THE EFFECTS OF DRUGS AND OTHER AGEN- 
CIES UPON THE RESPIRATORY MOVEMENTS. 
HORATIO C. WOOD, M.D., LL.D. and D. Cerna, M.D. 
Reprinted from the Journal of Physiology. 
Suppl. No., 1892. [From the Journal of Physiology. Suppl. No., 1892.] THE EFFECTS OF DRUGS AND OTHER AGENCIES 
UPON THE RESPIRATORY MOVEMENTS. By 
HORATIO C. WOOD, M.D., LL.D. (Yale), assisted by 
DAVID CERNA, M.D, 
In physiological therapeutics a stimulant is a substance which increases 
functional activity. Accordingly, a vascular stimulant is one which 
increases the arterial pressure; or to speak more minutely, a cardiac or 
an arterial stimulant is one that increases the output of force by the 
heart or by the vaso-motor system. When, however, the function of 
respiration is in question, a stimulant, as the word is practically used by 
most pharmacologists, seems to be simply a substance which increases 
the rapidity of the respiration, since in almost all recorded experiments 
with drugs of the class, the experimenter has simply noted the rate of 
the respiration. Increased activity of rate does not however necessarily 
imply increased activity of the function. Thus, a rapid pulse may be a 
very feeble pulse, and an arterial sedative may increase the rate of the 
pulse though depressing most thoroughly the functional activity of the 
circulation. In like manner, it is shown by our experiments that very 
rapid breathing may coexist with very little movement of air. It is 
evident that the proper definition of a respiratory stimulant would be, 
that it is a substance which increases the amount of air taken in and 
out of the lungs in a fixed time. 
Such considerations as these have led us to undertake the following 
research, which has for its object the determination of the respiratory 
movement of air as affected by different drugs and different agencies. 
The mode of research is in itself simple enough. It consists essentially 
of connecting the trachea of the animal with a tube which, in turn, is 
connected with two ordinary mercurial valves, the one of which allows 
the air to enter, the other the air to escape; the mercurial valve of 
expiration being, in turn, connected with an india-rubber bag or reser- 
voir from which the air is drawn through by means of a suction-pump. 
The rabbit would be an excellent animal for a research like the 
present, were not a certain amount of muscular force required to force 
the expired and inspired air through the mercurial valve. It is evident DRUGS AND RESPIRATORY MOVEMENTS. 
871 
that the muscular strength of the animal must be such that the very 
feeble resistance offered by the valves shall not be sufficient to em- 
barrass respiration to the slightest extent. For this reason we have 
employed dogs. There are, however, two practical difficulties in the 
way of the experimenter, which can only be overcome by great care in 
estimating the results obtained by the experiments. The dog having 
practically no sweat gland, cools himself through forced respiration; 
further, in the dog, panting is the chief expression, not only of mus- 
cular and arterial excitement but also of purely nervous or emotional 
excitement. To illustrate the effect of excitement upon the respiration 
of the dog, we make one or two citations from our records of experi- 
ments. 
Exp. I. A dog weighing 9 kilos, in a state of great emotional excite- 
ment, was found to be moving 082 cubic foot of air per minute; twenty 
minutes afterwards, however, when he had become quiet, he only passed 
through his lungs o‘os foot per minute. In another experiment (Exp. 
II.) a dog weighing about 10 kilos, when quiet passed OT4 cubic foot 
per minute; fifteen minutes later, when he had been only moderately 
excited, he passed 027 cubic foot per minute. 
There is scarcely any stimulant which by a direct action upon the 
respiratory centres is capable of so exciting respiration in the dog as is 
emotion; so that in order to get the normal standard with which the 
effects of the remedy may be compared, it is essential that the experi- 
menter wait until the animal has become calm. In order also to make 
even the results thus obtained positive, it seems essential to check them 
by experiments made when the animal is rendered unconscious, and 
therefore incapable of emotional excitement, by chloral or other drugs, 
even though these drugs be distinct respiratory depressants. 
In estimating the effect of a respiratory depressant, such as chloral, 
it is plain that the calming influence of the drug must be allowed for, 
as possibly having immense influence. In this case, also, the physio- 
logist must check his first results by noting the effects of repetitions of 
the dose of the chloral or other sedative remedy after unconsciousness 
has been reached; it being plain that in a true respiratory sedative a 
repeated dose should cause repeated fall of respiration, although the 
first dose had produced unconsciousness. 
As the dog protects itself from high external heat through the 
respiration, it is to be expected that heat is in the dog a powerful and 
direct respiratory stimulant. In endeavouring to experimentally test 
the truth of this a priori reasoning, we placed the body of the dog in a 872 
H. G. WOOD AND D. GERNA. 
double metallic box, so arranged that the animal lay comfortably in his 
trough, not in contact anywhere with the metallic surface, with the 
head out of the box, and the mouth and breathing apparatus connected 
with the air of the room; we then filled the double metallic box with 
hot water. In this way, as much as possible, we avoided producing 
pain or excitement, or interfering with the respiration or the supply of 
fresh air to the animal. As illustrating the effect produced we briefly 
outline two experiments. (Exp. Ill,), a dog, weight not noted, with 
a rectal temperature of 392 C., breathing at the rate of 20 a minute, 
moving in the same period 014 foot per minute, was surrounded with 
water at 73° C. Five minutes afterwards the respiratory rate had risen 
to 42, and the air moved to 0'23 foot per minute; fifteen minutes after 
this, the rectal temperature of the dog was 40-8 C., the respiratory 
rate 58, and the air moved 03 foot per minute. The animal having 
been lifted out of the box, in fifteen minutes the rectal temperature 
had fallen to 39'8 C,, the respiration to 22, the air moved to OT6 foot. 
The animal was replaced in the box, in 15 minutes the rectal tempera- 
ture had risen to 40 9 C., the respiration to 82, the air moved to 042 
foot per minute. Again taken out of the box, in half-an-hour the rectal 
temperature had dropped to 393 C., respiratory rate to 18, the air 
moved to 0T foot per minute. 
In a second experiment, the air movement in a very small dog was 
006 per minute, the rectal temperature being 393 C., and the tempe- 
rature of the air 60 F.; when under the influence of a box tempe- 
rature of 70 0., the rectal temperature had been raised to 40 3 0., the 
air movement was increased to 012, A little later, when the rectal 
temperature was 425, the air movement was 025. It is worthy of 
being put on record, as one of the phenomena of over-heating or 
thermic fever in the dog, that by-and-by the air movement lessens. 
Thus, five minutes before the animal just spoken of died from the 
over-heating, the air movement was 016, the rectal temperature being 
43 0. 
In a number of experiments, which it is not necessary to further 
detail, we have obtained concordant results, and have proven that in the 
dog heat is a most powerful stimulant to the respiratory centres. Any 
clinician who has noted the effect of fever in increasing the respiratory 
rate in man, must, it seems to us, recognize that as in the dog so also 
in the man is heat a powerful respiratory stimulant; the difference in 
the man and the dog in this respect being in degree rather than 
in kind. DRUGS AND RESPIRATORY MOVEMENTS. 
873 
Sometime since, Dr Lauder Brunton called attention to the great 
importance of maintaining the bodily temperature in narcotic poisoning, 
and showed that in the dog the fatal effects of otherwise lethal doses of 
narcotics might be set aside by placing the animal in heated chambers. 
Our experiments naturally suggest that as in narcotic poisoning the 
animal usually dies of respiratory paralysis, the antagonistic effect of the 
heat is due to its stimulating respiratory centres. In order to test this 
explanation, we have made two experiments, one with morphine and one 
with chloral, which we append. 
Experiment IY. 
Period 
Eect. 
temp. 
Movement 
of air cu. ft. 
Eesp. 
rate 
Eemarks 
i 
C. 
38-5 
0-16 
42 
Weight 7*7 kilos. 
2 
Given 12 grs. morphine into jugular in 
divided dose. 
3 
37-2 
0-15 
Complete narcotism ; paraplegia. Dog 
now put in hot box, and kept there, 
getting abundant air for respiration. 
4 
39-3 
0-38 
94 
Dog returned to box. 
5 
39-5 
0-37 
100 
Experiment Y. 
1 
38 
0-16 
21 
Weight 5-5 kilos. Given 3 grs. chloral. 
2 
37-5 
013 
18 
Dog given 5 more grs. chloral. 
3 
0-12 
22 
Complete unconsciousness. 3 grs. more 
chloral given. 
4 
Dog was now put into hot box. Rectal 
temperature, through a misunder- 
standing, not taken. 
5 
0-27 
100 
Dog taken out; afterwards replaced. 
6 
40 
0-67 
90 
Dog taken out of box and allowed to 
stay out. 
An examination of the records just given will show the enormous 
effect of heat upon the respiration in narcotism. The first dog was 
completely narcotized (its spinal cord indeed being almost completely 
paralyzed) by 12 grains of morphia. During the narcotism the rectal 
temperature had fallen 103 C. below the norm. When by means of 
external heat the rectal temperature was raised about one degree above 
the norm, the respiratory rate was more than doubled, and the 
movement of air in the chest increased from OTS cubic foot per minute, 
to o'3B cubic foot. 874 
H. a WOOD AND D. CERNA. 
In the second experiment, a small dog was completely narcotized 
by 11 grains of chloral, with pronounced fall in the rectal temperature 
and the reduction of air movement per minute from 016 cubic foot to 
012 cubic foot, but when by means of the hot box the rectal tempera- 
ture of the animal was put up two degrees above the norm, the air 
movement rose to nearly five times the normal amount. 
These experiments demonstrate that the stimulating effect of heat 
upon the respiratory centres is as great in the narcotized as in the 
normal animal. They also explain the way in which heat protracts or 
even saves life during narcotism, and enforce the necessity—by means of 
the hot water bath or bed—of overheating the human body when 
respiratory paralysis from the action of some narcotic agent is 
threatened. 
Before attempting the experimental study of the influence of indivi- 
dual drugs upon the amount of air taken in and expelled from the lungs, 
we made a series of experiments to determine the effect of section of the 
pneumogastric upon the respiratory movement of air. The only experi- 
ments upon this subject with which we are acquainted are those of 
Rosenthal, who states that the amount of air inspired in a given time 
by the rabbit is not affected by section of the pneumogastric, although 
in doves the amount is diminished. Our own experiments upon the 
dog not under the influence of any drug are five in number. 
Experiment VI. 
Time 
min. 
Eate of resp. 
Cubic feet 
movement of 
Eemarks 
air per min. 
0 
1-0 
Weight of dog 18 kilos. Dog somewhat 
excited. 
10 
40 
0-68 
Dog quiet. 
15 
1-7 
Vagi were now cut. 
24 
3-5 
40 
60 
3-0 
60 
80 
3-1 
Experiment VII. 
0 
69 
0-3 
Weight of dog 10 kilos. 
10 
Par vagum cut. 
12 
43 
0-47 
25 
21 
0-3 
35 
84 
0-43 
Breathing very irregular. DRUGS AND RESPIRATORY MOVEMENTS. 
875 
Time 
min. 
Rate of resp. 
Cubic feet 
movement of 
Remarks 
air per min. 
0 
36 
0-7 
Weight of dog 15 kilos. Dog very quiet. 
5 
Par vagum cut. 
17 
12 
0-35 
30 
9 
0-48 
Dog very quiet. 
Experiment IX. 
0 
66 
0-44 
Weight of dog 9 '7 kilos. 
10 
Par vagum cut. Next period 15 mins, 
after section. 
28 
18 
0-28 
43 
18 
0-24 
Dog very quiet. 
Experiment X. 
0 
69 
0-39 
Dog not struggling. 
10 
Par vagum cut. 
12 
33 to 53 
0-46 
Dog struggling part of time. 
20 
18 to 24 
0-24 
Dog quiet. 
30 
24 to 108 
0-36 
Much of the time respiration very short 
and rapid. 
Experiment VIII. 
On examination these records will show that in Exp. VI. the section 
of the vagi was followed by a great rise both in the number of respira- 
tions and in the amount of air expired; the last period at which the 
experiment was studied being forty-five minutes after the section of the 
vagus. In Exp. YIL, although the respiration fell finally to less than 
one-third of what it had been before section of the vagi, there was no 
sensible reduction in the amount of air expired; indeed, during a 
portion of the time, with lessened respiratory rate, there was pronounced 
increase of air movement. Later in the experiment, nearly half-an-hour 
after section of the vagi, for reasons not very evident, the rate increased 
and the movement of the air was greater than before the section. In 
Exp. VIII. both rate and air movement were distinctly lessened after 
the section of the vagi, the rate falling from one-third to one-fourth of 
what it had been previous to the section, and the air movement being 
but a little over one-half what it had been before section. In Exp. 
IX., again there was a decrease both in rate and in amount of air moved, 
the rate falling to a little over one-quarter, the movement of air to a little 
over one-half of what it had been before the section. In Exp. X., the 
respiratory rate fell directly after the section of the vagi, but the amount 
of air moved increased. Some minutes later, with the respiratory rate 876 
H. G. WOOD AND D. CERNA. 
about one-third what it was before section, the movement of air was 
reduced about one-third; after this again the respiration increased in 
frequency to at least the norm, and the inspired air also became 
practically the same as before the section. 
These experiments show that the action of section of the vagi upon 
air movements in the dog varies; that usually, when the rate falls and 
the ordinary slow full breathing of pneumogastric section is obtained, 
the total amount of air moved is less than the norm; on the other 
hand, in some cases after section of the par vagum, the gain in the 
extent of the respiratory movements more than compensates for the loss 
in rate. 
It is also plain that the influence of section of the vagi upon the 
respiratory movements may be in the dog dominated by general or 
emotional excitement, disturbances of temperature, etc. All our experi- 
ments were made with the dog kept at a uniform temperature, so as to 
put aside this source of error. Every effort was also made to keep the 
dog as quiet as possible, and the following experiment was also 
instituted, in which by the benumbing influences of chloral, disturbing 
influences should be shut out from the respiratory centre. 
Experiment XI 
Time 
min. 
Drug 
chloral 
5 °/0 sol. 
Cubic feet 
movement of 
air per min. 
Bate of 
resp. 
Remarks 
0 
1-0 
129 
Weight 20 kilos. 
5 to 20 
25 c.c. 
22 
0-68 
60 
Completely chloralized. 
25 
Par vagum divided. 
28 
0-5 
114 
38 
0-3 
58 
In this experiment the usual effect of chloral in reducing the 
respiratory rate and the movement of air was obtained. Under these 
circumstances section of the vagus was followed by an increase of the 
respiratory rate, which increase soon, however, in great part subsided. 
Even during the period of increased rate the movement of air was less 
after than before the cutting of the nerve, and when the rate a little 
later fell to near what it had been before section the movement of air 
became less than half what it had been before section. 
These experiments, when taken together, seem to us to warrant the 
conclusion that in the dog the general tendency is towai'ds a lessened 
movement of air after section of the vagi, but that this tendency is not DRUGS AND RESPIRATORY MOVEMENTS. 
877 
sufficiently strong to prevent its being set aside by disturbing causes ; 
and that sometimes after section of the pneumogastrics the respiratory 
movement of air is not only not lessened but is increased without our 
being able to assign a reason for the exceptional results. 
Respiratory Depressants. 
Chloral. 
The first drug which we studied was chloral. We have already 
given one or two experiments with this drug, and add in tabular form 
five more. 
Before chloral 
After chloral 
Exp. 
Cubic feet 
movement 
of air 
normal 
Resp. 
rate 
Chloral 
injected 
10 % sol. 
Movement 
of air 
during 
anaosth. 
Resp. 
rate 
Remarks 
XII. 
0-22 
54 
5 c.c. 
0-11 
30 
Weight 6'8 kilos. 
XIII. 
0-27 
66 
5 c.c. 
5 c.c. 
(N r—1 
o 6 
72 
58 
Weight 8’2 kilos. 
XIY. 
0-4 
74 
20 c.c. 
5 c.c. 
0-19 
0-14 
54 
34 
Weight 12*7 kilos. 
XY. 
0-22 
64 
10 c.c. 
01 
31 
Weight 7 kilos. 
XYI, 
0-15 
35 
10 c.c. 
10 c.c. 
0-12 
0-9 
32 
30 
A study of the above table will show that in all the experiments the 
reduction in the amount of inspired air produced by complete chloraliza- 
tion is very pronounced. In many cases the decrease of respiratory air 
movement amounts to fifty per cent., and sometimes even to seventy-five 
per cent. The results which we have obtained by the use of chloral 
are concordant, and demonstrate that in the dog chloral is a true 
respiratory depressant, markedly reducing the respiratory 
movement of air. 
The action of chloral upon man is evidently similar to that which it 
exerts upon the dog, and the conclusion which has been reached in our 
experiments is applicable to human beings. 878 
H. a WOOD AND D. GERNA. 
Morphine. 
The next drug which we studied is morphine. We give in the 
following table six experiments with the drug. 
Time 
min. 
Morphine sulph. 
injected jugular 
5 °/o sol. 
Movement 
of air 
cubic ft. 
Resp. 
rate 
Remarks 
0 
0-17 
70 
Weight of dog 12 kilos. 
5 
10 c.c. 
Respiration at once arrested. Arti- 
tidal resp. resorted to; after a few 
minutes, natural breathing. 
18 
0-07 
17 
28 
0-11 
25 
Experiment XVIII. 
0 
0-08 
13 
Weight 15 5 kilos. 
5 
5 c.c. 
Breathing stopped entirely. Arti- 
ficial respiration resorted to. 
15 
0-08 
12 
22 
5 c.c. 
25 
0-05 
12 
32 
5 c.c. 
37 
005 
12 
40 
5 c.c. 
46 
o-i 
12 
54 
5 c.c. 
59 
0-06 
11 
63 
10 c.c. 
68 
0-10 
12 
Respirations very deep. Coma, 
72 
15 c.c. 
75 
0-08 
12 
Reflexes increased. 
Experiment XIX. 
0 
0-11 
36 
Weight 7‘5 kilos. 
5 
1-5 c.c. 
9 
0-04 
13 
12 
1-5 c.c. 
16 
0-09 
40 
20 
3 c.c. 
25 
0-052 
12 
32 
0-052 
12 
Complete anaesthesia. 
40 
3 c.c. 
45 
0048 
14 
49 
3 c.c. 
54 
0-048 
14 
58 
6 c.c. 
63 
0-1 
20 
Violent jerking or convulsive move- 
ments. Cheyne-Slokes respiration. 
68 
006 
Experiment XVII. DRUGS AND RESPIRATORY MOVEMENTS. 
879 
Experiment XX. 
Time 
min. 
Morphine sulph. 
injected jugular 
5% sol. 
Movement 
of air 
cubic ft. 
Eesp. 
rate 
Remarks 
0 
0-12 
42 
Weight 7'7 kilos. 
5 
2-5 c.c. 
Breathing stopped. Artificial resp. 
for 3 minutes. 
17 
0-06 
24 
20 
0-056 
24 
22 
1-25 c.c. 
28 
0-07 
21 
Experiment XXI. 
0 
0-31 
42 
Weight 19 5 kilos. 
5 
0-27 
42 
6 
5 c.c. 
10 
0-04 
10 
15 
01 
15 
In almost all our experiments with morphine we found that the first 
injection of the drug into the jugular vein, even if the quantity 
employed were not very large, produced an immediate arrest of respira- 
tion so severe and so permanent, that in order to save the animal 
artificial respiration had to be resorted to. After this first injection 
enormous amounts of the alkaloid were tolerated with comparatively 
light effect. Immediately after recovery from the first injection, the 
respiratory movement of the air was usually greatly reduced, but if the 
experiment were continued respiration often recovered itself, and 
though enormous amounts of the drug had been employed and coma 
produced, the air movement often finally became almost or altogether 
equal to the norm. Thus in Exp. XVIII., a dog weighing 15J kilos 
took 50 c.c. of a 5 °/0 solution of morphine, which is equal to grammes 
or about 37 grains of the alkaloid; yet at the end of the experiment the 
air movement as well as the rate of respiration were practically what 
they had been in the beginning. In Exp. XIX., a dog weighing 7-5 
kilos took 18 c.c. without distinct change in the air movement. 
In all these experiments in which, after a very large dose of 
morphine, the increase took place in the respiratory movements, the 
reflexes were markedly increased, and often violent convulsive move- 
ments present. As it is well known, morphine has in the lower animals 880 
11. G. WOOD AND D. CERNA. 
a marked stimulating influence upon the spinal cord; and as in our 
experiments, the increase of the respiratory movement of air late in 
the morphine poisoning was always associated with distinct evidences 
of spinal excitement, it is probable that the increased respiration was 
dependent upon or connected with this spinal excitement. 
The detailed explanation of the action of morphine upon the respira- 
tory function in the dog still remaining uncertain, it is very difficult, if 
not impossible, to apply the results which have been obtained with dogs 
to the study of the action of the drug upon the respiratory function in 
man. 
Respiratory Stimulants. 
The drugs which are commonly reputed to be respiratory stimulants, 
whose action upon the movement of air we have studied, are atropine, 
strychnine, and cocaine. 
In our experiments with these alkaloids, we have been careful to see 
that the temperature of the animal and its surroundings was kept 
uniform; and in order to avoid any fallacy which might arise from the 
emotional or other excitement produced by the drug, increasing the 
respiratory movement, we have made with each drug three sets of 
experiments; first, upon the normal animal: second, upon the animal 
partially narcotized with morphine; third, upon the animal completely 
chloral ized. 
As has already been shown, the action of morphine upon the 
respiratory function of the dog is so peculiar that at present much 
importance cannot be attached to experiments made with a supposed 
respiratory stimulant on a dog narcotized with an opiate. On the other 
hand, the chloralized dog is not only entirely freed from the disturbing 
influence of emotion, but is also under the influence of a consistent and 
persistent respiratory depressant; and any drug which is a true respira- 
tory stimulant ought to demonstrate its activity upon the chloralized 
animal. 
We have made four experiments upon the normal dog with the 
sulphate of atropine, using always the one and a half per cent, solution 
injected into the jugular vein. These experiments are as follows: 
Atropine. DRUGS AND RESPIRATORY MOVEMENTS. 
881 
Experiment XXII. 
Time 
min. 
Atropine 
1-2% 
solution 
Movement 
of air 
cubic ft. 
Resp. 
rate 
Remarks 
0 
0-09 
19 
Dog extremely fat and sluggish ; 
weight 32 kilos. 
5 
0-1 
12 
10 
5 c.c. 
18 
0-31 
43 
Five mins, after injection dog breath- 
ing convulsively; otherwise quiet. 
25 
0-17 
23 
Dog very quiet. 
37 
5 c.c. 
43 
0-4 
104 
Breathing irregular in rate. 
53 
0-22 
34 
55 
5 c.c 
61 
0-36 
72 
73 
0-16 
24 
75 
10 c.c. 
83 
0-18 
48 
Dog, when let out, able to walk stag- 
geringly. 
Experiment XXIII. 
0 
0-22 
136 
Dog, weight 26 kilos. 
5 
10 c.c. 
12 
0-36 
125 
18 
0-48 
110 
30 
0-42 
52 
31 
10 c.c. 
43 
0-22 
48 
* 
50 
0-22 
27 
52 
10 c.c. 
55 
0-1 
16 
Dog died directly after last observa- 
tion. 
Experiment XXIV. 
0 
0 05 
11 
Dog, weight 10 kilos. 
5 
10 c.c. 
12 
0-08 
27 
15 
10 c.c. 
20 
014 
33 
• 
35 
0-09 
21 
• 
37 
10 c.c. 
42 
0-12 
20 
52 
0-12 
24 882 
11. G. WOOD AND D. CERNA. 
Experiment XXY. 
Time 
min. 
Atropine 
1-2% 
solution 
Movement 
of air 
cubic ft. 
Eesp. 
rate 
Eemarks 
0 
0-25 
81 
Weight 10‘2 kilos. 
5 
5 c.c. 
11 
0-32 
154 
16 
0-34 
150 
23 
0-46 
162 
25 
5 c.c. 
29 
0-40 
180 
35 
0-36 
180 
38 
10 c.c. 
44 
0-34 
180 
49 
0-29 
52 
10 c.c. 
58 
0-34 
156 
63 
0-37 
65 
10 c.c. 
70 
0-33 
140 
72 
10 c.c. 
76 
0-26 
78 
82 
0-34 
180 
Dog had long been perfectly quiet and 
paralyzed. 
88 
20 c.c. 
93 
0 09 
88 
Dog killed. 
The first effect of the atropine is to enormously excite the respiratory 
function; this primary excitement is soon followed, unless the dose of 
atropine have been very great, by a distinct fall in the air movement, 
which fall, however, is not sufficient to overcome the first rise, so that the 
air movements remain for a long time distinctly above the norm. 
Thus, in Exp. XXII., 5 c.c. increased in eight minutes the air move- 
ment from 0T to 0 31, but seven minutes later the movement was OT7, 
which figure was increased by a second injection of 5 c.c. to 0 4, followed 
in ten minutes by a fall to 0'22. In this experiment the dog was a very 
large one, weighing 32 kilos, and although altogether 25 c.c. of the 
atropine solution were given, the air movement at the end was nearly 
double what it was in the beginning. 
An examination of Exp. XXIY, will show that the results were 
completely parallel to those just discussed. In Exp. XXY, the final 
result of repeated injections amounting in all to 70 c.c. was to reduce DRUGS AND RESPIRATORY MOVEMENTS. 
883 
the air movements much below the norm. In Exp. XXIII. the dog 
was watched until just before death from the atropine, and in this case 
also, after a period of great increase in the air movement, a gradual 
reduction took place: nevertheless, it is somewhat remarkable that the 
movements of the air continued so large almost up to death; the amount 
being OT per minute just before the animal ceased to live. 
In regard to the amount of increase attained by atropine, in the 
first experiment the increase was 300 °/0; in the second, 100 °/0; in the 
third, 100 °/o 5 and in the fourth not quite 100 °/0. 
The experiments which we have made with Morphine and Atropine 
are as follows: 
Experiment XXVI. 
Time 
min. 
Atropine 
l°/o 
solution 
Movement 
of air 
cubic ft. 
Resp. 
rate 
Remarks 
0 
0-1 
25 
Animal under influence of 10 c.c. of 
1 °/0 solution of morphine. Weight 
12 kilos. 
5 
5 c.c. 
10 
0-1 
25 
12 
5 c.c. 
18 
0-06 
20 
20 
5 c.c. 
27 
0-06 
15 
Experiment XXVII. 
0 
0-072 
24 
Air movement been reduced by 5 c.c. 
of 5 °/0 sol. of morphine from 0-12. 
Weight 7 kilos. 
5 
1 c.c. 
10 
0-068 
Profound anaesthesia. 
13 
1 c.c. 
16 
0-056 
24 
21 
2 c.c. 
25 
0-068 
24 
29 
0-078 
18 
35 
2 c.c. 
40 
0-058 
18 
44 
3 c.c. 
50 
0-068 
30 
Killed. 884 
H. G. WOOD AND D. CERNA. 
Experiment XXVIII. 
Time 
min. 
Drug 
Movement 
of air 
cubic ft. 
Resp. 
rate 
Remarks 
0 
30 c.c. 
0-065 
Dog normal. Weight 10 kilos. 
20 
atropine 
1% 
0-12 
22 
24 
5 c.c. 
32 
morphine 
1% 
0-032 
14 
In looking over these experiments it will be noted that in Exp. 
XXVI. and XXVII. the atropine failed entirely to increase the respira- 
tory movements of air in the dog under the influence of opium; indeed 
there seemed to be a distinct decrease in the air movement after the 
exhibition of the atropine. In Exp. XXVIII. a dog 10 kilos in weight, 
whose air movements had been nearly doubled by the exhibition of 30 c.c. 
of a one per cent, solution of atropine, was given 5 c.c. of the one per- 
cent. solution of morphine, the result being a fall of nearly seventy-five 
per cent, in the air movements. 
The results of these experiments are rather surprising, and are 
difficult of explanation. It is possible, however, that the doses of 
morphia were too large for their influence to be overcome by atropine. 
At any rate, before any positive conclusions can be fairly drawn, further 
experimentation seems essential. 
The experiments with chloral and atropine are as follows: DRUGS AND RESPIRATORY MOVEMENTS. 
885 
Experiment XXIX. 
5% sol. 
chloral, 
1 °/0 sol. 
atropine 
Movement 
of air 
cubic ft. 
Time 
min. 
Eesp. 
rate 
Remarks 
0 
30 c.c. 
chloral 
0-15 
Weight 8-9 kilos. 
20 
0-08 
30 
25 
5 c.c. 
atropine 
28 
0-2 
Cheyne-Stokes breathing, with violent 
rapid breathing in paroxysms, then 
quiet slow breathing. 
33 
0-2 
36 
3 c.c. 
atropine 
42 
GO 
r—4 
o 
Breathing as before. 
45 
15 c.c. 
chloral 
48 
0-1 
Some evidence still of Cheyne-Stokes, 
but paroxysms very slight. 
55 
10 c.c. 
chloral 
66 
0-096 
Experiment XXX. 
0 
0-12 
22 
Dog, weight 18-3 kilos: had taken 
before record 13 c.c. chloral solution. 
5 
10 c.c. 
10 
atropine 
0-22 
32 
. 
15 
0-19 
20 
5 c.c. 
23 
atropine 
0-36 
92 
28 
5 c.c. 
32 
atropine 
0-34 
88 
36 
5 c.c. 
40 
atropine 
0-24 
44 
In these experiments the results are concordant. We were able in 
chloralized dogs, by the use of atropine, to increase the air movement 
250 per cent. In Exp. XXIX. it was found possible, by a re-injection 
of chloral, to reduce for a second time the air movement; the antago- 
nism between the respiratory actions of the chloral and atropine being 
very plain. 886 
H. C. WOOD AND D. GERNA. 
These experiments show that both in the normal and in the 
chloralized dog, the salts of atropine greatly increase the respiratory 
movement of air, and lead to the conclusion that atropine is a direct 
and powerful stimulant to the respiratory function. 
The experiments which we have made with strychnine upon the 
normal animal are as follows: 
Experiment XXXI. 
Time 
min. 
Strychnine 
grammes 
Aii- 
movement 
cubic ft. 
Resp. 
rate 
Remarks 
0 
0-05 
95 
Weight 9’kilos. 
3 
0-0002 
12 
0-0004 
19 
0-11 
74 
Dog quiet,buthas spasms when touched. 
27 
0-06 
42 
0-0004 
50 
0-06 
30 
Pronounced spasms. 
56 
0-11 
33 
Dog very quiet. 
Experiment XXXII. 
0 
10 
0-0005 
0-14 
54 
Weight 9-9 kilos. 
20 
0-31 
Died three minutes later 
Experiment XXXIII. 
0 
o-i 
Weight 9-9 kilos. 
5-15 
0-0007 
25 
0-46 
Dog quiet. 
33 
0-21 
Experiment XXXIV. 
0 
0-09 
30 
Weight 8 kilo? 
2 
0-0005 
14 
0-1 
25 
23 
0-09 
24 
26 
0-0005 
33 
0-14 
28 
Reflexes abnormally active. 
42 
0-12 
24 
46 
0-0005 
51 
0-154 
27 
Slight spasms. 
60 
0-36 
94 
Dog quiet. 
70 
0-262 
88 DRUGS AND RESPIRATORY MOVEMENTS. 
887 
Experiment XXXV. 
Time 
min. 
Strychnine 
grammes 
Air 
movement 
cubic ft. 
Eesp. 
rate 
Remarks 
0 
0-5 
Weight 9 kilos. 
5 
0-0002 
9 
0-6 
10 
0-0001 
15 
0-85 
Distinct reflex tremors. 
Experiment XXXVI. 
0 
0-14 
Weight 10 kilos. 
5 
0-007 
10 
0-27 
15 
0-31 
Dog died shortly after last, in spasms 
Experiment XXXVII. 
0 
0-16 
Weight 10 kilos. 
5 
0-00045 
15 
0-19 
18 
0-0007 
25 
0-36 
Experiment XXXVIII. 
0 
0-12 
Weight 8 kilos. 
3 
0-00075 
7 
0-13 
10 
0-00076 
15 
0-26 
An examination of the table given above will show that the results 
are concordant, and that the injection of strychnine produces an extra- 
ordinary increase in the respiratory air movement; the increase in 
Exp. XXXI. amounting to over 100 per cent.: in Exp. XXXII. to over 
100 per cent.: in Exp. XXXIII. to over 250 per cent.: in Exp. XXXIV. 
to 300 per cent.: in Exp. XXXV. to 75 per cent.; and in Exps. XXXVI, 
XXXYIL, and XXXVIII., to considerably over 100 per cent. 
With Morphine and Strychnine we have performed a single ex- 
periment, Exp. XXXIX. (see over). 
The record in this will show that under the influence of the 
strychnine there was an increase in the air respiratory movement of 
60°/0, which increase was afterwards almost completely overcome by a 
re-injection of the solution of morphine. 888 
H. G. WOOD AND D. GERNA. 
Experiment XXXIX, 
Time 
min. 
5 o/0 sol. 
morphine, 
1-4 °jo sol. 
strychnine 
Movement 
of air 
cubic ft. 
Resp. 
rate 
Remarks 
0 
0-1 
15 
Weight 19 ’5 kilos. Reduced by 5 c.c. 
5 °/0 solution of morphine from 0-27. 
5 
0-75 c.c. 
strychnine 
15 
0-16 
15 
Convulsive startings. 
18 
0-15 
24 
25 
8 c.c. 
morphine 
30 
0-16 
Convulsive twitchings still. 
40 
3 c.c. 
morphine 
43 
0-15 
12 
Convulsive movements still. 
50 
5 c.c. 
morphine 
55 
0-11 
15 
The experiments upon chloralized animals are as follows: 
Experiment XL. 
Time 
min. 
Chloral. 
5 «/o sol. 
strychnine, 
grammes 
Movement 
of air. 
cubic ft. 
Eesp. 
rate 
Eemarks 
0 
0-22 
54 
Weight 6-8 kilos. 
0-20 
15 c.c. 
chloral 
25 
0-122 
30 
Animal chloralized. 
28 
0-0003 
strychnine 
35 
0-138 
45 
48 
0-174 
48 
51 
5 c.c. 
chloral 
GO 
0-108 
36 
63 
0-0003 
strychnine 
72 
0-146 
46 
82 
0-15 
57 
84 
0-0002 
Immediately slight spasms. 
strychnine 
94 
0-184 
48 
101 
0-144 
Slight spasms. 
103 
0-0002 
Immediately death in spasms. 
strychnine DRUGS AND RESPIRATORY MOVEMENTS. 
889 
Experiment XLI. 
Time 
min. 
Chloral. 
5 «/0 sol. 
strychnine, 
grammes 
Movement 
of air. 
cubic ft. 
Eesp. 
rate 
Remarks 
0 
0-17 
20 c.c. 
chloral 
0-27 
56 
Weight 8-2 kilos. 
35 
0-142 
60 
36 
0-0008 
45 
strychnine 
0-228 
79 
47 
0-0005 
54 
strychnine 
0-26 
87 
55 
0-292 
72 
57 
0-0005 
65 
strychnine 
0-261 
72 
Dog killed. 
Experiment XLII. 
0 
0-39 
74 
Weight 12-7 kilos. 
0-20 
25 c.c. 
chloral 
35 
0-14 
34 
36 
0-0005 
Complete anaesthesia. 
strychnine 
43 
0-536 
82 
Dog quiet. 
44 
10 c.c. 
chloral 
52 
0-154 
35 
55 
0-0005 
strychnine 
• 
61 
0-236 
62 
62 
0-0005 
strychnine 
65 
0-34 
78 
Eye reflexes return. 
68 
15 c.c. 
chloral 
74 
0-126 
36 
Reflexes gone. 
0 
0-276 
60 
Weight 7-5 kilos. 
0-60 
40 c.c. 
75 
0-114 
32 
85 
0-138 
86 
0-001 
strychnine 
96 
0-13 
34 
98 
0-001 
strychnine 
108 
0-26 
38 
116 
0-26 
51 
Experiment XLIII. 890 
H. G. WOOD AND D. GERNA. 
The results in the above experiments are concordant. In Exp. XL., 
the respiratory air movement, which had fallen to forty per cent, under 
chloral, was restored nearly to the norm. In Exp. XLI., after a 
similar fall under chloral, the respiratory air movement was increased 
distinctly beyond the norm. In Exp. XLIL, before the chloral the air 
movement was 0 39, after the chloral it was o*l4, and was increased by 
the strychnine to 0*536. In Exp. XLIIL, before the chloral the air 
movement was 0*276, after the chloral it fell to o*ll4, but was practically 
restored to the norm by the strychnine. 
The experiments which we have made with strychnine upon normal 
and narcotized animals, are all in accord in showing that the alkaloid 
powerfully influences the respiratory movement of air, and that it is 
therefore a true respiratory stimulant. 
Cocaine. 
The experiments made with cocaine upon the normal animal are as 
follows: 
Experiment XLIY. 
Time 
min. 
1 °/0 sol. 
cocaine 
Movement 
of air. 
cubic ft. 
Eesp. 
rate 
Remarks 
0 
0-254 
20 
Weight 11*3 kilos. 
5 
3 c.c. 
15 
0-48 
24 
19 
5 c.c. 
25 
0-402 
24 
35 
0-54 
no 
40 
0-66 
125 
Animal restless; very excited. 
Killed. 
Experiment XLY. 
0 
0-186 
22 
Weight 10-5 kilos. 
5 
5 c.c. 
12 
0-28 
28 
15 
5 c.c. 
30 
0-42 
40 
40 
0-65 
90 
52 
064 
112 
67 
0-714 
140 
Killed. DRUGS AND RESPIRATORY MOVEMENTS. 
891 
Experiment XLYI. 
Time 
min. 
1 °/o sol. 
cocaine 
Movement 
of air. 
cubic ft. 
Eesp. 
rate 
Eemarks 
0 
0-072 
18 
Weight 5-2 kilos. Very quiet. 
2 
3 c.c. 
10 
0-108 
21 
12 
3 c.c. 
16 
0-11 
19 
19 
5 c.c. 
Violent tetanoid convulsions. 
23 
0-098 
20 
28 
0-072 
15 
Very quiet. 
30 
3 c.c. 
34 
0-062 
21 
Very quiet. 
36 
4 c.c. 
40 
0-25 
36 
Violent convulsions. 
43 
3 c.c. 
Died directly after last dose. 
The above experiments are all concordant in showing that cocaine 
in the normal animal enormously increases the amount of air movement; 
the increase being usually greatest when the tetanoid convulsive move- 
ments produced by toxic doses of cocaine are marked. Under these 
circumstances the increase may amount to two to three hundred per 
cent. 
The only experiments which we have made with cocaine upon the 
narcotized animal are as follows: 
Experiment XLVII. 
Time 
min. 
5 °/0 sol. 
chloral 
1 °/0 sol. 
cocaine 
Movement 
of air. 
cubic ft. 
Eesp, 
rate 
Remarks 
0-30 
45 c.c. 
chloral 
Weight 11-3 kilos. 
35 
0-272 
120 
Corneal reflex very slight. 
40 
8 c.c. 
cocaine 
45 
0-164 
42 
50 
10 c.c. 
cocaine 
55 
0-184 
60 
68 
5 c.c, 
cocaine 
63 
0-22 
67 
5 c.c. 
cocaine 
0-17 
48 892 
H. C. WOOD AND D. CERNA. 
Experiment XLYIII. 
Time 
min. 
5 % sol. 
chloral, 
1 % sol. 
cocaine 
Movement 
of air. 
cubic ft. 
Eesp. 
rate 
Remarks 
0-20 
20 c.c. 
Weight about 10 kilos. 
chloral 
24 
0-14 
23 
25 
6 c.c. coc. 
31 
0-14 
26 
34 
0-2 
33 
Very restless. 
41 
0-22 
24 
50 
0-16 
22 
52 
4 c.c. coc. 
57 
0-22 
33 
62 
0-22 
30 
65 
4 c.c. coc. 
Violent tetanoid convulsions at once. 
72 
0-26 
36 
An examination of the above records will show that Exp. XLVIII. 
in which the animal had received nearly 20 c.c. of the 5 °/0 solution of 
chloral per kilo, the cocaine very distinctly affected the respiratory air 
movement, in fact nearly doubling it; whilst in Exp. XLVIL, in which 
the animal received 45 c.c. per kilo, cocaine was powerless to increase 
the air movement, which steadily and persistently fell under the 
continuing influence of the chloral. 
The conclusions which are deducible from the experiments which we 
have made with cocaine, are: that it acts as a powerful respiratory 
stimulant, whose influence, however, fails in the presence of an 
overwhelming dose of a respiratory depressant. 
Comparative Value of the Respiratory Stimulants. 
The experiments which we have made prove that the three alkaloids, 
atropine, strychnine, and cocaine, are all respiratory stimulants, increas- 
ing the amount of air taken in and out of the lungs; exerting action, 
apparently, by a direct influence upon the nerve-centres which preside 
over the respiratory movements. The question which of these alkaloids 
is the most powerful and reliable in practical medicine, can scarcely be 
answered positively by means of experimentation upon the lower animals. 
It has, however, seemed worth while to make a comparative study, as 
throwing some light upon the practical value of the remedies. 
In the first series of experiments we took three dogs, as nearly alike 
in weight and other characteristics as possible, and injected into the 
jugular vein of each of them 2 c.c. per kilo, of the 5 °/0 solution of chloral, DRUGS AND RESPIRATORY MOVEMENTS. 
893 
and then tested the effect of cocaine, atropine, and strychnine, upon the 
respiratory air movements. In the second series of experiments 3 c.c. 
of the chloral solution per kilo of weight were administered. 
Experiments upon dogs which had received 2 c.c. per kilo of 
a 5 % solution of Chloral. 
Time 
min. 
i 
Drug 
Movement 
of air. 
cubic ft. 
Resp. 
rate 
Remarks 
0 
0-07 
28 
Weiglit 6-1 kilos. Reflexes gone. 
5 
3 c.c. 
Immediate violent tetanoid con- 
4 % sol. 
vulsions; Anally cramps, asphyxia; 
cocaine 
artificial resp. kept up a minute, 
restored to life. 
.12 
0-14 
46 
Still convulsions. 
17 
0-12 
33 
Still convulsions. 
27 
0-08 
24 
28 
2 c.c. 
1 7o SOL 
atropine 
33 
0-09 
26 
36 
2 c.c. 
1% sol. 
atropine 
40 
0-13 
30 
43 
2 c.c. 
1 % sol. 
atropine 
* 
47 
0-12 
37 
50 
2 c.c. 
1 % sol. 
atropine 
54 
0-14 
Experiment XLIX. 
0 
0-16 
90 
Weight 5-9 kilos. Very cpiiet. 
Reflexes very weak. 
3 
3 c.c. 
1 % sol. 
atropine 
7 
0-15 
54 
12 
7 c.c, 
l%sol. 
atropine 
17 
0-14 
22 
0-14 
45 
Experiment L. 894 
H. C. WOOD AND D. GERNA. 
Experiment LI. 
Time 
min. 
Drug 
Movement 
of air, 
cubic ft. 
Resp. 
rate 
Remarks 
0 
0-066 
24 
Weight 5-8 kilos. 
7 
012 c.c. 
1 % sol. 
strychnine 
12 
0-092 
18 
22 
0-098 
24 
Dog killed. 
Experiment upon dogs which had received S c.c. per kilo of 
a 5 °/0 solution 
of Chloral. 
Experiment LIE 
Time 
min. 
Drug 
Movement 
of air. 
cubic ft. 
Eesp. 
rate 
Eemarks 
0 
0-37 
140 
Weight 18 kilos. 
5 
3 c.c. 
Dog ceased breathing directly after 
1 •/. sol. 
injection. Artificial respiration 
cocaine 
required to bring him to. 
10 
0-24 
28 
25 
0-29 
28 
27 
2 c.c. 
1% sol. 
cocaine 
30 
0-39 
44 
Dog struggling. 
35 
0-52 
48 
42 
0-53 
104 
Experiment LIU. 
0 
0-25 
50 
Weight 22 kilos. 
5 
5 c.c. 
l%sol. 
9 
atropine 
0-46 
85 
15 
0-39 
102 
20 
5 c.c. 
1 % sol. 
26 
atropine 
0-45 
70 
35 
0-52 
96 
41 
10 c.c. 
1 «/0 sol. 
49 
atropine 
0-43 
114 DRUGS AND RESPIRATORY MOVEMENTS. 
895 
Experiment LIY. 
Time 
min. 
Drug 
Movement 
of air. 
cubic ft. 
Eesp. 
rate 
Remarks 
0 
0-25 
128 
Weight 15'8 kilos. 
5 
0’1 c.c. 
1% sol. 
strychnine 
10 
0-31 
160 
17 
0-39 
180 
20 
0'4 c.c. 
1 % sol. 
strychnine 
26 
0-33 
196 
30 
0’2 c.c. 
1 % sol. 
strychnine 
35 
0-34 
168 
Tetanic spasms. 
45 
Dog died of strychnine poisoning. 
An examination of the results which we have tabulated will show 
that the cocaine doubled the air movement after the 2 c.c. of chloral per 
kilo, and increased the air movement nearly fifty per cent, after the 3 c.c. 
The atropine did not increase the air movement after the 2 c.c, of chloral 
materially, but more than doubled the air movement after the 3 c.c.; 
whilst the strychnine increased the air movement to fifty per cent, after 
the 2 c.c., and also after the 3 c.c. of chloral solution. 
In endeavouring to formulate from these six experiments a conclusion 
as to the comparative value of the three respiratory stimulants, an almost 
insuperable difficulty appears in the lack of uniformity of result. We 
can assign no reason why the atropine failed in the one case and acted 
so extraordinarily in the other. This irregularity or inequality of action, 
however, is paralleled in the experiments with atropine which we 
recorded earlier in this paper; since the atropine failed to increase the 
respiratory air movement in every experiment which we made upon the 
dog narcotized with morphia. 
The influence of the cocaine as a respiratory stimulant has through- 
out our research been found very pronounced, and in these recent 
experiments its influence was even more marked than that of strychnine. 
Cocaine, however, in Exp. XLYII. did not increase in the chloralized dog 
the movement of air. On the other hand, in no experiment with 
strychnine have we failed to obtain a result, and we think, therefore, whilst, 896 
H. C. WOOD AND D. GERNA. 
at times and perhaps usually, the influence upon the respiratory air 
movement of atropine and of cocaine is greater than that of strychnine, 
yet strychnine is more positive and certain in asserting its influence in 
the face of powerful respiratory depressant drugs than are the other 
alkaloids. 
Although the conclusions which we have reached have been based 
solely upon the results of experiments made upon dogs, we think they 
are in accord with results obtained by clinicians in the treatment of 
disease, and that they apply to the man as well as to the dog. The 
difficulty with the use of massive doses of cocaine and strychnine in 
practical medicine is the danger that attends their action on other 
portions of the nervous centres than the respiratory tract, and atropine, 
though probably not the most certain and powerful, seems the 
safest drug of the three, when it has been determined to get to the 
fullest possible influence of the agent used. We would call attention, 
however, to the fact that in Exp. XLIX., after cocaine had been given 
to the point of producing convulsions, and the first excitement of the 
respiratory movement had somewhat subsided, atropine exerted a pro- 
nounced influence in increasing respiration; and we believe that the 
best results can be obtained in practical medicine, by the simultaneous 
use of two or more of the respiratory stimulants. Cocaine and 
strychnine have so much similarity of action upon the nerve-centres 
that the use of one will probably increase any danger that may have been 
incurred by the administration of large doses of the other. The relations 
of atropine to cocaine and strychnine, however, are different, and it 
would seem that by the consentaneous use of atropine and strychnine, 
or of atropine and cocaine, may be obtained the advantages of what has 
been denominated by Dr H. C. Wood in his Treatise on Therapeutics, 
as “crossed action;” the two drugs touching and reinforcing one 
another in their influence upon the respiratory functions, and spreading 
wide apart from each other in their unwished for and deleterious 
actions. 
University of Pennsylvania, 
June 20, 1892. 
CAMBRIDGE : PRINTED BY C. J. CLAY, M.A. AND SONS, AT THE UNIVERSITY PRESS.