Part 6
M. Fontana seems too hastily to have adopted the opinion, that the sciatic nerves, when divided, are probably never reunited by truly nervous structure, because no reunion took place during the very short period which he suffered to elapse between their division, and their subsequent examination. In the experiments, which I have related, the progress towards reunion seems to have borne a very exact proportion to the time the nerves had remained divided; and, in an experiment related by Dr Monro, where the sciatic nerve of a frog had been divided a year previous to the death of the animal, the reproduction was advanced so far as to have the appearance of being perfect. Nor can I doubt, that both the sensibility and the motion of the limb would have been restored, had the animal been permitted to live a sufficient length of time. The following fact renders the supposition at least extremely probable.
In the first volume of the Edinburgh Medical Essays, the case of a Captain of a man of war is related, who entirely lost the use of his right arm, in consequence of a gun-shot wound received in his neck. The circumstances of the case are such as leave no reason to doubt, that the loss of the power of motion, in this gentleman’s arm, was owing to the division of the cervical nerves proceeding to the arm: yet both the full use, and strength of this arm, were restored, after a period of about two years and a half. A proof perfectly satisfactory that an actual regeneration of nerves had, in this case, taken place; and if in this, one sees no reason why it should not equally take place in any other part of the body.
It might be difficult to assign a satisfactory reason for the very speedy reproduction of the intercostal, parvagum, and recurrent nerves, when compared with the great length of time required for the reproduction of others. May it not be owing to the very profuse manner in which they are supplied with arteries, probably both in an ascending, and in a descending direction; from above, by the superior, and from below, by the inferior laryngeal arteries?
It appears upon the whole, therefore, tolerably certain, that the sanguiferous system contributes more immediately than the brain to the support of that condition of muscles and of nerves, upon which the phenomena of contraction depend; since that condition is much more injured by intercepting the influence of the former than of the latter.
Every experiment and observation, which has been made upon the subject of nutrition, and of the reproduction of parts, clearly demonstrates that nerves and muscles, in common with every other part of the body, derive their structure from the arteries; and it is evident, that upon this structure their several properties must in some measure depend. But M. Galvani’s discovery of a subtile influence, which may be transmitted apparently from one part of an animal to another through foreign media, may reasonably give rise to a conjecture that the phenomena exhibited by nerves and by muscles may perhaps depend more immediately upon some such influence; and reasons exist, which might induce some to suspect that even this is derived from the blood.
_Experiments suggested by some opinions of M. Fontana._
From the greatest number of experiments, perhaps, ever made by one physiologist, M. Fontana has been led to conclude, that the venom of the viper, opium, and several other poisons, which he examined, produce no effects whatever, when applied immediately to nerves and muscles alone, but that they destroy life, by exerting their influence upon some subtile principle existing in the blood.
Independent of the experiments, published by M. Fontana, on this subject, his opinion respecting the existence of such a principle may be thought to receive no inconsiderable countenance, from the opinions of Harvey and of Mr Hunter, concerning the life of the blood, and from those experiments, by which Mr Hewson has demonstrated, that changes are instantaneously produced upon the coagulability of the blood, by passions of the mind, and whatever else affects the action of the heart and arteries. An experiment made by Dr Alexander of Halifax, and published at this place in the year 1790, in his excellent Thesis, ‘De partibus corporis quae viribus opii parent,’ may at first appear a sufficient refutation of M. Fontana’s opinion.
He found that thirty three drops of a strong solution of opium in water, injected into the jugular vein of a large rabbit, destroyed it, as in M. Fontana’s experiments, in four minutes and a half; whereas, the same quantity injected into the crural vein in each leg of another rabbit, with an interval of twenty six minutes between the two injections, although it rendered the animal sleepy and stupid for a few hours, did it no material or permanent injury. Hence, Dr Alexander concludes, that the opium, injected into the jugular vein, did not destroy the animal by acting upon the blood alone, since if it had, the same effect, should have been produced, by introducing an equal quantity into any other vein of the body; but a quantity double of that, which had occasioned death when introduced into the jugular vein, failed to occasion it when introduced into the crurals.
It is not, however, by one experiment, formidable as it must be allowed to be, that the innumerable hosts brought to the contest by M. Fontana ought to be combated. Besides, it might be objected even to this one, that the opium was introduced into veins, from which it must have been so much longer in passing to the arterial blood, than from the jugular vein, and consequently so much more diluted, and perhaps too altered in its nature before it got there, as might be sufficient to account for the difference of result in the two cases compared.
The opportunity afforded by M. Galvani’s discovery, of putting the truth of the opinion held by M. Fontana more fully to the test, and the possibility which presented itself, that if any such principle, as he supposes in the blood, should really be found to exist there, it might prove to be identically the same with that discovered by M. Galvani, induced me to make the following experiments.
EXPERIMENT I.
Having selected two frogs as nearly as possible of the same size and vigour, I deprived one of its blood by opening, first, one of its crural veins, then, a crural artery, and last of all, the heart. To assure myself of the complete evacuation of its blood, I next injected water into its heart, and immediately afterwards forty drops of a strong aqueous solution of opium[14].
I then removed the sternum of the other frog, and having made an opening into the ventricle of its heart, injected into it likewise forty drops of the solution. Less blood was effused in doing this, than one would at first expect; for the ventricle contracts so strongly, immediately after the incision, as to prevent much blood from passing out, unless the incision be made, as it was in the other frog, purposely large.
The moment, at which each injection was made, was accurately noted, and the time expended in evacuating the blood from the first frog, was allowed for. The frog, from which the blood had been withdrawn, ceased to contract, when irritated, very nearly an hour before the other, even calculating not from the time of injection, but from the moment I began to bleed it; nor could I by means of the metals excite contractions in it, for upwards of a day before they had ceased to be excitable in the other frog.
EXPERIMENT II.
As evacuating the blood from a living animal is rather a severe operation, and might have occasioned some fallacy in the last experiment, by subjecting the frog, in which this was done, to a greater degree of pain, and consequently of exhaustion, than what the other was subjected to, I crushed the brains of two other frogs before I proceeded, as in the former experiment, to withdraw the blood from one of them. Instead of forty, I injected no more than thirteen drops of the strong solution of opium, into each of the hearts of these frogs. The instant the injection had entered, both hearts became white, and ceased from contracting. Forty eight hours after the injection of the opium, the contractions excited by the metals in the frog, deprived of its blood, had become very slight, particularly in the limb whose vein and artery had been opened. The other frog still continued to contract with so much vigour, as to raise its body from the plate of zinc, upon which it was laid. Seventy two hours after the injection, no contractions could be excited in the frog, from which the blood had been withdrawn, except some very slight ones in the leg, whose artery and vein had not been opened. The contractions in the legs of the other frog, continued still so vigorous as to raise its body from the plate, and some were produced even by mechanical irritation.
Ninety six hours after the opium had been injected, (both the frogs having lain out of water all night,) that without blood was found quite putrid. In the other, the contractions, produced by exciting the legs, were sufficiently strong to move the feet: as the body, however, had become putrid and offensive, it was thrown away.
EXPERIMENT III.
The heads of two other full grown and lively frogs, having been crushed, their hearts were laid bare, and the blood was evacuated from one of them, as in the former experiments. A small portion of the skull of each then being removed, eight drops of the strong solution of opium was injected upon their brains. At least half the quantity seemed to return from the wound. Both frogs became instantaneously motionless after the injection, but, in about an hour, were considerably recovered.
Spontaneous motions continued during more than fifty hours, in the legs of that from which the blood had not been drawn, and contractions were excitable by the metals, upwards of 24 hours after they had ceased to be so, in that from which the blood had been drawn.
The following experiments may be deemed still more satisfactory, than the preceding, from the circumstance of the comparison having been instituted, between the effects of opium, upon different, but similar parts of the same frog, differently circumstanced.
EXPERIMENT IV.
One of the crural arteries of a frog having been included in a tight ligature, as near as possible to the body, I suffered four days to elapse, and then injected through a perforation in its skull, eight drops of the strong solution upon its brain, and in a direction towards its spinal marrow. This frog continued most violently convulsed for more than an hour, and, in two, was to all appearance dead. When laid upon zinc, and excited with silver, the contractions were not at first perceptibly stronger in one leg than in the other. After eight hours, however, they were evidently most strong in the leg whose artery remained free. After 21 hours, this difference became still more decided. At the end of 34 hours, scarcely any contractions could be excited in the leg whose artery had been tied; though they continued vigorous in the other; and, at the end of 46 hours, they had ceased altogether to be excitable, in the leg whose artery was tied. In the other, they continued during several hours afterwards.
EXPERIMENT V.
Having tied one of the crural arteries of another frog, I filled its stomach, immediately afterwards, with a saturated solution of opium in water. The difference between the strength, and the continuance of the contractions, excited by the metals, in the two legs of this frog, was not so great as in the former; yet still the difference was considerable in favour of that leg in which the artery remained free.
EXPERIMENT VI.
In two other frogs, in each of which a crural artery had been tied, and the solution of opium (without regard being paid to quantity), repeatedly injected underneath their skulls immediately after; the contractions appeared to be very little weaker in the legs, whose arteries were tied, than what they were in the legs in which they were not tied, and they continued excitable during an equal length of time in both.
EXPERIMENT VII.
Having tied the crural artery of another frog, I immediately filled both its stomach and abdomen with a strong solution of opium. In an hour after this, it was to appearance quite dead. At the end of eight hours, the contractions, excited by the metals, had become very feeble in the leg whose artery was tied, in comparison of what they were in the other leg; and, at the end of twelve hours, no contractions could be excited in any part of the frog, except in the leg whose artery remained free. In this they continued excitable about an hour longer.
As it was possible, that the more speedy exhaustion of the legs, in which the arteries were tied, might have been owing in some measure to the pain, occasioned by that operation, I repeated the experiment with the following variation.
EXPERIMENT VIII.
I first divided the sciatic nerves, in both legs of two frogs, and then tied the crural artery in one leg of each. Eight drops of the solution of opium were immediately afterwards injected upon their brains. But the event of this experiment was precisely the same with the majority of those before related. The contractions excited by the metals, in the legs whose arteries were tied, were uniformly more feeble, and of shorter duration, than those excited in the other legs: yet it is evident, that, in all these experiments, the very reverse of this ought to have taken place, had it been true, as M. Fontana has asserted, that opium has no effect upon any part of the body, except through the medium of the blood.
The experiments however, which I am now to relate, may perhaps appear still more satisfactory.
EXPERIMENT IX.
Having laid equally bare both the sciatic nerves of a frog, at the upper part of its thighs, I passed a ligature round one of them, and drew it as tight as it was well possible, without dividing the nerve. I then removed a portion of its skull, and with a small brush, kept it constantly wet with laudanum during several hours. The frog soon became convulsed; and, during ten or twelve hours, continued in that state of exquisite sensibility, which opium never fails to produce in these animals. It may here be worth remarking, that, while they are in this state, the slightest touch of a feather, or even breathing upon them, excites instantaneous convulsions. The leg whose nerve was tied, remained paralytic during this time, but when it was laid upon zinc and excited with silver, it contracted as strongly as the other. After forty three hours, the contractions were very feeble in the leg whose nerve was not tied, but still vigorous in the other. After fifty three hours, no contractions could be excited in any part of the frog, except in the leg whose nerve was tied. In this they were sufficiently strong to move the foot, and continued so for more than an hour longer.
EXPERIMENT X.
One of the crural nerves of another frog having been tied in a similar manner, eight drops of the strong solution of opium were injected upon its brain. The animal instantly became motionless, but, in less than an hour afterwards, was considerably recovered.
The contractions, excited by the metals, in the leg whose nerve was free, soon became more feeble than those excited in the leg, whose nerve had been tied. This disproportion, between them, continued increasing during ninety six hours, after the opium had been injected, when contractions could no longer be excited in the leg whose nerve remained free. In that, in which the nerve had been tied, they continued upwards of 4 hours afterwards.
EXPERIMENT XI.
Immediately after having divided the sciatic nerve, in one thigh only, of three other frogs, I injected as much of the strong solution of opium underneath their skulls, as could possibly be retained. The legs, in which the nerves had been divided, continued contractile several hours after the others had ceased to be so.
Hence, then, we see no reason for suspecting that the more speedy cessation of contractions in those legs, in which the crural arteries were tied, than in those on which no operation was performed, was owing to the pain occasioned by such operation, since even the more painful operations of tying or dividing the sciatic nerves, were attended with no such effect.
Upon the whole, therefore, it appears, that the conclusion which M. Fontana draws from his numerous experiments with opium, ‘That the circulation of the blood and humours in the animal machine, is the vehicle for opium, and that, without this circulation, it would have no action on the living body,’ is the very reverse of that which I am warranted to draw from the experiments I have just related; since the parts, most affected by the action of opium, were not those in which the circulation remained most entire, but those in which it had been almost altogether interrupted; and since in two parts where the circulation remained equal, and entire, the action of opium was rendered unequal, by interrupting the communication of one of them, by means of nerves, with the parts to which the opium was applied.
The existence, consequently, of any such principle in the blood, as that supposed by M. Fontana to exist there, is rendered far too problematical, even to allow me to expect that it can ever be proved: far less that it may turn out to be the same with that discovered by M. Galvani, or with that, whatever it may be, upon which the phenomena of nerves and of muscles may depend.
Footnote 13:
Essays Physical and Literary.
Footnote 14:
This solution, which is the same that I employed in all my subsequent experiments, was of the same strength with that used by Dr Alexander in the greater number of his, viz. an ounce of crude opium mixed in a mortar with two ounces and a half of water, and filtered through paper, after having remained twelve hours, in a close corked bottle, near a chamber fire.
APPENDIX.
I was unwilling to interrupt the narration of the preceding experiments, by the mention of the following facts, which they afforded me an opportunity of observing, as they were not immediately connected with the objects on account of which the experiments were instituted; and I have yet some few to relate, which, from the haste with which these sheets were prepared for the press, I had omitted to insert in their proper places.
1. In one of my first experiments, in which I had occasion to suffer a frog to remain tolerably entire, so long as contractions could be excited in any part of its body, I was surprised to find, on removing its sternum, that its heart had ceased to contract, nor could be roused by the application of any stimulus whatever, notwithstanding the contractions in its hind legs, excited by the metals, were still vigorous, and continued so for several hours afterwards. On paying particular attention to this circumstance in another frog, upon whose brain opium had been injected, I found that its legs continued excitable, upwards of forty hours longer than its heart. This discovery of the continuance of the contractile power, in the muscles of the posterior extremities, so long after its disappearance in the heart, is so contradictory to the opinion generally received upon this subject, and long established among physiologists, that I can scarcely expect it should be credited, by those who may not themselves have opportunities of observing it. It is a fact, however, of which, in the course of these experiments, I have had the most satisfactory and uniform proofs, both in such frogs as have, and in such as have not, been under the influence of opium. If a different opinion has hitherto been held by experimentalists upon this subject, it should be recollected, that, till the discovery made by Galvani, we had no means of ascertaining the presence of the contractile power of muscles, which had not, at the same time that they indicated its continuance, a tendency to destroy it, and consequently to render it impossible for us to trace its natural progress to extinction.
I have, more than once, observed the same circumstance in both cats and rabbits.
2. Dr Alexander, in his excellent Thesis already quoted, tells us, that the contractility of all the voluntary muscles of frogs was destroyed in the course of a very few minutes, by injecting eight drops of a strong solution of opium in water, (similar to that which I employed) upon the surfaces of their brains. But that the contractions of their hearts did not appear to be much, if at all, affected by this treatment. In all the similar experiments, which I have made, the event has been very different. I have not found it possible by any quantity, either of aqueous or of spirituous solution of opium, injected upon the brains of frogs, to produce that rapid extinction of the contractility of their voluntary muscles, of which Dr Alexander speaks. They commonly recovered in less than an hour, from the complete insensibility and paralysis, first occasioned by the injection of the opium, and after that time, their spontaneous motions almost always continued for several hours longer, and, by the application of the metals, contractions were excitable even for days. Their hearts, as I have already said, uniformly lost their susceptibility of the action of stimuli, long before their posterior extremities.
3. The arguments against the antiquated doctrine of transudation, through parts of a living body, are already so numerous and satisfactory, that it may be thought unnecessary to notice in this place, a decisive one so far as relates to the skin of frogs, at least, which may be deduced from the fact already mentioned; that so long as the skin was suffered to remain upon the limbs of frogs, placing them in water, very evidently preserved the contractility of their muscles, whereas when the skin was taken off, the muscles became hard, and incapable of contracting, in a very few hours. Had there been a possibility of water soaking through the skin, this difference could not possibly have had place.
4. In speaking of some of the relations, which subsist between the influence discovered by Galvani and the nerves, I omitted mentioning the following facts.
A very different effect is produced by applying the metals to the brain or spinal marrow of frogs, from what is produced by applying them to their nerves. In the latter case, I have observed, that every muscle, to which a nerve below the part touched is distributed, is brought into instant contraction. But no muscles are brought into contraction, when the metals are applied to the brain or spinal marrow, except such as derive their nerves from the part immediately in contact with the metals. The influence does not stimulate or pass along the spinal marrow, as it would along the trunk of a nerve, to affect all other nerves branching off from it.