
Hansen, Aa., 1576 
Hansen, A. T„ 1230, 1231 
Hansen, D. B., 906 
Hansen, J. T., 269, 607, 
1646, 1647, 1745, 1746 
Hanson, J. S., 2253 
Hara, J., 2313 
Harabedian, A., 2679, 2682, 
2683 
Harboe, M., 695 
Hardenberg, H. C., Jr., 2055 
Hardewig, A., 264 
Harley, J. H., 2282 
Harlin, R., 1966 
Harmel, M. H., 916 
Harnack, G.-A., von, 668 
Harper, H. A., 2361 
Harris, A. S., 1841 
Harris, E. D., Jr., 100 
Harris, J. D., 295. 876, 1427, 
1428, 1429, 1430, 1431. 
1432, 1433, 1434, 1435, 
1436, 1437. 1438, 1439, 
1440, 1441, 1449, 1452. 
1453, 1454, 1462, 1494, 
1495, 1496, 1497, 1517 
Harris, J. G., 1826 
Harris, J. S., 879, 934, 945 
Harris, P., 359, 391, 399 
Harris, R. H„ 2140 
Harrison, C. S., 2931 
Hart, J. S„ 1345 
Hartelius, H., 975, 976 
Harter, J. R. R., 14 
Hartl, H., 1957 
Hartman, B., 2777, 2784, 
2915, 2917, 2919 
Hartmann, H.. 656, 1775. 
1807 
Harvey, E. N., 252, 2055 
Harvey, R. B., 717, 744, 
1793, 2453 
Harveyson, K. B., 2454 
Hassam, D„ 978, 2190 
Hasse, H. M., 2441 
Hasselman, M., 2721 
Hastings, A. B., 1087 
Hastings, B. J., 1161 
Hasumura, N., 477, 487, 
1062 
Hatletveit, E., 48 
Haugaard, N., 1911, 2054 
Hauty, G. T., 2523 
Hawkins, R. D., 1310 
Hawkins, W. R., 2534 
Haxholdt, B. F., 1231 
Hayden, R., 951 
Haymaker, W., 1623, 1665 
Haynie, G. D„ 972, 1159 
Hays, R. M., 972, 1159 
Haywood, C., 1520, 2055 
Heath, C., 907 
Hebb, D. O., 2778 
Heberling, E. J., 1344 
Hecht, H. H., 407 , 608 
Hedrick, D., 2294, 2295 
Hegnauer, A. H., 1259 
Hehir, R. M., 168 
Heim, L. M., 583, 584 
Heimann, J., 518 
Heinonen, A. O., 669 
Heise, J. J., 194 
Heisey, S. R., 979 
Hekhuis, G. L., 1657 
Held, D., 979 
Helfrich, P., 2935, 2936 
Hellegers, A., 449, 643 
Heller, M. F., 1534 
Heller, M. L., 87, 1867, 
2402 
Hellinger, R., 926 
Heilman, K., 1266 
Hellon, R. F., 1275 
Hellstrom, B., 1312 
Hemingway, A., 49, 533, 
534, 1329. 1944 
Hemmingsen, E., 1868, 2884, 
2885 
Hempleman, H. V., 1599, 
1708, 1709, 1710, 1730, 
2086 
Hendley, E. D., 398 
Hennessy, T. G., 765 
Henning, G., 2185 
Henning, G. B., 2748 
Henriksen, E., 1961 
Henry, F. M., 1743 
Henschel, A., 1259 
Herbich, J., 2217 
Herman, I. H., 1903 
Herman, M., 836 
Herold, M., 301 
Heron, W., 2772, 2778, 2779 
H6roux, O., 1313, 1327, 1345 
Herring, M. E., 1633 
Herrington, L. P., 2337 
Herron. C. S., Jr., 498 
Hershgold, E. J., 734 
Hertig, B. A., 1267 
Hertz, C. H., 88, 90 
Hervey, G. R., 222 
Hess, M. E., 1911 
Hesser, C. M., 47, 241, 1209, 
1210, 2093 
Heston, W. E., 1962 
Hettinger, T., 204 
Heyman, A., 925, 1849, 2012 
Heymans, C., 830 
Heywood, P. M., 572 
Hiatt, E. P., 1956 
Hickam, J. B., 265 
Hickey, J. L., 1651 
Hickham, J. B., 1030, 1072 
Hiestand, W. A., 603, 2503 
Highman, B., 594, 780 
Hightower, N. C., Jr., 191 
Hild, R., 908 
Hildes, J. A., 1327 
Hill, A. B.. 2201 
Hill, C. G.. 1031 
Hill, J. R., 535 
Hill, W. F., 2756 
Hille, H., 908 
Hillmann, B. M., 1368, 1369, 
1382, 1384, 1400 
Himmelstein, A., 387, 388, 
399 
Hinchliffe, M. C.. 2950 
Hinchcliffe, R., 2338 
Hines, M., 1479 Hir—Kar 
INDEX OF AUTHORS 
Hirschberger, W., 564 
Hirschfeld, B. E. E., 2454 
Hirschi, W. L., 878 
Hitchcock, C. R., 2140 
Hitchcock, F. A., 193, 578, 
1781, 1785. 1786, 1787, 
1789, 1795, 1796, 1869, 
1875 
Hobbs, M. E., 2322 
Hobby. G., 2539 
Hock, R. J., 735 
Hodgkinson, M. M., 941 
Hodgson, G., 1866 
Hodr, J., 1916 
Hoeck, L. E.. 1953 
Hoffer, P. B., 437 
Hoffman, B. F., 2722 
Hoffman, C. J., 110 
Hoffman, H. S., 1514 
Hoffman, J., 2790 
Hogan, B. W„ 15 
Hogan, J. R., 878 
Hogancamp, C. E., 404 
Holaday, D. A., 2642, 2644 
Holden, H. S„ 2508 
Holderness, B. W., 2855 
Hollaender, A., 1912 
Hollander, P. B., 442 
Holling, H. E„ 89 
Hollinger, G. W., 712 
Holloway, R. J., 496 
Hollyhock, W. M., 1543, 
1601 
Holmberg, G., 319, 831, 975, 
976 
Holmdahl, M. H., 978, 2403 
Holmgren, B., 241 
Holmstrom, F. M. G., 1782 
Honda, Y., 477, 487, 1062 
Hong, S. K„ 224, 2894 
Honig, C. R., 909 
Hoogendijk, J. L., 2122, 
2123, 2124, 2150 
Hook, O., 1602, 1619, 1666 
Hooper, J. M. D., 1009 
Hopkins, A. L., 890 
Hopkins, L. T., Jr., 516 
Hopkinson, W. I., 2141, 
2144, 2157 
Hoppe, E. T„ 2156 
Horan, L. G., 910 
Hornbein, T. F., 400, 478, 
479, 670, 2880 
Horner, T. L., 2197, 2198 
Hornsey, S., 1177, 1910 
Horres, A. D., 2509 
Horsley, A. W., 383 
Horsten, G. P. M., 338 
Horton, B. D., 2019, 2020, 
2021, 2087 
Horvath, S. M., 465, 1263. 
1314, 1336 
Horwitz, O., 89, 1852 
Hosier, R. M., 2510, 2514 
Houde, R. W., 994 
House, D. G., 2496 
House, H. P„ 1426 
Houssay, H. E. J., 412 
Houston, C. S., 609, 768 
Howard, A., 1177 
Howard, R. B., 2719 
Howard-Flanders, P., 2142 
Howe, A., 892 
Howell, B. J., 224 
Howell, I. B. L., 50, 225, 
1017 
Howell, T. W., 356 
Howland, W. S., 298, 994 
Hoy, P. A., 540 
Hsieh, A. C. L., 1300 
Huber, H„ 205 
Huckabee, W., 643 
Hudson, D., 1050 
Huff, J. W., 1390 
Huff, R. L„ 765 
Hugelin, A., 306, 577 
Hughes, J. P. W., 2203 
Huiskes, J. W., 2116, 2117 
Hull, W. E.. 234, 1808 
Hultborn, K. A., 1963 
Hultgren, H. N„ 610 
Hultman, H. L., 2438, 2491 
Humm, J. H., 1077, 1163 
Hunter, D., 1577 
Hunter, J., 418, 1846 
Hiirlimann, A., 401 
Hursh, J. B., 2310 
Hurt, H. H., Jr., 460 
Hurtado, A., 616, 755, 756, 
757, 758, 773, 776, 782, 
832 
Huseby, H. W. S„ 2618 
Husfeldt, E., 1231 
Hutchinson, J. C. D., 2965 
Hutchison, J. H„ 2143, 2144 
Hutt, B. K., 1314, 1336 
Hutton, R. F., 2937 
Hyde, R. W., 927 
lampietro, P. F., 206, 1268, 
1315, 1316, 1321, 1322, 
2703 
Ibeas, D. I., 1919 
Ikezono, E., 464 
Ilk, S. G., 736 
Illingworth, C. F. W., 179, 
2145 
Ingalls, T. H„ 565 
Ingberg, B., 2966 
Ingvar, D. H.. 79, 90, 1870 
Innes, J. R. M., 783 
Intoccia, A., 1346 
Ireland, R. G., 1424. 1806 
Irving, L., 1323 
Isomaki, A. M., 1643 
Israel, J., 2644 
Italic, H„ 2819 
Itskovitz, H., 1911 
lurkov, I. A. or lu. A., 267 
Ivanov, I. I., 1521 
Ivanov, K. P., 2146 
Ivanov, P. N., 1652 
Ivy, A. C., 1603, 2504 
Ivy, H. K., 1603 
Jaaskelainen, V., 91 
Jack, D. B., 2511 
Jackson, D. M., 955 
Jackson, J. M., 2106 
Jackson, M. M., 2902 
Jacobinzer, H., 2269 
Jacobs, G. E., 1340 
Jacobs, M. B., 2282 
Jacobs, M. H., 500 
Jacobs, R. L., 1491 
Jacobson, F. H., 1317 
Jacobson, J. H., 2151 
Jacobson, S. L., 2524 
Jacox, H. W., 2171 
Jagodzinski, R. B., 2085 
James, A. D., 16, 17 
Jameson, A. G., 392 
Jamieson, D., 2034, 2056, 
2096, 2097, 2103, 2104, 
2179 
Tanney, G. M., 14, 2967, 
2968 
Jarrett, A. S., 1535, 1536 
Jay, B. E., 92 
Jenkins, B. H., 1557 
Jenkins, E. K., 1031 
Jenkins, H. M., 1401 
Jensen, D. J., 2551, 2556 
Jensen, F. G., 2426 
Jewell, H. A., 696 
Jockers, C. R., 1093 
Joels, N., 424, 833, 911, 912, 
2254 
Johansen, K„ 93, 402, 2882 
Johnson, B. B., 1088 
Johnson, E. T., 94 
Johnson, J. E., 143, 144, 
1624, 2563. 2564, 2565, 
2582, 2592, 2593, 2594 
Johnson, M. N., 1642 
Johnson, P. C., 1114, 2065, 
2067, 2068, 2069 
Johnson, T. F., 207 
Johnson, W. J., 1180 
Johnston, A. D., 1623, 1665 
Johnston, D. R., 1341 
Johnston, G. I., 64 
Johnston, H., 2317 
Johnston, R. F., 913 
Jones, G. M., 208, 209, 1537, 
2694 
Jones, H. H., 1468 
Jones, N. C. H., 1126 
Jones, R. E., 918 
Jones, R. M., 1266 
Jones, R. W., 1026, 1054 
Jongbloed, J., 1817 
Joos, H. A., 917 
Jordan, E. C., 914, 965, 966 
Jordan, J., 95, 2339 
Jordan, L. W., 1538 
Jorgensen, K., 35, 141 
Josse, J. W„ 422 
Jovy, D., 705 
Judmaier, F., 1964 
Jukes, M. G. M., 1046, 1110 
Jullien, G., 1711, 1765 
Jung, R., 297 
Jiiptner, H., 2938 
Jurtshuk, P., Jr., 1489, 1490 
Just-Viera, J. O., 2455 
Kadetz, W., 269, 1646, 1647, 
1745, 1746 
Kagarise, R. E., 96, 210, 
2562, 2566 
Kahn, D. S., 413 
Kahn, H. E., Jr., 2019, 2020, 
2021, 2087 
Kaim, J. T., 1134 
Kaine, H. D., 2723 
Kaiser, G., 1851 
Kalff, G., 455 
Kalinin, P. I., 1539 
Kalinowski, M., 896 
Kalla, R„ 1482 
Kdllay, K„ 393 
Kaiser, M. H., 1603 
Kaiser, S. C., 282 
Kamemans, F., 2018 
Kammermeier, H., 499 
Kampffmeyer, H., 403 
Kandel, E. R., 320 
Kang, B. S., 224 
Kanter, G. S., 1269, 1270, 
1271 
Kanwisher, J. W., 134 
Kao, F. F„ 916, 1032 
Kaplan, E., 2561 
Kaplan, N. O., 1967 
Kaplan, S. A., 1164 
Kappauf, W. E., 1402 
Kardesch, M., 404 
Karler, R., 97, 712, 877 
Karlson, K. E., 2450 INDEX OF AUTHORS 
Kar—Laz 
Karmen, A., 2340 
Karvonen, M. J., 669, 2321 
Kasamatsu, A., 321, 322 
Katsaros, B., 839, 956, 1047 
Katz, L. N., 386, 898, 899 
Katz, M. S., 1385 
Katzman, R., 1089 
Kaufman, B. D., 1990 
Kaufman, L. R., 19 
Kazemi, H., 1053 
Keast, R. W.. 2820, 2895 
Keatinge, W. R., 1299, 1318, 
1319, 1347, 1364 
Keator, J. E., 638 
Keegan, H. L., 2939 
Keeley, J. L., 2456 
Kehar, N. D., 1282 
Keller. A. P„ Jr., 1540 
Kelley, H. G., 2147 
Kelley, R. L., 1311 
Kellogg, R. H., 481, 607, 
681, 742, 759, 760, 761, 
1033, 1059, 1060, 1156, 
1157, 1158 
Kelsey, P. A., 1386, 1442 
Kemp, W. E„ 1646, 1647 
Kemph, J. P., 1785, 1786, 
1796, 1869 
Kennedy, T. J., 1135 
Kensler, C. J., 2316 
Kent, L. R., 834 
Kem, J. D., 1578 
Kerr, M. M., 2143, 2144 
Kerridge, D. F., 463 
Kessler, E. K., 2769 
Kettunen, K. O., 1667 
Kety, S. S., 266 
Keys, A., 283, 2312, 2321 
Khairallah, P. A., 506 
Kiang, N. Y., 1480 
Kibrick, A. C., 98 
Kidd, D. J., 1202, 1203 
Kiessling, R. J., 1211, 1212, 
1712, 1713 
Kihlman, B., 1945 
Killick, E. M., 380 
Killion, P. J., 1090, 1136 
Killos, P. J., 2931 
Kilmore, M. A., 323, 549, 
1034, 1842 
Kimeldorf, D. J., 739 
Kinde, L„ 2427 
Kindwall, E. P., 1579, 1604, 
1605 
King, A. H„ 1567 
King, B. D., 464 
King, B. T., 2654, 2655, 2656 
King, C. T. G., 957, 1091, 
1092, 1104, 1115, 1116, 
1121 
King, M., 2294, 2296 
King, R. B., 2512 
Kinney, J. A. S., 1370, 1371, 
1375, 1387, 1403 
Kinsey, J. L., 18, 2210, 2457. 
2458. 2540, 2657, 2658, 
2659, 2780 
Kipshidze, N. N., 566 
Kitzinger, C., 1278 
Kleeman, C. R., 1259 
Klein, K. E., 705 
Klein, L. J., 2012 
Klein, R. L., 405 
Kleinerman, J., 505 
Kleinfeld, M., 1644, 2292 
Kleitman, N.. 2715, 2724 
Kletschka, J., 2327 
Kline, H., 2151 
Kline. R. F., 708 
Klocke, F. J., 1851, 2404 
Kloos, K., 888, 1137 
Klopper, P. J., 2150 
Knight, C. E., 2551 
Knight, J. J., 1443, 1530 
Knight, P. T., 49 
Knott, J. R„ 1227 
Knowles, J. H., 1965, 2401, 
2405 
Knox, F. G., 2075 
Knudson, L., 1966, 2149 
Kobayashi, T., 2488 
Kobrick, J. L.; 1359 
Koch, A., 2148 
Kocot, S. L., 168 
Koeff, S. T., 99 
Koenig, E. H., 2722 
Koepchen, H. P., 1048 
Koga, E„ 322, 324 
Kohl, O. A., 1444 
Kohn, K., 2459 
Koide, Y., 1481 
Koiranskii, B. B., 2341 
Kojima, K., 175 
Kolder, H., 205, 1783, 1801, 
1802, 1803, 1809, 1810. 
1813 
Koledinov, V. I., 1668 
Kollias, J., 532, 835 
Kolmodin, G. M., 325 
Kolodina, N. S., 2341 
Koncen, R. E., 149 
Konig, A., 839 
Konig, K., 1861 
Konikoff, J. J., 211, 2541 
Konishi, T., 290 
Konno, K., 1033 
Konno, M., 1481 
Konstantinov, V. A., 326 
Kooperstein, S. L, 1645 
Koopman, B. O., 2695 
Kopelman, H., 1025 
Koranyi, E. K., 2725 
Kornblueh, I. H., 2330, 
2342, 2343, 2356, 2357, 
2365, 2366 
Korner, P. I., 406 
Kornetsky, C., 2769 
Koroxenidis, G. T., 1277 
Kottenhoff, H., 2377 
Rough, R. H., 1006, 2006, 
2007, 2029, 2035, 2036 
Kovach, A. G. B., 393 
Kovacs, G. V., 1310 
Kovalenko, E. A., 267 
Kozlov, N. V., 1138 
Kratochvil, C. H., 1691, 
2314 
Krauskopf-, J., 1477, 1482 
Kreider, M. B., 1316, 1320, 
1321. 1322, 2726 
Krementz, E. T., 1966, 2149 
Kreuzer, F., 87, 100, 101, 
102, 452, 671, 672, 673, 
2250, 2251 
Krieger, K., 674 
Kriewaldt, F. H., 651 
Krog, H., 1323 
Krog, J., 93, 402, 1306 
Kroll, J. A., 2116, 2117 
Kronberger, L., 2460 
Krone, J. G.. 702, 777 
Kroon, B., 2116, 2117 
Krueger, A. P„ 2344, 2345, 
2346, 2347, 2348, 2349, 
2350, 2351, 2352 
Kruger, P. D., 2205 
Krum, A. A., 712 
Krumholz, R. A., 2315 
Kruse, J. C., 110 
Kubicek, W. G., 507 
Kuhl, W. J., Jr., 1324 
Krzywicki, H. J., 278 
Kuhn, L. A., 2151 
Kuida, H., 407, 608 
Kullander, T., 2428 
Kunzmann, H., 456 
Kuo, P. T., 1852 
Kurland. G. S„ 396 
Kuznetsov, A. G., 1652 
Kvittingen, T. D., 2513 
Kylstra, J. A., 2193, 2194, 
2195, 2196 
Laarmann, A., 1669 
Laba, L., 1541 
Laborit, H., 1776 
Labrosse, C. J., 2436 
Labrousse, Y., 606, 664, 665. 
1015, 1884, 1885 
Ladell, W. S. S., 1272, 1273, 
1286 
Ladner, K., 2096 
LaFia, D. J., 323 
Lahiri, S., 680 
Lalli, G., 697, 762, 1804 
Lam, C. R., 2451 
Lambert, R. J. W., 2429 
Lambertsen, C. J., 196, 438, 
457, 471, 486, 621. 675. 
763, 764, 790, 791, 856, 
915, 958, 974, 980, 1006, 
1011, 1035, 1036, 1037, 
1038, 1213, 1581, 1733, 
1818, 1819, 1886, 1976, 
1977, 1990, 2006, 2007, 
2008, 2009, 2010, 2028, 
2029, 2035, 2036, 2218, 
2406, 2461, 2525, 2526, 
2821, 2963 
Lamphier, T. A., 1580 
Lamport, H., 1274 
Lanari-Zubiaur, F. J. B., 
408, 409 
Landmesser, C. M., 468, 1039 
Langdon, D. E., 1893 
Lange, R. L., 407, 608 
Lange-Andersen, K., 1306, 
1312, 1351, 2904 
Langevin, R. W., 1949 
Langley. L. L., 1117 
Lanphier, E. H., 1040, 1041, 
1181, 1214, 1215. 1714, 
1753, 2137, 2196, 2407, 
2815, 2822, 2896, 2897, 
2909, 2972 
Lansberg, M. P., 585 
Largent, E. J., 1287 
Larson, H. E., 2823 
1232, 1233 
Laties, V. G., 1325, 1348, 
2770 
Lassen, N. A., 1230, 1231, 
Laub, J., 2353 
Laughlin, H. P., 2727 
LaVeme, A. A., 836 
Lawrence, J. H., 625, 629, 
723, 724, 765 
Lawrence, K. D., 2640 
Lawrence, M., 567, 1445, 
1483, 1492, 1498 
Lawrie, J. A., 1250 
Lawson, D. D., 179, 1996, 
2174, 2175, 2266, 2267, 
2270, 2271 
Lawson, J. H., 2446 
Lawson, W. H., Jr., 927 
Lawton, A. H., 128 
Lazarow, A., 66 
Lazzaroni, A., 1515 Lea—Mar 
INDEX OF AUTHORS 
Leach, W. G.. 152, 1261, 
1298 
Leandri, M., 1711 
Leather. R. P., 2152 
LeBlanc, J. A., 1326, 1327, 
1349. 1354 
Ledingham, I. McA., 179, 
1996, 2106, 2153, 2172, 
2176, 2177, 2192, 2266, 
2267, 2276, 2278 
Lee, F. D„ 2192 
Lee, G. B., 1374, 1400 
Lee, G. de J., 2408 
Lee, R. E., 1164 
Lee, R. H., 1778, 2490 
Lee, T. S., 1309 
Lee, W. L., Jr., 1871, 1954 
Lefrancois, R., 1016 
Leftwich, C. I., 1890, 2569 
Lehan, P. H., 1854 
Lehmann, G., 2706 
Lehmann, H. E., 2725 
Lehr, D. E., 357 
Leiderman, P. H., 2788, 
2794 
Leigh, W. H., 2940, 2941 
Leighton, H. L., 2290 
Leith. E. C., 1033 
Leivestad, H., 508 
Lemaire, R., 316 
LeMessurier, D. H., 2884, 
2885 
Lemieux, G., 1146, 1147 
Lemley, J. M., 410 
Lending, M., 981 
Lenggenhager, K., 2462 
Lenhoff, H. M., 1967 
Lennox, M. A., 2219 
Lenzo, J. E., 2755 
Leon, H. A., 730, 1175, 1248 
Leonard, J. M„ 2542, 2605, 
2619 
Leong, G. F., 496 
Lerche, D„ 956, 1047 
Leriche, R., 2463 
Lesky, E., 2464 
Leusen, I. R., 466, 982, 1042 
Leve, L. H., 249 
Levine, R. R., 2316 
Levine, S., 568, 1968 
Levitin. H., 1093, 1133 
Levowitz, B., 2450 
Levy, E. Z., 2781, 2785 
Levy, J. V., 2154 
Levy, L., 271, 272, 1226 
Lewin, J., 384 
Lewis, A. M., 2020 
Lewis, B. M., 394, 395, 411, 
412 
Lewis, H, E., 1264, 1582 
Lewis, N., 1044, 1045 
Lewis, P. R., 2728, 2729 
Lewis, W. G., 1389, 1390, 
1406 
Ley, H., 2200 
Leyden, C. J., 2960, 2969 
Li, W. K., 916, 1032 
Libet, B., 2155 
Liebermann, L., 253 
Liebow, A. A., 2465, 2466, 
2479 
Liess, G., 1670 
Ligou, J. C., 966 
Lilienthal, J. L., Jr., 1043 
Liljestrand, A., 837 
Lillehei, J. P., 2220 
Lilly, J. C„ 2782, 2783 
Lim, T. P. K., 536, 1328 
Lin, T. M.. 1603 
Linaweaver, P. G., Jr., 110, 
438, 1734 
Lincoln, R. S., 2696 
Lind, A. R„ 1275 
Lindahl, L. E. H., 2378 
Lindberg, E. F., 2922 
Linde, H. W., 918, 935 
Linde, L. M., 1044, 1045 
Linder, E., 129 
Lindgren, G.. 1583, 1602 
Lindholm, A., 1050 
Link, H. J., 1491 
Linquette, Y., 2398 
Lins Filho, W., 654 
Lipinski, C. E., 828 
Lippincott, B. B., 194 
Lister, J., 952 
Littler, T. S., 1460, 1516 
Litwin, J., 375 
Livingston, R. B., 809 
Lloyd, B. B., 959, 1046 
Lloyd, D. P. C„ 327 
Lobban, M. C„ 2728, 2729 
Lochner, W., 1978, 2008 
Loeb, M., 1446 
Loeschcke, G. C., 1894 
Loeschcke, H. 838, 839, 
844, 956, 960, 983, 1047, 
1048, 1049, 1094 , 2006, 
2007, 2036 
Logan, J. A., 1715 
Logan, W. D., 2509 
Logothetopoulos, J., 1126 
Lohr, B., 1946 
Lokin, E., 2117 
Lo Monaco, T., 676 
Long, D. R., 1622 
Long, R. T. L., 1234, 1235, 
1236 
Longson, D., 1139 
Loomis, W. F., 525, 1118 
Loovas, I., 2749 
L6pez, A., 617 
Lord, G. P., 1182 
Loughead, W. M., 413 
Lovejoy, F. W., 917 
Loveland, N. T., 2753, 2754 
Loveless, M. H., 2376 
Lovell, F. W., 560, 1677 
Lovelock, F. J., 435 
Lowe, H. J„ 103 
Lowell. F. C., 1249 
Lowenberg, W. E., 2001 
Lowrance, P. B., 543 
Loyning, Y., 1351, 2272 
Lozano, R., 284, 646, 758 
Lubbers, D. W., 77, 78, 79, 
80, 1870 
Lubin, A., 2733, 2736, 2751, 
2767 
Luby, E. D., 2710, 2755 
Lucas. B. G. B„ 177, 414 
Ludwig, G. D., 44 
Luft, U. C., 256, 536, 586, 
737, 1744, 1790 
Lukas, C. A., 864, 1069 
Lukas, D. S., 104 
Lund-Iversen, L., 1463 
Lundgren, C., 2422, 2824 
Lundgren, N. P. V., 1050, 
1077, 1163 
Lundin, G., 268, 353, 1843 
Lunnon, J. B., 1266 
Luria, S. M., 1372, 1415 
Lurie, A. A., 918, 2008 
Luthardt, T., 515, 538 
Lutz, W., 2467 
Lynch, M. T., 1249 
Lyon, B., 2649 
Lyons, C., 108 
Lyons, H. A., 212, 1111 
Lyons, M. J., 2317 
Maag, C. H.. 1211, 1212 
Maartens, P. R., 2180 
MacArthur, J. D„ 961 
MacCanon, D. M., 1925, 
1926, 1927, 1928 
MacDonnell, J. A., 999 
Macfarlane, W. V., 2939 
MacFayden, D. J., 447 
MacHattie, L., 1947 
Machowicz, P. P., 929 
Macintosh, F. C., 2825 
Mack, C. L., 1073, 2009 
Mackay, D. E., 1716, 1754 
Mackay, R. S., 2970 
Mackworth, J. F., 1447 
Mackworth, N. H., 1447, 
2697 
MacQuigg, R. E., 2475 
Madarasz, I., 415 
Magalhaes, J. R., 381 
Mahoney, G. H., 2971 
Mahony, D. V., 352 
Maio, D. A., 105 
Makitalo, R., 91 
Malamed, S., 1929, 1930, 
1931 
Malette, W. G., 328, 482, 
1095, 1625, 1811 
Malhotra, M. S.. 1276, 1288, 
2468, 2469, 2470 
Maliszewski, T. F., 2318 
Malkin, V. B., 1652 
Malmdjac, J., 490, 587 
Malmo, R. B., 2730 
Malone, F. L„ 1388, 1391 
Manax, W. M., 2190 
Manfredi, F,, 792 
Manger, W. M., 978 
Manley, E. S.. Jr., 1119 
Manning, R. T., 516 
Manolescu, N., 1844 
Mansurov, A. R., 1771 
Mantegazzini, P., 1987, 1991, 
1992, 2077 
Marbach, G., 2739 
Marbarger, J. P., 107, 269, 
713, 1295, 1646, 1647, 
1745, 1746 
Marcelli, J., 2543 
Margaria, R., 962, 2918 
Margolis, G., 2107 
Marine Nationale, 1755 
Maritz, J. S., 213 
Markley, K., 722 
Markman, G. I., 1668, 1671 
Marks, R. A., 1353 
Markus, G., 106 
Marotta, S. F., 107, 1746 
Marra, V., 640 
Marriott, H. L., 2202 
Marshall, H. W., 1845 
Marshall, J. R., 2010 
Marshall, L. H., 721 
Marshall. R., 2972 
Marshall, R. J., 1277 
Marshall, W. E.. 2791 
Marshall, W. H., 320 
Marshall, W. W., 2156 
Marticorena, E., 610, 612, 
613, 614, 619 
Martin, E. J., 2308, 2309 
Martin, F. L., 1912 
Martin. H. B., 270, 2258 
Martin, N. T., 2974 
Martin, R. J., 202 
Martin, S. P., 1107 
Martin. T. L., 2354 
Martins, J. K., 2826, 2827 INDEX OF AUTHORS 
Mar—Nah 
Marx, T. I., 1872 
Mashkov, G. V., 2472 
Masland, R. L., 2471 
Masoro, E. J., 1343, 1350 
Massion, W. H., 844, 845, 
1948 
Masucci, F., 1316 
Mated, G., 47, 963 
Mather, G. W., 1329 
Mathis, P., 301 
Matthews, B., 738 
Matthews, C. M., 2030 
Matthews, J. G., 528 
Matthews, M. B., 2408 
Maudsley, R. H., 2157 
Mauney, F. M., 2012 
Maurizi, J., 2137 
Mauro, M., Jr., 1672 
Mautz, F. R„ 2514 
Maxfield, M. E., 1337 
May. R. T., 1542, 1543 
Mazzella, G., 641, 642 
Mazzone, W. F., 2423 
McAllister, R. A., 2158, 
2270, 2271 
McArdle, L., 883, 919, 920 
McArthur, K. T., 108 
McCabe, F. J., 2660 
McCallum, I. A. N., 2925 
McCallum, R. I., 1626, 1673 
McCally, M., 1365 
McCarty, G. B., 528 
McClement, J., 388 
McConnaughey, W. E., 
2527, 2528, 2595, 2596, 
2620 
McConnell, W. J., 793 
McCoy, G., 916 
McDowell, J., 1756 
McElroy, W. T., Jr., 509 
McFarland, R., 510 
McGiff, J. C., 416, 2319 
McGrath, J. J., 2679, 2682, 
2683 
McGregor, M., 214 
MvGurk, F. C. J., 2355, 
2357 
McHardy, G. J. R., 579 
Mcllroy, M. B., 526 
McKenzie, R. E., 2777, 2784, 
2915, 2917. 2919 
McKeown, T., 428, 615 
McKerrow, C. B., 215 
McLeish, H., 1879 
McNeill, R. S., 2256 
McNulty, W. P., Tr„ 2478, 
2479 
McPhail, M. F. M., 2143 
McQuarrie, D. G., 840 
Mead, J., 242, 243, 270, 1852 
Meda, E., 452 
Meduna, L. J., 841, 842 
Meehan, J. P„ 1330 
Meester, J. N., 1584 
Mefferd, R. B., Jr., 709, 715, 
716 
Mego, J. L„ 957, 1118, 1121 
Mehlman, B., 914 
Mei, S. S., 1032 
Meigs, J. W., 2203 
Meijne, N. G., 2018, 2116, 
2117, 2118, 2159, 2160, 
2161, 2162, 2163, 2164, 
2173 
Meketon, M., 1355 
Melchelke, K., 908 
Melman, E., 303 
Melville, K. I., 441 
Mendelson, J., 2788, 2794 
Mendenhall, R. M., 2293 
Meneely, G. R., 410 
Mengel, C. E„ 2019. 2020, 
2021, 2087 
Mensch, M. H., 2018 
Meredith, W., 2749 
M£rer, P„ 1656 
Merrick, A. W., 511, 512 
Merton, P. A., 2698 
Meschia, G., 449, 643 
Mestern, J., 981 
Metcalfe, J., 643 
Metz, B., 784, 881, 2721 
Meyer, A., 569 
Meyer, J. S., 83, 109, 312, 
329, 330, 331, 374, 417, 
418, 903, 964, 1846 
Mezzano, M., 459 
Miasnikov, V. A., 2472 
Michael, G., 513 
Michaelis, M., 2191 
Michel, C. C„ 766, 1032 
Michel, E. L„ 1949, 2973 
Michielsen, C. E., 110 
Michielsen, E. J., 2618 
Middleton, G. D., 2221 
Migeon, L., 1529 
Mikami, G„ 175 
Miles, G. G.. 2621, 2974 
Miles, S. C„ 20, 216, 244, 
419, 483, 794, 1216, 1217, 
1421, 1693, 1847, 2430, 
2515, 2529, 2661, 2828, 
2829, 2898, 2942 
Milic-Emili, G., 484, 1895 
Milic-Emili, J., 217 
Milledge, J., 680, 766 
Miller. A., 843 
Miller, E. F„ 1827 
Miller, F. A.. 49. 886, 887, 
889, 921. 1051 
Miller, F. S„ 514, 537 
Miller, H„ 610 
Miller, J. A., Jr., 514, 537 
Miller, R. R„ 2567, 2597, 
2622, 2623, 2630 
Miller. S. L., 1183, 1218 
Miller, W. F., 146 
Millikan, C. H., 1165 
Mills, A. W., 1331 
Mills, J. N„ 1139, 2731 
Minard, D., 1278 
Minehart, J. R„ 2330. 2356, 
2357 
Minkh, A. A., 2358, 2359, 
2360 
Minter, C. C„ 111, 112, 113 
Mirovich, N. I., 1521 
Mirsky, A. F., 2769 
Misrahy, G. A., 291, 292, 
1484 
Mitchell, J. H., 820 
Mitchell, R. A., 365, 648, 
770, 839, 844, 845, 1049, 
1052 
Mitchell, W. L„ 2883 
Mithoefer, J. C., 373, 672, 
673, 1053, 2409, 2410 
Mitnick, L. L., 2709 
Mittler, S., 2294, 2295, 2296, 
2297 
Mittman, C., 2245 
Miyagishima, R. T., 2436 
Mochizucki, M., 445 
Moeller, C. E., 1872 
Molbert, E„ 570 
Molt, R„ 2238, 2242 
Molfino, F., 180 
Molish, H. B„ 2649, 2674 
Molomut, N., 1923 
Mommaerts, W. F. H. M., 
506 
Monks, J. J., 1854 
Monrad-Krohn, G. H., 332 
Monroe, R. G., 922 
Monson, M., 1323 
Moody, J. A., 1389, 1390 
Mook, G. A., 114 
Moon, P. K., 1603 
Moore, E. J., 1117 
Moore, G. E., 1960 
Moore, N. M„ 2255 
Moore, R., 1338, 2091 
Moretti, G„ 1558, 1763, 
2473, 2474 
Morgan, T. E., Jr., 1950 
Moriarty, J. D., 846, 847 
Morimoto, M., 1481 
Morocutti, C., 308 
Morrice, J. K. W„ 848 
Morrill, S. N„ 1469 
Morris, A., 1385 
Morris, G. O., 2732, 2733 
Morris, J. A., 1848 
Morris, L. E., 1227 
Morrison, J. F., 213, 1284 
Morrow, A. G„ 1234, 1238 
Morton, J. W., 2411 
Morton, R„ 1332, 1334 
Moruzzi, G., 1993 
Moschella, L., 2943 
Moser, K. M„ 126 
Mosesson, E., 2830 
Mosher, W. A., 1184 
Moslener, C.:D., 1544, 2831, 
2832, 
Moss, W. G., 1339 
Mosterd, W. L., 2833 
Mostofi, F. K„ 1798 
Motley, H. L„ 1890, 2291, 
2568, 2569 
Mott, J. C, 300 
Moulder, P. V., 420 
Moulton, G. A., 2191 
Mudge, G. H., 542 
Muehlbaecher, C. A., 1178 
Mueldener, B., 519 
Mueller, G. C„ 1915 
MiiHer, D., 2226 
Muller, K. J., 1137 
Mullinax, F. P, Jr., 1820 
Munck, O., 1230, 1231, 1232, 
1233 
Mundie, J. R., 1484 
Mungo, A., 1545, 1674 
Munoz, J., 758 
Murawski, B. J., 2734 
Murdaugh, H. V., 2883 
Murphree, H. B., 2658 
Murphy, C. M„ Jr., 2565 
Murphy, S. D., 2288 
Murray, E. I., 2735, 2736, 
2756 
Musgrove, J. E., 2475 
Musick, J. K„ 2598, 2631, 
2632 
Musselman, N. P., 2222 
Muysers, K., 115 
Myers, C. K.. 1435, 1436, 
1437, 1438, 1439, 1440 
Naaman, Y., 523 
Nadel, J. A., 2320 
Nadig, P. W., 1939, 2071 
Naegle, S., 513 
Naeraa, N., 35 
Naess, A., 2513 
Nagaha, M., 1481 
Nagy, Z., 393, 541 
Nahas, G. G„ 218, 421, 422. 
534, 611, 914, 923, 965, 
966, 978, 984, 985, 1329, 
1970, 2190, 2399 Nai—Pol 
INDEX OF AUTHORS 
Naimark, G. M., 1184 
Naito, C., 691 
Naitoye, A., 672, 687 
Nakamura, K., 477 
Nakamura, Y., 324 
Nakano, Y., 1481 
Nall, M. L.. 21 
Naquet, R„ 309, 310, 311, 
333 
Narvaes, E., 722 
Nashimoto, I., 1627 
Nath, S„ 460 
Natsui, T., 477 
Naylor, P. F. D„ 116 
Nazarkin, V. la., 1606 
Nefedov, lu. G., 2208 
Neil, E„ 423, 424, 830, 833, 
911 
Neisler, J. J., 1600 
Neptune, E. M„ Jr., 2059, 
2060 
Nessler, C. G., Jr., 100, 101 
Nestler, F. H. M., 117, 2570 
Netsky, M. G., 2471 
Neufeld, O., 1969 
Neugebauer, W., 425, 795 
Neville, J. R., 105, 118, 119 
Newman, W., 435, 2405 
Newsom, B. D., 739 
Newton, J. L., 732 
Newton, J. M„ 1355 
Newton, N. L., 2094 
Ngai, S. H„ 343, 849, 967, 
1029 
Nicholas, D. J. D„ 1967 
Nichols, G„ Jr., 1096, 1140, 
1141, 1161, 1162, 2210, 
2901 
Nickel, J. F„ 543 
Nicoloff, D. M., 1082 
Niden, A. H„ 2245 
Nielsel, W., 120 
Nielsen, C. B., 2361 
Nielsen, M.. 467, 485, 990, 
1874, 2004 
Niessen, H. J., 2199 
Nims, R. M., 278 
Ninow, E. H., 2662 
Nixon, C. W„ 850 
Noell, W. K., 491, 586, 1828, 
1829 
Nolan. M. F., 261 
Noltenius, H., 562 
Norberg, R. E., 194 
Norins, A'. L., 1026, 1054 
Norman, J. C., 22 
Norman, J. N., 2143, 2158, 
2172, 2176, 2192, 2266, 
2267, 2276 
Normann, N., 851 
Northup, D. W., 439, 529, 
1812 
Norton, C. P., 1620 
Nottie, H. R„ 1279 
Nourrit, P., 1546 
Novack, P., 924 
Nuckolls, J. G., 2165 
Nungesser, W. C., 1333 
Nurchi, R., 308 
Nussbaum, E., 2310 
Nutt, M. E., 955 
Nuttall, J. B., 2544 
Nye, R. E., Jr., 672, 917 
Nye, S. W„ 1939, 2049, 2082, 
2083 
Obal, F„ 415 
Oberst, F. W.. 2222 
Ochs. I. L„ 1559, 1560 
Odaglia, G., 180 
Odell, J. E., 391 
Odland, L. T„ 1628 
Odom, G. L., 944 
Ogilvie, C. M„ 2411 
O’Hare, J. J., 1448, 1449 
Okada, Y„ 2362 
Oleneva, G. N., 1485 
Ollodart, R. M„ 2185 
Olsen, C. R„ 2412. 2413 
Olsen, R. W., 1841 
O’Neal, J. D„ 2243 
Oppe, T. E„ 1009, 1882 
Oppenheimer, M. J., 2447, 
2483 
O’Reilly, M. E„ 64 
Orie, N. G. M., 1821 
O’Riordan, J. L. H„ 1010 
Orma, E., 2321 
Ormond, D., 1815 
Osborne, J. S., 2322 
Osipkova, T. A., 1668, 1671 
Osterhout, S., 2165 
Otey, E. S, 458, 550, 881 
Otis, A. B„ 350, 768, 817, 
2264 
Owen, S. G„ 438, 486, 621, 
1990, 2008 
Owens, G., 973 
Pace, N., 351, 592, 607, 710, 
712, 759. 760 
Pace, W.jG., 2147 
Paeslack, V., von, 2223 
Palecek, F„ 1055 
Pallotta, R., 1750 
Palmer, W. F., 190 
Palmgren, R., 1486 
Palmieri, V. M„ 1585 
Paltarokas, J., 269 
Pando, B., 595 
Panfilov, A. S.. 1613, 1638 
Panjang, (n), 23 
Panov, A. G., 2166 
Pannacciulli, I., 459 
Paolucci, G., 1804 
Pappenheimer, J. R., 2011, 
2414 
Tapper, E. M., 897, 2190 
Paredes, D., 595 
Parker, G. W., 1766 
Parkinson, J., 174 
Parma, M., 2077 
Parmeggiani, L., 121 
Parola, M. P., 1735 
Parrack, H. O., 1464 
Parry, T. M., 810 
Parshina, E. A., 1521 
Parsons, V., 740, 1607, 1767 
Pascalov-Stoenescu, L., 1844 
Paschkis, K. E., 706 
Pashalian. S., 2650, 2663, 
2664 
Pasquier, P., 2213 
Passonneau, J. V., 194 
Patel, Y. J., 1989 
Paton, D. C., 2187 
Paton, W. D. M., 548, 1582, 
1599, 1648, 1673 
Patouillet, C., 2602a, 2603, 
2604 
Patterson, J. L., Jr., 925, 930, 
931, 1849 
Patti, M., 2875 
Patton, B. C., 952 
Patton, F. M„ 2561 
Patty, F. A., 2298 
Patz, A., 1951, 1952, 1953 
Paul, W. M.. 429 
Pauling, L„ 1185 
Payne, J. P., 852 
Payne, R. B., 1289 
Peck, A. S., 1039 
Peck, R. E., 828 
Pecora, L. J., 2238, 2834 
Pegg, J. H., 2197, 2198 
Peirano, J. H„ 2431, 2432 
Peirce, G., 89, 1852 
Pelikan, E. W., 2316 
Pell, S., 1499 
Penaloza, D„ 602, 612, 613, 
614, 619 
Penneys, R., 122 
Penrod, K. E„ 2098, 2099, 
2100, 2101 
Pepler, R. D., 219, 1280, 
2737, 2757 
Perdriel, G., 2686 
Perkins, J. F., Jr., 198, 796, 
839, 1056 
Permutt, S., 225, 460, 992, 
2258 
Perot, P. L., Jr., 1994, 2037 
Perret, C., 1896 
Perrimond-Trouchet, R., 
1586, 1729, 1747, 1776 
Pestalozza, G., 1515 
Peter, H., 2476 
Peter, J., 213, 1284 
Peters, R. M.. 189, 426, 853, 
1057, 1877 
Petersen, P. B., 2219 
Peterson, A. P. G., 1465 
Peterson, D. B., 874 
Peterson, L. H., 238 
Peterson, R. E., 220, 2720 
Petit. J. M.. 484, 1832 
Pettersson, H., 2495 
Pettie, C. R., 1450 
Petty, T., 677 
Petukhov, M. I., 527 
Pevsner, L., 1603 
Pfeifer. K., 1569, 1979, 2835 
Pfleiderer, G., 519 
Pfrommer, J. R., 1587 
Philip, R. B„ 2477 
Phillips, A. F., 52, 53 
Phillips. J. H., Jr., 926 
Phillips, L„ 2295 
Phillips, N. E., 187, 729 
Phleps, D. R., 2944 
Piatt, V. R., 2554, 2555, 
2567, 2571, 2572, 2573, 
2574 
Piazza, T. E., 468 
Picard, D., 1546 
Piccoli, P., 1608 
Pichotka, J., 515, 538, 539 
Pic6n-Reitegui, E., 284, 698, 
723 
Piersol, G. M., 2343 
Piiper, J., 85, 480, 1097, 
1865 
Pilmer, R. B„ 1956 
Pincock, A. C., 42 
Pinkerton, H. H., 181 
Pintilie, I., 1844 
Pinto, D., 2167 
Pippitt, R. G., 580 
Pirojnikoff, L., 2749 
Pitman, A. L., 2629, 2633, 
2634 
Pittinger, C. B., 263, 271, 
272, 1227, 1228, 1229 
Pitts, R. F., 1086, 1131 
Plaine, H. L., 1913 
Plane, P., 490, 587 
Platts, M. M., 968 
Plum, F.. 571, 854, 870 
Polak, A., 972. 1159 
Polanyi, M. L., 68, 168 
Poletaev, M. I., 2208 INDEX OF AUTHORS 
Pol—Saf 
Polgar, G., 123 
Pollard, D.. 200 
Pollock, G. H., 829 
Poke, J. W., 1265, 1311 
Popova, E. O., 1652 
Popovic, V., 2074 
Poppel, M. H.. 1675 
Portnov, F. G., 2363 
Porton, W. M., 1791 
Posner, J. B„ 571 
Poles, J., 855 
Poth, E. J., 124 
Potter, V. R., 773, 776 
Poulton, E. C., 1451 
Powe, W. E., 1402 
Powell, H. M., 1186 
Powell, R. C., 1045 
Power, G., 927 
Prachuabmoh, K., 2448 
Prato, Y., 769 
Pratt, A. J., 652, 711 
Pratt, A. V., 1962 
Pratt, C. H., 1403 
Prenderville, P., 2496 
Presbitero, R. H., 2836 
Preziosi, T. J., 2551 
Price, H. L., 303, 918, 928, 
935 
Price, M. L„ 918 
Price. W. E„ 2053 
Prickett, C. M., 1409 
Prime. F. J., 1058 
Prokopovich, N. B., 553 
Provins, K. A., 1332. 1334, 
1356 
Pryor, W. W., 1030, 1792 
Prystowsky, H., 643 
Pugh, L. G. C. E„ 221, 222, 
678, 679, 680, 741, 767, 
1822, 2254 
Quappe, O., 1866 
Quarrington, B., 802 
Quartley, C. E., 2041 
Quastel, J. H., 1180 
Quemada, E. V., 182 
Quinn, M., 1259 
Quinn, M. J., 2792 
Rabbie, J. M„ 2774 
Rackow, H., 40 
Rahn, H„ 85, 125, 427, 817, 
940, 1098, 1219, 1865, 
1883, 1947 , 2404, 2407, 
2415, 2894, 2899 
Raison, J. C. A., 223 
Rail, W. L., 1629 
Rakoskie, T. L., 14 
Ralli, E P„ 1324 
Rallison, M. L., 878 
Ramaswamy, S. S., 1288 
Ramlo, J. H., 1152 
Ramos, J. G., 345 
Rampal, C., 1711 
Ramsay, A. G., 544 
Ramskill, E. A., 2550, 2572, 
2573 
Randall, B. F„ 151 
Randt, C. T„ 1176 
Rankin, I., 2255, 2256, 2259 
Rapela, C. E., 929 
Rapoport, K. M., 2224, 2273 
Rashbass, C., 1220, 1609, 
1717, 1718 
Rath, C. E., 2516 
Rathe, G., 644 
Ratschow, M., 1850 
Ravin, A., 1838 
Ravina, A., 2945 
Ravina, J. H„ 2945 
Ravner, H„ 2624, 2625 
Rawlins, J. S. P., 1630 
Rawnsley, A. I., 1441, 1442, 
1452, 1453, 1454 
Ray, E., 2793 
Ray, S. N„ 1288 
Raybin, H. W., 2269 
Rayburn, C. J., 947 
Raymon, F., 2504 
Raymond, V., 1676, 1719 
Raynaud, J., 606, 665, 1015, 
1884, 1885, 1895 
Rebaudo, G., 624 
Recavarren, S., 596 
Record, R. G., 428, 615 
Rector, F. C., Jr., 1142 
Redding, J. S„ 2517, 2518, 
2519 
Reed, D. J., 681, 742, 1059, 
1060, 1158 
Reed. W. A„ 516 
Reed, W. S„ 2530 
Reeves, J. L., 781 
Refsum, H. E., 969 
Reilly, N., 1518 
Reindell, H., 1861 
Reiman, A. S., 1143 
Remensnyder, J. P., 820 
Remezov, P. I., 2166 
Remmers, J., 673 
Renfrew, S., 1996 
Rennie, D. W., 224, 2011, 
2075 
Resner, E. P., 24 
Resnik, J., 1927, 1928 
Reusse, U., 1914 
Reynafarje, B., 517, 758, 
773, 774, 775, 776, 1335 
Reynafarje, C., 625, 645, 
646, 724, 758 
Reynolds, G. E., 1893 
Reynolds, S. R. M., 429, 
2920 
Rhodes, P. G., 126 
Richards, D. W., 946, 988, 
1061 
Richards, J. B„ 1120, 1305 
Richards, V., 2154, 2167 
Richardson, B. W„ 648, 770, 
844 
Richardson, D. W., 930, 931 
Richardson, J. C., 572 
Richardson, L. D., 622, 701 
Richmond, D. R, 1814, 2499 
Richter, R. W., 1631 
Rickels, K., 856 
Rickert, F. J., 2975 
Ridley, R. W., 71 
Rieben, P. A., 366 
Riedesel, M. L., 1281 
Riedstra, J. W., 857 
Rigatto, M., 357 
Riggs, A., 647 
Riggs, D. S., 273 
Riley, M. B., 734 
Riley, R. L., 127, 225, 460, 
768, 1043, 2258 
Rinfret, A. P., 1187, 2323 
Ringler, W., 80 
Rioch, D. McK., 2665 
Riopelle, A. J., 1487 
Rising, J. D., 1632 
Riu, R., 1532 
Rivera, J. C„ 1757 
Rizzo, P., 293 
Roach, C. G., 2635 
Roback, G., 1603 
Robbins, E. F„ 107 
Robert, P., 1547 
Roberts, A., 1188 
Roberts, A. D., Jr., 1142 
Roberts, B. L., 158 
Roberts, F. E., 128 
Roberts, F. M., 2976 
Robie, R. R., 1677 
Robin, E. D., 858, 1099, 
2738 
Robinson, S., 732 
Robinson, W. T., 1675 
Rocha, G., 2946 
Roche, L., 1529 
Rochester, D. F., 264 
Rockert, H.. 2095 
Rockhold, W. T., 2503 
Rodarte, J. R., 191 
Roddie, I. C„ 360, 882, 883, 
919, 920 
Rodil, D„ 523 
Roger, A., 2876 
Rollin, L. T„ 878 
Rombola, G., 1678 
Roorbach, E., 1050 
Rods, A., 400, 426, 478. 479, 
670 
Root, W. S., 34, 453, 461, 
523 
Roote, J., 1355 
Rooth, G., 129 
Rose, N. R., 2137 
Rosenbaum, D. A., 1787, 
1795 
Rosenberg, R. S., 993 
Rosenstein, R., 859 
Ross, D. M., 1281 
Ross, J., Jr., 1851 
Ross, J. C., 2315 
Ross, M. R., 98 
Ross, R. M„ 2158 
Rossanigo, F., 430 
Rota, P., 430 
Roth, E., 2545 
Roth, L. J., 977 
Rotta, A., 595, 616, 617 
Rotthoff, F., 2487 
Rough ton, F. J. W., 452, 
1864 , 2250, 2251, 2257 
Rougier, R., 2398 
Roundy, R. W., 2635 
Rouse, W., 381 
Rowe, B., 2837 
Roxburgh, H. L., 2636 
Rdzsahegyi, I., 1548, 1662, 
1679 
Ruben, A. M., 2645 
Ruben, H. E., 2645 
Rubin, L. S., 1357 
Rubinstein, I., 2750, 2752 
Rubio, C., 595 
Rucquoi, R., 2494 
Rudin, D. O., 1995 
Rudolph, S. J., Jr., 1633 
Rudomfn, Z. P., 334 
Rudzik, J. R„ 622 
Rueckert, R. R., 1915 
Riiedi, L., 1488 
Ruff, G. E., 2781, 2785 
Ruhm, K. B., 2053 
Russek, M., 431 
Russo, E., 2838 
Ruszel, J., 1541 
Rutter, W. J., 1907 
Ryan, A. P„ 1371, 1375 
Ryan, J. M., 1030 
Sabel, B., 1111 
Sacchitelli, F., 1680 
Sacchitelli, G., 1680 
Sackler, A. M., 1489, 1490 
Sadove, M. S., 2643 
Safar, P„ 2517, 2518, 2519. 
2646, 2647 Sai—Skr 
INDEX OF AUTHORS 
Said, S. I., 130, 131, 225, 
1873 
St. John, A. D., 1872 
St. Louis. F. G., 2979 
Saito, K.. 487, 1062 
Saito, Y., 322, 324 
Salazar, H. A., 758 
Saldana, M., 597 
Saline, M.. 2520 
Saling, E., 132 
Salisbury, P. F., 366, 432 
Saltzraan, H. A., 792, 2012, 
2033 
Salzano, J., 551, 905, 1063 
Samet, P., 1064 
Sams, W. M., 2947 
Samueloff, M., 912 
Sanborn, W. R., 16, 17 
Sanchez, C., 758 
Sandberg, N. E., 1366, 1367 
Sanders, J. I., 168 
Sanders, R. J., 1236, 1237, 
1238 
Sanger, C., 2127, 2128, 2168, 
2169, 2170, 2171 
San Martin, M., 769 
Santa-Man'a, E., 595 
Santa-Maria, L. J., 1784 
Santos, G. W., 1637 
Sapov, I. A., 2102 
Sataloff, J., 1500 
Saunders, L. Z., 783 
Saunders, P. R., 2948 
Saunders, R. A., 96, 133, 
210, 2566, 2575, 2576 
Savich, A. A.. 254 
Sax, N. I., 2282, 2299 
Sayen, J. J., 1852 
Scano, A., 743, 1823, 1824, 
1825, 2546 
Scarborough, W. R., 126 
Schaefer, K. E„ 797, 798, 
812, 813, 860, 861, 862, 
863, 864, 957, 970, 971, 
996, 1065, 1066, 1067, 
1068, 1069, 1074, 1088, 
1090, 1092, 1118, 1121, 
1136, 1140, 1141, 1144, 
1145, 1160, 1161, 1162, 
1166, 1182, 2013, 2014, 
2332, 2364, 2465, 2466, 
2478, 2479, 2531. 2532, 
2577, 2890, 2891, 2900, 
2901 
Schaefer, V. H., 1491 
Schaertlin, C. E., von, 341 
Schaff, G., 2721, 2739 
Schaftner, F., 1954 
Schein, E. H., 2756 
Schenk, E. A., 822 
Schiau, S., 1844 
Schieve, J. F., 932, 933, 944 
Schilder, D. P., 1188 
Schildkraut, H. S., 1871, 
1954 
Schiller, A. A., 376, 398, 462 
Schiller, I. W., 1249 
Schilling, J. A., 717, 744, 
1793, 2453 
Schlesinger, L., 2488 
Schmidt, C. F., 354, 355, 457, 
2006, 2007, 2029, 2036 
Schmidt, E. A., 1446 
Schmidt, P. H., 1455 
Schmitz, E., 1748 
Schneck, S. A., 1634 
Schneider, M., 335 
Schneiderman, H. A., 1179 
Schock, G. J. D., 2921 
Schoemaker, G., 2161, 2162, 
2163, 2164 
Schoeniger, E. L., 2125 
Scholander, P. F., 134, 508, 
1306, 1351, 1868, 2412, 
2413, 2884, 2885 
Scholander, T„ 2740, 2741 
Scholes, N. W., 347 
Scholl, H., 519 
Scholl, J. A., 1580 
Schollmeyer, W., von, 2225 
Scholz, P., 539 
Scholz, W., 564, 573 
Schonbaum, E., 1313 
Schonthal, H., 956 
Schopp, R. T., 488, 489, 
1070 
Schreiner, B. F., 672 
Schreiner, H. R., 1189, 1250 
Schripsema, L., 2164 
Schroder, S., 36 
Schroeder, G., 1681 
Schroeder, K. R., 1026, 1054 
Schubert, W., 2480, 2481, 
2482 
Schulte, J. H., 1549, 2786 
Schulthess, G. v., 1501 
Schultz, L. P., 2933 
Schumacher, K., 618 
Schuman, B. J., 1645 
Schwartz, A., 435 
Schwartz, I., 1366, 1367, 
1372, 1373, 1386, 1395, 
1415, 2666 
Schwartz, S. I., 2119 
Schwartz, W. B.. 953, 972, 
1143, 1146, 1147, 1159 
Schwarz, B., von, 2226 
Schwarz, M. J., 1085 
Schwedenberg, T. H., 2227 
Schweitzer, A., 471, 1011, 
1012 
Schwerd, W., 135 
Scofield, H„ 1104 
Scokel, P. W., 1117 
Scott, A. C., 2176 
Scott, M. J., 367, 368, 369 
Scott, O. C. A., 1910 
Scott, T. H„ 2772, 2779 
Scribner, B. H., 1148, 1149 
Seabury, J. C., 2883 
Sealby, R. L„ 805 
Sealy, W. C., 879, 934, 945 
Seaman, W. B., 2171 
Searle, W. F., Jr., 1444, 2426, 
2960, 2968, 2977 
Sears, C. H., 86 
Sears, D. F., 1100, 1190 
Sebelien, J., 1758 
Sechzer, P. H., 935 
Seed, J. C., 994, 995 
Segar, W. E., 1081 
Segel, N., 359 
Seguin, J. J., 736 
Seldin, D. W., 1129, 1142 
Selkurt, E. E., 545, 546 
Seltzer, H. S., 2723 
Semagin, V. N., 2742 
Semple, S. J. G., 67, 915, 
998, 1038 
Sendroy, J., Jr., 2243 
Senelar, R., 1799 
Senturia, B. H., 1561 
Sergeant, R. L., 1251, 1252 
Sessa, G., 1545, 1610, 1674 
Seusing, J., 245, 246, 1588, 
1980 
Sevcik, M., 2557 
Severinghaus, J. W., 136. 
137, 138, 139, 648, 770, 
844, 845 
Sexton, M. S., 1391 
Shanes, A. M., 1519 
Shapiro, R., 1134 
Sharma, B. K., 1276 
Sharma, D. C., 1282 
Sharma, H. S., 2973 
Sharp, G. R., 179, 1996, 
2172, 2266, 2267, 2276, 
2277, 2278 
Sharp, G. W. G., 2743 
Sharpey-Schafer, E. P., 1853, 
2408 
Shaw, D. B., 2307 
Shchupakov, N. N., 1695 
Shelby, R. W., 1550 
Sheldon, T. H., 318 
Sheldon, W. F„ 1852 
Shelford, W. O., 2433 
Shenkin, H. A., 924 
Shepard, R. H., 127, 225, 
2258 
Shephard, R. J., 745, 936, 
1071, 1101, 1897 
Shepherd, J. T., 920. 1277, 
2324 
Sherwood, W., 2051 
Shields, L. V., 1935 
Shilling, C. W., 25 
Shillito, F. H., 1759 
Shimazono, Y., 324 
Shinabarger, E. W., 291, 
1484 
Shmavonian, B., 2749 
Shooter, J. R., 2791 
Shrinegesh, M. M., 1642 
Shuler, R. L., 2602a, 2603, 
2604 
Shulman, N. R., 2556 
Shurley, J. T., 2787 
Shust, V„ 1611 
Sideman, M., 746 
Siegel, A. I., 2664 
Siegel, B. V., 2155 
Siegel, S. M., 2079 
Siehoff, F., 115 
Sicker, H. O., 792, 865. 1030, 
1072 
Siesjo, B„ 79, 88, 90, 140, 
1870 
Siggaard, O., 141 
Silber, R. H., 2720 
Sillar, W., 2176 
Sillery, R. J., 1682 
Silliman, J., 657 
Silver, G. A., 866 
Silver, I. A., 52, 53, 54, 55. 
1958 
Silver, L. A., 1112 
Silverman, D., 2365, 2366 
Sime, F., 602, 614, 619 
Simeone, F. A., 890 
Simmons, D. H., 1044, 1045 
Simons, D. G., 2533 
Simonson, E., 433 
Simpson, J. H., 917 
Simpson, M. E., 629 
Sims, R. O. S„ 1551 
Singer, K„ 1860 
Singer, M. M., 648, 770 
Singer, M. T„ 2732, 2753 
Singer, R. B„ 1083, 1102, 
1132 
Sipple, J. H„ 460 
Siri, W. E„ 285, 724, 765 
Sisson, G. M„ 226 
Sivaraman, R., 1276 
Sivertson, S. E., 2416 
Skeggs, L. T., Jr., 142 
Skoglund, C. R., 325 
Skorobogatova, A. M., 2367 
Skrypin, V. A., 771 INDEX OF AUTHORS 
Sku—Tay 
Skupp, S. J., 98 
Slager, U. T., 1466, 2578 
Slark, A. S.. 2839. 2840 
Slobody, L. B.. 981 
Sloerdahl, J.. 1683 
Slonim, N. B., 1838 
Slorach, S. A., 2743 
Sluyter, M. E., 2164, 2173, 
2274, 2275 
Small, H. S., 984, 985, 1970 
Smart, R. C., 2610 
Smith, A. M., 868 
Smith, A. N., 2186 
Smith, B., 1353 
Smith, C„ 2024 
Smith, C. A.. 286 
Smith, C. W., 1854, 1918, 
1921, 2068, 2069 
Smith, D. C„ 631, 632, 652, 
704, 707,711,718,719, 720 
Smith, G., 179, 1996, 2106, 
2143, 2174, 2175, 2176, 
2177, 2192, 2266, 2267, 
2270, 2271, 2276, 2277, 
2278 
Smith, H., 485 
Smith, J. A., 867, 1412. 1413 
Smith, J. E.. 2565 
Smith, J. S„ 1142 
Smith, L. L.. 1732 
Smith, N., 1363 
Smith, P. E., Jr., 1337 
Smith, R. F., 2345. 2346, 
2347, 2348, 2349, 2350, 
2351, 2352 
Smith, R. W.. 1848 
Smith, S. H„ Jr., 170, 2626, 
2637 
Smith, S. W., 1416 
Smith, T. C.. 303, 2255, 2259 
Smith, W. D., 143, 144, 2570 
Smith, W. W., 2012, 2021. 
2033, 2087 
Smithline, C. M., 2855 
Smolichev, E. P., 649 
Smyth, M. G., 915, 1038 
Smythe, C. McC., 543 
Smythe, D. S., 1906 
Snell, A. C., Jr., 1939 
Snell, F. M., 145 
Snidal, D. P., 1003 
Snider, H. H., 262 
Snyder, H. M., 803 
Snyder, J. F., 1612, 1732, 
1768 
Snyder, R. A., 230, 1261, 
1298 
Snyder, W. E., 1872 
Sobel, H., 746 
Soderberg, U., 2744 
Soegard, H., 2211 
Soffe, A. M„ 924 
Sokoloff, B., 2339 
Sokoloff, L„ 906, 937 
Solodkov, A. S., 1684 
Solomon, L. N., 1502 
Solomon, P., 2788, 2794 
Solov’eva, L. M., 2707 
Song, S. H., 224 
Sonnenschein, R. R., 1997, 
2037 
Sorensen, H. R., 1231 
Sosin, V. V., 1635 
Sottano, E. Y., 650 
Soule, G. I., 26 
Soussen, G., 336 
South, F. E., Jr., 1191, 1242, 
1243, 1253 
Spach, M., 2033 
Spain, D. M., 1923 
Spalter, H. F., 987 
Spaulding, M., 1580 
Specht, H., 186, 188, 274, 
721, 772, 1363, 2841, 2893, 
2905, 2908, 2978 
Spector, W. S„ 2300, 2579 
Speicher, F. P., 2343 
Sperling, H. G., 1374, 1400 
Spioch, F. M., 2241 
Spitzer, J. J., 509 
Spoto, A. P., 792 
Spradley, J. F., 292 
Springer, S., 2933 
Sproule, B. J., 146 
Spurr, G. B„ 1314, 1336 
Spyropoulos, C. S., 1522 
Squires, P. C., 1389, 1390, 
1404, 1405, 1406, 2699 
Squires, R. D., 1317 
Stacher, A., 2217 
Stacy, R. W., 1004 
Stainsby, W. N., 350 
Stamm, W., 1103 
Stanfield, A., 2855 
Stanger, J. K„ 1673 
Stanimirovitch, J., 198 
Stanmeyer, W. R., 1104 
Stapleton, G. E., L912 
Stapleton, J. F., 168 
Stargel, R„ 1355 
Stark, F„ 2156 
Stark, J. E„ 2465, 2466 
Stark, J. M., 2158 
Starr, A., 64 
Statzula, F. R., 24 
Staub, N. C„ 147 
Stauffer, H. M., 2483 
Stavney, L. S., 870 
Steegman, A. T., 337 
Steggerda, F. R., 197, 686, 
688 
Steigerwald, B. J., 2368 
Stein, M., 1113 
Stein, S. N., 840, 1120, 1164, 
1255, 1994, 1997, 1998, 
1999, 2037 
Steinbacher, Th., von, 148 
Steinberg, H., 1192 
Steinberger, E., 1283 
Steinfield, W., 263, 1239 
Steinkamp, G. R., 2534 
Stembera, Z. K., 1916 
Stembridge, V. A., 1651 
Stemler, F. W., 2503 
Stennett, R. G., 2758 
Stephens, W. M., 869 
Stern, A. C„ 2580 
Stern Hanf, M., 2018 
Stevens, J., 873, 2177 
Stevenson, J. A. F., 736 
Steward, D. J., 1636 
Stewart, B. D., 938 
Stewart, W. K., 434 
Stickley, E. E„ 271, 272 
Stickney, J. C., 440, 554, 1812 
Stine, P. T., 149 
Stockinger, L., 1803 
Stoenescu, R., 1844 
Stoian, M., 1844 
Stokinger, H. E., 2288, 2293, 
2301, 2302, 2303, 2581 
Stone, D. J., 435 
Stone, N. H„ 1082 
Stone, R. W., 526 
Stonehill, R. S., 1766 
Stopps, G. J., 1337 
Storey, C. F., 2401 
Storms, J. R., 27 
Storstein, O., 1855, 1898, 
1971 
Stover, A. D„ 295, 876 
Stow, R. W., 150, 151 
Straburzynski, G., 896 
Strauss, J. S., 2949 
Stringa, C., 1905 
Stroud, M. W., Ill, 1073, 
2008, 2009, 2029, 2035 
Stroud, R. C., 227, 436, 939, 
940, 1074, 1899, 2417, 
2901 
Strydom, N. B., 213, 1284 
Stuart, D. G., 228 
Stubbs, R. A., 152 
Stunkard, H. W., 2950 
Stuntz, S. E., 798, 864, 2667 
Stupfel, M., 139 
Sturkie, P. D., 382 
Stutman, L. J., 651 
Suarez, J. R. E., 650 
Subiria, R., 595 
Suckling, E. E., 2722 
Sudduth, H. C., 2060 
Sugioka, K., 1856 
Suit, H. D., 229 
Sullivan, L. P., 2057 
Sullivan, W. J„ 1131 
Sultzer, M. R., 906 
Sunahara, F. A., 230, 620 
Sunahara, P. I., 2255 
Suntych, F., 1685 
Suntychova, M., 1685 
Surwillo, W. W., 2730 
Sussman, K. E., 652 
Sutton, C. H., 2044 
Suzuki, 2745 
Svanberg, L., 353 
Swan, H„ 938, 952 
Swan, H. E., Jr., 2502 
Swan, H. J. C„ 361, 1845, 
1900 
Swanson, A. G., 870 
Sweat, M. L., 524 
Sweeney, E. J., 1371, 1375, 
1414, 1417, 1418 
Swets, J. A., 1407 
Sybil, E. W., 1263 
Sydnor, K. I., 524 
Synkovd, J., 2557 
Szabd, G., 393 
Tabakin, B. S., 2253 
Taborelli, R. V., 1814 
Tabusse, L„ 1839, 1857 
Tagliaferro, A., 2484 
Takacs, L., 393 
Takahashi, K., 2228, 2229 
Talbot, J. H., 785 
Talley, R. C., 2245 
Tamas, A. A., 2304 
Tanaka, R., 2058 
Tang, P. C., 871 
Tank, E. S„ 2040, 2110, 
2111, 2112, 2113 
Tanner, C. W., 2206, 2207 
Tanner, G. S., 878 
Tanner, J. M., 222 
Tanner, W. P., Jr., 1407 
Tapley, N. du V., 2171 
Tappan, D. V., 773, 774, 
775, 776 
Tarlov, I. M., 314, 315 
Tasaki, I., 286 
Tatarelli, G.. 2842, 2843, 
2875 
Taube, H., 2289 
Taylor, D. W., 2015, 2016, 
2022, 2072, 2073, 2088, 
2089 
Taylor, E. W., 2558 
Taylor, G. D., 1552, 1553 
Taylor, H. J., 1221, 1704, 
1710, 2844 Tay—Web 
INDEX OF AUTHORS 
Taylor. H. L.. 281, 2311 
Taylor, J. D.. 2485 
Taylor, W. L., 1637 
Taylor, Z„ 60 
Tazaki, Y.. 109, 903 
Teichner, W. H„ 1358, 1359, 
1360 
Teillac, A., 373, 664, 665, 
1016, 1884, 1885 
Temin, H. M„ 565 
Temine, P., 2951 
Templeton, J. Y., Ill, 803 
Ten Cate, J., 338 
Teng, H. C., 1129 
Tenney, S. M., 184, 672, 
673, 687, 909. 1122, 1123, 
1150, 1151, 1193 
Teodorescu, V., 1844 
Terman, J. W., 682 
Terry, R. N„ 2452 
Terwilliger, D. E., 2135 
Terzioglu, M., 699 
Tester, A. L.. 2952 
Thaler. V. H., 2781, 2785 
Therman, P. O., 872 
Thews, G., 79, 120 
Thibault, P., 1589 
Thilenius, O. G., 437 
Thomas, F. S., 153, 154, 155, 
156, 2565, 2599, 2600, 
2601 
Thomas, J. J., Jr., 2059, 
2060 
Thomlinson, R. H., 2127, 
2128, 2169 
Thompson, A. M., 1105, 
1106 
Thompson, J. R., 2375 
Thompson, R. H., 1338 
Thomson, J. D., 1686 
Thorn, W., 518, 519 
Thorne, J. L., 608 
Thorp, C. E., 2305 
Tiisala, R., 1922 
Timiras, P. S., 583, 584, 712 
Ting, E. Y., 2894 
Todd, A. R„ 1158 
Tohe, J., 1866 
Tokuyasu, K., 275 
Tomasello, R. M., 1842 
Tomashefski, J. F., 1759, 
2234, 2279 
Tonndorf, J., 588 
Topliff, D„ 230 
Towers, A. G., 2141 
Townsend, F. M., 1677 
Townsend, J., 194 
Trapani, I. L., 653 
Trapp, W. G., 2178 
Travis, D. M., 858, 1107, 
2738 
Tredokas, L. J„ 1955 
Tredid, T. J., 2094 
Trethewie, E. R., 941, 2268 
Treumann, H. J., 2722 
Troisi, F. M., 799 
Trouillez, M., 1696 
Trowbridge, W. V., 1254 
Tsao, M. U„ 99, 157 
Tsivilashvili, A. S., 1771 
Tsukerman, B. G., 33 
Tuller, M. A„ 357 
Tureman, J. R„ 2551, 2556 
Torino, G. M„ 392, 2260, 
2261 
Turner, E. R., 2041 
Turner, J., 438, 621 
Turpin. F. H„ 158 
Tuttle, M. J„ 1031 
Tyler, D. B„ 2746 
Tyler, J. M„ 217, 1246 
Tynan, E., 1580 
Udintsev, N. A„ 501 
Ukolova, M. A., 2747 
Ukvol’berg, L. la., 2341 
Ullmann, E„ 1130 
Ullrick, W. C., 702. 777 
Ulmer, R. G., 1491 
Ulvedal, F„ 1950 
Umstead, M. E„ 159, 160, 
161, 2560, 2565, 2582 
U.S. Air Force. 1590, 2583 
U.S. Department of Health, 
Education, and Welfare, 
28 
U.S. Navy, 29, 30, 31, 162, 
163, 247. 1222, 1397, 1456, 
1591, 1725, 1726, 1727, 
1728, 1737, 1738, 1739, 
1740, 1760, 1761, 1769, 
1981, 1982, 2212, 2379, 
2434, 2497, 2498, 2535, 
3536, 2537, 2668. 2789, 
2845, 2846, 2847, 2848, 
2849, 2850, 2851, 2852, 
2853, 2910, 2953. 2980, 
2981. 2982 
U.S. NRG, 800, 1290. 1361, 
1457, 1723, 1724, 1736, 
1983, 2090, 2204, 2486, 
2584, 2585, 2586, 2587, 
2588, 2854, 2983 
Utterback, R. A., 1229 
Vacca, C., 700 
Vadnay, A., 99, 157 
Vail, E. G., 1785, 1788, 1789, 
1794, 1795 
Vakar, M. I., 1771 
Valdivia. E., 622, 701, 778, 
786 
Valdivieso, J., 284, 646 
Valentin. H„ 2487 
Valle, G. D., 2855 
Valtin, H.. 672, 1150, 1151 
Van Bergen, F. H„ 49. 889, 
921, 1051 
Van Citters, R. L„ 2879 
Van Dam, L., 134 
Van de Wouwer, P„ 2494 
Van Den Brenk, H. A. S„ 
2034, 2056, 2091, 2096, 
2097, 2103, 2104, 2179 
Vander Eecken, H. M., 2435 
Van Dyke, D. C„ 629 
Van Epps, E. F„ 1229 
Van Fossan, D. D., 520 
Van Harreveld, A., 339, 340, 
574, 575 
Van Heyningen, R. E., 1285 
Van Holten, I„ 301 
Van Liere, E. J., 439, 440, 
528, 529, 554 
Van Liew, H. D.. 164, 165, 
166, 167, 251, 1075, 1108 
VanLingen, B., 2249 
Van Middlesworth, L., 1346 
Vannitamby, M., 129 
Van Zyl, J. J. W„ 2180 
Varco, R. L„ 49, 889, 921, 
1051 
Variakojis, D., 269, 1647, 
1745 
Varma, D. R., 441 
Varnauskas, E., 2258 
Varvis, C. J„ 190 
Vasiliev, L. L„ 2369, 2370 
Vaughan, J. A., 1316 
Vaughan, P. E., 351, 592, 
759, 760, 761 
Vaughan Williams, E. W., 
942 
Vavala, D. A„ 623, 1633 
Vawter, G. F„ 713, 1295 
Veeger, W., 1821 
Vegter, J. J. M„ 1821 
Velasquez, T„ 616, 744, 747, 
758 
Venditti, G., 697 
Venrath, H„ 2487 
Verel, D„ 463 
Verhoeven, A. F. P. M., 683 
Verity, M. A„ 1835 
Vermeulen-Cranch, D. M. 
E„ 2118, 2148. 2164 
Vernon, J., 2790 
Verzir, F„ 733, 2371 
Vetter, H. H„ 2855 
Viadro, M. D.. 1613, 1638 
Viles, P. H., 943 
Villalonga, J., 654 
Villee, C. A., 1089 
Violette, F„ 1779, 1800 
Vipond, H. J., 2743 
Virtue, R. W., 938, 2058 
Visser, B. F., 1076 
Vogel, J., 32, 2465. 2466, 
2797 
Voigt. G. C., 2518, 2519 
Voino-Yasenetskii, A. V., 
2000 
Von Oettingen, W. F., 2306 
VonSchelling, H., 1392, 1393 
Von Weiss, J. F.. 873 
Wagemaker, H., 2005 
Wagemann, W., 2230 
Wagner, W. D., 2302. 2303 
Wahrenbrock, E. A., 2197, 
2198 
Wald, G., 2262 
Walder, D. N., 1599, 1626, 
1648, 1653, 1673 
Walder, P., 251 
Waldhausen, J. A., 1236 
Waldron, T. J., 2856 
Walker, F„ 1957 
Walker, I. G., 2092 
Walker, J., 2708 
Wallenius, G., 2003 
Walser, M., 1255 
Walter, W. G.. 342 
Walters. R. H., 2748, 2791, 
2792, 2793 
Waltz, A. G., 329, 330, 331, 
964 
Waltz, J. M., 873 
Wang, M., 2151 
Wang, S. C„ 343, 787, 849. 
2380 
Wangensteen, O. H., 2039 
Ward, M.. 680, 779 
Ware, P. F.. 168 
Warren, J. V., 377 
Warshaw, L. J., 1923 
Wasserman, A. J., 930, 931 
Wasserman, L. R., 765 
Watanabe, K., 2714 
Waterlow, J. C., 725 
Watkinson, D. A., 2125 
Watson, S„ 1551, 1984 
Watson, T. R„ Jr., 87, 102. 
1867, 2402 
Watson, W. J., 2061 
Watts. D. T., 1291, 2326 
Wayne, H. H„ 684, 1596 
Weale, R. A„ 1411 
Weaver, O. M., 874 
Webb, J. L„ 442 Web—Zyl 
INDEX OF AUTHORS 
Webster, A. P., 1741 
Webster, I. W., 2512 
Webster, J. C., 1502 
Wechsler, R. L., 2325 
Weeks, M. H., 2222, 2265 
Wehrkamp, R. F., 1360 
Weiner, J. S.. 1266, 1285 
Weiner, K., 655 
Weinstein, S. A., 875 
Weiss, A. K., 1339, 1352 
Weiss, B., 1325, 1348 
Weiss, H. S., 1956 
Weitzner, S. W., 218, 464, 
984, 985 
Welch, B. E., 206, 1950, 
2538 
Weller, M. A., 344 
Wells, C. E., 855 
Wells, J. G., 185, 727, 744, 
749 
Welter, A. N., 1125 
Weltraan, A. S., 1489, 1490 
Wendahl, R., 2749 
Wendel, H., 438, 486, 621, 
2008 
Wersall, J., 1936 
West, C. D„ 2711 
West, J. B., 680, 685 
West, J. R., 946, 987, 988 
West, J. W., 2488 
West, L. J., 2712 
Westerholm, B., 1605 
Westfall, T. C., 2326 
Westlake. E. K., 1058 
Wetherbe, M. B., 1814 
Wever, E. G., 567, 1492 
Wexler, D„ 2788, 2794 
Weybrew, B. B„ 2418, 2659, 
2669, 2670, 2671, 2672, 
2673, 2674, 2675, 2771, 
2795. 2796, 2797 
Whalen, W. J., 347, 443. 
1917 
Whaley, R. D„ 858, 2738 
Wharton, C. R„ 1956 
Whatley, T.. 1849 
Wheat, J., 2977 
Whedon, G. D., 1338 
Wheeler, H. O., 897 
Whelan, R. F„ 920. 2444, 
2445 
White, C. E., 232, 1458, 
1462, 1467, 1554 
White, C. S.. 801, 1050, 
1077, 1163, 1814, 2499 
White, C. T., 1408 
White, H. A.. 2258 
White, J. C., 2573, 2574, 
2638 
White. P. D., 2877 
Whitehead, R. W., 810, 947 
Whitehead, W. F., 447 
Whitehorn, W. V., 702, 777, 
2017 
Whitehouse, R. H., 222 
Whittenberger, J. L., 922, 
1078 
Widdicombe, J. G., 1079 
Wiederhielm, C., 169 
Wieland, H., 2231 
Wiener, S., 2954 
Wienke, R. E., 1377, 1394, 
1395 
Wiersma, C. A. G., 345 
Wiggers, C. J., 401 
Wilber. C. G., 2886 
Wildermuth, O., 2181 
Wilinski, F. T., 2222 
Wilkinson, R. T., 2700, 
2759, 2760, 2761, 2762, 
2763, 2764, 2765, 2766 
Wilks, S. S., 2220, 2232, 
2233, 2234, 2263, 2314 
Willard, P. W., 465 
Willcox, M. L„ 657 
Willey, C. H., 2328 
Williams, D. D., 170, 171, 
172, 173 
Williams, E. E., 957, 1092, 
1116, 1121 
Williams, E. K., 2644 
Williams, E. S.. 589 
Williams, H. L., 2733, 2736, 
2751, 2754, 2767 
Williams, K. G„ 177, 2144, 
2157 
Williams, M. M. D., 1245 
Williams, R. B„ 1164 
Williams, W. L., 1944 
Willis, M. P., 1396 
Wills, J. H., 282 
Wilson, B. D., 2496 
Wilson, G., 2857 
Wilson, G. M., 55 
Wilson, L D.. 1151 
Wilson, J. L., 99 
Wilson, J. N., 1908 
Wilson, J. S., 377 
Wilson, J. T., 1644 
Wilson, R. H., 65, 92 
Wilson, S. A. W., 2496 
Wilson, T. O., 99 
Wilson, W P., 865, 932, 933, 
944 
Wiltner, W., 393 
Wing. K. G., 294, 295, 876, 
1459 
Winkler, K., 1231 
Winsor, T., 2372 
Winzler, R. J., 37 
Wise, D. A., 1770, 2676 
Wittenberg, J. B., 276 
Wittenborn, A. F., 1762 
Witzleb, E. W., 444, 445, 
804 
Wohlzogen. F. X., 1813 
Woldring, S., 973 
Wolf, C. E., 523 
Wolf, R., 60 
Wolff, H. S., 222 
Wollman, H„ 303, 980, 1037 
Womack, G. J., 1621 1858 
Wong, H. Y. C., 207 
Wood, E. H„ 361, 1833, 
1834, 1845, 1900, 2922 
Wood, J. A., 946, 988 
Wood, J. D., 2061 
Wood, W. B., 248, 249, 1713 
Woodbury, D. M.. 97, 877, 
878 
Woodbury, R. A., 1119 
Woodhead, M. M„ 1510, 
1511, 1512, 1513 
Wool, G. N.. 462 
Woolley, D. E., 590 
Woolmer, R. F., 174 
Worden, J. L„ 2373, 2374, 
2375 
Work. G. W., 2639 
Workman, R. D., 249, 1409, 
1720, 1721, 1722, 2423 
Worth, G., 115 
Worth, W. S., 278 
Wortmann, H., 1639 
Wright, G. W., 72, 469, 476 
Wright, H. C.. 2469, 2470 
Wright, J., 2880 
Wright, P. G., 2303 
Wright, R. A., 1956 
Wulf, R. J., 1194 
Wiinsche, O., 233, 656, 
1592, 1654, 1749 
Wyndham, C. H., 213, 1340 
Yaffe, C. D., 1468 
Yagi, S., 175 
Yaglou, C. P., 2984 
Yamaki, T., 2151 
Yamamoto, W. S., 1080 
Yantis, P. A., 1445 
Yarbrough. O. D., 2858 
Yeager, G. H., 2455 
Yevich, P. P., 2222 
Yoffee, H. F.. 910 
Yoshida, M., 1481 
Yoshikawa, Y., 1481 
Yoshimoto, C„ 41, 460 
Yost, D. H., 1491 
Young, A. B., 1686 
Young, D. R„ 1243, 1256 
Young, I. M., 67, 1110 
Young, J. A., 2640 
Young, J. E., 2815 
Young, W. A., 2307 
Young, W. G., Jr., 879, 934, 
945 
Youniss, R. P., 2418, 2675, 
2677, 2678 
Yu, P. N. G., 917 
Zaccone, G., 2484 
Zagorskii, IU. M., 2105 
Zakhary, R., 514 
Zakopoulos, K. S., 2877 
Zanchetti, A., 346 
Zangheri, E. O., 650 
Zapata, C., 595 
Zarnstorff, W. C., 51 
Zechman, F., Jr., 234, 905, 
2964 
Zhironkin, A. G-, 258, 1701 
Ziatiushkov, A. I., 33 
Zijlstra, W. G., 114 
Zilov, G. N., 1901 
Zinn, D. J., 2955 
Zinzzer, H. F., 1852 
ZoBell, C. E., 1523 
Zocche, G. P., 235 
Zorn, O., 2205 
Ziilch, K. J.. 576 
Zylberberg, B., 2376 INDEX OF SUBJECTS 
Reference is given to page numbers 
Acclimatization to hypoxia, 49, 73 
ACTH, effect on hypoxia tolerance, 
71 
Adrenal cortex, effects of carbon di- 
oxide on, 106, 107 
Adrenal hyperplasia in noise, 143 
Adrenalectomy, protection in oxygen 
poisoning, 192 
Adrenalin, effect on oxygen toxicity, 
209 
Age, effect on erythropoietic activity, 
58, 73 
Air ions, 231 
Airway calibre, effect of carbon di- 
oxide, 98 
Airway resistance, effect on lung dam- 
age following explosive decom- 
pression, 182 
Alcohol, effect on cold survival, 137 
Allowable oxygen at depth, formula 
for, 166 
Altitude acclimatization, effect on tol- 
erance to carbon monoxide, 224 
Ammonia levels in hypoxia, 41 
Anoxemia in the presence of high 
alveolar P02, 213 
Aseptic bone necrosis, 153, 159 
Atelectasis following oxygen breath- 
ing, 212 
Atelectasis from explosive decompres- 
sion, 181 
ATP levels in hypoxia, 42 
Auditory problems, 141 
Aviators’ dysbarism, treatment of, 170 
Blood brain barrier, effect of carbon 
dioxide on, 94 
Blood flow during breath holding, 236 
Blood flow in hypoxia, 21 
Blood volume in hypoxia, 61 
BMR in hypoxia, 65 
Bowel viability, effect of helium, 120, 
205 
Bradycardia in oxygen breathing, 184, 
201 
Bradycardia of diving mammals, 20, 
236, 274 
Breath holding, 234 
Breath holding, effect of nitrogen, 117 
Breathing patterns in divers, 39 
Breathing resistance, effect on carbon 
dioxide retention, 97 
Breathing resistance, effect on oxygen 
consumption, 276 
Bronchial tone, oxygen effects, 189 
Bubble formation, physiology of, 11 
Burn treatment with negative air 
ions, 232 
Carbogen, use following carbon mon- 
oxide poisoning, 225 
Carbon dioxide absorption, 254 
Carbon dioxide breathing, hazards of, 
81 
Carbon dioxide, effects on 
nervous system, 76, 107 
heart and circulation, 83 
blood, 90 
cerebrospinal fluid, 93 
respiration, 95, 107 
metabolism, 102 
endocrines, 106 
sweating, 109 
oxygen convulsions, 210, 211 
kidney, 109 
spleen, 112 
tolerance, 112 
acclimatization, 112 
pathology7, 113 
Carbon dioxide respiratory response, 
effect of oxygen, 202 
Carbon dioxide stores, specific sites 
of. 103 
Carbon monoxide, 219 
in submarines, 219 
clinical picture, 221 
pathology, 221 
mechanisms of toxicity, 222 
uptake and elimination, 223 
tolerance and acclimatization, 224 
treatment, 225 
Carbon monoxide dissociation curve, 
223 
Cardiac anomalies at altitude, 55 
Cardiac glycogen in hypoxia, 65 
Cardiac muscle action potentials in 
hypoxia, 22 
Cardiac output, effects of heat, 122 
Cardiac output, effects of hypoxia, 28 
Catecholamines, effects of carbon di- 
oxide on,107 
Catecholamines, effects of cold on car- 
bon dioxide, 128 
Catecholamines, (urine) following 
sleep deprivation, 265 
Cerebrospinal fluid pressure, effect of 
carbon dioxide on, 94 
Chemoreceptors, response to changes 
in pH, 96 
Chlorpromazine, protection from oxy- 
gen toxicity, 193 
Chokes, 152 
Chromosomal breakage in oxygen, 195 
Ciliary movement, effect of air ions, 
231 
Clo units indicated for cold immer- 
sion, 131 
CNS oxygen tension during oxygen 
breathing, 203 
Cochlear microphonic, effect of car- 
bon dioxide, 80 
Cochlear potentials, effects of hy- 
poxia, 13, 16 
Cold, physiological effects of 
acclimatization, 134 
performance in cold, 136 
immersion problems, 137 
Cold resistance, effects of hypoxia, 46 
Conduction velocity, effect of carbon 
dioxide on, 85 
Convulsions, effects of oxygen and car- 
bon dioxide on, 112 
Convulsions, (oxygen) , 198 
Coronary flow in hypoxia, 24 
Cortisone, effects on oxygen toxicity, 
192 Critical closing pressure, effect of cold 
on,127 
Cytochrome levels in hypoxia, 23 
Hartford tunnel construction, 153 
Decompression sickness, 151 
clinical picture, 153 
case reports, 155 
incidence, diagnosis and prognosis, 
158 
etiology, 158 
prevention and treatment, 160 
decompression procedures, 160 
helium-oxygen administration, 166 
oxygen administration, 168 
recompression treatment and sick- 
ness, 170 
preselection tests, 175 
drugs and hypothermia in decom- 
pression sickness treatment, 178 
Decompression tables, 160 
Diamox, effect on inspired carbon di- 
oxide, 91, 111 
Diamox, effect on PD2 in hypoxia, 61 
Diet, effect on hypoxia tolerance, 72 
Diffusing capacity, effect of oxygen, 
189 
Diffusing capacity of lungs, effect of 
exercise, 223 
Diffusion capacity of lungs, carbon 
dioxide effects on, 97 
Diuresis during water immersion, 276 
Diurnal rhythms, 264 
Drowning, 246 
Duty and rest periods, 264 
Dysbarism, treatment of, 170 
Ear defender (U-51R) use in noise, 
148 
Ear, nose and throat disturbances, 
150 
EKG anomalies during oxygen breath- 
ing, 201 
EKG changes during breath-hold 
dives, 236 
EKG in hypoxia, 24, 54 
Electrolyte transfer, effect of carbon 
dioxide, 102 
Electroretinogram, effect of oxygen, 
184 
Erythropoiesis, stimulus of hypoxia, 
36, 58 
Erythropoietic activity, oxygen effect, 
187 
Erythropoietic stimulating factor in 
hypoxia, 58 
Exercise, effects of oxygen breathing 
on oxygen debt, 183, 187 
Explosive compression, 182 
Explosive decompression, 178 
heart and circulation, 179 
respiration, 180 
gastrointestinal system, 180 
pathology, 181 
tolerance, 181 
Fatty acid levels in hypoxia, 44 
Flicker fusion frequency at increased 
pressure, 116 
Fluid breathing (pressure oxygenated 
solutions), 218 
Frenquel, protection against narcosis, 
116 
Gas density, effects on respiration, 10 
Gas embolism, symptoms of, 240 
Gas embolism treatment of, 241 
Gastrointestinal motility, effect of 
noise on, 144 
Gastrulation, effects of oxygen, -193 
Glomerular filtration rate, effects of 
heat on,123 
Glutahione, effect on oxygen toxicity, 
200, 206 
Glycine, use of to prevent hypother- 
mia in water, 132 
Hearing loss following noise exposure 
under pressure, 145 
Heart rate in hypoxia, 21 
Heat, physiological effects of, 122 
performance, 126 
Helium voice, 120 
Hematocrit in hypoxia, 69 
Hemoglobin, hypoxic effects on, 36, 57 
Heparin use in treatment of bends, 
178 
Hyaline membrane formation in oxy- 
gen, 194 
Hydrostatic pressure, effect on cell 
cleavage, 149 
on the resting potential of a nerve, 
149 
Hydroxycorticosteroids following sleep 
deprivation, 265 
Hydroxytrpytamine, effect of air ions 
on, 232 
Hyoscine, effect on cold survival, 137 
Hyperglycemia, as induced by heat, 
122 
Hypertrophy of the heart in hypoxia, 
49 
Hypophysectomy, protection in oxy- 
gen poisoning, 192, 208 
Hypothermia, use of in bends treat- 
ment, 178 
Hypoxia, effects on 
Special senses, 13 
nervous system, 17, 51 
muscle, 20, 53 
heart and circulation, 20, 54 
blood, 36, 57 
CSF, 41 
respiration, 39, 62 
alimentary tract, 41, 64 
Hypoxia, effects of (com.) 
metabolism, 41, 64 
endocrines, 45, 66 
temperature, 45, 68 
kidney, 47, 69 
effect of carbon dioxide, 48 
Increased atmospheric pressure effects 
on 
heart and circulation, 10 
respiration, 10 
kidney, 11 
Inert gases, 114 
nitrogen, 115 
xenon,119 
krypton,119 
helium, 120 
Infant diuresis in hypoxia, 47 
Intrapulmonary air trapping, 241 
Iron absorption in hypoxia, 57 
Isolation, sensory deprivation and 
confinement, 270 
Kreb’s cycle, effects of carbon dioxide, 
103 
Kreb’s cycle, effects of helium, 120 
Lactic acid in hypoxia, 65 
Limits of oxygen breathing, 175 
Liver glycogen, effect of cold, 135 
Liver glycogen, effects of carbon di- 
oxide on,104, 106 
Lung damage induced by oxygen and 
carbon dioxide, 107 
Lung inertance, effects of increased 
pressure, 11 
Lung rupture, pressures for, 242 
Lung volume, changes during immer- 
sion, 276 
Lymph/arterial PC2 differences, 187 
Maximum allowable times for carbon 
monoxide exposure, 220 
Mitochondria, effects of oxygen, 194 
Motion sickness, 234 
Myoglobin content in hypoxia, 53 
Nitrogen narcosis, 115 
Noise, 143 
physiological and pathological ef- 
fects, 143 
hearing defects from noise ex- 
posure, 145 
effects of noise on efficiency, 147 
sound protection in noise, 148 
protection against noise, 148 
Oculocardiac reflex, effect of carbon 
dioxide on, 85, 92 Otitis externa therapy, 151 
Oxygen administration during de- 
compression, 168 
Oxygen hemoglobin dissociation 
curve, effects of carbon dioxide 
on, 90 
Oxygen intoxication, 182, 197 
central nervous system, 198 
special senses, 183 
cardiovascular system, 184, 186 
blood, 187, 202 
lymph, 187 
respiration, 176, 202 
muscle, 200 
metabolism, 190, 205 
endocrine glands, 192, 208 
effect on cold threshold, 193 
effects on mitosis, 193 
pathology, 194, 212 
therapy, 196 
alimentary tract, 205 
effect of body temperature, 209 
kidney, 210 
tolerance, 210 
performance, 212 
treatment, 214 
Oxygen ventilation equivalent, effect 
of oxygen breathing, 188 
Ozone poisoning, 226 
Performance, effect of carbon dioxide, 
80 
Performance, submarine operations, 
264 
Peristalsis, effect of air ions, 231 
Physical standards for divers, 175 
Pitression, inhibitory effects of carbon 
dioxide on, 110 
Plasma potassium, effect of carbon 
dioxide on, 85, 93 
Plasma potassium, effect of hypoxia 
on, 60, 67, 69 
Plasma proteins in hypoxia, 60 
Pressor response in cold water, 131 
Psychological standards for divers, 
175 
Pulmonary circulation, effects of 
hypoxia, 26, 54 
Pulmonary resistance, effect of oxy- 
gen, 185 
Radon, 229 
Recompression treatment of bends, 
170 
Red cell volume, effects of carbon 
dioxide on, 92 
Renal blood flow in hypoxia, 69 
Repetitive diving, principles of, 167 
Saturation dive bends, treatment of, 
170 
SCUBA diving accident, effect of 99 
percent nitrogen, 17-18 
SCUBA diving, special problems of, 
272 
nervous system, 274 
cardiovascular system, 274 
respiration, 274 
kidney, 275 
oxygen consumption, 276 
spatial orientation, 276 
dangerous fish and other marine 
organisms, 277 
underwater breathing apparatus, 
279 
Selection of divers and submarine 
personnel, 258 
Sensitivity to carbon dioxide, 119 
Shivering, effect of carbon dioxide, 
80 
Shivering threshold, oxygen effects, 
193 
Sleep deprivation, 265 
Sleep deprivation, effect of body tem- 
perature, 266 
Sleep deprivation, effect on body per- 
formance, 268 
Stibine poisoning, 226 
Submarine escape procedures 
breath holding, 234 
escape procedures, 238 
gas embolism, 240 
underw’ater blast injuries, 245 
drowning, 246 
Succinic acid, use in carbon monoxide 
poisoning, 225 
Succinoxidase, effect of air ions on, 
231 
Sulfhydrl groups, susceptibility to 
OHP, 207 
Surface decompression, advantages 
of, 164 
Synaptic transmission, effects of hy- 
poxia, 16 
Tachycardia during breath holding, 
236 
Tactile discrimination in cold, 130 
Thiourea, protection in OHP, 206 
Thyroxine, effect on oxygen toxicity, 
209 
Tissue half-times, 12 
Tobacco smoke, 229 
Tooth calcification, effects of carbon 
dioxide on, 104 
Tri-iodothryomine, effect on cold 
survival, 135 
Tritanomalous color perception, 138 
Tyne tunnel construction, 156 
Unconsciousness during breath hold 
dives, cause of, 235, 247 
Underwater blast injuries, 245 
Vasoconstriction during oxygen 
breathing, 200 
Ventilation and air conditioning, 251 
Vestibular damage following carbon 
monoxide exposure, 221 
Vision problems, 138 
acuity, 138 
color vision, 138 
night vision and dark adaptation, 
141 
underwater vision, 141 
visual performance, 140 
Visual field, effects of oxygen, 183 
Y'itelline circulation, effects of oxy- 
gen, 184 
Whooping cough, treatment with 
hypoxia, 63 
Xenon narcosis, 119 
☆ U.S. GOVERNMENT PRINTING OFFICE: 1967 O 233-416