1544 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



clamp release, results in a large increase in cardiac 

 work associated with a decrease in oxygen usage 

 (334). These observations taken together stress the 

 importance of the aortic pressure and of the develop- 

 ment of tension by the heart in the control of oxygen 

 utilization. 



Chemical Composition of the Blood 



The chemical composition of the blood and tissue 

 fluids within the myocardium has been found to be of 

 great importance in determining the volume of 

 coronary flow. 



asphyxia. Asphyxia, in which the carbon dioxide 

 content of the blood increases and the oxygen con- 

 tent decreases simultaneously from cessation of 

 breathing, is accompanied by a large increase in 

 coronary inflow in the anesthetized dog. Within 30 

 to 60 sec after cessation of respiration, the flow in both 

 systole and diastole increases, averaging about 200 

 per cent, and this occurs before any significant change 

 in aortic pressure or heart rate ( 1 47 ). 



hypoxia. When the oxygen content of fully saturated 

 arterial blood of normal hematocrit is decreased by 

 exposing it to successive mixtures of oxygen and 

 nitrogen, containing progressively less oxygen (100% 

 O2 down to 5 % 2 ), the resultant arterial hypoxia 

 induces profound increases (200-300 %) in coronary 

 arterial inflow in both systole and diastole in the 

 fibrillating heart, isolated heart, heart-lung prepara- 

 tion, and anesthetized dog, but the oxygen consump- 

 tion is not changed (26, 113, 147, 167, 182). In the 

 anesthetized dog, as the arterial oxygen saturation 

 decreases, the coronary A-V oxygen difference and 

 coronary sinus oxygen content are decreased as the 

 oxygen extraction increases. For example, starting 

 with a control coronary sinus oxygen content of 4.2 

 vol per cent and saturation of 20 per cent, the coro- 

 nary A-V oxygen difference may be decreased to 3 

 vol per cent and the coronary sinus oxygen to 1 vol 

 per cent, while the oxygen extraction may be in- 

 creased to 95 per cent. Similar findings are reported 

 in man (181). Eventually, heart rate, blood pressure, 

 and cardiac output may be elevated, presumably 

 from the marked increment of cardiac contractility 

 arising from stimulation of the sympathetic nervous 

 system (408) since anoxia has only a depressant 

 effect on the completely isolated heart (242). The 

 increase in coronary flow precedes any change in 

 these parameters and maximal coronary dilatation 



occurs when the arterial saturation falls to about 20 

 per cent of normal. 



Since the flow effects of systemic anoxia produced 

 by artificial respiration with air and nitrogen and of 

 local myocardial anoxia by underperfusion or by 

 cyanide injection (147) into the coronary artery 

 are similar, it is concluded that they all depend upon 

 the anoxia produced, and probably upon the presence 

 of this anoxia in the myocardium. Since the blood 

 pressure does not change and the ratio of pressure to 

 flow increases throughout the cardiac cycle, it is 

 also concluded that anoxia causes a relaxation of the 

 walls of the coronary vessels. To what extent this is 

 active, that is, a direct effect on smooth muscle of the 

 coronary vessels, and to what extent, if any, extra- 

 vascular support has been lowered, cannot be as- 

 certained by these experiments. By using the technique 

 already described of prolonged vagal stoppage of the 

 heart for separation and fractionation of flow deter- 

 minants, coronary perfusion with saturated blood 

 has been compared to perfusion with somewhat 

 unsaturated blood. The resulting flow increase in the 

 beating heart, in the latter instance, is shown to be 

 about equally divided between a decreased extra- 

 vascular compression and an active vessel relaxation 



(158)- 



The ultimate cause of the decrease in coronary 

 vascular resistance in the presence of hypoxemia is 

 not known, but it could arise from a direct action of 

 low arterial oxygen content of the blood on the smooth 

 muscle of the coronary vessels (182) or from hypoxia 

 of the myocardium. To differentiate these possi- 

 bilities, open-chest experiments have been made 

 on fibrillating dog hearts, involving coronary per- 

 fusions with blood at varying levels of saturation and 

 at high perfusion pressures which increased the coro- 

 nary flow until coronary sinus blood became relatively 

 rich in oxygen (26). In the presence of a quite high 

 coronary perfusion pressure, considerable lowering of 

 arterial oxygen content (to 10 vol per cent) does not 

 increase coronary flow. An increase in flow occurs 

 only at coronary sinus oxygen levels less than 5.5 

 vol per cent. Since the coronary sinus oxygen content 

 probably closely reflects tissue oxygen content, this 

 finding suggests that arterial oxygen content is not 

 critical in the regulation of coronary flow but that 

 coronary vasodilation in hypoxemia is related to 

 myocardial hypoxia (myocardial oxygen content). 

 Finally, experiments are reported in which the coro- 

 nary arteries of the isolated heart are perfused with a 

 fully saturated hemoglobin solution whose oxygen 

 content is varied by dilution. In this situation, as the 



