I4'22 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



oi various kinds, for the most part still uncharacter- 

 ized, are released locally to play a more or less essen- 

 tial role in determining the pattern of circulatory 

 adjustments. Since these materials rarely enter the 

 blood in amounts sufficient for detection it is extremely 

 difficult to evaluate their contribution. Tissue gas 

 exchange is an exception because oxygen and carbon 

 dioxide content of the blood entering and leaving the 

 tissues is easily measured, but the influence of other 

 agents must be studied indirectly. 



oxygen. Even assessing the role of the blood gases is 

 dillicult because it cannot be said with any certainty 

 how oxygen and carbon dioxide concentrations are 

 distributed within the capillary network. The abun- 

 dance of intercommunications makes it likely that a 

 relatively uniform admixture of blood occurs. Never- 

 theless, the gradient between artery and vein must 

 be reflected in a similar tissue differential so that 

 vessels like those on the periphery of the hepatic 

 lobules contain more highly oxygenated blood than 

 those entering the central veins. Hypoxia, per se, seems 

 to have relatively little effect upon the hepatic circula- 

 tion. Hypoxia does result in the rapid deterioration of 

 the perfused liver with the development of obvious 

 swelling and decreased perfusibility, but whether 

 these changes are to be ascribed to active vascular 

 changes or to cellular swelling alone does not seem to 

 have been subjected to systematic study (132). 

 Torrance (291) found no evidence of any change in 

 intrahepatic resistance to flow (internal calorimetry) 

 in anesthetized rabbits after complete occlusion of the 

 arterial and venous inflow tracts for 2 min. More 

 prolonged (2 hours) ischemia of the liver in anesthe- 

 tized, splenectomized dogs by occlusion of the hepatic 

 artery and diversion of the portal inflow via an ex- 

 ternal shunt to the jugular vein produces a complex 

 splanchnic vascular response, according to Selkurt 

 (265, 266). He found that arterial blood flow dropped 

 to 66 per cent of control on restoration of hepatic 

 perfusion in association with a rise in intrahepatic and 

 a fall in mesenteric resistances that together resulted 

 in a marked increase in portal venous pressure. This 

 work indicates, as does that of Torrance (291), that 

 "reactive hvperemia" does not develop in the liver 

 and it agrees with the more recent findings of Fischer 

 el al. ( 1 28) in showing hepatic arteriolar constriction. 

 Seneviratne (270) has noted sinusoidal dilatation 

 after 1 hour of airway obstruction in mice and rats 

 but in this instance carbon dioxide retention cannot be 

 eliminated as the cause. Of course, prolonged hypoxia 

 also elicits widespread compensatory adjustments 



in the systemic circulation in which the hepatic and 

 splanchnic bed might be expected to participate and 

 which may produce changes opposed to those resulting 

 from its action locally. Thus, perfusion of the mesen- 

 teric vasculature in an isolated innervated segment of 

 a dog's intestine with hypoxic blood resulted in vaso- 

 dilation and increased flow (26), in line with Selkurt's 

 observations following protracted anoxia. When the 

 animal was allowed to breath a low oxygen mixture, 

 however, reflex mesenteric vasoconstriction developed 

 to a degree commensurate with the arterial oxygen 

 content. Mesenteric and portal venous distensibility 

 also decreases under these circumstances and it may 

 be presumed that reflex venoconstriction contributes 

 to the development of portal venous hypertension and 

 results in a reduction in splanchnic blood volume 

 during hypoxia. 



carbon dioxide. The effect of hypercapnia is par- 

 ticularly dillicult to follow owing to interference by 

 an array of striking concomitant adjustments that 

 include hyperventilation, peripheral vasodilation, 

 hypertension, tachycardia, and an increase in cardiac 

 output (247). To circumvent these obstacles, the 

 splanchnic hemodynamic effects of elevated arterial 

 carbon dioxide tensions were studied by Epstein and 

 his associates (123) in normal human subjects during 

 light general anesthesia with thiopental and nitrous 

 oxide. Arterial carbon dioxide tension could be main- 

 tained at a constant level (Pa co , = 56 mm Hg on the 

 average) by mechanically controlled respiration with 

 an appropriate gas mixture following neuromuscular 

 blockade with succinylcholine. Under these circum- 

 stances, interference with the response by an increase 

 in ventilation could be eliminated. Nevertheless, the 

 over-all response appeared to be inconsistent and 

 erratic; mean arterial pressure rising in six subjects, 

 falling in two, and not changing in five in association 

 with a fall in EHBF in nine but with little or no change 

 in EHBF in four. Splanchnic vascular resistance 

 always increased, however, EHBF changing in accord 

 with the balance between the perfusing pressure and 

 resistance. Since blood flow tended to fall, the splanch- 

 nic vasoconstriction appeared usually to be somewhat 

 in excess of that elsewhere in the body. Circulatine; 

 splanchnic blood volume also decreased significantly 

 in ten subjects and, since hypercapnia has been found 

 to increase portal venous pressure, the change may be 

 interpreted as evidence of constriction of splanchnic 

 veins. The vasoconstrictive response is probably 

 mediated through the central nervous system, since 

 several investigators (132, 216) have found that in- 



