6I2.2I:6I5.7I2.

32

THE RESPIRATORY MOVEMENTS IN GRADUAL

HYDROCYANIC ACID POISONING.
BY HAROLD TAYLOR.
(From the Physiological Laboratory, Cambridge.)
L u M S D E N (3) has described various types of respiratory movements ob-
tained by cutting through the brain stem at different levels. The present
experiments have been carried out to ascertain whether the types of
respiratory movements described by Lumsden are found during the
different stages of HCN poisoning.
The centres which Lumsden assumes in the mammal are (1) the
pneumotaxic centre, (2) the "apneustic" centre, (3) the expiratory
centre, and (4) the gasping centre in this order, from above downwards.
He considers that normal respiration is under the control of the top two
centres, the other two centres only functioning in abnormal conditions.
Inspiration is under the control of the " apneustic " centre and the nervous
control of 'normal respiratory movements consists of alternate release and
inhibition of the apneustic centre. This alternate release and inhibition
of the apneustio centre is effected by the pneumotaxic centre which is
the centre most susceptible to changes in C02 and acid in the blood. The
lower two centres are normally inhibited by the upper two centres.
By cutting between the top two centres Lumsden was able to get
respiration of the "apneustic type," i.e. an inspiratory tonus which per-
sisted until deoxygenation of the blood brought the tonus to an end. By
cutting the brain stem lower down gasps only were obtained. The effects
of the possible expiratory centre are not obtained so easily.
Lu m s d en also found that the same effects were obtained in bulbar
anemia obtained by shutting off the blood supply to the brain. As the
effect of HCN is to prevent oxidation the action of HCN ought to be
similar to the effect of aneemia, provided that death does not take place
too rapidly. If the brain stem dies gradually under the influence of HCN
the various types of respiratory movements can be compared with those
claimed by Lumsden.
Evans(2) has studied the effect of injections of sodium cyanide on
 EFFECT OF HN -ON RESPIRATION. 125
the respiration and finds a marked increase in the respiratory rate and
amplitude at the beginning of cyanide poisoning with a subsequent
reduction in the rate of respiratory rhythm. As Evans's record of the
respiration was made by means of a tambour on the tracheal tube, only
movements of the air in the trachea are recorded and inspiratory tonuses
would not be recorded (Lumsden(6,7)). Evans also remarks that
different parts of the central nervous system are affected to a different
extent and that small doses of cyanide seem only to affect the cerebrum.
B unge (1) described the effect on the respiration of breathing cyano-
gen. His experiments, like those of Evans, are inadequate to show
whether or not "apneuses" were obtained.
Experimental procedure.
The respiratory movements have in most cases been registered by the
method advocated by Lumsden, i.e. glycerine tambours on the thorax
and the abdomen. In some experiments a tracheal tube has also been
-used, and with a few experiments on rabbits, Head's method of record-
ing the movements of a slip of diaphragm muscle has been utilized. The
majority of the experiments have been carried out on cats.
The tambour for use in the thorax was of the largest possible diameter
(8.5 cm.) to give a maximum movement to the recording tambour. The
abdominal tambour was much smaller (5-5 cm. diameter) as the record
here is easier to obtain. Each tambour was made of 'a double layer of
rubber with glycerine between the rubber surfaces, so that the surface to
be placed on the thorax or abdomen was always convex. The convexity
was not very marked, and the centre of each tambour was about 10 mm.
above the level of the sides. The thoracic tambour was placed on the
right side of the thorax to reduce the interference of the heart beat, and
the abdominal tambour was placed on the mid-line of the body, where
the respiratory movements are maximal. The tambours were fixed in
position by binding them with bandages, the pressure not being great
enough to interfere with the respiratory movements. The whole of the
abdomen was enclosed in bandages so that it was under equal pressure,
otherwise the position of maximum movement might have been altered.
The records were obtained by attaching these tambours by semi-pressure
tubing to Brodie tambours which recorded on the kymograph. On both
the abdominal and thoracic recording tambour inspiration was indicated
by an upstroke and expiration by a down stroke.
The HCN was used in gaseous form and was set up in a respiration
chamber of 6-3 cu. metres capacity. In most of the experiments the
 126 H. TA YLOR.
animal was inside the chamber and breathed through the nose and occa-
sionally through a tracheal tube. In experiments where air was pumped
into the lungs and a tambour placed on the tracheal tube, the animal was
outside the chamber and breathed the air in the chamber on an external
circuit via valves and a tracheal tube. This was also the case where
Head's method was used on rabbits. The kymograph was outside the
chamber, connection being made between the glycerine tambours on the
animal and the recording tambours by tubes which passed through
orifices in the glass, the chamber however being still air-tight.
The gaseous HCN was produced by pouring liquid anhydrous HCN
in a trough and blowing air over it by means of a fan. In each experi-
ment the concentration was analysed by drawing off 25 litres and absorb-
ing the HCN in caustic soda, the solution being then titrated against
silver nitrate. The error due to the breathing of the animal was very small,
although in a few experiments there might have been a reduction in the
HCN concentration owing to an observer having been in the chamber for
a considerable time.
The cats were all anesthetized by either chloroform or chloroform and
ether, whilst in the case of rabbits sodium luminal was injected and the
rabbit then chloroformed. The animal was placed in the chamber without
any HCN and a record of the normal respiration taken. The vagi were
then cut and the effects on the respiration were observed. The HCN
atmosphere was then set up and the record of the respiratory movements
obtained until the animal died. The vagi were cut to aid the formation
of apneuses, as Lumsden found them difficult to obtain in bulbar aneemia
with the vagi intact. A number of experiments were done with the vagi
intact.
Effect of HCN on the cat's respiration.
Twenty-five experiments were done on cats, the concentration of
HCN varying from 0-38 g. per cu. metre to 0-23 g. per cu. metre. The
most usual concentration was of the order of 0 30 g. per cu. metre. The
cats varied very much in the length of time they survived, but with the
lower concentrations the cat could be got to live for 2 hours and generally
lived for 30 minutes.
The typical effect of HCN is shown on the kymograph tracing. In
the figures given the thoracic tracing is the upper one and the abdominal
tracing the lower one. As the animal was breathing HON the effects
developed gradually as the HCN accumulated in the blood stream. By
this means the effects were spaced out, and by varying the concentration
of HON the time between the onset of HCN poisoning and death could
 EFFECT OF HCN ON RESPIRATION. 127
be extended so that each phase was clearly presented. The disadvantage
of injecting HCN solution was that the maximum effect was obtained
very rapidly and only the later phases could be examined with any
certainty.
In the tracing with a chloroformed cat the first effect of the HCN was
to cause a slight increase in the amplitude of the respirations, but not in
the rate, although the rate might increase to some extent immediately
afterwards. Fig. 1 shows the first effects of the HCN on a cat with
the vagi cut.

Fig. 1. Beginning of effect of HCN (Cat). Top: thorax. Bottom: abdomen.

Time in secs. HCN =037 g. per cu. metre.

Next the respiration tended to become irregular, short periods of

inspiratory tonus being mixed with normal respirations. During this
phase also the record was quite liable to be unreliable owing to the HCN
causing muscular movements in the cat. These movements did not occur
when the cat was heavily under the anaesthetic. Inspiratory tonuses now
became more marked and for a time respiration is all of the " apneustic "
type and increasing in amplitude. These are shown in Fig. 2. The "ap-
neuses" showed on both the thoracic and abdominal tracings and were
very rarely sustained contractions, there being some slight movements
of the lever in the inspiratory position.
128 H. TA Yl OR.
The lengths of the "apneuses" differed widely, the longest obtained
being 20 seconds, although normally they were of 6 to 8 seconds' duration.
The slight movements at the peak of an " apneusis " always corresponded
to inspiration when the experiment was tried with a tambour on the
tracheal side tube.
The length of time of the "apneusis" gradually diminished as the

'JUITITITMITIMMI jF111ITTTYfIll rryl rM MT. r,,M.

Fig. 2.

Fig. 3.
Fig. 2. "Apneuses" (Cat). Top: thorax. Bottom: abdomen. Time in secs.
HCN =0-37 g. per cu. metre.
Fig. 3. "Apneustic gasps (Cat). Top: thorax. Bottom: abdomen. Time in sees.
HCN =0-37 g. per cu. metre.

HCN became more effective and a phase of "apneustic gasps" was

obtained, i.e. gasps with two or three peaks as shown in Fig. 3. The change
from "apneuses" to gasps was gradual, the last signs of "apneuses"
being gasps with two peaks. Gasping then followed, the amplitude of
the gasps being generally much greater than that of respirations, but
after a time the amplitude diminished fairly quickly and the animal died.
Gasps are shown in Fig. 4 just before death. Figs. 1, 2, 3, and 4 are all
 EFFECT OF HCN ON RESPIRATION. 129
from the same cat: Fig. 2, 6 minutes from the setting up of the HCN;
Fig. 3, 17 minutes and Fig. 4, 30 minutes.
If the animal died too rapidly the " apneuses " might not be marked
and only appeared as a few gasps with double peaks.
When gasping took place the movements were at their maximum
amplitude, thle gasp appearing to be a sudden maximal contraction of
the inspiratory muscles. The mouth always opened during gasping irre-
spective of whether the animal was breathing via the nose or a tracheal

I-I

Fig. 4. Fig. 5.
Fig. 4. End of gasping (Cat). Top: thorax. Bottom: abdomen. Time in sees.
HCN =0 37 g. per cu. metre.
Fig. 5. Gasping: rise in thoracic tracing (Cat). Top: thorax. Bottom: abdomen.
Time in sec. HCN =0-32 g. per cu. metre.

tube. The mouth was also open during some of the longer apneuses. When
a gasp took place the abdominal lever rose before the thoracic lever and
reached the summit first. In many cases the beginning of a rise of the
abdominal lever coincided with a slight downward movement below the
base line of the thoracic lever, after which the thoracic lever rose rapidly.
This is the case in Fig. 4. The fact that the abdominal lever moved first
PH. LXIX. 9
 130 H. TA YLOR.
and was sometimes accompanied by a fall of the thoracic lever might be
due to the diaphragm having contracted slightly before the intercostal
muscles.
Besides the effects described in many cases temporary rises of either
the thoracic or abdominal lever have occurred (Fig. 5). The lever rose
to a maximum and then fell back to normal gradually, the total time
having been of the order of 1 or 11 minutes, with the respirations or gasps
superimposed.
The normal effects of HCN on the cat's respiration reproduce types
of respiratory movements similar to those obtained by Lumsden by
section of the brain stem. The effects are obtained in the same order as
by cutting through the brain stem in sections from above downwards.
Lumsden's experiments were done mostly on cats, so the experiments
with HON can be compared with them.
The effects show a gradual changing of the respiration from a normal
to an "apneustic" type. This "apneustic" phase is not as marked as
when obtained by sections in the brain stem, as probably the whole of
the brain is affected to some degree by the HCN. The gasping phase at
the end is almost identical with the phase obtained by cutting low down
in the brain stem. The "apneustic" phase and the gasping phase seem
to be running together for a short time as shown by "apneustic" gasps
obtained. No trace of an expiratory centre was found.
Irregularities are sometimes found in the abdominal tracing during
the early stages of the gasping phase. These will be discussed later.
Effect of HCN on the rabbit's respiration.
Lumsden (3) has pointed out that rabbits differ from cats in the effect
obtained by cutting through the brain stem. The effect of the vagus is
more marked and the positions of the sections show differences. Their
reaction to HON is also different in some respects.
Twelve experiments were done on rabbits, the HON concentrations
varying from 0-31 g. per cu. metre to 0-42 g. per cu. metre, with an average
of 0-38 g. per cu. metre (i.e. a higher concentration than for cats). The
rabbits could easily be made to survive 30 minutes, and would appear to
survive indefinitely in the case of lower concentrations.
The experiments were carried out in the same way as the experiments
on cats, only 0-2 g. of sodium luminal was injected intravenously half an
hour before the chloroform was administered. The same glycerine tam-
bours were used in both cases.
The chief difference between the effect on rabbits and that on cats
 EFFECT OF HCN ON RESPIRATION. 131
was that "apneuses" were not obtained except in rare cases. On only
one experiment with a rabbit were "apneuses" obtained.
In the rabbit the preliminary effects of the HCN, i.e. a slight increase
in the amplitude of the respirations, were the same. The respiration, after
some irregularities, settled down to a steady rhythm, but after a time
the amplitude decreased and there was a cessation of respiration. This
pause extended sometimes for 3 or 4 minutes and the animal appeared
to be dead. Gasps, however, of small amplitude then began to appear.
In some cases at the beginning of gasping the abdominal lever gave 4n
upward stroke, whilst the thoracic lever registered a down stroke suggest-
ing contractions of the diaphragm alone of sufficient power to suck in
the thorax. The gasps increased in amplitude up to a maximum and
then began to decline, whilst at the end the thoracic tracing sometimes
registered a small down stroke only. Occasionally there would be a short
pause between two sets of gasps. Fig. 6 shows the beginning, end and

2
Fig. 6. Gamping (Rabbit). Top: thorax. Bottom: abdomen. Vagi cut:
(1) Beginning. (2) Late middle period. HCN = 0-42 g. per cu. metre.

the middle period of gasping in a rabbit. It will be noticed that at

the beginning the abdominal and thoracic levers register in opposite
directions.
A pause between the breathing and the gasping was not always
obtained, but seemed to be the general rule.
9-2
132 H. TA YLOR.

Effect of pumping air when animal is affected by HCN.

When air was pumped in and out of a cat's lung during the gasping
stage under HCN poisoning, the pumping did not produce apncea although
the cat was not breathing quickly. The muscular signs of gasping such
as opening the mouth, etc., continued during the action of pumping,
although the rate of ventilation was considerably quicker than the normal
gasping. The effect was the same in a rabbit where it was shown by using
HIead's method of recording the contractions of a slip of diaphragm
muscle. Lumsde n(5) states that in an animal gasping as a result of a
section of the brain stem, C02 and 02 will affect the rhythm and amplitude
of the gasps, but apncea cannot be produced. Thus the gasping produced
by HCN resembles the gasping produced by section of the brain stem in
that apncea cannot be produced by over-ventilation.
Over-ventilation did produce a change in the character of the gasps

Fig. 7. Double abdominal movements (after pumping'air) (Cat). Top: thorax.

Bottom: abdomen. Vagi cut. Time in sees. HCN=0-28 g. per cu. metre.
 EFFECT OF HCN ON RESPIRATION. 133
in the cat, but not the rabbit. The abdominal lever now registered two
strokes to one on the thoracic lever, the extra stroke taking place whilst
the thoracic lever was at rest. The movements were quite regular and
gradually passed off, but could be reproduced easily. The extra move-
ment was sometimes of larger amplitude than the gasp. These are shown
in Fig. 7. They sometimes appeared in the normal tracing of HON
poisoning between the " apneustic " and the gasping state, and occasion-
ally preceding an " apneusis." The movement seemed to be due to a con-
traction of the abdominal muscles, but it is not accompanied by any
passage of air in or out of the trachea.
In an animal, cat or rabbit, which had been allowed to reach the
gasping stage, artificial ventilation with the same HCN mixture produced
rapid failure of all respiratory movements. Presumably more HCN was
absorbed, and the rate of detoxification in the body could not keep pace
with the absorption.
Influence of the vagus on "Apneuses."
Lumsden(7) has pointed out that the "apneuses" were difficult to
obtain in bulbar ansemia if the vagi were intact. Apneuses were not very
marked in cats with intact vagi during HCN poisoning. Short " apneuses,"
however, do appear, and occasionally " apneuses" appear which pass off
again leaving long respirations. If the vagi were cut after the onset of
HON poisoning " apneuses " followed, though not always immediately, de-
pending on the degree to which the cat was affected. The vagi appeared to
inhibit "apneuses" as found by Lumsden in sections of the brain stem.

CONCLUSIONS AND SUMMARY.

The effect of HCN on the respiration gives the same series of pheno-
mena as found by Lumsden by cutting sections at various levels of the
brain stem. The effects are obtained in the same order as those given by
the cuts from above downwards.
The action of HCN on cats is what would be expected by assuming
the successive elimination of the " pneumotaxic " and "apneustic " parts
of the respiratory mechanism. In the rabbit both these mechanisms, if
they exist separately as such, seem to be eliminated together, but gasping
is very similar to gasping in cats.
Over-ventilation with air does not produce apncea in a gasping animal,
nor do the respiratory movements stop during the act of over-ventilation.
In a cat the form of the gasps is altered after artificial ventilation.
134 H. TA YLOR.
Artificial ventilation with the HCN mixture produces failure of the
respiratory movements.
Cutting the vagi appears to aid the formation of apneuses produced
by HCN.
I must thank Prof. J. B arcro ft, at whose suggestion the work has
been carried out, for much valuable advice and criticism.

REFERENCES.
1. Bunge, B. Arch. exp. Path. Pharmak. 12. p. 41. 1880.
2. Evans, C. L. This Journ. 53. p. 17. 1919.
3. Lumsden, T. Ibid. 57. p. 153. 1923.
4. Lumsden, T. Ibid. 57. p. 354. 1923.
5. Lumsden, T. Ibid. 58. p. 80. 1924.
6. Lumsden, T. Ibid. 59. Proceedings, p. lvii. 1924.
7. Lumsden, T. Ibid. 59. Proceedings, p. lviii. 1924.