IS THERE A FUNDAMENTAL DIFFERENCE BETWEEN THE CONTRACTION OF THE HEART AND ORDINARY STRIATED MUSCLE1 BY THOMAS J. MAYS, M.D., PROFESSOR OF EXPERIMENTAL THERAPEUTICS AND PHYSIOLOGY IN THE PHILADELPHIA POLYCLINIC AND COLLEGE FOR GRADUATES IN MEDICINE. REPRINTED FROM THE TRANSACTIONS OF THE COLLEGE OF PHYSICIANS OF PHILADELPHIA, MAY, 1890. ON THE CONTRACTION OF THE HEART AND ORDINARY STRIATED MUSCLE. By THOMAS J. MAYS, M.D., PROFESSOR OF EXPERIMENTAL THERAPEUTICS AND PHYSIOLOGY IN THE PHILADELPHIA POLYCLINIC AND COLLEGE FOR GRADUATES IN MEDICINE. [Read May 7, 1890.] The work on which the remarks of this paper are based was performed by myself in Professor Kronecker's laboratory, and under his direction, during the winter of 1882 and 1883, and a preliminary report of the same was published in the Verhand- lungen d. physiologischen Gesellsch. zu Berlin, Jan. 12,1883. And although no efforts have been made since then to push the investigation further, I desire to present it to the College to-night for the purpose of considering its bearing on the general question of muscular contraction more fully than was possible in the prefatory announcement already made. It is well known that under certain conditions the degree of contraction of a skeleton muscle varies with the strength of the stimulus which is applied to it. In other words, the more intense the stimulus the higher and longer will the muscle-curve become. Thus in the following diagram, which is copied from Dr. Brunton's work on Pharmacology, Therapeutics, and Materia Medica, p. 121, it is shown that a weak electric stimulus of 15 cm. distance between the primary and secondary coil of the induction apparatus produces a lower contraction than if the stimulus is increased to 12 cm., 13 cm., or 14 cm. distance be- tween the two coils. Since the investigations of Bowditch, Kronecker, Stirling, 2 THOMAS J. MAYS, and others into the nature of cardiac contraction, our works on physiology teach that the heart differs widely in its mode of contraction from that of a striated or skeleton muscle. Thus Landois states {Lehrbuch der Physiologic des Menschen, 3te. Aufl. 1883, p. Ill) that in the case of the heart " the feeblest stimulus Fig. 1. Tracing of the contractions of a muscle with stimuli of varying strength. The numbers indicate the distance in centimetres of the secondary from the primary coil in the induction apparatus. As. and Des. indicate the ascending and descending direction of the current. which is capable of calling forth a contraction acts like the strongest-the most complete or maximum contraction being, therefore, induced by the weakest or minimum stimulus." In Hermann's Handbuch'der Physiologic (Band 4a. S. 350) Aubert, writing on the rhythmic movements of the heart, says that on stimulating the frog's ventricle with different intensities of the induction current, Bowditch always found that the stimulus which produced a contraction at all provoked a maximum contraction. Dr. Stirling, the translator of Landois's Physiology, says (vol. i. p. 120, 1886): " It is quite clear, therefore, that the relation of the strength of the stimulus to the extent of the contraction of the cardiac muscle is quite dif- ferent from what occurs in a muscle of the skeleton, where within certain limits the amplitude of the contraction bears a relation to the stimulus, while in the heart the contraction is always maximal." The stimulus which produced a cardiac contraction at all gave rise to the fullest and most complete contraction, and therefore a maximum is not better than a minimum stimulus. The cause for this diversity of behavior is supposed to be CONTRACTION OF THE HEART. 3 inherent in the structure of the heart-muscle itself. Thus Aubert (Hermann's Handbuch, Bd. 4a, p. 348) states in sub- stance that in view of these anatomical developments con- cerning the cardiac nerves it must be admitted that the mus- cular elements of the heart partake of the function of nerve fibres, and that on account of these anatomical variations the heart differs in its function from that of other striated muscles. In the abstract it is very difficult to see why such a manifesta- tion of contractility should prevail in the cardiac and not in a voluntary muscle; although under ordinary circumstances there can be no doubt concerning its existence, as anyone who has devoted much attention to the physiology of the isolated heart can testify. During the first month in which I was engaged in studying the influence of pure and diluted blood on the frog's heart this characteristic action always displayed itself in its accus- tomed manner. Toward the end of this period I found, or at least thought I found, evidence that this organ manifested a tendency to respond to maximum and minimum electric stimuli, by giving slight differences in the elevation of its tracings. This took place at first only when the blood in the heart became more or less wholly carbonized, as always hap- pens toward the close of an experiment of this kind. So soon as the heart was refilled with fresh blood, and was sufficiently revived, not a trace of this difference could be observed, and hence it seemed very probable that if the heart were filled with blood which had been kept for some time, and which had therefore undergone spontaneous carbonization, these pulse variations could be made to reappear. This was done and the assumption was verified. In a short time I became able so to adjust the relationship between the heart and its blood-contents as to call forth these pulse differences at will, as is demonstrated by the following tracings : Now, why did previous investigators come to the conclusion that a fundamental difference existed between the contraction of the heart and a skeleton muscle ? This, I believe, is due in the first place to the greater irritability of the heart muscle, 4 THOMAS J. MAYS, and in the second place to a lack of refinement in our experi- mental methods-i. e., the method which is adapted for stimu- lating ordinary striated muscle is not specially applicable in the case of the heart. There can be no doubt that the effects Fig. 2. Tracings representing the contractions of the frog's heart when stimulated by opening induction shocks every four seconds. The figures below the tracings indicate in cm. the distance between the primary and secondary coil of the induction appa- ratus. The arrows point out the direction in which the tracings are to be read. of a maximum and a minimum stimulus are alike so far as customary experimentation on the heart is concerned, but I think my experiments demonstrate that this does not reveal the true nature of cardiac contractility. First, then, as to the greater irritability ot the heart. Re- peated experimentation has taught me that so soon as this is reduced, which may be done either by allowing the heart to work until it becomes fatigued, or by filling it with blood which has been standing in a cool place for forty-eight or seventy-two hours, the difference in the pulse-elevation ap- pears ; or this may develop, too, if the heart is well exhausted and then filled with fresh blood. I often found that it took a long time to subdue a very irritable heart to the point where 5 CONTRACTION OF THE HEART. it showed these differences-often requiring to be filled and fatigued three or four times in succession before this took place, and even when this occurred, if, for some unaccountable reason, the irritability of the heart rose again, this phenomenon disappeared or was lost to a great degree. While, then, as a rule, it is necessary to blunt the irritability of the heart before this pulse difference manifests itself, it is also true that once in a while a heart is met in which this appears in the fresh or normal state, and from the very beginning of the experiment. Of such hearts, however, I only found one instance in my experiments. Its irritability was low at the outset, but grew during the experiment, yet the pulse difference remained throughout. It seems that when this property of producing pulse variations is once thoroughly developed it will generally remain until the heart is wholly disabled. That this whole matter resolves itself into a question ot irritability is still further substantiated by the fact that when the irritability of a voluntary or ordinary striated muscle is exaggerated, it loses its power of differential response to maximum and minimum stimuli, and behaves precisely as the heart muscle does under ordinary circumstances. Thus the experiments of Wundt1 and of Walton2 show that during strychnine poisoning " a stimulus which is strong enough to produce any reflex contraction in a muscle produces a max- imum contraction, and the muscle will not react more strongly if the greatest possible stimulus is applied. The range of stimuli through which the contraction varies with the intensity of the stimulus, becomes shorter as the effect of the poison in- creases, and when a certain grade of poisoning is reached the step is infinitesimal from a stimulus which produces no con- traction to one which produces a maximum." (Walton.) When irritability is viewed, therefore, as it exists normally in voluntary muscle, it is seen that varying degrees of contrac- 1 Untersu chun gen zur Mechanik der Nervencentren, 2 Abtheilung, S. 70, ff. 2 Reflex Movements of the Frog under the Influence of Strychnine. Journal oi Physiology, vol. iii. p. 308. 6 DISCUSSION. lion are obtained from this organ when varying degrees of electric stimulation are applied to it; but this differential re- sponsiveness vanishes so soon as its irritability is increased through the influence of strychnine. Now the irritability of the normal heart I regard as being analogous to that of vol- untary muscle under the influence of toxic doses of strychnine, for here, in virtue of the heightened irritability of the heart, the degree of electric stimulation which provokes a cardiac contraction at all is too powerful to produce anything else than a maximum contraction. It seems probable, then, that if, in- stead of blunting the irritability of the heart through fatigue, as had to be done in most of my experiments, the grade of the induction current between the point which gives no contraction and the point which gives a contraction, were attenuated more finely than that which the ordinary induction apparatus affords, the heart would respond as readily to maximum and minimum stimuli by giving out maximum and minimum contractions as is the case with voluntary muscle. DISCUSSION. Dr. Henry Hartshorne : This subject so especially belongs to those who are engaged in physiological experimentation and are familiar with its recent progress, that I do not feel competent to say much upon it, and what I have to say is rather interrogative and somewhat aside from what appears to be immediately relative. I have been led in my thoughts on the subject largely by the title of the paper qs announced-"Is there a Fundamental Difference Between the Contraction of the Heart and that of Striated Muscle ? " It seemed to me that the first question is whether or not the heart muscle is itself a striated tissue, as it has been commonly called ? That is a histological question. Here, as elsewhere, physiology and histology are best studied together. The statement has been made that by strong acetic acid the striae could be made to disappear. I presume that there is no doubt that this can be done, but there is good evidence that when such results occur, they are due to a destructive action. It seems to be shown that the difference between the muscular structure of the heart and smooth muscle is decided. The striae are something more than transitory superficial lines. The heart is really composed of distinctive cell forms. Weissmar found that in different classes of animals there is a difference, and he asserted that in the frog, and DISCUSSION. 7 also in lizards and fishes, there are fusiform fibres which are striated. As we pass to the higher animals the striae become more marked. To be as brief as possible, I will say that the proof of the cell-structure which is an essential part of striated muscular tissue, is clear as regards the heart muscular tissue ; that there are anastomoses is important; these cells with intervals between them nevertheless have lateral communications. The absence of sarcolemma and the scantiness of connective tissue are important. That the intervening material between the cells is different from the cells is shown by Bruck's experiments with polarized light. These showed that while the cell substance is doubly refracting, such is not the case with the intervening material. There is, again, confirmation to some extent from pathology. In Rind- fleisch's Pathological Histology is given an account of the examination of a heart in which there was diffuse inflammation of the muscular tissue. Rind- fleisch's description as it bears upon this question is in brief that " the mus- cular fibres were collectively divided by cross rents into short parallelograms, a phenomenon which we frequently meet with in the pathological histology of striated muscles." This remark was entirely apart from any physiological consideration. Supposing it to be the case that we have a certain difference between the heart muscular tissue and other striated tissue, it still seems to me that the two are essentially identical. The heart-muscle is intermediate between involuntary muscle and voluntary striated muscle. Such transitions are said by Kuss in his Physiology to occur in the muscles of the tortoise. The construction of the muscle of the heart is peculiar in the absence of sar- colemma, in the presence of lateral anastomoses, which are rare in smooth muscles, and in the presence of ganglia. The heart is an organ entirely unique. It is the only organ in which the muscle is the organ. The bladder and the uterus both have muscular tissue, but they differ in important respects. The ganglia permit a correlation of the different parts of the heart, and the lateral anastomoses make that very complete. This is also favored by the absence of sarcolempia. All these things help to make the heart a unit in action. This arrangement must produce an economy of irritability. It seems to me not so much an increase of irritability, as an economy of it, so that every stimulus takes effect upon the whole heart, which is not true of other muscles. When stimulation is applied to a voluntary muscle, it does take some effect throughout the muscle, but the complexus of effect must be greater in the case of the heart than in any other muscle ; and this seems to account for what has been mentioned by Dr. Mays, that even slight stimulus will produce a complete contraction as well apparently as a maximum one. That the irritability may be greater I would not pretend to deny, but it is possible that the construc- tion of the heart for economy of irritability may have much to do with it. As to the evidence in regard to the amount of contraction, I would ask whether there is not this difference of some importance, that while the mus- 8 DISCUSSION. cles of movement have a kind of action which is measurable by graphic arrangements, the heart in its normal action is under a condition of required opposition or resistance. I think that it has been shown by Blasius that the greatest work of the frog's heart is done under a resistance equivalent to 35 mm. of mercury. In Dr. Mays's experiments we have very little resistance. If such resistance were present, and it were possible then to measure the work done, it might be found that there was a difference in the amount of work done under a maximum and under a minimum stimulation. Dr. Mays : I do not know that I have much to add to what I have already said. I never could understand why it was that the heart should always make a maximum contraction under any degree of stimulation while in the skeleton muscles we have just the opposite, although this has hitherto been shown to be true. We know that in the higher animals the heart bears a close analogy to the striated muscles, but this does not hold so well in the lower orders of animals. But I have not dealt with the heart so much from a histological as from a physiological standpoint. I think that this experi- ment has a certain bearing upon the action of the human heart. The ques- tion is whether the heart in all conditions of health or disease, in standing, sitting, or lying, makes a full and complete contraction, or whether it merely becomes slower in its action. We must consider that in these experiments the conditions are different from what they are in the body, but I think that if we can with these crude experimental methods get a maximum and min- imum contraction from the heart and skeleton muscles, we should suppose that the same would hold true of the heart muscle at least under certain con- ditions. I think that I have demonstrated this by these experiments, although they have not been carried as far as I expect to carry them at some future time. 1829 Spruce Street, Philadelphia.