THE HEPATIC: CIRCULATION 



1419 



experiments. In the rat, however, the rise in hepatic 

 blood flow appeared to be less than the rise in arterial 

 pressure indicating a local vasoconstriction less than 

 that elsewhere in the body. Perhaps the differences 

 in results are attributable to differences in the 

 dosage — the lower doses inducing vasodilation of the 

 mesenteric arterioles by stimulation of /3-receptors. 

 Certainly if portal venous pressure rises together with 

 hepatic blood flow, as it seems to in man (187), it is 

 possible that mesenteric vasodilation dominates the 

 circulatory pattern, masking a moderate degree of 

 intrahepatic vasoconstriction. Whether a reflex me- 

 diated through the central nervous system also con- 

 tributes (21) remains uncertain. Norepinephrine, in 

 contrast, is clearly vasoconstrictor but as with epineph- 

 rine, nothing is known about its effect upon the 

 individual components in the intact hepatic and 

 splanchnic bed. The data available are too frag- 

 mentary and unreliable to permit even a tentative 

 synthesis. 



Direct visual examination of the vessels within the 

 splanchnic bed gives further support to the view that 

 medullary amine usually tends to evoke a complex 

 vasoconstrictive response. Seneviratne (270) and 

 Wakim (299) agree in reporting that epinephrine 

 applied directly to the surface of both the mammalian 

 and amphibian liver produces contraction of the 

 sinusoids, presumably as a result of constriction of 

 hepatic arterioles and portal venules. No obvious 

 effect upon the visible portal and hepatic veins was 

 evident, however. A similar response was observed 

 when the drug was injected into the portal vein. 

 Interestingly, when the drug was given via the vena 

 cava, the response was delayed and then replaced by 

 "overactivity of the circulation in the whole liver, 

 both as to number of active sinusoids and as to en- 

 gorgement and rate of flow of blood in them." Similar 

 responses have been reported in the gastrointestinal 

 tract (132). Serial angiography also yields evidence of 

 intrahepatic vasoconstriction in rat, rabbit, cat, dog, 

 and the monkey (101). Intraportal injection of ad- 

 renalin (10-20 ,ug) resulted in changes like those 

 produced by stimulation of the splanchnic nerves — 

 i.e., a reduction in the number of fine vessels demon- 

 strable by the circulating contrast medium together 

 with an inconsistent diminution in calibre of the larger 

 portal vessels. Daniel & Pritchard (101) noted further 

 that "the rapid transhepatic passage of the portal flow 

 which was observed after administration of adrenaline 

 was associated in some but not all experiments with a 

 change in the distribution of the contrast medium 

 within the liver. . . . Frequently there was evidence 



of an unequal distribution of the blood flow within 

 the liver, illustrating that a differential use was being 

 made by the portal venous blood of the various path- 

 ways through the liver." Much more work is required 

 to sort out the data available and to evaluate by more 

 precise methods the pattern of flow and pressure 

 redistribution throughout the splanchnic bed during 

 the action of epinephrine and norepinephrine. 



acetylcholine. Little consistent change appears in 

 the isolated perfused splanchnic circulation following 

 the administration of acetylcholine regardless of the 

 method employed in its evaluation. Bauer et al. (25) 

 were unable to obtain a definite response in the 

 perfused liver of the dog, cat, or goat. If the "arterial 

 tone" was "high" an intra-arterial injection of ace- 

 tylcholine appeared to produce a relaxation com- 

 parable to that induced by histamine. Relatively 

 small doses intra-arterially, however, acted upon the 

 perfused goat's liver somewhat like adrenaline, that 

 is, "arterial and portal tone were increased, liver 

 volume diminished, and outflow practically 

 unchanged. . . . this effect of acetylcholine was of the 

 parasympathetic type, in that it was completely 

 abolished by atropine, which left those of adrenaline 

 and histamine unchanged." Chakravarti & Tripod 

 (81) found that acetylcholine produced an easily 

 detectable effect upon the circulation through the 

 perfused liver if adrenaline were added to the per- 

 fusate in order to provide a "vasoconstricted state" 

 in which a vasodilator action could be more easily 

 elicited. Unlike adrenaline or histamine, acetylcholine 

 had no action when injected into the portal vein. 

 Andrews et al. (13) reported results similar to these. 

 In most of their studies of the perfused canine liver, 

 acetylcholine in doses ranging from 0.35 to 15.0 ng 

 injected into the hepatic artery produced no change in 

 arterial inflow, and a fall in both portal inflow and 

 hepatic outflow with a rise in volume; but when adren- 

 aline (0.1 fig per ml) was added to the perfusate 

 acetylcholine raised the arterial inflow and slightly 

 decreased portal venous inflow with a rise in both 

 total outflow and volume. When injected into the 

 portal vein, acetylcholine produced the same response 

 as that produced by intra-arterial injection but 10 to 

 1 5 times the amount was required for an equivalent 

 effect. Administration of eserine equalized the re- 

 sponse to arterial and venous administration indicat- 

 ing that the difference might be due to greater de- 

 struction of acetylcholine in the portal vessels. They 

 interpreted their results as indicating a weak vaso- 

 constrictive response in the portal vein and hepatic 



