by Starling [1914] and Daly [1925].

Transcription

1 PROPERTIES OF THE PERIPHERAL VASCULAR SYSTEM AND THEIR RELATION TO THE SYSTEMIC OUTPUT. BY HENRY BARCROFT. Harmsworth Scholar, St Mary's Hospital, London. (Experiments performed in the Physiological Laboratory, Cambridge.) STUDIES on circulation models have been made in the past by Weber [1850], Krogh [1912] and others, and on heart-lung preparation systems by Starling [1914] and Daly [1925]. The objects of the present research are to show: (1) That an artificial scheme described below has properties similar to those of the dog's peripheral vascular system. (2) That experiments performed with this artificial peripheral vascular system explain the paradoxical effect of occlusion of the thoracic aorta which I have described in a previous paper [1931]. I. METHOD. Dogs weighing approximately 10 kilos were used. A.C.E. aneesthesia was employed. A diagram of the apparatus actually used for the experiment is shown in Fig. 1. The clamps E and D were placed on the artificial peripheral vascular system at positions corresponding to X and Y in Fig. 2. The rest of the apparatus was the same as the heart-lung apparatus described by Starling [1914] except that the heating spiral was placed between the venous reservoir and the heart. The heart-lung apparatus was substituted for the vessels connecting the thoracic aorta with the inferior vena cava. The heart-lung apparatus was then clamped off at B and J, while the mechanical stromuhr [Barcroft, 1929], which had previously been filled, was inserted at 0. The clamps at B and J were removed. The vagi were cut. The superior vena cava and brachiocephalic artery were ligatured. The artificial peripheral vascular system was filled with warm defibrinated blood and the circulation through it established

2 PERIPHERAL VASCULAR SYSTEM. by the simultaneous removal of the clamps at E and D to Q and R respectively. H 187 To Fig. 1. Diagram of apparatus used in-experiments in which an artificial peripheral vascular system was perfused by the animal's heart. Cannula K was placed centrally in the thoracic aorta; cannula H was placed centrally in the inferior vena cava. The arterial blood-pressure manometer was attached at A. 13-2

3 188 H. BARCROFT. II. THE NATURE OF THE ARTIFICIAL PERIPHERAL VASCULAR SYSTEM. The artificial peripheral vascular system is shown diagrammatically in Fig. 2. It has the following essential features: 1. The tube A represented the brachiocephalic artery, B the superior vena cava, C the thoracic aorta and D the inferior vena cava. Fig. 2. R3 03 R6 Diagram of artificial peripheral vascular system attached to the animal's heart and lungs. Description in text. 2. The resistance R, represented the resistance of the arteries and arterioles supplied by the brachiocephalic artery. The resistances R2 and R3 represented the resistance of the arteries and arterioles supplied by the thoracic aorta. 3. The resistance R4 represented the resistance of the capillaries and veins drained by the superior vena cava. The resistances R5 and R6

4 PERIPHERAL VASCULAR SYSTEM. 189 represented the resistances of the capillaries and veins drained by the inferior vena cava. These six resistances were similar. The relation between flow through any one of them and the pressure difference between the two sides of that resistance is shown in Fig. 3. Each resistance was a slit in a piece of sheet rubber. 4. C, was an extensible part of the artificial peripheral vascular system and represented the capillary bed supplied by the brachiocephalic artery / / 120 /~~ Fig. 3. Curve I. Ordinate: arterial blood-pressure in mm. Hg. Abscissa: blood flow through brachiocephalic artery in c.c. per minute. Curve II. Ordinate: pressure difference between the two sides of any of the resistances R1-R2 in mm. Hg. Abscissa: flow through the resistance in c.c. per minute. The curves for all six resistances lie within the broken lines. 5. C2 and C3 represented the extensible capillary bed supplied by the thoracic aorta. The cardinal feature of the extensible parts C1, C2 and C3 was that equal increments in the volume of blood which they contain do not produce equal increments of pressure but progressively greater increments of pressure. In earlier models these extensible parts were made of rubber bags which possessed this property. These, however, were replaced by vertical glass tubular reservoirs which

5 190 H. BARCROFT. were conical in shape. This arrangement had the advantage that at any moment the height of the fluid in the tubes could be noted and hence the pressures and volumes of blood in those extensible parts determined. The use of the word "extensible" as applied to such a system requires some explanation. It is intended to mean merely that the tubular reservoirs could hold quantities of blood varying according to the internal pressures. Fig. 4. Pressure volume curves of extensible parts of artificial peripheral vascular system. I, Curve for C2 or C3. II, Curve for C,. Ordinate: cubic content in c.c. Abscissa: pressure in mm. Hg. The relation between the pressure in each of the extensible parts and the volume of liquid it contained is shown in Fig. 4. Thus alterations in the distribution of the blood between CQ, C2 and C3 were easily measured.

6 PERIPHERAL VASCULAR SYSTEM. 191 III. COMPARISON OF PROPERTIES OF ARTIFICIAL PERIPHERAL VASCULAR SYSTEM WITH COMPARABLE PROPERTIES OF ANIMAL S PERIPHERAL VASCULAR SYSTEM. (1) Changes in the systemic output and arterial blood-pressure following various comparable experimental procedures. The comparison between the behaviour of the animal's vascular system and the artificial peripheral vascular system attached to the heart and lungs is to be seen in Table I. This table is compiled from TABLE I. Changes in systemic output and arterial blood-pressure following comparable experimental procedures in the animal and in the artificial vascular system. The figures in heavy type refer to the animal; those beneath to the heart and lungs attached to the artificial peripheral vascular system. Final systemic Percentage output change in (c.c. per systemic Experimental procedure min.) output Iniection of 50 c.c. blood Complete aorta occlusion of thoracic Complete artery occlusion of brachial Complete occlusion vena cava of superior Complete occlusion of inferior vena cava Simultaneous occlusion of thoracic aorta and inferior vena cava Simultaneous occlusion of brachial artery and superior vena cava Partial path occlusion of whole aortic Initial arterial bloodpressure (mm. Hg) Initial systemic output (c.c. per min.) Final arterial bloodpressure (mm. Hg) No change typical tracings taken during experiments on the animal and described in a previous paper [1931]. The artificial peripheral vascular system was used in six experiments. The publication of all the tracings is not practicable. Only the tracings for the variations in arterial bloodpressure and in systemic output after complete occlusion of the thoracic aorta (Fig. 5) and after partial occlusion of the ascending aorta (Fig. 6) are shown. Throughout this series of observations no alteration in the adjustment of the artificial peripheral vascular system was made, other than changes in the blood content. The various great vessels referred to in the table were of course represented artificially in the artificial peripheral vascular system. Table I shows that in each case the variations

7 192 H. BARCROFT. of the blood-pressure and systemic output in the two preparations are comparable. Fig. 5. Tracing I. Animal 1. At X the thoracic aorta was completely occluded. At Y the occlusion was removed. Tracing II. Artificial peripheral vascular system attached to animal's heart and lungs. At X tube C (Fig. 2) was completely occluded. At Y the occlusion was removed. Both tracings show that this procedure caused increase in the arterial bloodpressure and in the total systemic output. BP, arterial blood-pressure. S = 24 c.c., 24 c.c. passed through the stromuhr between successive vertical strokes of the record. T, time in seconds. (2) Blood-pressures and systemic output. The residual blood-pressure after applying clamps at points X and Y, Fig. 2, was approximately 30 mm. Hg. If the distensibility of the veins

8 PERIPHERAL VASCULAR SYSTEM. 193 had been allowed for in the artificial peripheral vascular system the residual pressure would have been much less. The systemic output, Fig. 6. Tracing I. Animal 1. At A and at B a screw clamp placed on the ascending aorta was tightened incompletely. Tracing II. Artificial peripheral vascular system. At A a screw clamp placed at X, Fig. 2, was incompletely tightened. Both tracings show that this procedure caused a rise in the arterial blood-pressure and a diminution in the total systemic output. BP, arterial blood-pressure tracing. S = 24 c.c., 24 c.c. passed through the stromuhr between successive strokes of the record. T, time in seconds. arterial and venous pressures varied between the limits generally observed in the animal.

9 194 H. BARCROFT. (3) Relation between arterial blood-pressure and blood flow through the peripheral vascular system. Measurements of the arterial blood-pressure and blood flow through the brachiocephalic artery were made in a preparation which allowed the arterial blood-pressure to be altered at will. The relationship between arterial blood-pressure and blood flow through the brachiocephalic artery was determined for a wide range of pressures. This relationship is shown in Curve I, Fig. 3. The resistances used in the artificial peripheral vascular system and shown in Fig. 2 were constructed as alike as possible. Two of these resistances in series have, as nearly as possible, the same pressure flow relationship as shown for the animal's brachiocephalic artery in Fig. 3. (4) Relativeflows through the thoracic aorta and brachiocephalic artery. Since the flow through the thoracic aorta was found to be double the flow through the brachiocephalic artery in the preparation described previously [1931], the artificial peripheral vascular system used in the present investigation was designed so that the flow through the circuit representing the vessels supplied by the thoracic aorta had double the flow through the circuit representing the vessels supplied by the brachiocephalic artery. All six resistances in the artificial system were alike (Fig. 2), thus these conditions were obtained. (5) Capillary blood volume, blood-pressure and distensibility. The animal's large and distensible capillary bed has been imitated by the conical tubes C, C2 and C. (Fig. 2). Usually these contained about 200 c.c. of blood which amounts to 30 p.c. of the blood volume of a 10 kilo dog. The pressure in C,, C2 and C. was approximately 30 mm. Hg, being nearly the same as the figure found by Landis [1930]. The pressure volume relations of C1, C2 and C3, shown in Fig. 4, are of the same type as Roy [1881] found for arteries and veins, equal increments of volume producing progressively larger increments of pressure. Table I is evidence that the behaviour of the two vascular systems is comparable and therefore it seems very probable that this type of capillary pressure volume relationship actually does exist in the animal. Fig. 4 also shows that since C. is less distensible than C2 or C3 it has been necessary to assume that the capillary bed supplied by the brachiocephalic artery is less distensible than that supplied by the thoracic aorta.

10 PERIPHERAL VASCULAR SYSTEM. 195 (6) Redistribution of the blood after various procedures. As has been pointed out already the distribution of the blood in the artificial peripheral vascular system itself and the transferences of blood between it and the heart and lungs were readily measurable. Such measurements are shown in Table II. Very few corresponding measurements have been made in the animal. In a previous paper [1931] the TABLE II. Redistributions of the blood observed in the artificial peripheral vascular system after various experimental procedures. Volume change Volume change in c.c. m in c.c. in extensible extensible parts C2 and Ca parts C, representing representing capillaries capillaries Experimental procedure Injection of 50 c.c. blood Complete occlusion of thoracic aorta Complete occlusion of brachial artery Complete occlusion of superior vena cava Complete occlusion of inferior vena cava Complete occlusion of thoracic aorta and inferior vena cava Complete occlusion of brachial artery and superior vena cava Partial occlusion of whole aorta at one point supplied by thoracic aorta supplied by brachial artery Volume change in cardiopulmonary system average of two determinations showed that after complete occlusion of the thoracic aorta the vessels it supplied yielded up 45 c.c. of blood; this is considerably smaller than the transferences shown in Table II after the comparable procedure. In the animal an average of 47 c.c. of blood was transferred to the vessels drained by the inferior vena cava after complete occlusion of this vessel. This figure is only slightly smaller than the corresponding figures in Table II. The factors which determine these redistributions of blood are: (a) changes in the systemic flow; (b) changes in the arterial bloodpressure. They would appear to act in the following manner: (a) Changes in the systemic flow mean: (i) Corresponding changes in the pulmonary flow, and as Daly [1928] has shown, the volume of blood in the lungs is a function of the pulmonary flow.

11 196 H. BARCROFT. (ii) Corresponding changes in the volume of blood pooled in the ventricles of the heart. Patterson, Piper and Starling [1914] have shown that the systolic volume of the heart is increased by increase in output. (b) Changes in the "arterial blood-pressure cause: (i) Corresponding changes in the coronary flow and therefore changes in the output of the heart and flow through the pulmonary artery as shown by Anrep and Bulatao [1925]. This will influence the cardiopulmonary blood volume for the reasons given in section (a) above. (ii) Corresponding changes in the volume of blood pooled in the left ventricle. Patterson, Piper and Starling [1914] have shown that increase in the arterial pressure is accompanied by increase in the systolic volume of the heart. If both arterial blood-pressure and systemic output are increased then all these factors will act synergically to produce an increase in the cardio-pulmonary blood volume. Referring to Table II it will be seen that after the injection of blood and after complete occlusion of the thoracic aorta, both of which procedures cause increase in systemic flow and blood-pressure, there is an increase in the volume of blood in the heart and lungs. After complete occlusion of the inferior vena cava and after complete occlusion of the superior vena cava, both of which procedures cause a decrease in the arterial blood-pressure and in the systemic output, there is a decrease in the cardio-pulmonary blood volume. After complete occlusion of the brachiocephalic artery which causes a small increase in the blood-pressure with a small decrease in flow the cardiopulmonary blood volume shows a variable change. While after simultaneous occlusion of the thoracic aorta and after simultaneous occlusion of the brachiocephalic artery and superior vena cava, which procedures both cause a relatively large drop in the systemic output compared with the blood-pressure rise, there is of course a diminution in the cardiopulmonary blood volume as previously described [1931]. IV. THE APPARENT EXPLANATION OF THE PARADOXICAL INCREASE IN THE SYSTEMIC OUTPUT AFTER COMPLETE OCCLUSION OF THE THORACIC AORTA. The experiments described above lead to the following explanation of the effects of complete occlusion of the animal's thoracic aorta. Occlusion of the thoracic aorta is followed by a passive collapse of the vessels it supplies. The blood which drains away is accommodated in the remainder of the vascular system mainly as follows:

12 PERIPHERAL VASCULAR SYSTEM. (1) In the capillary bed supplied by the brachiocephalic artery. The increase in the content of these capillaries is responsible for the increase in the total systemic output. This increase in the systemic output is the consequence of: (a) The pressure volume relations of this capillary bed. (b) The pressure flow relations of these capillaries and veins. (c) The properties of the heart as a pump as enunciated by Starling [1914]. (2) In the cardio-pulmonary system. It accumulates here owing to: (a) The distension of the pulmonary vessels by the increased pulmonary flow. (b) The distension of the chambers of the heart which accompanies its increase in the.performance of work. The above analysis suggests certain factors relevant to the increased systemic output during exercise, other than the lowering of the mean respiratory pressure [Daly, 1927] and the pumping action of the muscles [Tigerstedt, 1909]. These factors will form the subject of a future paper. SUMMARY. 1. Daly's preparation, consisting of the dog's heart and lungs attached to an artificial peripheral vascular system, has been adapted to study quantitatively the factors responsible for changes in the systemic output and arterial blood-pressure in the animal itself. 2. The properties and behaviour of this artificial peripheral vascular system are shown to be comparable with the properties and behaviour of the dog's peripheral vascular system. 3. Evidence is brought forward to show that the capillaries have the same type of pressure volume relation as Roy has shown to be possessed by the arteries and veins. 4. With the aid of this preparation the paradoxical increase in the systemic output in the animal after complete occlusion of the thoracic aorta is probably explained. 5. The initiation of transferences of blood between the cardiopulmonary system of the animal and its peripheral vascular system after various procedures is shown. I am very grateful to Prof. B arcr oft for his criticism and advice. 197

13 198 H. BARCROFT. REFERENCES. Anrep, G. and Bulatao, E. (1925). J. Phy8iol. 60, 175. Barcroft, H. (1929). J. Phy8iol. 67, 402. Barcroft, H. (1931). J. Phy8iol. 71, 280. Daly, I. de B. (1925). J. Phy8iol. 60, 103. Daly, I. de B. (1927). J. Phy8iol. 63, 81. Daly, I de B. (1928). J. Phy8iol. 65, 422. Krogh, A. (1912). Skand. Arch. Phy8iol. 27, 227. Landis, E. M. (1930). Amer. J. Phy8iol. 93, 353. Patterson, S. W. and Starling, E. H. (1914). J. Phy8iol. 48, 357. Patterson, S. W., Piper, H. and Starling, E. H. (1914). J. Physiol. 48, 465. Roy, C. S. (1881). J. Phy8iol. 3, 125. Tigerstedt, C. (1909). Skand. Arch. Phy8iol. 22, 115. Weber, E. H. (1850). Ber. Sdchs. Gme. Wi&M. p. 196.