ration, the sounds of the heart become modified, and the modifications run as follow: 1st. The abnormal condition is confined in the primary stage to the right side; gradually it extends to the left, but the right catches it first; a result which, from the conformation of the chest, is easily traced out in the dog. The kind of modification of sounds is invariably the same; it consists in a gradual disappearance of the first sound, and in the production of a peculiar sharp or accented second sound. I have observed this state extending over twenty-four hours, and, in one instance, over two days, during the whole of which period, there could only be distinguished one sound, and that the second. In time, however, this peculiarity passes away, and in place of a first normal sound, a gentle and musical purr obtains, which ultimately becomes a loud and peculiarly well-marked systolic bruit. This sound established, it is comparatively permanent. If the animal does not die from the acuteness of the attack, the murmur remains for weeks. In one instance, it was well marked in a dog for five weeks, the animal in the meantime having recovered his health, as it seemed, completely. In one instance, these endocardial symptoms were accompanied with wellmarked pain in the joints and limbs; this pain crippled the animal, and it was curious to observe that the pain was rarely for a day at a time in the same limb. Sometimes the animal limped with one hinder limb; in a few hours he would be using that limb freely, but would not trust a fore limb to the ground, and so on, but this case was exceptional. The joints in this instance were found normal after death, but the death was not produced until many weeks after the acute symptoms had passed away. Such are the symptoms produced by the use of the acid poison.. I would now beg special attention to the pathology which attends these symptoms in their several stages. For the sake of connecting pathology with symptom, I would divide the symptom, keeping purely to those which are endocardial, into four stages. (a.) The stage when the action of the heart is simply excited, the sounds being normal. (b.) The stage when the first sound is lost, and the second accented. If the animal be killed, or if it die during the first of these stages (a), the valves, whether auriculo-ventricular or semilunar, are free and not thickened, but the endocardial surface throughout is of a brilliant vermilion colour. Even the pale margins or flaps of the valves have a pinkish hue; there is also over the membrane throughout, a villous or velvety appearance, and beads are abundant. The pathological signs of this stage often come on in an extraordinarily brief period after the injection; as soon, in fact, as the injected fluid finds its way through the heart, the injection of the endocardial surface is developed. In the first well-marked illustration of this stage, the pathological indications were brought out in a period of six hours. But I have since performed three experiments, in one of which the fluid injected into the peritoneum was absorbed within an hour, and the injection of the endocardial surface was well pourtrayed. In the other experiments, one on a rabbit, the other on a cat, the same events occurred in two hours. In the second stage (b), when the first sound is lost, the mischief, on whichever side it may be, is confined to the auriculo-ventricular valves. The whole structure of the valve is thickened andœedematous.' I have seen the segments of the tricuspid valve fixed in this swollen condition, resembling each an injected uvula, and lying so close to each other, that when the heart was contracting, they must have cushioned against each other, thus fulfilling their office of preventing regurgitation, passively, i. e., without tension or movement. In this edematous stage, if the valve be pricked with a needle, a clear white lymphy fluid exudes, and by frequent pricking, the valve structure emptied of its effusion, collapses and assumes a flaccid condition, In the third stage (c), the valves remained thickened, but the red colour and ædematous state were both reduced: Beneath the endocardial surface of the valve, there is a paleness as from coagulated effused lymph. If the needle is applied now, there is no exudation; the valve has some limited play, unless it is bound down by adhesion, and its structure is firm. Beads which generally fringe the margin of the valves all round, from being cedematous prominences in the earlier stages, are pearly looking and are moderately firm. In the fourth stage (d), when the systolic murmur is purely marked, the valves have shrunken, and have regained imperfect play, but are still thickened and unyielding. Beads which may be present are extraordinarily firm, their presence adding not a little to the loudness and musical character of the systolic murmur. I have confined my description so far to the changes which are produced in the tricuspid or mitral valves. The disease, in a word, is mainly confined to one or both of these structures. A very slight thickening, not sufficient at any time to interfere seriously with their duties, is all I have ever observed in the semilunar valves of either side. The simple facts connected with the production of artificial endocarditis having been thus demonstrated, we may turn with advantage to the consideration of certain questions suggested by the facts themselves-questions which all may reason upon from the facts, and by the discussion of which the ultimate practical meaning of the experimental results may be elicited. The experiments have a bearing of great interest in relation to the physiology of the sounds of the heart.-In every instance where the first sound was lost, and inspection of the heart was made during that stage, four instances, the auriculo-ventricular valves were so modified that their tension was clearly impossible. In every instance where the systolic murmur was established, the same valves were implicated, but in a different way, i.e., they were found restored partly to their action, but indurated in structure. In every case throughout the whole series the second sound was always distinct; in no case, at any stage, were the semilunar valves so implicated as to lead to the inference that their action was impaired. Better than any physiological physical inquiry, these results prove to my mind that the systolic sound is due to tension of the auriculor ventricular valves, and the second sound to tension of the semilunars. What can be more conclusive? Two animals are well-they have two sounds to their hearts, and two sets of valves in alternate play; the animals are made ill by experiment, and the first of these sounds is entirely lost; you listen to the heart for hours, and there is the one solitary tick; it is listening to a clock; you destroy, and cut down to the heart of one of these animals in this stage, and you find the ventricular valves inactive; you let the second animal have longer respite, and the first and lost sound returns, but modified as a murmur. You kill and cut down to the heart of the second animal, and you find the ventricular valve in a position to act, it is true, but devoid of flexibility, incapable of tension, and as it were fitted up for the production of murmur by the blood stream. The production of symptoms so specific by the simple act of introducing an acid into the circulation is another point of interest.-In commenting on this fact of production, I have carefully avoided on all occasions from connecting it. too closely with any theory of disease occurring spontaneously in the human subject. That the fact is full of meaning in relation to the disease, endocarditis, in the human subject, is undeniable; and I feel safe (while faintly tracing out such relationship), in offering the following propositions: 1. That lactic acid present in the blood, will produce endocarditis. 2. That lactic acid could not exist in the blood without producing endocarditie mischief. A question has been asked me many times, viz., whether other acids than lactic introduced into the circulation in the same way would not produce the same effects? From the composition and from the influence exerted on blood by certain other acids, viz., acetic, formic, and citric, I inferred that a similar influence on the heart to that produced by the lactic was at least probable; and I shall notice presently something positive on this point. But before so doing, I would impress strongly the argument that, although half a dozen analogous substances having the properties of acids, should produce the analogous symptoms and pathology when introduced into the body (by virtue of the same law as makes them exert analogous chemical results out of the body), such occurrence would not, as has been superficially assumed, reduce the value of the experimental evidence already collected in its bearings on disease. Let the reasoner, for the moment, forget all old analytical speculations regarding the origin of diseases in which endocarditis is a symptom. Let him then take up as a new and simple proposition, any day proveable by experiment, that endocarditis may be artificially produced by introduction into the body of one of a limited series of analogous compounds. Let him after this return to his analytical mode of research, and if in that manner he should find present in the human body, in a case of endocarditis which did not produce disease, one of the very agents by the use of which he had been enabled to elicit the same disease by synthesis, then I contend that such observer has arrived as near to a specific cause as he can arrive by any experiment whatever. The connexion then of an acid poison in the body, with endocarditis as a result, in cases of rheumatic endocarditis, seems to stand as follows: Synthesis entirely and as completely as synthesis is capable, supports the connexion. The synthesis is positive and demonstrative. The analysis is corroborative, but has not yet advanced beyond theory. In acute rheumatism analysis has only found an acid poison of the producing series in the excreta. It is absurd certainly to assume that ounces of an acid of the producing series, thrown off from the skin of a sick man, should not be derived from his blood; and I shall be able to show that one reason of such acid poison not having been found in the blood of the rheumatic man is, that it has never been sought after in the right place. But I will not wait to support theory; it is most sound to state the pure fact that analytical demonstration of a producing poison in the blood is not yet supplied. But what of the other acids; on this point I have one valuable experiment. As acetic is nearest in its approach to lactic acid, I have performed with every possible care the experiment of introducing this acid into the circulation. The acid so introduced, produces many of the general symptoms caused by the lactic, and some disturbance of the heart. But the specific cardiac symptoms are wanting. Returning to the simple teachings of the experiments, there are certain local peculiarities of great importance to which allusion must be made. It is remarkable, that when the inner surface of the heart is affected by the acid poison, the mischief is mainly confined to the auriculo-ventricular valves. The semilunar valves escape as a general rule. In like manner, the lining coats of the blood-vessels do not seem to suffer any more than in rheumatic endocarditis. From this, one can but infer, that some certain histological peculiarity, as yet not understood, acts in unison with the peculiar poison to produce the lesion of the ventricular valves; and that some certain histological peculiarity, not as yet understood, tends to the protection of the aortic valves and lining coat of the vessels. This observation, small enough indeed in its individual meaning, assumes a much wider form, when it is considered with the local origin of diseases generally. It bases in fact this proposition, long previously theoretically conceived and admitted, but not so definitely proved. That a special poison, present in the blood and bathing all tissues, may have its influence, as a disease-producing agent, localized in one structure or organ. In the course of my description of the symptoms and morbid anatomy in the cases of endocarditis induced by experiment, I dwelt specially on the circumstance, that in these instances the disease was primarily manifested on the right side of the heart. At first sight, this occurrence is an anomaly, when compared with ordinary endocarditis, and hastily glanced at, would serve to break the idea of relationship between induced and spontaneous endocardial inflammation. But a little reflection dispels these hasty inferences, and offers not merely a proof of relationship, but an explanation absolutely of the known fact, that in spontaneous endocarditis, the left side of the heart is the common seat of the disorder. The cause of the difference in the two classes of cases, I mean the induced and the spontaneous, seems then to be simply this. In the cases of induced endocarditis, the poison introduced into the body by an absorbing surface finds its way into the circulation by the venous blood. It follows, that as the poison traverses the circulatory canals, it comes in contact with the inner surface of the right side of the heart first: in the pulmonic circuit it undergoes some loss, and so entering the left cavity is less active in its effects. In other words, the poison in these instances, in so far as the heart is concerned, is derived from the systemic circuit, and is lost in part in the pulmonic circuit. On the other hand, in rheumatic endocarditis the evidence all points to the supposition that the poison is a product of respiration. Hence, as the poison traverses the circulatory canals, it comes in contact, first, with the inner surface of the left side of the heart: while, in the systemic circuit, it undergoes loss or combination, so that the blood returning by the veins is not poisoned, and the right side of the heart escapes. Reversing the previous proposition, the poison in these cases, in so far as the heart is concerned, has a pulmonic origin, and a systemic destruction. The further inference from this argument also is, that the action of the producing poison, both in the artificial and the spontaneous endocarditis, is directly on the part affected; i.e., by contact with the endocardial surface. Let us examine this question from another point of view. Seeing that a certain series of changes are produced in the endocardial membrane when the necessary condition, viz., a producing poison, is present: our reason admits of but two modes by which the changes induced could originate. Either the poison has been carried into the affected part through the nutritive vessel or vessels of the part, and thus has produced its effect, a tergo, by interference with nutrition; or it has been applied to the free surface of the part, and has produced its effect by direct contact, like a blister applied to the skin. Many poisons have the privilege of producing their effects by both methods; but in reference to lactic acid and endocarditis, and in reference to an assumed rheumatic poison and endocarditis, there is no alternative but to accept that the action of the poison is by direct contact with the free surface. For the position of the question is this: that in the artificial endocarditis the right side of the heart is first affected; in the rheumatic endocarditis the left side is primarily, and by a general rule which has but rare exceptions, singly affected. Now, it is clear that, if the effect of the poison in these cases, one or other, were a tergo, i.e., by introduction to the endocardial surface through the nutritive vessel, the two sides of the heart would share equally in the catastrophe, inasmuch as they are both fed from a common source and the same blood. But if the action of the poison is by direct contact of the poison with the free surface of the membrane, the occurrence of endocarditis in the induced cases on the right side, and in the spontaneous cases on the left side, is easily and satisfactorily accounted for. The observations here made lead me to recur for a moment to a remark already offered relative to the methods which have been pursued by those chemists who have searched for an acid condition of blood in rheumatic cases. As far as I can discover, every inquiry in this direction has been made on venous blood. But it is obvious, if the foregoing arguments are correct, that the venous blood is never charged with the free poison. The poison being disposed of in the systemic circuit by elimination and combination can only be present in arterial blood, whither the chemist should turn for evidence. The experiments which I have had the good fortune to institute, for the production of endocardial inflammation, have enabled me in a measure to trace out some of the changes which result in the foundation of organic cardiac disease. The reader will, I trust, pardon me while I briefly offer a note on this subject. In artificial endocarditis the first morbid sign is simple vascularity of surface; the second, effusion of lymph into the subserous tissue; the third, coagulation of the effused fluid; and the fourth, either absorption of the effused matter, or the nutrition of this matter and its transformation into new and abnormal structure. Thus the ordinary sequences of the inflammatory process are the same in endocarditis as in other inflammatory types. On the pathology of ordinary endocarditis much discussion has at various times arisen respecting the origin of the bead formations so often met with, after fatal cases, fringing the margins of the valves. Some have argued that these beads are the result of exudation, others that they are simple deposits from the blood. Some years ago I was inclined to the deposition theory. I take the present opportunity, from positive knowledge, of retracting this view. Tracing the formation of the bead step by step in these later inquiries, I have demonstrative proof that the bead originates in an exudation beneath the endocardial surface. But, although the bead has this unquestionable origin, it is, I believe, often the basis of a secondary deposit from the blood. I have explained that in the cedematous stage of endocardial inflammation, the swollen surface gives out on puncture or slight pressure a plastic fluid. In endocardial inflammation the exuded matter sometimes finds its way to the free surface; and once exuded in this manner, it may, and probably does, form a favouring point for the direct deposition of fibrine from the blood. The advocates of the exudation theory and those of the deposition theory may therefore, in the main, be both right; but the former have the priority in the argument. The last point on which I would rest, relates to the connexions which may be presumed to exist between a free acid in the blood and the fibrine of the blood. As the blood is always alkaline in health, as the solution of fibrine is clearly due to the presence of alkali, and as the fibrinous deposition is common in acute rheumatism, the theory has been most ingeniously and ably propounded by Dr. Fuller, that the deposition in rheumatic fever is due to neutralization of the alkaline solvent of the blood. Consonant with this view, I had expected to find that in my experiments of introducing lactic acid into the blood, I should ensure free fibrinous deposition. Remarkably enough, in every instance, the reverse obtained; the blood in these cases was only feebly coagulated and rarely showed sign of free separation of fibrine. The explanation of this apparent contradiction could only be sought for by experiment with the acid, on blood itself. So going to the experiment, I found at once, that lactic acid, although it will but feebly dissolve condensed fibrine, has the same effect as a fixed alkali when added to blood newly drawn. The same power of holding blood fluid is possessed by the acetic and citric acids. We cannot, therefore, in observing the tendency to fibrinous deposition, retain the impression that the tendency to fibrinous deposition in rheumatism is due to neutralization of the true blood solvent, seeing that the assumed neutralizing agent is itself a fixed solvent of the blood; but we must take, rather, the two occurrences of an acid poison and an increase of fibrine as connected with a common cause and as coincidental pheno mena. In a few concluding sentences, I will put forward what seems nearest to the truth in reference to spontaneous rheumatic endocarditis and its cause. 1. The evidence, both analytical and synthetical, goes to prove that the disease is due to the presence of an acid poison having the properties of lactic acid but the evidence stops short, as yet, of absolute demonstration in the analytical part. 2. The synthetical evidence brings to the verge of demonstration the supposition that the action of the poison which produced the disease is direct on the free surface of the endocardial membrane; that the poison acts, in a word, after the manner of a local irritant. 3. The evidence, analytical as well as synthetical, points to the conclusion, that the |