minal, their experimental closure enables us to study the effects of the sudden stopping of the blood-supply (ischæmia) of the heart muscle upon the action of the heart. Results of Closure of the Coronary Arteries.-The sudden closure of one of the large coronary branches in the dog has as a rule either no effect upon the action of the heart beyond occasional and transient irregularity, or is followed after the lapse of seconds, or of minutes, by the arrest of the ventricular stroke, the ventricle falling a moment later into the rapid, fluttering, A B FIG. 38.-A, curve of intra-ventricular pressure, written by a manometer connected with the interior of the left ventricle; B, atmospheric pressure; C, time in two-second intervals. At the first arrow the ramus circumflexus of the left coronary artery was ligated; at the second arrow the heart fell into fibrillary contractions. The lessening height of the curve shows the gradual diminution of the force of contraction after ligation. The rise of the lower line of the curve above the atmospheric pressure indicates a rise of intra-ventricular pressure during diastole. The small elevations in the pressure-curve after the second arrow are caused by the left auricle, which continued to beat after the arrest of the ventricle (Porter, 1893). undulatory movements known as fibrillary contractions and produced by the inco-ordinated, confused shortenings of individual muscle-cells, or groups of cells. The auricles continue to beat for a time, but the power of the ventricles to execute co-ordinated contractions is lost. The Frequency of Arrest.-The frequency with which closure is followed by ventricular arrest depends on at least two factors-namely, the size of the artery ligated and the irritability of the heart. That the size of the artery is of influence appears from a series of ligations performed on dogs, arrest being never observed after ligation of the arteria septi alone, rarely observed (14 per cent.) with the right coronary artery, more frequently (28 per cent.) with the descendens, and still more frequently (80 per cent.) with the arteria circumflexa.2 The irritability of the heart is an important factor. In animals cooled by long artificial respiration, or by section of the spinal cord at its junction with the bulb, the ligation of the descendens arrests the heart less frequently than in vigorous animals which have been operated upon quickly. The frequency of arrest is increased by the use of morphia and curare.3 Changes in the Heart-beat.-Ligation destined to arrest the heart is followed almost immediately by a continuous fall in the intra-ventricular pressure during systole and a gradual rise in the pressure during diastole (see Fig. 38). The contraction and relaxation of the ventricle are often slowed. The force of the ventricular stroke is diminished. As arrest draws near, irregularities in the force of the ventricular beat are seldom absent. The frequency of beat is sometimes unchanged throughout, but is usually diminished toward the end; 1 The changes produced by subsequent degeneration are not considered here. 2 Porter: Journal of Physiology, 1893, xv. p. 131. 3 Porter: Journal of Experimental Medicine, 1896, i. p. 49. FIG. 39.-Showing fall in arterial pressure and diminished output of left ventricle in consequence of the ligation of the circumflex artery. The curve reads from left to right. It is one-half the original size. The upper curve is the pressure in the carotid artery. The unbroken line is atmospheric pressure. The next curve is the measurement of the outflow from the left ventricle, each rise and each fall indicating the passage of 50 c.cm. of blood into the aorta. The lower line is a time-curve in seconds. At the circumflex artery was ligated (Porter, 1896, p. 51). occasionally the frequency is increased. Both ventricles as a rule cease to beat at the same instant. The work done by the heart, measured by the blood thrown into the aorta in a unit of time, is lessened by ligation when followed by arrest (see Fig. 39). The Exciting Cause of Arrest.-There are two opinions concerning the exciting cause of the changes following closure of a coronary artery, some investigators holding for anæmia and others for mechanical injury of the cardiac muscle or its nerves in the operation of ligation. The latter base their claim on the frequent failure of ligation of even a main branch to stop the heart; on the fact that the heart of the dog has been seen to beat from 115 to 150 seconds after the blood-pressure in the aorta was so far reduced, by clamping the auricle and opening the carotid artery, as to make a continuance of the coronary circulation very improbable;' on the revival of the arrested heart by the injection of defibrinated blood into the coronary arteries from the aorta, by which means the dog's heart and even the human heart has been made to beat again many minutes after the total arrest of the circulation,-it being assumed, incorrectly, that the dog's heart cannot be made to beat after arrest with fibrillary contractions; and, finally, on the arrest with fibrillary contractions which some experimenters have caused by mechanical injury to the heart. To sum up, the argument in favor of explaining arrest with fibrillary contractions simply by the mechanical injury done the heart in the process of ligation consists of two propositions: first, anemia without mechanical injury does not cause arrest with fibrillary contractions; and second, mechanical injury without anemia does cause arrest. Against the second of these propositions must be placed the extreme infrequency of arrest from mechanical injuries. In more than one hundred 1 Tigerstedt: Skandinavisches Archiv für Physiologie, 1893, v. p. 71; Michaelis: Zeitschrift für klinische Medicin, 1894, xxiv. p. 270. ligations Porter observed not a single arrest in consequence of laying the artery bare and placing the ligature ready to be drawn, the only effect of the mechanical procedure being an occasional slight irregularity in force. Ligation of the periarterial tissues in ten dogs, the artery itself being excluded from the ligature, directly injured both muscular and nervous substance, but was only once followed by arrest. Nor does arrest follow the ligation of a vein, although the mechanical injury is possibly as great as in tying an artery. The direct stimulation of the superficial ventricular nerves exposed to injury in the operation of ligation does not produce the effects that appear after the ligation of coronary arteries. Against the remaining proposition stated above-namely, that anæmia without mechanical injury does not cause arrest with fibrillary contractions-it should be said that the frequency of arrest after ligation is in proportion to the size of the artery ligated, and hence to the size of the area made anæmic, and is not in proportion to the injury done in the preparation of the artery. The circumflex and descendens may be prepared without injuring a single muscle-fibre, yet their ligation frequently arrests the heart, while the ligation of the arteria septi, which cannot be prepared without injuring the musclesubstance, does not arrest the heart. It is, moreover, possible to close a coronary artery without mechanical injury. Lycopodium spores mixed with defibrinated blood are injected into the arch of the aorta during the momentary closure of that vessel and are carried into the coronary arteries, the only way left open for the blood. The lycopodium spores plug up the finer branches of the coronary vessels. The coronary arteries are thus closed without the operator having touched the heart. Prompt arrest with tumultuous fibrillary contractions follows. There seems, then, to be no doubt that fibrillary contractions can be brought on by sudden anæmia of the heart muscle.1 The gradual interruption of the circulation in the coronary vessels-by bleeding from the carotid artery, for example is followed by feeble incoordinated contractions not essentially different in kind from those commonly termed fibrillary contractions. The manner of interruption probably explains the difference in result. In the former case, namely, ligation or other sudden closure, the supply of blood to the heart muscle is suddenly stopped while the heart continues to work against a high peripheral resistance; in the latter, the anæmia is gradual and the heart works against little or no peripheral resistance. Recovery from Fibrillary Contractions. Fibrillary contractions brought on by clamping the left coronary artery in the rabbit's heart are often gradually replaced by normal contractions when the clamp is removed. The isolated cat's heart after showing marked fibrillary contractions during forty-five minutes has given strong regular beats for more than an hour. McWilliam and others have seen a number of spontaneous regular beats after the termination of fibrillary contraction. The dog's heart can be recovered by cooling the ventricles until all trace of fibrillation has disappeared, and then bringing the heart back to normal temperature by circulating warmed defi1 Porter: Journal of Experimental Medicine, 1896, 1. p. 65. brinated blood through the coronary vessels.' Recovery has also been obtained by passing immediately (within 15 seconds) a very rapid alternating current of not too great intensity.2 Closure of the Coronary Veins.-Closure of all the coronary veins in the rabbit produced fibrillary contractions after from fifteen to twenty minutes had passed. Their closure in the dog is said to be without effect 3-a negative result perhaps to be explained by the fact that a portion of the coronary blood finds its way to the cavities of the heart through the venæ Thebesii. Volume of Coronary Circulation.-Bohr and Henriques, taking the average of six experiments on dogs, found that 16 cubic centimeters of blood passed through the coronary arteries per minute for each 100 grams of heart muscle. The quantity passing through both coronary arteries varied in different animals from 20 to 64 cubic centimeters per minute; the quantity passing through the left coronary artery varied from 22.5 to 60 cubic centi FIG. 40.-Diminution of the force of contraction of the ventricle of the isolated cat's heart in consequence of diminishing the supply of blood to the cardiac muscle: 4, blood-pressure at the root of the aorta, recorded by a mercury manometer; B, intra-ventricular pressure-curve, left ventricle: the individual beats do not appear, because of the slow speed of the smoked surface; C, time in seconds; D, the number of drops of blood passing through the coronary arteries, each vertical mark recording one drop. As the number of drops of blood passing through the coronary arteries diminishes, the contractions of the left ventricle become weaker, but recover again when the former volume of the coronary circulation is restored. meters per minute. The hearts weighed from 51 to 350 grams. The method which Bohr and Henriques found it necessary to employ placed the heart under such abnormal conditions that their results can be regarded as only approximate. Porter supplied the left coronary artery of the dog with blood diluted one-half with sodium chloride solution (0.6 per cent.) by means of a tube (lumen 2.75 millimeters) inserted into the aortic opening of the left coro 1 Porter: American Journal of Physiology, 1898, i. p. 71. ? Prevost and Battelli: Journal de physiologie et de pathologie générale, 1900, p. 440. 3 Michaelis: Zeitschrift für klinische Medicin, 1894, xxiv. p. 291. Bohr and Henriques: Skandinavisches Archiv für Physiologie, 1895, v. p. 232. 5 Porter: Journal of Experimental Medicine, 1896, i. p. 64. nary artery and connected with a reservoir placed 150 centimeters above the heart. In one dog, weighing 11,500 grams, 318 cubic centimeters flowed through in eight minutes. In a second dog, weighing 9500 grams, 114 cubic centimeters passed through in four minutes. In the isolated heart of the cat strong and regular contractions are made on a circulation of about 4 cubic centimeters per minute, or even less, through the coronary system. The quantity passing through the veins of Thebesius into the left auricle and ventricle is very slight. The supply of blood to the heart-muscle is modified by ventricular contraction, not only in that the mean blood-pressure in the aorta is a function of the force of the heart-beat, but directly by the compression of the intramural vessels during systole. Thus, when a piece of the mammalian ventricle is kept beating by supplying it with defibrinated blood through its nutrient artery at a constant pressure, each beat can be seen to force the blood out of the severed vessels in the margin of the fragment. The effect of the contractions on the contents of the intranrural vessels can also be demonstrated in the living animal by incising a vein, or a ligated artery on the distal side of the ligature, and slowing the heart by stimulation of the vagus. At each systole of the ventricle blood is forced from the vessel. Moreover, lessening the frequency of contraction diminishes the volume of the coronary circulation-i. e., the outflow from the coronary veins, as may be shown in a record similar to that illustrated by Fig. 40. It is conceivable that the emptying of the intramural vessels by the contraction of the heart may favor the flow of blood through the heart-walls in two ways: first, by the diminished resistance which the empty patulous vessels should offer to the inflow of blood from the aorta when the heart relaxes; and, secondly, by the suction which might accompany the sudden expansion of the compressed vessels-expanding either by virtue of their intrinsic elasticity, or because of the pull of the surrounding tissues upon their walls, as the heart quickly regains its diastolic form. The problem thus raised may be attacked by suddenly connecting the distal portion of a coronary artery in the strongly beating heart of the living animal with a small reservoir of normally warm defibrinated blood at the atmospheric pressure. The connection can be made through a cannula tied into the artery (ramus descendens of the dog) or through a tube passed into the left coronary artery by way of the innominate artery and aorta. If each compression of the deeper branches of the artery were followed by an expansion sufficient to cause a noteworthy suction, the blood in the reservoir should be drawn into the artery, for this blood is the sole source of supply throughout the experiment, as the "terminal” nature of the coronary arteries prevents any material backflow from the distal branches. The results of these experiments showed that no appreciable suction can be demonstrated in the larger coronary arteries, even when a very sensitive minimum valve is interposed between the artery and the reservoir in order to prevent the possible masking of the suction by rising pressure accompanying the contraction of the ventricle. It is, therefore, necessary |