REMAEKS ON THE ACTION OP SNAKE POISON ON THE BLOOD.
By
G. C.
Rot, M.D., F.R.O.S. (Lond.)
of my experiments with snake posion, with a view to find out the antidotal power of some remedial agents, my inquiries were diverted into a different channel from the microIn
one
scopic appearance which the effusion at the seat of puncture presented. I introduced some dry cobra poison into the thigh of a fowl through a small valvular puncture, and stitched it up to prevent it flowing out. After death I examined the local effect of the poison, and found the cellular tissue around the puncture extensively infiltrated with greenish-looking serum. A little of this was scraped and put under the microscope, and it was found to contain a few blood corpuscles and numerous small cellular bodies. Now, where did these come from ? Were they new productions or some altered constituents of the blood ? Whilst watching the field, with this thought working in my mind, I saw presently some nuclei getting prominent on the surfaces of the blood globules, the attenuated cell membrane burst and gave exit to its contents which were found to be identical in size, appearance, and in the possession of a central dot, "with the cellular bodies above described. Thus one step in the process of inquiry was reached?that one of the local effects of the cobra poison was to produce an interstitial effusion which consisted chiefly of cellular bodies entangled in fluid plasma, these bodies being derived from the blood by the solution of the cell wall and liberation of its contents. Now, is the effect of cobra poison on the blood globules constant, and is it the result of a chemical, vital, or dynamical change? To determine this question, some goat's blood was procured. After separation of the clot, the bright crimsoncoloured fluid, about half an ounce in quantity, was treated with about two grains of the poison and kept under observation. A similar quantity was kept separate in another test tube for
a
In an hour the contents of the the sake of comparison. poisoned tube changed to a dark venous colour, and after 24 hours it was observed that, "Whilst the fluid without the poison had settled into two strata, a red crassamentum below and a
above, the poisoned tube remained uniformly microscope its corpuscles seemed somewhat swollen out and globular (?). No other change was visible in it beyond the commencement of incipient decomposition. Next day the external appearance of the fluid continued the same, but a marked change had taken place in its internal constituents, viz., disappearance of all trace of blood corpuscles, and the teeming of the field with vibriones in active movement, whilst in the unmixed blood the corpuscles were still entire and unchanged. This was the second acquisition in this step of my enquiry?that the local effect of cobra poison on blood was not that of a vital change. Its action on blood corpuscles was to destroy their tendency to adhesion and sink to the bottom, alter their colour, and produce speedy decomposition and dissolution of the cell wall. As the blood globules in Mammalia are not nucleated bodies, so nothing remained visible in the field of the microscope after solution of the membrane, whilst the blood of
limpid dark.
serum
Under the
fowls abounded with nuclei. Dr. Halford's cellular bodies found after death from snake-bite might have been the escaped contents of the white corpuscles of human blood. The third point for enquiry was?how far the appearances above noted would throw light on the modus operandi of cobra
poison, and death from its effects ? We have seen that the poison kills, so to speak, the blood corpuscles by its immediate topical
THE INDIAN MEDICAL GAZETTE.
action. As many of them as come into contact with it are at devitalized. They cease to adhere to each other and form
once
into rouleaux. They no longer cbange colour on exposure to air and absorb oxygen. The dark venous colour above referred in the iron of the to probably bears reference to some change
and the tendency to early decomposition bespeaks early The dissolution of the cell wall, which has been also noticed by Dr. Hilson in his published reports of two cases I is (vide Indian Medical Gazette, October 1873) hastened, believe, imbibition of fluid in consequence of precipitation of hsema-
blood,
death.
by
ine within the cell wall, followed by attenuation of the membrane and rupture. Some of the phenomena mentioned require a passing explanthe blood was noticed by Sir ation. Thus the venosity of and Dr. Brunton in their experiments, but they
Joseph Fayrer qualify their observation
with the remark that it turned red
on
I observed similar exposure to air. In my experiments, also, change, but it was not permanent, inasmuch as it resumed its original colour after a short interval. The difference will be
best detected by examining side by side the poisoned blood and In my another fresh specimen from a decapitated animal. experiment, No. I, the blood collected after death changed
dirty greenish colour in half an hour on the addition of speck of the poison. This change was so constantly observed, even without such an addition, that I believe I may take the liberty of setting it down as a settled question. Dr. Hilson refers to the blood in his cases as being claret-coloured and fluid, but the fluidity observed by him does not tally with that observed by me. My experiments, however, were conducted on inferior animals, and might not this fact, as well as the uncertainty of the species of snake by which his patients were bitten, afford some clue to the solution of the discrepancy ? Until further confirmatory observations are forthcoming, we must be content to place the question under the heading of undetermined facts. Early solution of the cell membrane I have characterized as a putrefactive change, and that the cobra poison has the power of producing speedy decomposition is corroborated by the experiments of Fayrer and Brunton, who observed into
a
another
the
same
condition in the muscles after death.
Granted, therefore, that
primary effect of cobra poison destroy the vitality of the blood corpuscles, I will try to explain the symptoms observed during life in accordance with that hypothesis. The blood ceases to be
on
the blood is of
a
the
nature to
carrier of oxygen and remains venous in colour. Nutrition of the organs, through which the poisoned blood flows, remains in abeyance, and the sensitive organs, as the nervous centres, are the first to sympathize. The patient feels as if
a
his sensibilities are the limbs. Actual
intoxicated,
and general weakness creeps over of the limbs I have seldom observed, for I have noticed in a fowl that the inability to move the legs was more owing to drowsiness than to actual loss of mobility. of a under The staggering gait snake poison is described patient as like that of a man under the influence of some
Though ordinary limb, a stronger
blunted, paralysis
volition may fail to
inebriating drug.
produce a response in the invariably elicits contractility, and reflex sensation is generally retained to the very last. The patient turns livid or blue in the face, his temperature falls, respiration is quickened, and deep somnolence ushers in a mode of death which we all know as characteristic of death by apnoea. In this stage the respiratory nervous centres may co-operate in hastening the fatal issue, and convulsions may be noticed. The respiration stops, though the heart continues to beat for a few stimulus
minutes after death. Thus it seems
probable
bite is not the result of the direct action of the poison on the nervous centres, as has been generally supposed, but on the Immediate application of a ligature above the seat of puncture stays the process of dissolution by limiting the action of the poison on a small portion of the blood itself. If the blood.
1, 1877.
quantity of poison introduced is insufficient to act on the mass of blood, recovery can be fairly expected, though the corpuscles destroyed may not be restored. In such cases, the inflammation of cellular tissue that follows is but an indication of the poor condition of the blood and septic poisoning. I have not been able to confirm the fact noticed in
Fayrer and I5runton's experiments of the poison proving fatal when swallowed. For though the bat, in my experiment No. Ill, died shortly after with profuse foaming at the mouth, and all the characteristic symptoms of snake poisoning, the same result was not observed in the case of fowls. It should be remarked that the bat was starving the whole night and was constantly biting and snapping at every thing since its capture,
which might have abraded the buccal
mucous membrane, absorption of the poison, whilst the fowls took it without any struggle. That the poison deteriorates in virtue by long keeping can be asserted without any fear of contradiction, and I have myself observed the difference in its activity as it grew older in my
affording
solution of
continuity
for
keeping.
From the hypothesis I have thus tried to enunciate, it will be evident that the antidotal power of remedies is questionable. We can try to life the and the
by eliminating
prolong
poison
devitalized blood by venesection, and substituting at the same time fresh blood by transfusion to keep up the function of the
vital organs, whilst oxygen must be suppliei by artificial respiration and the internal administration of such remedies as readily part with it in their sojourn in the circulation, such as creosote, chlorate of potash, deutoxide of hydrogen, sulphurous acid, &c. Inasmuch as the last also possesses antiseptic power, I will suggest its intravenous injection with a view to neutralize, if possible, the effects of the poison. In my future experiments, I will proceed according to these data and report the results
obtained therefrom,
EXPERIMENTS. June
18th, Hazctribagh.?The poison of a cobra ("kaota, was procured in October 1876, from Burdwan, and preserved tightly corked in a phial and excluded from light. It was a limpid fluid when fresh, but by long keeping had settled into a thick curdy substance, something like bits of caseine, with It had a faint ammoniacal smell. some fluid floating on the top. Under the microscope, the white bits were found to consist of granules. They were unaffected by acetic acid, but became more distinct on the application of liquor potassse. The poison of a gohlioora, which was obtained at the same time, had solidified into a dry white stuff. Experiment No. At
8-30 a.m., in weight,
a
quantity
of
poison
I. of
L-aola, about ?
a
introduced into the right thigh of a middle-sized fowl through a slit made in the skin, which was In 15 minutes it got stitched up.
grain
was
drowsy?30
subsequently
minutes closed its eyes, and the head drooped ; was disinclined to move, but hopped when pushed on ; became insensible and died in one hour. Chest opened immediately after death. The heart was contracting vigorously and contained fluid blood, which coagulated soon after exposure to air. A drachm of this was immediately collected in a test tube. It separated into two layers?a red serum and a congulum. The sanguinolent fluid was drained off and put into a test tube. On the addition of a speck of it changed in half an hour into a dirty greenish colour. Under the microscope the corpuscles were found separate.
poison
The cellular
that the fatal termination after snake-
[December
puncture of this
was
was
corpuscles
tissue in the immediate neighbourhood of the infiltrated with greenish-looking serum ; a little
scraped and
and examined.
of the corpuscles if about to come out.
some as
It consisted of a few blood small dotted cells. The nuclei of were found prominent on the cell wall,
numerous
morning, when it
was
The liquid wa3 kept over till next found to have retained its greenish colour
December 1,
A MIRROR OF HOSPITAL PRACTICE.
1877.]
but no trace of entire blcod corpuscles -was found, and the field bodies observed iu the previous was full of those cellular examination. Experiment No. II.
goat's blood was procured. The coaguseparated; the fluid was bright crimson in colour To one specimen, measuring nearly half an ounce, about 2 grains of the poison was added, and another was kept pure The colour of the poisoned blood as a standard of comparison. changed in one hour, and next day it was persistent. It remained uniformly dark, whilst the unmixed one had settled into two strata. The corpuscles of the pure blood were aggregated into masses, whilst the poisoned ones were distinct. On the 21st no blood corpuscle was found in the poisoned fluid, 19th June.?Some
lum was
were there any molecular bodies, but the field was teemThe corpuscles of the with vibriones in active movement.
neither
ing
pure fluid were entire. 21 st June? About a drachm of this poisoned blood was injected into the thigh of another fowl. It showed signs of poisoning in quarter of an hour, and died one hour after with all the
characteristic symptoms. Experiment No. III. 4th July.?A bat, captured the previous night, was made to take into its mouth some cobra poison of about a pea in size In quarter of an hour it grew lethargic, and did not attempt to bite when disturbed. In 20 minutes it was foaming at the
twitchings of the hind legs. It could not fix itself any longer on the wall, and died in that torpid state in half After death its blood was allowed to drain into a test an hour. tube. The contents of the corpuscles were found as if conmouth and had
tracted towards
the centre, and were encircled with a ring of the clot, which was originally
bright halo. The colour of bright crimson, had changed to
dark venous.
Experiment No. IY. 14th July.?Gave some poison of goJchoora, about a pea in size, to a fowl. It had a strong ammoniacal smell. The fowl swallowed it without any struggle. It felt drowsy in one hour, and showed disinclination^ move, but the effect passed off in another hour, and it was as active as ever. 15th July.?The same quantity of the poison was introduced under the skin of the same animal. The effect was stronger ; it dozed and sat still, but in two hours it was running about and completely shook off the effect. The poison had evidently loss its virtue. 26th July.?A fowl was made to swallow the poison of Jcaota about double the size of a pea. It showed no symptoms of poisoning. The same poison, about a pea in size, was introduced hypodermicallv into the same fowl two hours after. It died in one and half hour with convulsions, and all the other symptoms
poisoning. Its blood was examined after death and found undergone the some changes as were observed in the previous experiments. For confirmation, another fowl was made to swallow the same quantity of the poison, but it had no of snake
to
have
effect.
317
By
G. C.
Rot, M.D., F.R.O.S. (Lond.)
of my experiments with snake posion, with a view to find out the antidotal power of some remedial agents, my inquiries were diverted into a different channel from the microIn
one
scopic appearance which the effusion at the seat of puncture presented. I introduced some dry cobra poison into the thigh of a fowl through a small valvular puncture, and stitched it up to prevent it flowing out. After death I examined the local effect of the poison, and found the cellular tissue around the puncture extensively infiltrated with greenish-looking serum. A little of this was scraped and put under the microscope, and it was found to contain a few blood corpuscles and numerous small cellular bodies. Now, where did these come from ? Were they new productions or some altered constituents of the blood ? Whilst watching the field, with this thought working in my mind, I saw presently some nuclei getting prominent on the surfaces of the blood globules, the attenuated cell membrane burst and gave exit to its contents which were found to be identical in size, appearance, and in the possession of a central dot, "with the cellular bodies above described. Thus one step in the process of inquiry was reached?that one of the local effects of the cobra poison was to produce an interstitial effusion which consisted chiefly of cellular bodies entangled in fluid plasma, these bodies being derived from the blood by the solution of the cell wall and liberation of its contents. Now, is the effect of cobra poison on the blood globules constant, and is it the result of a chemical, vital, or dynamical change? To determine this question, some goat's blood was procured. After separation of the clot, the bright crimsoncoloured fluid, about half an ounce in quantity, was treated with about two grains of the poison and kept under observation. A similar quantity was kept separate in another test tube for
a
In an hour the contents of the the sake of comparison. poisoned tube changed to a dark venous colour, and after 24 hours it was observed that, "Whilst the fluid without the poison had settled into two strata, a red crassamentum below and a
above, the poisoned tube remained uniformly microscope its corpuscles seemed somewhat swollen out and globular (?). No other change was visible in it beyond the commencement of incipient decomposition. Next day the external appearance of the fluid continued the same, but a marked change had taken place in its internal constituents, viz., disappearance of all trace of blood corpuscles, and the teeming of the field with vibriones in active movement, whilst in the unmixed blood the corpuscles were still entire and unchanged. This was the second acquisition in this step of my enquiry?that the local effect of cobra poison on blood was not that of a vital change. Its action on blood corpuscles was to destroy their tendency to adhesion and sink to the bottom, alter their colour, and produce speedy decomposition and dissolution of the cell wall. As the blood globules in Mammalia are not nucleated bodies, so nothing remained visible in the field of the microscope after solution of the membrane, whilst the blood of
limpid dark.
serum
Under the
fowls abounded with nuclei. Dr. Halford's cellular bodies found after death from snake-bite might have been the escaped contents of the white corpuscles of human blood. The third point for enquiry was?how far the appearances above noted would throw light on the modus operandi of cobra
poison, and death from its effects ? We have seen that the poison kills, so to speak, the blood corpuscles by its immediate topical
THE INDIAN MEDICAL GAZETTE.
action. As many of them as come into contact with it are at devitalized. They cease to adhere to each other and form
once
into rouleaux. They no longer cbange colour on exposure to air and absorb oxygen. The dark venous colour above referred in the iron of the to probably bears reference to some change
and the tendency to early decomposition bespeaks early The dissolution of the cell wall, which has been also noticed by Dr. Hilson in his published reports of two cases I is (vide Indian Medical Gazette, October 1873) hastened, believe, imbibition of fluid in consequence of precipitation of hsema-
blood,
death.
by
ine within the cell wall, followed by attenuation of the membrane and rupture. Some of the phenomena mentioned require a passing explanthe blood was noticed by Sir ation. Thus the venosity of and Dr. Brunton in their experiments, but they
Joseph Fayrer qualify their observation
with the remark that it turned red
on
I observed similar exposure to air. In my experiments, also, change, but it was not permanent, inasmuch as it resumed its original colour after a short interval. The difference will be
best detected by examining side by side the poisoned blood and In my another fresh specimen from a decapitated animal. experiment, No. I, the blood collected after death changed
dirty greenish colour in half an hour on the addition of speck of the poison. This change was so constantly observed, even without such an addition, that I believe I may take the liberty of setting it down as a settled question. Dr. Hilson refers to the blood in his cases as being claret-coloured and fluid, but the fluidity observed by him does not tally with that observed by me. My experiments, however, were conducted on inferior animals, and might not this fact, as well as the uncertainty of the species of snake by which his patients were bitten, afford some clue to the solution of the discrepancy ? Until further confirmatory observations are forthcoming, we must be content to place the question under the heading of undetermined facts. Early solution of the cell membrane I have characterized as a putrefactive change, and that the cobra poison has the power of producing speedy decomposition is corroborated by the experiments of Fayrer and Brunton, who observed into
a
another
the
same
condition in the muscles after death.
Granted, therefore, that
primary effect of cobra poison destroy the vitality of the blood corpuscles, I will try to explain the symptoms observed during life in accordance with that hypothesis. The blood ceases to be
on
the blood is of
a
the
nature to
carrier of oxygen and remains venous in colour. Nutrition of the organs, through which the poisoned blood flows, remains in abeyance, and the sensitive organs, as the nervous centres, are the first to sympathize. The patient feels as if
a
his sensibilities are the limbs. Actual
intoxicated,
and general weakness creeps over of the limbs I have seldom observed, for I have noticed in a fowl that the inability to move the legs was more owing to drowsiness than to actual loss of mobility. of a under The staggering gait snake poison is described patient as like that of a man under the influence of some
Though ordinary limb, a stronger
blunted, paralysis
volition may fail to
inebriating drug.
produce a response in the invariably elicits contractility, and reflex sensation is generally retained to the very last. The patient turns livid or blue in the face, his temperature falls, respiration is quickened, and deep somnolence ushers in a mode of death which we all know as characteristic of death by apnoea. In this stage the respiratory nervous centres may co-operate in hastening the fatal issue, and convulsions may be noticed. The respiration stops, though the heart continues to beat for a few stimulus
minutes after death. Thus it seems
probable
bite is not the result of the direct action of the poison on the nervous centres, as has been generally supposed, but on the Immediate application of a ligature above the seat of puncture stays the process of dissolution by limiting the action of the poison on a small portion of the blood itself. If the blood.
1, 1877.
quantity of poison introduced is insufficient to act on the mass of blood, recovery can be fairly expected, though the corpuscles destroyed may not be restored. In such cases, the inflammation of cellular tissue that follows is but an indication of the poor condition of the blood and septic poisoning. I have not been able to confirm the fact noticed in
Fayrer and I5runton's experiments of the poison proving fatal when swallowed. For though the bat, in my experiment No. Ill, died shortly after with profuse foaming at the mouth, and all the characteristic symptoms of snake poisoning, the same result was not observed in the case of fowls. It should be remarked that the bat was starving the whole night and was constantly biting and snapping at every thing since its capture,
which might have abraded the buccal
mucous membrane, absorption of the poison, whilst the fowls took it without any struggle. That the poison deteriorates in virtue by long keeping can be asserted without any fear of contradiction, and I have myself observed the difference in its activity as it grew older in my
affording
solution of
continuity
for
keeping.
From the hypothesis I have thus tried to enunciate, it will be evident that the antidotal power of remedies is questionable. We can try to life the and the
by eliminating
prolong
poison
devitalized blood by venesection, and substituting at the same time fresh blood by transfusion to keep up the function of the
vital organs, whilst oxygen must be suppliei by artificial respiration and the internal administration of such remedies as readily part with it in their sojourn in the circulation, such as creosote, chlorate of potash, deutoxide of hydrogen, sulphurous acid, &c. Inasmuch as the last also possesses antiseptic power, I will suggest its intravenous injection with a view to neutralize, if possible, the effects of the poison. In my future experiments, I will proceed according to these data and report the results
obtained therefrom,
EXPERIMENTS. June
18th, Hazctribagh.?The poison of a cobra ("kaota, was procured in October 1876, from Burdwan, and preserved tightly corked in a phial and excluded from light. It was a limpid fluid when fresh, but by long keeping had settled into a thick curdy substance, something like bits of caseine, with It had a faint ammoniacal smell. some fluid floating on the top. Under the microscope, the white bits were found to consist of granules. They were unaffected by acetic acid, but became more distinct on the application of liquor potassse. The poison of a gohlioora, which was obtained at the same time, had solidified into a dry white stuff. Experiment No. At
8-30 a.m., in weight,
a
quantity
of
poison
I. of
L-aola, about ?
a
introduced into the right thigh of a middle-sized fowl through a slit made in the skin, which was In 15 minutes it got stitched up.
grain
was
drowsy?30
subsequently
minutes closed its eyes, and the head drooped ; was disinclined to move, but hopped when pushed on ; became insensible and died in one hour. Chest opened immediately after death. The heart was contracting vigorously and contained fluid blood, which coagulated soon after exposure to air. A drachm of this was immediately collected in a test tube. It separated into two layers?a red serum and a congulum. The sanguinolent fluid was drained off and put into a test tube. On the addition of a speck of it changed in half an hour into a dirty greenish colour. Under the microscope the corpuscles were found separate.
poison
The cellular
that the fatal termination after snake-
[December
puncture of this
was
was
corpuscles
tissue in the immediate neighbourhood of the infiltrated with greenish-looking serum ; a little
scraped and
and examined.
of the corpuscles if about to come out.
some as
It consisted of a few blood small dotted cells. The nuclei of were found prominent on the cell wall,
numerous
morning, when it
was
The liquid wa3 kept over till next found to have retained its greenish colour
December 1,
A MIRROR OF HOSPITAL PRACTICE.
1877.]
but no trace of entire blcod corpuscles -was found, and the field bodies observed iu the previous was full of those cellular examination. Experiment No. II.
goat's blood was procured. The coaguseparated; the fluid was bright crimson in colour To one specimen, measuring nearly half an ounce, about 2 grains of the poison was added, and another was kept pure The colour of the poisoned blood as a standard of comparison. changed in one hour, and next day it was persistent. It remained uniformly dark, whilst the unmixed one had settled into two strata. The corpuscles of the pure blood were aggregated into masses, whilst the poisoned ones were distinct. On the 21st no blood corpuscle was found in the poisoned fluid, 19th June.?Some
lum was
were there any molecular bodies, but the field was teemThe corpuscles of the with vibriones in active movement.
neither
ing
pure fluid were entire. 21 st June? About a drachm of this poisoned blood was injected into the thigh of another fowl. It showed signs of poisoning in quarter of an hour, and died one hour after with all the
characteristic symptoms. Experiment No. III. 4th July.?A bat, captured the previous night, was made to take into its mouth some cobra poison of about a pea in size In quarter of an hour it grew lethargic, and did not attempt to bite when disturbed. In 20 minutes it was foaming at the
twitchings of the hind legs. It could not fix itself any longer on the wall, and died in that torpid state in half After death its blood was allowed to drain into a test an hour. tube. The contents of the corpuscles were found as if conmouth and had
tracted towards
the centre, and were encircled with a ring of the clot, which was originally
bright halo. The colour of bright crimson, had changed to
dark venous.
Experiment No. IY. 14th July.?Gave some poison of goJchoora, about a pea in size, to a fowl. It had a strong ammoniacal smell. The fowl swallowed it without any struggle. It felt drowsy in one hour, and showed disinclination^ move, but the effect passed off in another hour, and it was as active as ever. 15th July.?The same quantity of the poison was introduced under the skin of the same animal. The effect was stronger ; it dozed and sat still, but in two hours it was running about and completely shook off the effect. The poison had evidently loss its virtue. 26th July.?A fowl was made to swallow the poison of Jcaota about double the size of a pea. It showed no symptoms of poisoning. The same poison, about a pea in size, was introduced hypodermicallv into the same fowl two hours after. It died in one and half hour with convulsions, and all the other symptoms
poisoning. Its blood was examined after death and found undergone the some changes as were observed in the previous experiments. For confirmation, another fowl was made to swallow the same quantity of the poison, but it had no of snake
to
have
effect.
317
