heart needs is supplied by increasing the tension of the gas in the plasma. Haldane kept his animals alive in oxygen at a pressure of two atmospheres after the oxygen-carrying function of the red corpuscles had been destroyed with carbon monoxide. The experiment has been repeated with the extirpated mammalian heart by Porter,' Locke,' and Rusch.3 Serum and even saline solutions will serve, if the oxygen tension is high or if the volume of oxygen reaching the tissues is increased simply by causing the nutrient liquid to circulate more rapidly.

Carbon dioxide is injurious to the heart when present in the circulating fluid in considerable quantities. The force of the contraction is reduced before the rate of beat. The heart poisoned with carbon dioxide often falls into irregular contractions, exhibiting at times "grouping" and the "staircase phenomenon, a series of beats regularly increasing in strength.

"

Organic Substances.—An unsuccessful effort has been made to prove that only solutions containing proteids, for example blood-serum, chyle, and milk, can keep the heart active. Recent observers have shown the incorrectness of this claim. A mixture of the inorganic salts, sodium chloride, potassium chloride, and calcium chloride, alone suffices. Locke found that the addition of 0.1 per cent. of dextrose to a suitable inorganic solution kept a frog's heart working under a load of 3.5 centigrams, and under an "after-load" of 3 centigrams in spontaneous activity for more than twenty-four hours. The sustaining action which dextrose appears to exercise is shared, according to him, by various other organic substances.

Physical Characteristics.-Heffier and Albanese, having observed that the addition of gum-arabic to the circulating fluid was of advantage, declared that the nutrient solutions should possess the viscosity of the blood. The favorable action of gum-arabic may, however, more probably be ascribed to the compounds which it contains rather than to its physical properties."

Mammalian Heart.-The success attained within the past two years in the isolation of the mammalian heart opens up an hitherto unexplored region in which systematic investigation will surely bring to light facts of wide interest and value. At present, however, little is known as to the constituents of the blood which are essential to the life of the mammalian heart. An abundant supply of oxygen is certainly highly important."

4

1 Porter: American Journal of Physiology, 1898, i. p. 511.

2 Locke: Centralblatt für Physiologie, 1898, xii. p. 568.

3 Rusch: Archiv für die gesammte Physiologie, 1898, Ixxiii. p. 535.

Langendorff: Archiv für Physiologie, 1893, p. 417; Ide: Ibid., p. 492; Oehrwall: Skandinavisches Archiv für Physiologie, 1897, vii. p. 222.

6

Locke: Journal of Physiology, 1895, xviii. p. 332.

Albanese: Archiv für experimentelle Pathologie und Pharmakologie, 1893, xxxii. p. 311; Archives italiennes de Biologie, 1896, xxv. p. 308.

Howell and Cooke: Journal of Physiology, 1893, xiv. p. 216.

Literature is given by Magrath and Kennedy: Journal of Experimental Medicine, 1897, ii. p. 13; and Hedbom: Skandinavisches Archiv für Physiologie, 1898, viii. p. 147. See also Hering: Archiv für die gesammte Physiologie, 1898, lxxii. p. 163; Bock: Archiv für experimentelle Pathologie und Pharmakologie, 1898, xli. p. 158; and Cleghorn: American Journal of Physiology, 1899, ii. p. 273.

Blood of Various Animals.-Roy gives some data as to the effect on the frog's ventricle of the blood of various animals. The blood of the various herbivora (rabbit, guinea-pig, horse, cow, calf, sheep), as well as that of the pigeon, were found to have nearly the same nutritive value in each case. That of the dog, of the cat, and more especially of the pig, while in some instances equal in effect to that from the horse or rabbit, were in other examples (from the newly killed animals) apparently almost poisonous. Cyon's early observation of the injurious action of dog's blood on the frog's ventricle has already been mentioned! Regarding the mammalian heart, experience has shown that it is best to supply the heart with blood from the same species of animal. The difficulties attending the use of blood from a different species are seen in the case of the dog's heart supplied with calf's blood. The heart dies sooner; œdema of the lungs takes place, impeding the pulmonary circulation and leading to engorgement of the right heart and paralysis of the right auricle; exudation into the pericardium often seriously interferes with the beat of the heart; and, finally, the elastic modulus of the cardiac muscle is apparently altered, permitting the heart to swell until it tightly fills the pericardium, when the proper filling of the heart is no longer possible through lack of room for diastolic expansion.

PART IV.-THE INNERVATION OF THE BLOOD-VESSELS.2 About the middle of the eighteenth century more or less sagacious hypotheses concerning the contractility of the blood-vessels began to appear in medical literature, but it was not until Henle demonstrated the existence of muscular elements in the middle coats of the arteries in 1840 that a secure foundation was laid for the present knowledge of the mechanism by which that contractility is made to control the distribution of the blood. More than a hundred years. before, indeed, Pourfour du Petit had shown that redness of the conjunctiva was one of the consequences of the section of the cervical sympathetic, but had called the process an inflammation, in which false idea he was supported by Cruikshank and others; and Dupuy of Alfort had noted redness of the conjunctiva, increased warmth of the forehead, and sweat-drops on ears, forehead, and neck following his extirpation of the superior cervical ganglia in the horse; Brachet, also, cutting the cervical sympathetic in the dog, had gone so far as to attribute the resulting congestion to a paralysis of the blood-vessels. But these were merely clever speculations, for the anatomical basis necessary for a real knowledge of this subject was wanting as yet. Henle furnished this basis, and at the same time reached the modern point of view. "The part taken by the contractility of the heart and the blood-vessels in the circulation," said Henle, "can be expressed in two words: the movement of the blood depends on the heart, but its distribution depends on the vessels." Nor did Henle stop here. It was now known that the vessels possessed contractile walls; it was

See also Bardier: Comptes rendus Société de Biologie, 1898, p. 548.
*See footnote to Part II., p. 148.

known further that these walls contracted when mechanically stimulated ; for example, by scraping them with the point of a scalpel; and various observers had traced sympathetic nerves from the greater vessels to the lesser until lost in their finest ramifications. It was therefore easy to construct a reasonable hypothesis of the control of the blood-vessels by the nerves. Henle declared that the vessels contract because their nerves are stimulated, either directly, or reflexly through the agency of a sensory apparatus. The ground was thus prepared for the physiological demonstration of the existence of "vasomotor" nerves, as Stilling began to call them. Four names are associated with this great achievement-Schiff, Bernard, Brown-Séquard, and Waller, each of whom worked independently of the others. Foremost among them is Claude Bernard, though not the first in point of time, for it was he who put the new doctrine on a firm basis. In his first publication Bernard stated that section of the cervical sympathetic, or removal of the superior cervical ganglion, in the rabbit, causes a more active circulation on the corresponding side of the face together with an increase in its temperature. The greater blood-supply manifests itself in the increased redness of the skin, particularly noticeable in the skin of the ear. The elevation of temperature may be easily felt by the hand. A thermometer placed in the nostril or in the ear of the operated side shows a rise of from 4° to 6° C. The elevation of temperature may persist for several months. Similar results are obtained in the horse and the dog.

The following year Brown-Séquard announced that "if galvanism is applied to the superior portion of the sympathetic after it has been cut in the neck, the dilated vessels of the face and of the ear after a certain time begin to contract; their contraction increases slowly, but at last it is evident that they resume their normal condition, if they are not even smaller. Then the temperature diminishes in the face and the ear, and becomes in the palsied side the same as in the sound side. When the galvanic current ceases to act, the vessels begin to dilate again, and all the phenomena discovered by Dr. Bernard reappear." Brown-Séquard concludes that "the only direct effect of the section of the cervical part of the sympathetic is the paralysis, and consequently the dilatation, of the blood-vessels. Another evident conclusion is that the cervical sympathetic sends motor fibres to many of the blood-vessels of the head."

While Brown-Séquard was making these important investigations in America, Bernard, in Paris, quite unaware of Brown-Séquard's labors, was reaching the same result. The existence of nerve-fibres the stimulation of which causes constriction of the blood-vessels to which they are distributed was thus established.

A considerable addition to this knowledge was presently made by Schiff, who pointed out in 1856 that certain vaso-motor nerves take origin from the spinal cord. The destruction of certain parts of the spinal cord causes the same vascular dilatation and rise of temperature that follows the section of the vaso-motor nerves outside the spinal cord.

At this time Schiff also offered evidence of vaso-dilator nerves. When

VOL. I.-13

the left cervical sympathetic is cut in a dog, and the animal is kept in his kennel, the left ear will always be found to be 5° to 9° warmer than the right. If the dog is now taken out for a run in the warm sunshine, and allowed to heat himself until he begins to pant with outstretched tongue, the temperature of both ears will be found to have increased. The right ear is now, however, the warmer of the two, being from 1° to 5° warmer than the left. The blood-vessels of the right ear are, moreover, now fuller than those of the left. When the animal is quiet again the former condition returns, the redness and warmth in the right becoming again less than in the left ear. The increase of the redness and warmth of the right ear over the left, in which the vaso-constrictor nerves were paralyzed, must be the result of a dilatation of the vessels of the right ear by some nervous mechanism. For if the dilatation of the vessels was merely passive, the vessels in the right ear could not dilate to a greater degree than those in the left ear which had been left in a passive state by the section of their nerves. This experiment, however, is by no means conclusive.

The existence of vaso-dilator fibres was placed beyond doubt by the following experiment of Bernard on the chorda tympani nerve, new facts regarding the vaso-constrictor nerves being also secured. Bernard exposed the submaxillary gland of a digesting dog, removed the digastric muscle, isolated the nerves going to the gland, introduced a tube into the duct, and, finally, sought out and opened the submaxillary vein. The blood contained in the vein was dark. The nerve-branch coming to the gland from the sympathetic was now ligated, whereupon the venous blood from the gland grew red and flowed more abundantly; no saliva was excreted. The sympathetic nerve was now stimulated between the ligature and the gland. At this the blood in the vein became dark again, flowed in less abundance and finally stopped entirely. On allowing the animal to rest the venous blood grew red once more. The chorda tympani nerve, coming from the lingual nerve, was now ligated, and the end in connection with the gland stimulated. Then almost at once saliva streamed into the duct, and large quantities of bright scarlet blood flowed from the vein in jets, synchronous with the pulse.

This experiment may be said to close the earlier history of the vaso-motor nerves. It was now established beyond question that the size of the bloodvessels, and thus the quantity of blood carried by them to different parts of the body, is controlled by nerves which when stimulated either narrow the blood vessels (vaso-constrictor nerves) and thus diminish the quantity of blood that flows through them, or dilate the vessels (vaso-dilator nerves) and increase the flow. The section of vaso-constrictor nerves, for example those found in the cervical sympathetic, causes the vessels previously constricted by them to dilate. The section of a vaso-dilator nerve, for example the chorda tympani, running from the lingual nerve to the submaxillary gland, does not, however, cause the constriction of the vessels to which it is distributed. And finally, it was now determined that vaso-motor fibres are found in the sympathetic system as well as in the spinal cord and the cerebro-spinal nerves.

It remained for a later day to show that vaso-motor nerves are present in the veins as well as in the arteries. Mall has found that when the aorta is compressed below the left subclavian artery, the portal vein receives no more blood from the arteries of the intestine, yet remains for a time moderately full, because it cannot immediately empty its contents through the portal capillaries of the liver against the resistance which they offer. If the peripheral end of the cut splanchnic nerve is now stimulated, the portal vein contracts visibly and may be almost wholly emptied. Thompson' has extended the discovery of Mall to the superficial veins of the extremities. He finds that the stimulation of the peripheral end of the cut sciatic nerve, the crural artery being tied, causes the constriction of the superficial veins of the hind limb. The contraction begins soon after the commencement of the stimulation, and usually goes so far as to obliterate the lumen of the vein. Often the contraction begins nearer the proximal portion of the vein and advances toward the periphery. More commonly, however, it is limited to band-like constrictions between which the vein is filled with blood. After stimulation ceases the constrictions gradually disappear. A second and third stimulation produce much less constriction. The superficial veins of the rabbit's abdomen are constricted by the stimulation of the cervical spinal cord at the second vertebra.

The observations of Bernard and his contemporaries led to a very great number of researches on the general properties and the distribution of the vaso-motor nerves, in the course of which a variety of ingenious methods of observation have been devised.

Methods of Observation.-One fruitful method of research has been already incidentally mentioned, namely, the direct inspection of the vessel, or region, the vaso-motor nerves of which are being studied.

A second method consists in accurately measuring the outflow from the vein. If the blood-vessels of the area drained by the vein are constricted by the stimulation of a vaso-motor nerve, the quantity escaping from the vein in a given period previous to constriction will be greater than that escaping in an equal period during constriction. This well-known method is especially available where an artificial circulation is kept up through the organ studied, as the blood drained from the vein does not then weaken the animal and thus disturb the accuracy of the observations."

A third method is founded on the principle in hydraulics that the lateral pressure at any point in a tube through which a liquid flows depends, other things being equal, on the resistance to be overcome below the point at which the pressure is measured. In the animal body the resistance to be overcome by the blood-stream varies with the state of contraction of the smaller vessels, and thus the variations in the lateral pressure of a given artery may, under certain restrictions, be used to determine variations in the size of the smaller 'Thompson Archiv für Physiologie, 1893, p. 104; Bancroft: American Journal of Physiology, 1898, i. p. 477.

2 Cavazzani and Manca: Archives italiennes de Biologie, 1895, xxiv. p. 33.