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HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



sues that is the primary factor which normally regu- 

 lates venous return and, therefore, also cardiac output. 

 That is, the degree of local dilatation of peripheral 

 vessels would increase with each increase in local 

 tissue activity; consequently, the return of blood to 

 the heart would be governed by tissue utilization of 

 oxygen. On summating all the individual flows 

 through all the individual tissues of the body we ob- 

 tain a summated value which equals venous return, 

 and, since this automatically equates with cardiac 

 output, the summated flows of the individual tissues 

 are also equal to the cardiac output. Therefore, if it 

 is true that oxygen lack in all individual tissues does 

 cause vasodilatation, then we find that in the final 

 analysis the rate of local oxygen utilization could be 

 the single most important controller of venous return 

 and cardiac output. Indeed, this is supported by 

 many isolated studies of the relationship between 

 oxygen utilization or oxygen lack and circulatory 

 blood flow, beginning with the study of Douglas 

 & Haldane (51) in 1922 in which it was shown that 

 oxygen lack increases the cardiac output to a con- 

 siderable extent, and extending through studies by 

 Gorlin and co-workers showing a greatly increased 

 cardiac output in severe oxygen lack (77), and a 

 more recent study by Huckabee (119) showing an 

 increase in cardiac output of as much as twofold 

 in animals poisoned with cyanide. 



Besides the acute peripheral dilatation that re- 

 sults from oxygen lack, a very marked additional 

 increase in tissue blood flow occurs over a period of 

 several weeks if excessive oxygen usage or oxygen 

 deficiency persists for this long period of time (130a). 

 This, however, results from increased ''vascularity" 

 of the tissues, that is, increased numbers of blood 

 vessels. Nevertheless, this too, despite its slowness to 

 develop, represents a very important and very power- 

 ful regulatory mechanism for control of venous re- 

 turn in response to oxygen need by the tissues. 



Aside from the experimental observations on the 

 control of venous return and cardiac output by oxy- 

 gen lack, there is one compelling theoretical reason 

 for believing that oxygen lack should be the main 

 controller of venous return and cardiac output, and 

 that is the following: Of all the essential substances 

 supplied to the tissues by the blood, oxygen is by far 

 the one most critically dependent upon an adequate 

 blood flow. For instance, blood flow can be de- 

 creased to as little as '20 normal, and adequate 

 quantities of glucose, fats, and proteins can still be 

 carried to the tissues. Also, if the depth of breathing 



is increased, carbon dioxide can be carried away 

 from the tissues in adequate quantities even when 

 the cardiac output is decreased to as little as }/\§ 

 normal. On the contrary, the tissues become severely 

 damaged from anoxia whenever cardiac output 

 remains only slightly below normal for a prolonged 

 period of time. Therefore, it is readilv obvious that 

 oxygen transport to the tissues is normally markedly 

 "flow limited," while the transport of no single 

 other essential substance to or from the tissues is 

 limited to a significant extent under normal or any- 

 where near normal conditions. For this reason, it is 

 especially reasonable that oxygen should be the major 

 regulator of venous return and cardiac output; this 

 would provide a closed loop regulatory system that 

 would help to maintain an adequate supply of oxygen 

 to all the tissues at all times. 



VENOUS PRESSURES 



The regulation of venous pressure is inextricably 

 related to the regulation of venous return and car- 

 diac output, as has already been pointed out in 

 both the simplified and more complex circuit analy- 

 ses presented earlier in this chapter. All the different 

 significant factors which affect right atrial pressure 

 have already been discussed. On the other hand, 

 the right atrial pressure is not the same as the more 

 peripheral venous pressures. Therefore, we need 

 now to conclude our discussion of the return of blood 

 to the heart by summarizing the different factors 

 that determine the peripheral venous pressures. 

 These include, first and paramount, the right atrial 

 pressure itself. In addition, they include a) resistance 

 to blood flow along the veins, b) rate of blood flow 

 in the veins, and c) hydrostatic pressure effects. 



EFFECT OF RESISTANCE TO FLOW IN THE VEINS. Dilated 



central veins are so large that they have almost no 

 resistance to blood flow, but semicollapsed veins, 

 on the other hand, have very high resistance. This 

 effect is particularly important at the different com- 

 pression points where the veins pass over the ribs 

 or lie against some relatively solid organ (52, 53). 

 In the ordinary circulation, therefore, the resistance 

 to venous flow is not negligible, principally because 

 of the compression points against the veins. On the 

 other hand, when the right atrial pressure rises to a 

 very high value, blood can dam up in the veins, 

 elevating the pressures in the veins to values equal 



