Experiments and Observations

Experiments in which the Crural Arteries of Frogswere tied as near to the Trunks of their Bodies,as where the Nerves had been divided in the former ExperimentsEXPERIMENT I

Both crural arteries of a full grown frog having been laid bare, one of them was tied. The leg, in which this was done, became instantly weaker than the other, and rather dragged when the animal was put into water. The frog, however, could still jump about with great agility. Four hours after this operation, it was killed by crushing its brain. It continued to move its legs spontaneously, when touched, during more than two days after this, and contractions were excitable by the application of the metals for two days longer. Sometimes it appeared rather doubtful, which leg contracted most vigorously, but, in general, the leg in which the artery remained free did so, and contractions could be excited in it, more than an hour after every means to excite them in the other leg had failed.

EXPERIMENT II

Ligatures were passed round the crural arteries of two other frogs, and one of them was suffered to live thirty six hours afterwards, before its head was crushed: the other four days. In these, the disproportion between the vigour and continuance of the contractions in the compared legs, was so much greater than in the preceding experiment, as to leave no doubt of the effects produced by tying an artery. The leg, whose artery had remained tied four days, never contracted near so strongly as its fellow, and contractions had ceased to be excitable in it, upwards of twenty hours before they had ceased in the leg, whose artery had not been tied.

From these experiments, it appears decidedly, that a much greater detriment to that condition of a limb, upon which contraction depends, is induced by interrupting its circulation, than by intercepting its communication with the brain.

But still, as the effects arising from the interception of the influence of the brain, and of the circulation, were not compared with each other in the same but in different animals, whose age, relative strength, &c. might possibly differ, I thought proper to repeat the comparison, in the following manner.

Experiments in which the Sciatic Nerve was divided on one side,and the Crural Artery tied on the otherEXPERIMENT I

I divided the sciatic nerve of one leg, and tied the crural artery of the other, in a large frog. Scarcely any blood was lost in doing either. Two days after this, I strangled it. During the first 24 hours, the leg, in which the nerve had been divided, appeared to contract with most vigour; after this period, the difference between them became more doubtful; but the contractions were at no time stronger in the leg, whose artery was tied, than in that whose nerve was divided.

EXPERIMENT II

The same operations were performed upon a large female frog full of spawn. Four hours afterwards, she was observed covered by a male, who had been treated in a similar manner. I mention this circumstance, as it tends to prove that the pain occasioned by the operation was probably not so great as to produce much fallacy.

On the day following, she had spawned, and on the sixth day from the operations, she was strangled. When laid upon a plate of zinc, and excited by means of a rod of silver, the contractions were found extremely feeble in the leg whose artery had been tied, and ceased altogether in about twenty-two hours after her death. In the leg, whose nerve had been divided, they appeared as vigorous as they usually are in legs to which no injury has been previously done, and continued excitable upwards of two days after they had ceased to be so in the other.

EXPERIMENT III

Having tied the crural artery on one side, and divided the sciatic nerve on the other, on three full grown male frogs, I strangled them all on the sixth day following. My motive for killing the frogs, subjected to such experiments, either in this manner or by crushing their heads, will be obvious. It was of consequence to preserve their circulation as entire as possible, and, at the same time, avoid the continuance of pain, which by exhausting all the parts of the body, whose communication with the brain was not interrupted, might considerably have affected the result of the experiments.

The contractions excited by means of the metals, were, in all these instances, likewise as much more strong and durable in the legs, whose nerves had been divided, than what they were in the legs, whose arteries had been tied, as what I had found them to be in the preceding experiment.

Having thus found, that a diminution of the circulation of a part, was accompanied with a proportionable diminution of the respective powers of nerves and muscles in that part, I next proceeded to examine if an increased circulation would be attended with a proportionable increase of these powers. That this is actually the case, with respect to the nerves, the few facts which I have related of the eye, in a state of inflammation, have a tendency to prove; and we all know how much the sensibility of every part of the body is increased, by an increase of vascular action. That a similar relation subsists between an increased action of the arteries, and the contractile power of muscles, is, I think, proved by the following experiment.

Experiments made with a view of ascertainingsome of the Effects of InflammationEXPERIMENT I

I have before said that if a living and entire frog be set upon a plate of zinc, contractions can very seldom be produced in any part of its body by passing a rod of silver over it, so that the silver, the frog, and the zinc, may be all in contact with each other. But, I have found in upwards of twenty experiments, that when inflammation had been excited in one of the hind legs of a frog, by irritating it with a brush, contractions uniformly took place in that leg when the metals were applied to it, although none had been produced in it before it was inflamed, nor could still be produced in the other leg which remained in its natural state.

EXPERIMENT II

Having previously excited inflammation, by means of a brush, in the foot and leg of a healthy and large frog, I cut off its head. The contractions excited by the metals in the inflamed leg were in vigorous and instantaneous jirks; those in the sound leg more languid and difficultly excited. Spontaneous motions continued at this time nearly the same in both. Till the end of the second day, after this frog’s head had been taken off, the contractions excited in the inflamed leg continued uniformly, and beyond all comparison more vigorous than what I could by any means excite in the sound leg. But, after this time, the inflamed leg became hard as a piece of wood; probably in consequence of the effusion to which the inflammation had given rise.

The event of five similar experiments was so nearly the same, that I should be thought unnecessarily minute, were I to relate them in detail.

We are now perhaps prepared to account for the deficiency of contractile power in those legs, whose sciatic nerves had been divided, the one, between three weeks and a month, the other, six weeks, compared with its continuance in the leg, whose nerve had been divided upwards of three months. It appears, from the circumstances of those experiments, that some of the arteries, appropriated to the supply of the sciatic nerves of frogs, have the same course with the nerves themselves; since the deposition of new matter could in all be traced from the upper division of the nerves. It is obvious, therefore, that the part of the nerves below the division, must have been deprived of so considerable a portion of their usual arterial supply, as in time would occasion some alteration in their structure, and consequently in their powers. We accordingly find that such alteration of structure, and such deficiency of power, had actually taken place. It is further probable, that, in proportion as the supply from the arteries was restored, the powers of that nerve, which had been three months divided, had been likewise restored. This supposition is countenanced by every instance in which nerves are reproduced; as we find the functions of the parts in which they had been divided, are not immediately, but gradually restored.

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 opium14.

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.