Circulation," Anrep and Starling(l) were unable to obtain evidence of

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1 CARDIOVASCULAR REFLEXES. BY I. DE BURGH DALY AND E. B. VERNEY (Beit Memorial Research Fellow). (From the Physiology Institute, Cardi.) DURING an investigation of the "Central and Reflex Regulation of the Circulation," Anrep and Starling(l) were unable to obtain evidence of a reflex mechanism being involved in the production of cardiac slowing in response to a rise in aortic pressure'. They used the crossed circulation method described by Anrep(2) in which the head derived its blood supply from a heart-lung preparation and the rest of the animal received blood from its own heart. It occurred to us that the negative results obtained might have been due to a rise in venous pressure occurring simultaneously with the rise in aortic pressure and so neutralising any tendency for the heart rate to become slower (Bainbridge(3)). The possibility that the low carbon dioxide content of the blood perfusing the brain contributed to their results was also considered; they did, however, use a carbon dioxide-air mixture for ventilation of the heartlung preparation in some of their experiments. In order to study the problem further we devised a method in which the aortic pressure, the head arterial pressure and the head blood flow could be varied at will in the intact animal. Care was taken not to overventilate the lungs. Method. Dogs were used in all experiments and were fully anaesthetised with chloralose, 1 decigram per kilo body-weight being injected intravenously. Morphia was not administered. The blood of the animal was defibrinated and artificial respiration applied; a carbon dioxide mixture was not used. A screw clamp was placed on the thoracic aorta as low down in the chest as possible. A cannula was inserted into the central end of the subclavian artery and counected to a Pavlov and Stolnicov stromuhr (4, 5), similar to the pattern recently used by Anre-p. The brachio-cephalic artery was then tied close to its origin from the aorta and a cannula inserted pointing towards the brain; this was connected to the other end of the st-romuhr. In two experiments the 1 At a later date using the innervated heart-lung preparation With a CO2 mixture supplied to the lungs, Anrep obtained evidence of reflex slowing. (Communicated to the Physiol. Soc., Nov. 14th, 1925.)

2 CARDIOVASCULAR REFLEXES. 269 brachio-cephalic artery was divided between ligatures and cannulae inserted into the distal and proximal ends. These cannule were joined to the output and input openings respectively of the stromuhr; in these experiments the left subclavian artery was ligatured. The blood flow through the head was controlled by a screw clamp on the rubber tube connecting the cannula in the central end of the subelavian artery (or of the brachio-cephalic) and the stromuhr. In some experiments the pressure in the right auricle was taken by means of a saline manometer, the upper end of which was in connection with a loose rubber membrane tambour. Mercury manometers joined by side tubes to the input (central to the screw clamp) and output connections of the stromuhr measured the aortic and head arterial pressures respectively. The stromuhr measured the amount of blood passing through the head, neck and right fore-leg. The procedure was as follows. The blood flow through the head was measured and then the clamp on the aorta was partially screwed up. The clamp on the brachio-cephalic artery was then tightened to such an extent as to bring back the pressure of the head blood supply to its initial value; sometimes the aortic clamp and the brachio-cephalic clamp were screwed up simultaneously. The flow through the stromuhr was again recorded. Finally, both clamps were released and the flow through the stromuhr recorded. In two experiments the temperature of the blood was taken in the right auricle; no alterations were observed as a result of adjusting the clamps as described. Reversing the direction of the blood flow through the stromuhr caused a slight kick on the blood-pressure records but did not influence the temperature in the right auricle or the heart rate. Results. Extracts from the protocols of three experiments are given in the table. It will be seen that a rise in aortic pressure with the head arterial pressure kept constant or even slightly diminished produced a slowing of the heart rate (Exps. 1, 3). A rise in aortic pressure with the head pressure constant caused a diminished blood flow through the head, and if after raising the aortic pressure the brachio-cephalic clamp was adjusted so that the flow through the head was unaltered, the cerebral arterial pressure was found to be increased (Exps. 1, 2). We obtained, therefore, in response to a rise in aortic pressure, a reflex slowing of the heart rate and a reflex vaso-construction of part or of the whole of the vascular bed supplying the head, neck and right foreleg. After section of the vagi, the reiflex slowing of the heart was abolished but the reflex vaso-constriction persisted (Fig. 3).

3 270 I. DE BURGH DALY AND E. B. VERNEY. The blood flow and the arterial pressure of the perfused head in the experiment published by Anrep and Starling were 335 c.c. per minute and 95 mm. Hg respectively. In our own experiments 14 observations gave an average arterial blood-pressure of 91 mm. Hg (limits mm. Hg) and an average blood flow of 75 c.c. per minute (limits c.c. per minute), that is, a flow approximately one-fourth of that obtained by Anrep and Starling. TABLE. Preure in M.B.-P. Flow through Heart Temp. C. right auricle, head in c.c. rate in right Exp. mm. saline Head Aorta per min. per min. auricle I Aorta compressed Brachio-cephalic artery compressed Aorta and brachio-cephalic artery compresed Both released a Aorta compressed Brachio-cephalic artery compressed Both released b Aorta and brachio-cephalic artery compressed Both released Time 0 15" 1' O" 1' 25" 3t 0" 0 10"-50" 1' 0" 1' 10"-1' 45" 1'55" Typical tracings (Figs. 1, 2) show that the slowing of the heart rate in response to a rise in aortic pressure takes place almost immediately. If the aortic pressure was kept up for any length of time there was generally a progressive acceleration of the heart rate after the initial slowing; this acceleration was not sufficiently marked during the period over which our observations extended for the heart rate to return to the same value obtaminng before the aortic pressure was raised. In one experiment we used the same technique but in addition the lower half of the animal was removed by a section through the lowest thoracic vertebra, the aorta being connected to an artificial resistance and the inferior vena cava to a large rubber reservoir in the manner described by one of us(6) for making the closed circuit heart-lung preparation. On raising the artificial resistance and adjusting the clamp on

4 CARDIOVASCULAR REFLEXES. 271 the brachio-cephalic artery so as to maintain the cerebral arterial pressure constant, we obtained a marked slowing of the heart rate to 54 beats per minute. Fig. 1. Partial compression of aorta followed by partial compression of brachio-cephalic artery. The figures below the aorta blood-pressure tracing denote the heart rate per minute. Time tracing = 5 secs. R.A. = pressure in right auricle. The figures immediately above the signal marker represent the blood flow through the head in c.c. per minute. Discussion. Our experiments demonstrate that a rise in aortic pressure causes reflex slowing of the heart when the pressure of the blood supplying the head, neck and right fore-leg remains constant. In those experiments in which partial compression of the aorta produced a rise of pressure in the right auricle, there was still cardiac slowing present, so it would appear that the reflex initiated by aortic pressure increase causing slowing of the heart is stronger than the reflex initiated by an increase in venous

5 272 I. DE BURGH DALY AND B. B. VBRNEY. pressure which causes acceleration of the heart rate. The reflex slowing is dependent upon the integrity of the vagi. Fig. 2. Simultaneous compression of aorta and brachio-cephalic artery at A. At B both released. In this Fig. and in Fig. 3 the figures above the time marker denote the blood flow through the head during the interval between the dotted lines. Time tracing= 5 secs. With regard to the accompanying vaso-constriction of part or of the whole of the vascular bed of the head, neck and right fore-leg, we have not sufficient experimental evidence to account for its production. It occurs after vagal section when the stellate ganglia are intact, and in one experiment was accompanied by an acceleration of the heart rate. With the exception of the experiment in which we made the closed circuit heart-lung preparation, the suprarenal glands were intact; the possibility that adrenaline complicated our results was therefore not absolutely ruled out. It is to be noted that the experiments which we have described do not decide as to the site of the receptors engaged in the reflex changes in cardiac rate. They may be in the aorta, in the heart, or even in the lungs.

6 CARDIOVASCULAR REFLEXES CONCLUSIONS. 1. A method by which the blood-pressure and blood flow to the head, neck and right fore-leg can be varied independently of the aortic pressure in the intact animal, is described. Fig. 3. Same experiment as Fig. 1. Vagi cut. At A, compression of aorta and brachio-cephalic artery. At B, both released. 2. A rise in aortic pressure causes reflex slowing of the heart when the cerebral pressure is kept constant.

7 274 I. DE BURGH DALY AND E. B. VERNEY. The expenses of this work were defrayed in part by a grant from the Government Grants Committee of the Royal Society to one of us (I. de B. D.). REFERENCES. 1. Anrep and Starling. Proc. Roy. Soc. B, 97.? Anrep. Ibid. B, 97. p Bainbridge. This Journ. 50. p Stolincoov. Arch. f. Physiol. p Pa i(ov.; 1kid. p., Daly. This,J urn. 60, p