On considering impartially all the facts that have been adduced in this inquiry, an impression must be felt that the doctrine of the sympathetic action of those poisons which produce merely a nervous local impression is insecurely founded. But an experimentum crucis is still wanted to decide the question.
2. Of the Action of Poisons through Absorption.—If doubts may be entertained whether poisons ever act by the transmission of local impulses, from the part to which they are applied, along the nerves to the organ upon which they act, no reasonable doubt can be entertained that many poisons act through the medium of absorption into the blood.
Poisons are believed to act through the blood for the following reasons. First, they disappear during life from the shut cavities or other situations into which they have been introduced; that is, they are absorbed. Several clear examples to this effect have been related by Dr. Coindet and myself in our paper on oxalic acid. In one experiment four ounces of a solution of oxalic acid were injected into the peritoneal sac of a cat, and killed it in fourteen minutes; yet, on opening the animal, although none of the fluid had escaped by the wound, we found scarcely a drachm remaining.[[20]] In recent times Professor Orfila has proved that various poisons, such as arsenic, tartar-emetic, and acetate of lead, disappear in part or wholly from wounds into which they had been introduced.[[21]] Next, many poisons act with unimpaired rapidity, when the nerves supplying the part to which they are applied have been previously divided, or even when the part is attached to the body by arteries and veins only. Dr. Monro, secundus, proved this in regard to opium;[[22]] and the same fact has been since extended by Sir B. Brodie and Professor Emmert to wourali,[[23]] by Magendie to nux vomica,[[24]] by Coullon to hydrocyanic acid,[[25]] by Charret to opium,[[26]] and by Dr. Coindet and myself to diluted oxalic acid.[[27]] Magendie’s experiment was the most precise of all: for, besides the communication with the poisoned part being kept up by a vein and an artery only, these vessels were also severed and reconnected by two quills. Farther, many poisons will not act when they are applied to a part of which the circulation has been arrested, even although all its other connections with the body have been left entire. This has been shown distinctly by Emmert in regard to the hydrocyanic acid; which, when introduced into the hind-leg of an animal after the abdominal aorta has been tied, produces no effect till the ligature be removed, but then acts with rapidity.[[28]] An experiment of a similar nature performed by Mr. Blake with the wourali poison yielded the same result.[[29]] Again, many poisons act with a force proportional to the absorbing power of the texture with which they are placed in contact. This is the criterion which has been commonly resorted to for discovering whether a poison acts through the medium of the blood. It is applicable, however, only when the poison acts sensibly in small doses; for those which act but in large doses cannot be applied in the same space of time over equal surfaces of different textures. The difference in the absorbing power of the different tissues has been well ascertained in respect to a few of them only. The most rapid channel of absorption is by a wound, or by immediate injection into a vein; the surface of the serous membranes is a less rapid medium, and the mucous membrane of the alimentary canal is still less rapid. Now it is proved of many poisons that, when applied in similar circumstances to these several parts or tissues, their activity is proportional to the order now laid down. Lastly, it has been proved of nux-vomica, that if the extract be thrust into the paw of an animal after a ligature has been tightened round the leg so as to stop the venous, but not the arterial circulation of the limb, blood drawn from an orifice in a vein between the wound and the ligature, and transfused into the vein of another animal, will excite in the latter the usual effects of the poison, so as even to cause death; while, on the contrary, the animal from which the blood has been taken will not be affected at all, if a sufficient quantity be withdrawn before the removal of the ligature. These interesting facts, which are capable of important practical applications, were ascertained by M. Vernière.[[30]]
On weighing attentively the arguments here brought forward, it seems impossible to doubt, that some poisons are absorbed into the blood before they act, and that their entrance into the blood is not a mere fortuitous antecedent, but a condition essential to their action.
But it is farther held that poisons which act through absorption, do so by being conveyed in substance along with the blood to the part where their action is developed,—that their action eventually depends on the organ, whose functions are thrown into disorder, becoming impregnated with poisoned blood. Now, the arguments detailed above do not absolutely prove this conveyance and impregnation. They show that poisons enter the blood, and act somehow in consequence of entering it; but they do not prove in what manner the action subsequently takes place.
It was at one time indeed supposed that the same facts, which prove their admission into the blood, proved also their transmission in substance to the organs acted on by them. But Dr. Addison and Mr. Morgan have shown that this is not a legitimate conclusion, and that a different theoretical view may be taken of the facts,—namely, that the action may really take place by the poison producing on the sentient extremities of the nerves of the inner membrane of the blood-vessels a peculiar impression which is conveyed through the nerves to the part ultimately affected.[[31]] They have endeavoured to found this theory upon evidence, that the poison is not carried beyond the venous system; or that, if conveyed farther, it is carried incidentally, and not for the purpose of impregnating the textures of the organ which suffers. The evidence they have brought forward on this head is chiefly the following. 1. Poisons which act on a particular organ at a distance do not act more quickly when introduced into the artery which supplies it, than when introduced into its vein, or even into the principal artery of a distant part of the body.[[32]] 2. If a poison be introduced into a great vein with a provision for preventing its passage towards the heart, it will act with as great rapidity, as if no obstacle of the kind existed. Thus, if the jugular vein, secured by two temporary ligatures, be divided between them and reconnected by a tube containing wourali, the animal will not be affected more quickly on the removal of both ligatures, than on removing only the ligature farthest from the heart.[[33]] 3. The arterial blood of a poisoned animal is incapable of affecting another animal. Thus, if the carotid artery and jugular vein of one dog be divided, and both ends of each reciprocally connected by tubes with the divided ends of the corresponding vessels of another dog, and extract of nux-vomica be introduced into a wound in the face of one of them,—the animal directly poisoned alone perishes, and the other remains unharmed to the last.[[34]]
These are at first view strong arguments against the transmission of poisons with the blood to the organs remotely acted on; and the facts on which they are founded are on the other hand easily explained under the new theory advanced by the authors, that the medium of action is the nerves which supply the inner membrane of the blood-vessels. But their inquiries, however ingenious and plausible, have not stood the test of physiological scrutiny. Their first experimental fact has been contradicted by Mr. Blake; who has found that the wourali poison, which does not begin to act for twenty seconds when injected into a vein, will produce obvious effects in seven seconds only if injected into the aorta through the axillary artery.[[35]] The second experiment, showing that poison confined in a vein will act although prevented by a ligature from reaching the heart, is held by the opponents of Dr. Addison and Mr. Morgan to be fallacious, in as much as the blood behind the ligature may be carried backwards till it meets with an anastomosing vein and is so carried by a collateral vessel to the heart. To the third experiment it may be objected, that there was, in the mode in which they conducted it, no satisfactory evidence that the reciprocal circulation was kept up by the carotid artery and jugular vein. And this will appear an important objection to every one practically acquainted with experiments of transfusion. For on the one hand it is exceedingly difficult, in such complicated experiments, to prevent coagulation of the blood in one vessel or another, before the connection of all the arteries and veins is established; and on the other, it may be urged, as Mr. Blake has done, that the pressure of the blood in the distal end of the carotid artery in the animal not directly poisoned may be equal, or even superior, to the pressure in the proximal end of the same vessel in the other animal,—so that the blood may not pass from the latter into the former, although it should continue fluid.
In opposition to the theory of Dr. Addison and Mr. Morgan, and in support of the doctrine, that poisons act by being carried in substance with the blood into the tissues of the remote organs on which they act, a variety of important experimental evidence has been brought forward since the publications of the Essay of these gentlemen. In the first place, the concurrent testimony of a great number of recent chemical inquirers establishes undeniably, that poisons absorbed into the veins of the part to which they are applied are to be detected throughout many of the tissues of distant organs. This fact will be enlarged on and illustrated presently. Secondly, on the authority of Mr. Blake, and in contradiction of the experiments of Dr. Addison and Mr. Morgan, it appears that, as already stated, poisons act more quickly when injected into the aorta than into the venous system; a fact which is easily understood, on considering that when injected into the aorta they reach their destination directly, whereas, if injected into a vein they must first arrive at the right side of the heart, and then be transmitted through the circle of the pulmonary circulation before reaching even the aorta. Thirdly, the relative rapidity with which poisons act on different animals follows the ratio of the velocity of the circulation in each. Thus, Mr. Blake found, that in the horse nitrate of baryta is conveyed by the circulation from the jugular vein to the carotid artery in sixteen seconds, and that strychnia injected into the jugular vein begins to act on the nervous system after exactly the same interval: That in the dog chloride of barium passes from the vein to the artery in seven seconds, and extract of nux-vomica begins to act as a poison in twelve seconds: That in the fowl the passage of the blood seems to take place in six seconds, and the nitrate of strychnia to act in six seconds and a half: And that in the rabbit the passage of the blood is effected in four seconds only, and the first signs of the action of strychnia occur in four seconds and a half.[[36]]
On the whole, then, it may be considered as well established, that probably all, but certainly some, poisons,—of the kind whose topical action does not consist in causing destruction or inflammation of the textures to which they are applied,—produce their remote effects solely by entering the blood, and through its means impregnating the organs which are acted on at a distance. And farther, if this doctrine be admitted as established, it may also be allowed, that many poisons which do cause topically destruction or inflammation, and remotely the usual sympathetic effects of these changes of structure, also possess the power of affecting distant organs through the medium of the blood.
Of the discovery of Poisons in the Blood.—Such being the case, it becomes an object of paramount interest, with reference both to the practice of medical jurisprudence, to inquire whether poisons can be detected in the circulating fluids, or generally in parts of the body remote from the place where they are introduced.