PHYSIOLOGICAL SOCIETY,

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PROCEEDINGS OF THE PHYSIOLOGICAL SOCIETY, March 16, 1929. A central chemical control of the heart rate. By R. J. S. MCDOWALL. (King's College, London.

1 PROCEEDINGS OF THE PHYSIOLOGICAL SOCIETY, March 16, A central chemical control of the heart rate. By R. J. S. MCDOWALL. (King's College, London.) Provided adequate measures are taken to avoid the effects of sensory stimulation and of extensive operative procedures, asphyxia of the cerebral centres in a chloralosed cat, whether produced by general asphyxia, occlusion of the cerebral-arteries, cerebral compression, or by supplying asphyxial blood from another animal, causes a marked acceleration of the heart. This occurs after the vagi have been divided and the suprarenal glands have been removed. The acceleration takes place prior to the better known slowing of the heart which occurs in asphyxia or cerebral aneemia from central stimulation of the vagus. The acceleration is not related to any changes in pressure in the various blood vessels and must be looked upon as being due to the chemical effect of the asphyxia on the sympathetic. This is supported by the fact that the cardiac acceleration may be much delayed by over-ventilation of the animal prior to the production of cerebral anaemia. The central control of the heart rate may thus be somewhat similar to the control of respiration. Observations on the respiratory exchange of hibernating mammals. By P. A. GORER and M. S. PEMBREY. (Physiological Laboratory, Guy's Hospital.) The very low respiratory quotients which have been obtained during the torpidity of hibernating mammals have been subjected to criticism. Some observers have been unable to obtain such quotients, but this failure appears to be due to the awakening of the animal during the experiment. On the other hand when such low quotients are admitted as correct findings it is maintained that they can be explained by the enhanced solubility and consequent retention of carbon dioxide in the cold body of the animal. b

2 xxii PROCEEDINGS OF THE PHYSIOLOGICAL To meet such criticisms a series of observations has been made upon hedgehogs and upon two marmots, given by Prof. Yandell Henderson. The chief results can be condensed in the following table: Marmot II Date x 24. x 15. xi i /9. i /10. i 1' ii 0.10 Marmot I 15. ii 0-14 Marmot II 15. i Hedgehog Date v 0. xi i 3/4. i 12. ii 12/13. ii 13/14. ii H20 C02 02 CO vol. T. of animal grm. grm. grm. 0, vol. (0C.) *15 3* * * *64 8* * *63 1* * (coi) {9-2 (rectum) 110 (mouth) {12 (mouth) I 11 (rectum) f T. of air (0C.) * (rectum) (mouth) I 8*6 10*5 9 11*75 Remarks (hours) 2 Active; well fed 2, 1, 3,, 2 Torpid 24, 24,, i P, i,, (rectum)) 9 i (mouth)j X72 i 1*37 8* (rectum) Re- H30 C00 02 C02vol. T. of animal T. of air marks grin. grin. grin. 03 vol. (O C.) (00.) (hours) * (coil) 1*37 2l (coil) * *10 1* (coil) 1* (coil) 1* (coil) * (coil) * Wt. of animal = 494 grim Waking. VP 2 Active 2 IV 2 22* Torpid Claude Bernard's conception of the internal environment. By J. S. HALDANE. Prof. L. J. Henderson entitles his valuable recently published book on Blood as A Study in General Physiology, and at the same time treats blood as a physico-chemical system. It may escape notice that he thus makes a very far-reaching fundamental assumption; and the matter is -so important that I venture to bring it before the Society. He refers to the authority of dlaude Bernard in justification of his procedure; but in so doing he seems to me to have altogether misunderstood Bernard's conclusion. Bernard was the first to formulate the extremely fruitful,9 VP P,, Sp

3 SOCIETY, MARCH 16, xxiii idea that the blood of a living animal is an internal medium kept remarkably constant as regards its physico-chemical conditions by the coordinated influence upon it of the various organs of the body. He accepts as fundamental the coordination -thus displayed. -L. J. Henderson, on the other hand, treats the blood as simply something which, as the result of various "buffer" reactions occurring within itself, is not as readily disturbed in its physico-chemical conditions as other liquids would be. We can, for instance, add a good deal of acid or alkali to blood without much disturbing its reaction. Or if we simultaneously add carbon dioxide and abstract oxygen from it there is a similar diminution of the disturbance which would be produced by either addition of carbon dioxide alone, or abstraction of oxygen alone. These buffer reactions are of great importance and interest, but they were unknown to Bernard, and do not in any way modify his conception of the coordinated activity of organs by which the conditions in the blood are kept constant. This coordinated activity is an essential part of his conception of blood in the liing body, whereas L. J. Henderson leaves it out of account, thus turning blood in the living body into what for a physiologist is a mere artefact, and completely disregarding Bernard's principle. It seems to me that if we disregard the coordination we have disregarded all that is characteristic of life, and that therefore the book in question cannot be regarded as a study in General Physiology, but only as a study in Physical Chemistry. To come to details, L. J. Henderson treats the constancy of reaction in the living body as if it depended on the physico-chemical properties of blood. In actual fact this constancy depends during health on the coordinated activity of the kidneys and respiratory organs, in accordance with Bernard's principle, and in various indivdual parts of the body the constancy depends on the coordinated or regulated influence of the circulation. Not all the buffering in the world would keep the reaction constant otherwise, though the buffering greatly smooths the regulation. In the human body acid in excess is being continuously produced, partly as ionized sulphuric and other non-volatile acids, and partly as ionized carbonic acid. The formation of acid is constantly being exactly compensated by the excretion of acid urine and formation of ammonia on the one hand, and on the other by the washing out of carbon dioxide through the lungs. The exact coordination or regulation of these activities is the essential matter, and the quantitative investigation in various directions of physiological coordination in recent times has separated the old mechanistic physiology of last century from recent physiology.

xxiv PROCEEDINGS OF THE PHYSIOLOGICAL The normal responses of the kidneys and respiratory organs depend on the simultaneous maintenance of many conditions included under the comprehensive word

4 xxiv PROCEEDINGS OF THE PHYSIOLOGICAL The normal responses of the kidneys and respiratory organs depend on the simultaneous maintenance of many conditions included under the comprehensive word "health"; but we assume this maintenance in quantitative investigations of physiological function. If, following L. J. Henderson, we neglect the coordination of organs in General Physiology, we are, it seems to me, taking a step backwards. As one who has been closely connected during the last thirty years with the development of B e r n a r d's conception, as well as with the development of knowledge as to the physical chemistry of blood, I wish, therefore, to express my dissent from what appears to me to be Henderson's misinterpretation of Bernard. In my book, just about to be published, on The Sciences and Philosophy, I have discussed the subject from a wider standpoint, but before I had seen L. J. Henderson's book. It seems to me that apart from the central biological conception of specific coordination we cannot make even a beginning in the scientific treatment of General Physiology, whether we start from the unicellular organisms which Henderson unjustifiably assumes to consist of a physico-chemical system called "protoplasm," or from compound organisms with a well-defined internal environment between individual cells. The anti-diuretic action of the separated principles of the posterior lobe of the pituitary body. By A. HEMINGWAY and J. M. PETERSON. (Cardiff.) The results of other workers (1), (2) suggest that the separated principles of the posterior lobe of the pituitary body-" Vasopressin" and "Oxytocin "-have a diuretic action when injected into the aneasthetized animal, the former being the more potent. This has been confirmed by Gaddum(3). Whilst extracts of the whole posterior lobe have a similar action on the anaesthetized animal, they have an anti-diuretic action in arresting water diuresis, and also in the polyuria of diabetes insipidus and the excretion of urine by the perfused isolated kidney in the heart-lungkidney preparation as described by Starling and Verney. With a view to determining the presence or absence of this antidiuretic principle in vasopressin and oxytocin, and, if present, its distribution between the separated principles, a series of experiments has been performed using the heart-lung-kidney technique.

SOCIETY, MARCH 16, 1929. xx2v From these experiments it has been found that small amounts (.05 to 0*2 c.

5 SOCIETY, MARCH 16, xx2v From these experiments it has been found that small amounts (.05 to 0*2 c.c.) of the principles added to c.c. of circulating blood are sufficient to cause marked changes in urine output and salt concentration. The principles in these strengths are without any apparent effect on the heart-lung preparation itself. The following observations have been made: (i) Both vasopressin and oxytocin have a prolonged anti-diuretic action. (ii) The action of vasopressin is the more powerful. (iii) Accompanying the anti-diuretic action there is an increase in the chloride concentration of the urine and often an increase in the total output of chloride per unit of time. This latter effect appears to depend upon the initial rate of urine flow. When this is high the total chloride output is increased; when low it is often diminished, but in each instance there is an increase in the actual concentration. (iv) Vasopressin increases the resistance of the kidney to perfusion and diminishes the renal blood flow. This effect persists over a lengthy period. (v) Oxytocin has only a transient effect on renal circulation, as measured by the perfusion pressure and blood flow. 1. Kamm, Aldrich, Grote, Rowe and Bugbee. Journ. Amer. Chem. Soc. 50. p Bugbee and Simond. Amer. Journ. Physiol. 85. p Gaddum. This Journ. 65. p A frog's heart chamber. By B. A. MCSWINEY. The apparatus illustrated in Fig. 1 was designed for experiments on the frog's heart. The chamber is made up from sheet vulcanite, the strips being cemented and screwed together. The electrodes, crystal detectors function excellently, are mounted on a movable strip of vulcanite which may be fixed in any given position by the screw shown in Fig. 1. Fine adjustment is made by movement of the electrodes. To record the contractions of the heart an aluminium lever fitted with a frontal glass pointer is used. The lever is held by a thread suspensiocn, and the position of the lever adjusted by altering the position of the screws, A, through which the cotton is threaded. The frontal writing point is easily made and has been found very suitable in practice. A fine

6 xxvi PROCEEDINGS OF THE PHYS. SOC., MAR. 16, glass pointer is threaded through a narrow glass cuff. The pointer is bent in the flame, so that one arm is pressed against the drum paper. The cuff is attached to the lever by Chatterton cement. The chamber may be lined with sheet cork. Fig. 1.

Oxytocic activity. It is stated that 1 c.c. of oxytocin contains 12 units. single, multivalent, active principle, or whether a number of active

Oxytocic activity. It is stated that 1 c.c. of oxytocin contains 12 units. single, multivalent, active principle, or whether a number of active SOME PROPERTIES OF THE SEPARATED ACTIVE PRINCIPLES OF THE PITUITARY (POSTERIOR LOBE). BY J. H. GADDUM (National Institute for Medical Research). EXTRACTS of the posterior lobe of the pituitary gland have