REPORT ON PHYSIOLOGY 
By II. P. Bowditch, M.D. 
Effect of Apncea on Convulsions-. 
Fileiine (Reichert and Du Bois Reymond’s Archie, 18*73, p. 361) 
reports experiments made under Munk’s directions to determine the 
effect of forced artificial respiration on the normal respiratory move- 
ments and on the convulsions produced by strychnia. The author 
confirms the conclusions of Rosenthal, and rejects those of Brown- 
Sequard (Archives de Pliysiologie, iv. p. 204). For a better compre- 
hension of the subject, a brief account of the experiments and conclu- 
sions of the latter observer may be given. Having found that in 
guinea pigs, rendered artificially epileptic, the attacks could be cut 
short by directing a stream of carbonic acid forcibly against the mu- 
cous membrane of the pharynx, Brown-Sequard was led to suppose 
that the arrest of the movements of respiration (apnoea) and of strych- 
nia convulsions, which is effected by forced artificial respiration, is 
due, not to a superoxygenation of the blood, as Rosenthal supposed, 
but to an inhibitory action of the vagus, and perhaps other nerves, on 
the nervous centres of the medulla and cord. Three series of experi- 
ments lent force to this hypothesis. In the first place, it was found, 
that after section of the cervical cord or the vagus nerves, forced arti- 
ficial respiration produced neither apnoea nor arrest of strychnia con- 
vulsions. Secondly, injection of carbonic acid from below upwards 
through the larynx (the animal breathing through a tracheal canula) 
caused immediate arrest of respiration. Thirdly, injection of carbonic 
acid into the lungs caused immediate cessation of the convulsions due 
to loss of blood. 
These experiments of Brown-Sequard, Filehne repeats and criticizes. 
He finds, in the first place, that neither the section of the cervical 
cord nor that of the vagus nerves prevents the production of apnoea by 
artificial respiration. It does not occur so readily as under normal 
conditions, owing, as Filehne supposes, to disturbances of the circula- 
tion, caused by these nervous lesions, lie finds, too, that strychnia 
convulsions are stopped by artificial respiration, as described by Ros- 
enthal, and that the fatal effects of the poison can thus be warded off. 
In this respect, his observations are at variance with those of Ross- 
bach (Gentralblatt fur die medicinischen Wissenschaften, 18*73, p. 369), 
who denies that artificial respiration has any effect upon the intensity 
or the duration of the strychnia convulsions. This discrepancy 
Filehne explains by supposing that Rossbach did not use animals 
sufficiently alike in all respects for making comparative experiments. 
In regard to the effect of section of the vagi on this saving influence 
of forced respiration in strychnia poisoning, Filehne finds that a dose 
of strychnia, the effects of which can be warded off by forced respira- 
tion, becomes fatal on section of the vagi, but he also finds that an 
animal poisoned with strychnia and with vagi cut may be saved from 
death by forced respiration, while an animal similarly treated, but left 
to breathe naturally, dies in violent tetanus. He therefore concludes 
that the effect of section of the vagi in rendering fatal a non-fatal dose 2 
of strychnia is clue to a disturbance of the circulation which prevents 
the thorough oxygenation of the blood in spite of the vigorous artifi- 
cial respiration. The fact that the first appearance of tetanus in an 
animal thus treated coincides with a sensible diminution in the force 
of the heart’s contractions, is an argument in favor of this view. 
Filehne has also studied the effect of a stream of carbonic acid on 
the nasal and pharyngeal mucous membrane, and finds that when the 
stream is so directed that the gas comes in contact with the mucous 
membrane of the nostrils an arrest of the respiratory movements at 
once takes place, whereas no such effect is produced when the irrita- 
tion is applied to the trachea, larynx or fauces. This is a reflex, in- 
hibitory phenomenon, the nature of which has been carefully studied 
by Kratschmer (Wiener Sitzungs berichte, Band 62, abth. ii. June 17, 
1870), who has recognized the trigeminal nerve as the channel through 
which the inhibitory influence is conveyed. Filehne and Brown- 
Sequard agree, therefore, in regarding the arrest of respiration by a 
stream of carbonic acid directed into the air passages as an inhibitory 
phenomenon, though the latter observer does not, like the former, 
limit the surface, the irritation of which produces this effect, to the 
nasal mucous membrane. 
Brown-Sequard’s error is, according to Filehne, in confounding the 
stoppage of respiration thus produced with true apncea, which depends 
upon superoxygenation of the blood. Filehne finally makes experi- 
ments to determine whether the irritation by carbonic acid can produce 
not only stoppage of respiration, but also, as Brown-Sequard maintains, 
arrest of strychnia convulsions, and of artificially produced epilepsy. 
By the most carefully conducted experiments, he fails to convince 
himself that the stream of carbonic acid has any effect in shortening 
the convulsions either of strychnia or epilepsy. How such discordant 
results are to be reconciled is not easy to see, but Filehne suggests 
that, owing to the short and irregular duration (i'-l') of the artificial 
epileptic attacks, one can readily deceive one’s self as to the effect of 
applications made to arrest them. 
In this connection must also be mentioned the experiments of 
Ananoflf (Centralblatt fur die medicinischen Wissenschaften, 6 June, 
1874) on the effect of oxygen on increased reflex irritability. 
This observer gave a fatal dose of strychnia to two rabbits, and 
allowed one of them to breathe oxygen, while the other breathed at- 
mospheric air. The latter died in convulsions seven minutes after the 
administration of the poison, while the former had no convulsions 
whatever as long as the respiration of oxygen was kept up (twenty- 
eight minutes), and finally died with only slight spasms ten minutes 
after the oxygen had been removed. Inasmuch as the oxygen was 
conducted from the gasometer to the lungs of the animal under a cer- 
tain pressure, it was necessary to determine whether atmospheric air, 
breathed under the same pressure, would not produce the same effect. 
For this purpose, two rabbits were poisoned with strychnia, as before, 
and one of them made to breathe air coming from the gasometer under 
pressure, while the other breathed under natural conditions. In the 
former, tetanic spasms were produced by external irritation seven 
minutes, and death followed twenty minutes after the administration 
of the poison, while the latter died at the end of six minutes. 
A third experiment was made to determine the difference between 3 
the effect of oxygen and that of an increased amount of atmospheric 
air. Of two rabbits, both poisoned with strychnia, it was found that 
the one which breathed oxygen remained free from spasms as long &s 
the oxygen inhalation was kept up, while the one which breathed at- 
mospheric air under pressure had convulsions in seven, and died in 
twenty, minutes. From this, it seems evident that it is really the 
presence of oxygen in the blood which prevents the occurrence of 
strychnia convulsions, and from Rosenthal's exferiments it is clear 
that the amount of oxygen necessary to produce this effect can be 
forced into the blood by artificial respiration without having recourse 
to the inhalation of pure oxygen, though in the experiments of Ananoff 
the effect of breathing condensed air was only to retard and not to 
prevent the convulsive action of the poison. 
Muscles. 
Ranvier (Archives de Physiologie, vi. p. 5) calls attention to the dif- 
ference in appearance and physiological properties presented by the 
striped muscles of the same animal. He finds, for instance, that in 
the leg of the rabbit the semi-tendinosus, the adductor brevis, the 
quadratus femoris and the soleus have a redder color than the rectus, 
the vasti, the adductor magnus, the biceps, the gemelli, &c., which, in 
contrast to the others, are denominated “ pale muscles." This differ- 
ence in color is independent of the amount of blood which the muscles 
contain, for it persists after the vessels of the limb have been washed 
out with artificial serum. Corresponding to this difference in appear- 
ance is a difference in the nature of the contraction. The red musclo 
contracts much less promptly than the pale muscle under the influence 
of an electrical stimulus, and relaxes much more slowly when the 
stimulus is removed. The period of latent irritation and the duration 
of the single muscular impulse or shock* is from four to six times 
greater in the red than in the pale muscles, while the rapidity of stim- 
ulation which is sufficient to produce complete tetanus is correspond- 
ingly less. These differences are equally manifest, whether the irrita- 
tion is applied to the nerve or directly to the muscle. 
Histological differences are also noticed in the two sorts of muscles. 
In the pale muscles, the transverse striation is much more distinct 
than the longitudinal, while in the red muscles the longitudinal stria- 
tion is very well marked, and the transverse striae are not straight, as in 
the pale muscles, but formed of broken lines. Nuclei are much more 
abundant in the red than in the pale fibres. Muscles presenting these 
same differences are also found in various species of fish. 
Ranvier has also recently reported to the Societe de Biologie (Revue 
Scientijique, 6 June, 1874) a very ingenious method of studying the 
transverse striae of muscles. The method consists in using a histolo- 
gical preparation of a striped muscle for the production of a diffraction 
spectrum, the striae of the muscle producing the same effect upon the 
light as the fine lines ruled on glass, which are usually employed for 
this purpose. The spectrum thus produced is found to undergo no 
change when the muscle contracts, proving that the transverse striae 
of muscles do not disappear in contraction, as has been sometimes 
maintained. 
* It would, perhaps, be well to adopt the word “jerk,” as the equivalent of the French 
“ sccousse ” or the German “zuckung,” to express the contraction of a muscle in conse- 
quence of a single instantaneous irritation. 4 
Glycogenesis. 
Since the publication of the report on the glycogenic function of the 
liver, in January, 1873, considerable progress has been made in our 
knowledge of this function. The results of recent investigations have 
been admirably presented by Dr. T. Lander Brunton, in three lectures 
on the pathology and treatment of diabetes mellitus, published in the 
British Medical Journal for January and February, 1874. To these 
the reader is referred for details which would be out of place in this 
report. 
The so-called glycogenic function of the liver really consists of two 
separate and distinct processes: first, the formation of glycogen 
from the materials supplied by the food and its accumulation in the 
cells of the liver ; and, secondly, the change of this glycogen into 
sugar and its return to the circulation. The liver thus acts as a store- 
house, in which organic substances can be held in reserve when pre- 
sented in quantities greater than are needed for the immediate use of 
the organism, and from which they can be given out in a form adapted 
for rapid consumption whenever they may be needed. In this respect, 
the liver is analogous to the roots and seeds of plants, which accumu- 
late starch and cane sugar during one season’s growth, and at some 
subsequent period change it to glucose to provide for the further 
growth of the plant or for germination. This and other interesting 
analogies between plants and animals have been pointed out by Ber- 
nard in his lectures on “ vital phenomena common to plants and ani- 
mals.” (Bevue Scientifique, July-December, 1872.) 
It must not be supposed, however, that the liver is the only organ 
which acts in this way to store up organic substances for future use. 
The muscles have this same power, and it has been shown by Weiss 
(Wiener Sitzungsberichte, lxiv. p. 284) that they retain their glycogen 
more tenaciously than the liver, for a considerable amount of glycogen 
has been found in the muscles of starved animals after it has entirely 
disappeared from the liver, and muscles are found to retain their irri- 
tability as long as glycogen remains present in them. In the embryo, 
nearly all the tissues are found to contain glycogen. In fact, where- 
ever future growth or work is to be provided for, there glycogen seems 
to be accumulated. 
The first question which presents itself in the study of glycogene- 
sis is : What is the origin of glycogen ? The experiments of Dock, 
already reported,* have shown that the ingestion of glucose increases 
the amount of glycogen in the liver, and point to the direct transform- 
ation, by a process of dehydration, of the former substance into the 
latter. This view derives confirmation from the experiments of Schdpf- 
fer (Archie fur exp. Pathologie, i. p. 73), who, following the lead of 
Bernard, injected a solution of glucose into the crural vein of a rabbit, 
and found that glycosuria resulted, -while a similar injection into a 
radicle of the portal vein had no such effect, provided that it was not 
made too rapidly. It seems, therefore, that the liver has the power of 
removing from the blood, and storing up in the form of glycogen, the 
glucose brought to it from the intestine by the portal vein. This 
power is, however, not unlimited ; for, if the sugar be brought too 
rapidly into the portal system, either by absorption (Bernard Revue 
* This Journal, January 23, 1873. 5 
Scientijique, ii. 106G) or by direct injection, a portion of it will pass 
unchanged through the liver, reach the general circulation and be ex- 
creted by the kidneys. A similar effect may be produced by a liga- 
ture on the portal vein (Bernard, Revue Scientifique, ii. 1108). Here 
the sugar absorbed from the intestine reaches the general circulation 
by collateral channels, causing glycaemia and glycosuria. In this con- 
nection, it is interesting to note a case of diabetes reported by Andral, 
in which the autopsy showed obliteration of the portal vein. It should 
be mentioned here that the blood of the portal vein seems to contain 
sugar in an appreciable amount only while digestion is going on. 
Many observations seem to show that the glycogen of the liver may 
also be formed from albuminoid substances. Bernard has shown that 
the liver of a dog fed upon lean meat contains a much greater quanti- 
ty of glycogen than that of a fasting animal. Starving dogs, fed on 
gelatine and fibrin, have also been found to have an increased amount 
of glycogen in the liver. In the report of January, 18Y3, reasons 
were given for supposing that a certain amount of albuminoid material 
is absorbed unchanged from the intestine and is used for the formation 
of the tissues, while the peptones, after absorption, are not reconvert- 
ed into albumen, &c., but, by successive decompositions, reach the 
form of urea and are thus excreted. A natural extension of this hy- 
pothesis is, that the liver is the organ where the decomposition of pep- 
tones chiefly takes place, and that glycogen is the form in which the 
non-nitrogenous products of this decomposition are stored up. The 
occurrence of nitrogenous substances in the bile may be regarded as 
an argument in favor of this view. On the other hand, it has been 
found by Weiss ( Centralblattfiir diemedicirxischen Wissenschoften, 1873, 
p. 552) that hens, kept on a diet of fresh meat and fibrin, lose nearly 
the whole of the glycogen from their livers. How far this is to be 
regarded as indicating a fundamental difference between birds and mam- 
malia is a question to be settled by future investigations. 
There seems to be a pretty general agreement among those who 
have occupied themselves with the question of glycogenesis, that fatty 
substances in the food do not give rise to glycogen in the liver. It 
has, however, been shown by Luchsinger (Pjliiger’s Archiv, viii. 289) 
that glycerine, when taken into the stomach, causes an increase of 
glycogen in the liver; owing, probably, to a direct transformation of 
glycerine into glycogen, and not, as Weiss (loc. cit.) supposes, to the 
glycerine being used up in the place of the glycogen, thus allowing 
the latter to accumulate. It seems, therefore, probable (though not 
yet demonstrated) that the ingestion of fats may produce a similar 
effect, for Kiihne (Physiologische Chemie, 1868, p. 125) has shown that 
the pancreatic juice has the power of decomposing neutral fats into fat 
acids and glycerine. 
Whatever may be the particular articles of food which give rise to 
the formation of glycogen in the liver, there is no doubt that it accu- 
mulates in well-fed and disappears in starving animals. A change 
into glucose is, moreover, a necessary preliminary to its removal from 
the liver. 
The next question, therefore, is : how is this change into glucose 
effected ? That it is a process of fermentation is universally admitted. 
That the ferment which produces the change is brought to the liver by 
the blood seems pretty well established, for the observations of 6 
v. Wittisch (Pfluger's Archiv, vii. 28) and others, that a change of gly- 
cogen into sugar takes place after the vessels of the liver have been 
washed entirely free from blood, cannot be regarded as proving that 
the ferment is formed in the hepatic cells, since, as pointed out by 
Plosz and Tiegel (PfliigePs Archiv, vii. 391), the process of washing 
out the liver with pure water, as practised by v. Wittisch, is well 
adapted to dissolve out the ferment from the blood globules, which 
are supposed to contain it, and fix it in the coagulating hepatic 
parenchyma. 
Since, therefore, the ferment in question is contained chiefly, if not 
wholly, in the circulating blood, it is evident that anything which 
causes an increased flow of blood through the liver will, by bringing a 
larger amount of the ferment into contact with the glycogen, produce 
an increased formation of glucose. If glucose be thus formed in ex- 
cess of the needs of the system, so that it accumulates in the blood to 
an amount greater than one-third of one per cent. (Bernard)) it will 
be excreted by the kidneys, and glycosuria will result. Now, an in- 
creased flow of blood through the liver may be caused in various ways. 
In the first place, the stoppage of any of the larger arteries will, by 
raising the blood tension, force a larger supply of blood through the 
liver, the calibre of the hepatic vessels being supposed to remain un- 
altered. This is probably the explanation of the diabetes observed 
by Schiflf as the result of ligaturing large vessels. A rise of blood 
tension, also, is probably the cause of the diabetes which has been 
observed in the convulsions of asphyxia (Pavy, On Diabetes, pp. 62, 68 
and 145) and epilepsy (Trousseau, Clinique Medicate, 3d ed., ii. p. 136). 
A dilatation of the hepatic vessels, the blood tension remaining the 
same, will also cause an increased flow of blood through the liver. 
This dilatation may be the result either of direct or of reflex paralysis 
of the vaso-motor nerves of the liver. A direct paralysis of these 
nerves is the probable explanation of the diabetes caused by the sec- 
tion of the anterior columns of the cervical cord (Schiff, Zuckerbildung, 
p. 108), or by extirpation of the last cervical and first dorsal sympa- 
thetic ganglion (Cyon and Aladoff, quoted by Brunton, British Medical 
Journal, 1814, p. 39). The experiments of Cyon have rendered it 
probable that these lesions affect chiefly the size of the hepatic artery, 
causing little or no change in the calibre of the portal vein. 
A reflex paralysis or inhibition of these vaso-motor nerves may be 
produced by irritation of centripetal fibres in the vagus nerve, and 
glycosuria may be thus produced (Bernard, Physiologie Experimental, 
i. pp. 334-339). The well-known effect of a puncture of the floor of 
the fourth ventricle in producing glycosuria is probably to be re- 
ferred, in part at any rate, to an irritation of the vagus nerves at their 
origin, while the glycosuria sometimes noticed as the result of ether 
and chloroform inhalation (Schiff, Zuckerbildung, 124) seems to bo 
due to an irritation of the same nerves at their terminations in the 
lungs. It would seem, however, from recent observations of Seelig 
(Centralblatt fur die medicinischen Wissenschaften, 1813, p. 934) that 
the “sugar puncture” not only causes an increased change of glyco- 
gen into sugar in the liver, but also prevents the sugar which is 
brought to the liver by the portal vein from being stored up as glyco- 
gen in that organ. Seelig found that a starving animal which had re- 
ceived the “ sugar puncture ” showed little or no sugar in the urine, 7 
but that an injection of glucose into a mesenteric vein caused immedi- 
ate glycosuria, while a similar injection into a starving animal which 
had received no “ sugar puncture ” had no such effect. Similar re- 
sults were obtained by injection of glucose into the jugular vein, 
proving, according to Seelig, that 11 the diabetic animal is character- 
ized by an inability to use sugar for the nourishment of its body.” 
These results are hardly to be explained on the supposition that the 
“ sugar puncture ” causes merely a dilatation of the hepatic vessels, 
allowing more of the ferment contained in the blood to come in contact 
With the glycogen of the liver. Further experiments are needed, be- 
fore any satisfactory hypothesis can be advanced. 
The third question which presents itself in the study of glycogenesis 
is : What is the destination of the glucose which is formed in the 
liver in the manner above described '( That the healthy organism is 
able to consume all the sugar formed within itself is evident from the 
fact that normal urine contains no appreciable amount of sugar. It 
would even seem from the experiments of Tieffenbach (Centralblatt 
fiir die medicinischen Wissenschaften, 1869, p. 179) that still larger 
amounts may be consumed, for it was found that small quantities of 
glycogen or glucose could be injected into the veins or under the skin 
without causing glycosuria. In what particular part of the body sugar 
is consumed is a question not easy to settle, for it has been shown 
that sugar disappears very rapidly from the blood when withdrawn 
from the body. Hence, the importance of the rule laid down by 
Bernard (llevue Scientifique, iii. 43), when testing the blood for sugar 
only to use warm blood fresh from the vessels of the animal. It is not 
improbable that a similar rapid disappearance of sugar takes place in 
the circulating blood, irrespective of the organs through which it cir- 
culates. There is, however, reason to suppose that a very considera- 
ble sugar consumption takes place in the muscles, for it has been 
shown by Genersich (Ludwig's Arbeiten, 1870, p. 75) that defibrinated 
blood loses sugar on being conducted through a dog’s hind legs, 
freshly separated from the body, and still retaining their muscular 
irritability. This disappearance of sugar is, moreover, quite in ac- 
cordance with what is known of the effect of muscular activity in in- 
creasing the exhalation of carbonic acid. It cannot be supposed, how- 
ever, that glucose is directly oxidized to carbonic acid, for it has been 
shown (Bernard, Physiologie Experimental, i. 241) that blood shaken 
with oxygen does not lose its sugar faster than with other gases. 
Moreover, it has been found that as sugar disappears from the blood 
lactic acid takes its place, and muscles when kept in prolonged activity 
are found to have an acid reaction, due to the formation of lactic acid 
within them. There is, therefore, no reason to doubt that a change 
into lactic acid by a process of fermentation is the first step in the 
disappearance of glucose from the organism. This view is also in ac- 
cordance with the observations of Scheremetjewski (Ludwig's Arbeiten, 
1868, p. 114), who found that the injection of alkaline lactates into the 
blood caused an increased absorption of oxygen and exhalation of car- 
bonic acid, while an injection of glucose had no such effect. 
The experiments of Schultzen on phosphorus poisoning (Zeitschrift 
fiir Biologie, viii. 124, and Berliner Klinische Wochenschrift, 1872, p. 
417) throw light upon this subject. The action of phosphorus is, ac- 
cording to Schultzen, to arrest the processes of oxidation in the organ- 8 
ism, while those of fermentation go on unchecked. lie finds that in 
animals poisoned by phosphorus “ urea disappears from the urine, and 
is replaced by leucine and tyrosine, which, in the healthy organism, 
are converted into urea. No sugar appears in the urine, but a kind of 
lactic acid is found in quantities exactly proportional to the amount of 
sugar afforded to the animals by their food. This kind of lactic acid 
agrees exactly in its properties with the aldehyde of glycerine, and 
Schultzen considers the two bodies to be identical.”* The production 
of this substance from glucose by a process of fermentation seems, 
therefore, to be a necessary preliminary to oxidation, and if for any 
reason this preparatory fermentation does not take place, the glucose, 
not being oxidizable as such, is excreted by the kidneys, and glycosu- 
ria results. This seems to be the case in some forms of diabetes, and 
in the experiments of Scheremetjewski, above alluded to. 
To recapitulate briefly. The liver has two functions :—1st, that of 
forming and storing up glycogen ; and, 2d, that of forming sugar 
again from glycogen. The muscles probably possess both of these 
functions, and also a third function, viz., that of changing both the 
sugar they form and the greatest part of that which they receive from 
the blood into lactic acid, which undergoes combustion. 
Glycosuria may result, 
1st, from failure of the liver to convert into glycogen the sugar ob- 
tained from the food, either because it is brought in too large quantities 
to the liver, or because the liver has not the power to effect the change 
in question. This may be called alimentary glycosuria, and may be 
prevented by avoiding saccharine articles of food. 
2d, from an increased transformation of glycogen into sugar, due to 
accelerated circulation through the liver, or to a larger proportion of 
ferment in the organ or the blood. (The possible participation of the 
muscles in the production of both these sorts of glycosuria must be 
borne in mind.) 
3d, from a diminished consumption of sugar in the organism, “ due 
either (a) to insufficiency of the ferment, which should convert the 
sugar into lactic acid, (b) to an altered quality of the sugar which en- 
ables it to resist the action of the ferment, or (c) to diminished circu- 
lation through the muscles preventing the sugar from coming suffi- 
ciently into contact with the ferment. 
* Brunton’s third lecture, loc. cit. 
f Brunton, loc. cit. 
Reprinted from the Boston Medical and Surgical Journal, July 23,1874.