Bernstein found that the afferent nerves in Goltz's experiment were branches of the abdominal sympathetic, and discovered that the stimulation of the central end of the abdominal sympathetic in the rabbit was followed also by reflex inhibition of the heart.

The stimulation of the central end of the splanchnic produces a reflex rise of blood-pressure and, perhaps secondarily, a slowing of the heart. In some cases acceleration has been observed. According to Roy and Adami splanchnic stimulation sometimes produces a combination of augmentor and vagus effects, the augmentation appearing during stimulation and giving place abruptly to well-marked inhibitory slowing at the close of stimulation.

The results of stimulating various abdominal viscera have been studied by Mayer and Pribram. One of the most interesting of the reflexes observed by them was the inhibition of the heart called forth by dilating the stomach.

The stimulation of the cervical sympathetic does not give any very constant results on the action of the heart.

B. THE CENTRES OF THE HEART-NERVES.

Inhibitory Centre.-It has been already mentioned that the brothers Weber localized the cardiac inhibitory centre in the medulla oblongata. The efforts to fix the exact location of the centre by stimulation of various parts, either mechanically, by thrusting fine needles into the medulla, or electrically, cannot inspire great confidence because of the difficulty of distinguishing between the results that follow the excitation of a nerve-path from or to the centre and those following the excitation of the centre itself. According to Laborde, who also used this method, the cardiac inhibitory centre is situated at the level of the mass of cells known as the accessory nucleus of the hypoglossus and the mixed nerves (vagus, spinal accessory, glosso-pharyngeal).

The localization of the centre by the method of successive sections is perhaps more trustworthy. Franck has found that the separation of the bulb from the spinal cord cuts off the reflexes called forth by nerves that enter the spinal cord, while leaving undisturbed the reflex produced by stimulation of the trigeminus nerve.

On the whole, there seems to be no doubt that the cardiac inhibitory centre. is situated in the bulb.

Tonus of Cardiac Inhibitory Centre.-The cardiac inhibitory centre is probably always in action, for when the vagus nerves are cut, the heart-beat becomes more frequent.' The source of this continued or "tonic" activity may lie in the continuous discharge of inhibitory impulses created by the liberation of energy in the cell independent of direct external influences, or the cells may be discharged by the continuous stream of afferent impulses that must constantly play upon them from the multitude of afferent nerves. This latter theory, the conception of a reflex tonus, is made probable by the observations that section of the vagi does not increase the rate of beat after the greater part of the afferent impulses have been cut off by division of the 1 Hunt: American Journal of Physiology, 1899, ii. p. 397.

spinal cord near its junction with the bulb, and that the sudden decrease in the number of afferent impulses caused by section of the splanchnic nerve quickens the pulse-rate.

Irradiation. The slowing of the rate of beat observed chiefly during the expiratory portion of respiration disappears after the section of both vagus nerves. The slowing may perhaps be due to the stimulation of the cardiac inhibitory centre by irradiation from the respiratory centre.1

Origin of Cardiac Inhibitory Fibres.-Since the researches of Waller and others, it has been generally believed that the cardiac inhibitory fibres enter the vagus from the spinal accessory nerve, for the reason that cardiac inhibition was not secured in animals in which the fibres in the vagus derived from the spinal accessory nerve were made to degenerate by tearing out the latter before its junction with the vagus. These results have lately been called in question by Grossmann. The method employed by his predecessors, according to him, probably involved the destruction of vagus roots as well as those of the spinal accessory. Grossmann finds that the stimulation of the spinal accessory nerve before its junction with the vagus does not inhibit the heart. Nor does inhibition follow the stimulation of the bulbar roots supposed to be contributed to the mixed nerve by the spinal accessory.

Augmentor Centre.-The situation of the centre for the augmentor nerves of the heart is not definitely known, although from analogy it seems probable that it will be found in the bulb. That this centre is constantly in action is indicated by the lowering of the pulse-rate after section of the vagi followed by the bilateral extirpation of the inferior cervical and first thoracic ganglia. The division of the spinal cord in the upper cervical region after the section of the vagi has the same effect. Vagus inhibition, moreover, is said to be more readily produced after section of the augmentor nerves.

3

McWilliam has remarked that the latent period and the character of the acceleration often accompanying the excitation of afferent nerves may differ entirely from the characteristic effects of the excitation of augmentor nerves. The stimulation of the latter is followed by a long latent period, after which the rate of beat gradually increases to its maximum and, after excitation is over, as gradually declines. The excitation of an afferent nerve, on the contrary, causes often, with almost no latent period, a remarkably sudden acceleration, that reaches at once a high value and often suddenly gives way to a slow heart-beat. These facts seem to show that reflex acceleration of the heartbeat is due to changes in the cardiac inhibitory centre, and not to augmentor excitation. This view is strengthened by the fact that if the augmentor nerves are cut, the vagi remaining intact, the stimulation of afferent fibres, for example in the brachial nerves, can still cause a marked quickening of the pulseIn short, the action of afferent nerves upon the rate of beat is essentially

rate.

1 Laulanié: Comptes rendus Société de Biologie, 1893, p. 723. Compare Wood: American Journal of Physiology, 1899, ii. p. 352.

2 Grossmann: Archiv für die gesammte Physiologie, 1895, lix. p. 6.

3 Hunt: American Journal of Physiology, 1899, ii. p. 397.

the same, according to this observer, whether the augmentor nerves are divided or intact.

Roy and Adami believe that the stimulation of afferent nerves, such as the sciatic or the splanchnic, excites both augmentor and vagus centres. The augmentor centre is almost always the more strongly excited of the two, so that augmentor effects alone are usually obtained.

Action of Higher Parts of the Brain on Cardiac Centres.-Repeated efforts have been made to find areas in the cortex of the brain especially related to the inhibition or augmentation of the heart, but with results so contradictory as to warrant the conclusion that the influence on the heart-beat of the parts of the brain lying above the cardiac centres does not differ essentially from that of other organs peripheral to those centres.

Voluntary control of the heart, by which is meant the power to alter the rate of beat by the exercise of the will, is impossible except as a rare individual peculiarity, commonly accompanied by an unusual control over muscles, such as the platysma, not usually subject to the will. Cases are described by Tarchanoff and Pease, in which acceleration of the beat up to twenty-seven in the minute was produced, together with increase of blood-pressure, from vaso-constrictor action. The experiments are dangerous.'

2

Peripheral Reflex Centres. It is now much discussed whether the peripheral ganglia can act as centres of reflex action. According to Franck the excitation of the central stump of the divided left anterior limb of the annulus of Vieussens is transformed within the first thoracic ganglion, isolated from the spinal cord by section of its rami communicantes, into a motor impulse transmitted by the posterior limb of the annulus. This motor impulse causes, independently of the bulbo-spinal centres, a reflex augmentation in the action of the heart, and a reflex constriction of the vessels in the external ear, the submaxillary gland, and the nasal mucous membrane. This experiment, in conjunction with the facts in favor of other sympathetic ganglia acting as reflex centres,3 seems to demonstrate that some afferent impulses are transformed in the sympathetic cardiac ganglia into efferent impulses modifying the action of the heart. If this conclusion is confirmed by future investigations it will profoundly modify the views now entertained regarding the innervation of the heart.

The experiments of Stannius, published in 1852, have been the startingpoint of a very great number of researches on the innervation of the frog's heart. Stannius observed, among other facts, that the heart remained for a time arrested in diastole when a ligature was tied about the heart precisely at the junction of the sinus venosus with the right auricle. No sufficient explanation of this result has yet been given, nor is one likely to be found until the innervation of the heart is better understood. Stannius further 1 Van de Velde: Archiv für die gesammte Physiologie, 1897, lxvi. p. 232.

2 Franck: Archives de Physiologie, 1894, p. 721.

3 Langley and Anderson : Journal of Physiology, 1894, xvi. p. 435. The attempt of Prof. Kronecker to demonstrate a co-ordinating centre in the ventricles may be mentioned here (Zeitschrift für Biologie, 1896, xxxiv. p 529).

observed that after the ligature just described had been drawn tight, thus arresting the heart, the placing of a second ligature around the heart at the junction of the auricle and ventricle caused the latter to begin to beat again, while the auricle remained at rest. This second ligature, it is generally admitted, stimulates the ganglion of Bidder, and the ventricle responds by rhythmic contractions to the constant excitation thus produced. Loosening the ligature and so interrupting the excitation stops the ventricular beat.

PART III.-THE NUTRITION OF THE HEART.

The cells of which the heart-wall are composed are nourished by contact with a nutrient fluid. In hearts consisting of relatively few cells no special means of bringing the nutrient fluid to the cells is required. The walls of the minute globular heart of the small crustacean Daphnia, for example, are composed of a single layer of cells, each of which is bathed by the fluid which the heart pumps. In larger hearts with thicker walls only the innermost cells could be fed in this way. Special means of distributing the blood throughout the substance of the organ are necessary here.

Passages in the Frog's Heart.-In the frog this distribution is accomplished chiefly through the irregular passages which go out from the cavities of the heart between the muscle-bundles to within even the fraction of a millimeter of the external surface. These passages vary greatly in size. Many are mere capillaries. They are lined by a prolongation of the endothelium of the heart. Filled by every diastole and emptied by every systole, they do the work of blood-vessels and carry the blood to every part of the cardiac muscle. Henri Martin' describes a coronary artery in the frog, analogous to the coronary arteries of higher vertebrates. This artery supplies a part of the auricles and the upper fourth of the ventricle.

In the rabbit, cat and dog, and in man a well-developed system of cardiac vessels exists, the coronary arteries and veins. Their distribution in the dog deserves especial notice, because the physiological problems connected with these vessels have been studied chiefly in this animal.

Coronary Arteries in the Dog.-In the dog the coronary arteries and their larger branches lie upon the surface of the heart, covered as a rule only by the pericardium and a varying quantity of connective tissue and fat. The left coronary artery is extraordinarily short. A few millimeters after its origin from the aorta it divides into the large ramus circumflex and the descendens, nearly as large. The former runs in the auriculo-ventricular furrow around the left side of the heart to the posterior surface, ending in the posterior inter-ventricular furrow. The left auricle and the upper anterior and the posterior portion of the left ventricle are supplied by this artery. The descendens runs downward in the anterior inter-ventricular furrow to the apex. Close to its origin the descendens gives off the arteria septi, which at once enters the

1 Martin Comptes rendus Société de Biologie, 1893, p. 754.

inter-ventricular septum and passes, sparsely covered with muscle-bundles, obliquely downward and backward on the right side of the septum. The descendens in its farther course gives off numerous branches to the left ventricle and the anterior part of the septum. Only a few small branches go to the right ventricle. Thus the descendens supplies the septum and the inferior anterior part of the left ventricle. The right coronary artery, imbedded in fat, runs in the right auriculo-ventricular groove around the right side of the heart, supplying the right auricle and ventricle. It is a much smaller artery than either the circumflex or descendens. Each coronary artery keeps to its own boundaries and does not, in the dog, pass into the field of another artery, as sometimes happens in man.'

Terminal Nature of Coronary Arteries.-The coronary arteries in the dog, as in man, are terminal arteries, that is, the anastomoses which their branches have with neighboring vessels do not permit the making of a collateral circulation. Their terminal nature in the human heart is shown by the formation of infarcts in the areas supplied by arteries which have been plugged by embolism or thrombosis. That part of the heart-wall supplied by the stopped artery speedily decays. The bloodless area is of a dull white color, often faintly tinged with yellow; rarely it is red, being stained by hæmoglobin from the neighboring capillaries. The cross section is coarsely granular. The nuclei of the muscle-cells have lost their power of staining. The muscle-cells are dead and connective tissue soon replaces them. This loss of function and rapid decay of cardiac tissue would not take place did anastomoses permit the establishment of collateral circulation between the artery going to the part and neighboring arteries. The terminal nature of the coronary arteries in the dog has been placed beyond doubt by direct experiment. It is possible to tie them and keep the animal alive until a distinct infarct has formed.3

The objection that one of the coronary arteries can be injected from another, and that therefore they are not terminal, is based on the incorrect premise that terminal arteries cannot be thus injected, and has no weight against the positive evidence of the complete failure of nutrition following closure. The passage of a fine injection-mass from one vascular area to another proves nothing concerning the possibility of the one area receiving its blood-supply from the other. Such supply is impossible if the resistance in the communicating vessels is greater than the blood-pressure in the smallest branches of the artery through which the supply must come. It is the fact of this high resistance, due to the small size of the communicating branches, which makes the artery "terminal." This condition of high resistance is really present during life, or infarction could not take place.

The terminal nature of the coronary arteries is of great importance with regard to the part taken by them in the nutrition of the heart. Being ter1 Baumgarten: American Journal of Physiology, 1899, ii. p. 243.

2 See also the description by Kolster: Skandinavisches Archiv für Physiologie, 1893, iv. p. 14, of the infarctions produced experimentally in the dog's heart.

3 Porter: Archiv für die gesammte Physiologie, 1893, lv. p. 366.

* Michaelis: Zeitschrift für klinische Medicin, 1894, xxiv. p. 289.