THE HEPATIC CIRCULATION 



I 42 I 



these matters will not be considered here. Interfer- 

 ence with autonomic transmission, no matter how 

 produced — whether by competition for receptor sites, 

 by depletion of stored transmitters, by changes in 

 membrane permeability or polarization, by change in 

 synthesis or degradation, or even by surgery — makes 

 possible a more meaningful appraisal of the relative 

 importance of neural, humoral, and local circulatory 

 determinants. 



Denervation by any method does not seem to pro- 

 duce significant change in the blood flow in any part 

 of the splanchnic and hepatic vascular bed. Mesen- 

 teric vasodilation, increased hepatic blood flow, and 

 partial splenic contraction have been reported shortly 

 after section of the splanchnic nerves, splenic nerve, 

 and lumbodorsal sympathectomy, but these reactions 

 seem to be temporary (132). Wilkins and his associates 

 (310) have found that the EHBF was definitely higher 

 and splanchnic vascular resistance "significantly" 

 lower in 13 patients with hypertensive vascular disease 

 2 weeks after the Smithwick procedure. In six patients 

 studied 4 to 6 months later, EHBF had returned to 

 control values. Circulating splanchnic blood volume 

 has also been found to increase after sympathectomy 

 (42). High spinal anesthesia induces a fall in EHBF 

 that may be accounted for by the coincidental fall in 

 blood pressure in the absence of change in resting 

 splanchnic resistance (201). Section of the vagus has 

 no obvious effect (147). 



Hexamethonium appears to be capable of blocking 

 cholinergic transmission within autonomic ganglia 

 though it does not block the response to sympathetic 

 nerve stimulation (92, 133, 245). During ganglionic 

 blockage, blood flow through the splanchnic bed 

 decreased in dog and man only to the extent to which 

 arterial pressure was reduced. The circulating 

 splanchnic blood volume, in contrast, was found to 

 expand significantly in the dog in the absence of 

 detectable change in portal venous or sinusoidal 

 pressures (92). These data are consistent with the view 

 that basal arteriolar cross section in the splanchnic 

 and hepatic beds at rest does not depend exclusively, 

 if at all, upon the integrity of the autonomic nerve 

 supply. Such a statement does not imply that no 

 change occurred in the vascular smooth muscle. 

 Whatever change in tone that may have occurred was 

 evidently not sufficient to result in dilatation of the 

 arterioles. It has been suggested that the contrasting 

 arteriolar and venous reactions can be explained on 

 the basis of Laplace's law, the difference in radii 

 accounting chiefly for the relative effectiveness of the 

 distending pressures at each level. 



After administration of adrenergic blocking drugs 

 (ergotamine, Dibenzyline, Dibenamine, Ilidar), epi- 

 nephrine, norepinephrine, and neural stimulation 

 fail to induce the usual arteriolar vasoconstriction in 

 the liver, gastrointestinal tract, or spleen (159-161, 

 223). Norepinephrine appears to elicit little or no 

 change of any kind under these circumstances, 

 whereas epinephrine now causes vasodilation in the 

 mesenteric and splenic vessels. The effect of neural 

 stimulation is also reversed to some extent in the gut 

 and spleen. Both are without any demonstrable effect 

 upon the liver. These findings have been interpreted 

 as evidence for vasodilator /3-receptors in the mesen- 

 teric and splenic arterioles. Since study of the behavior 

 of the veins, with special reference to their volume 

 capacity, has not been made during adrenergic block- 

 ade, it is impossible to say whether these findings 

 apply in general to the other vascular levels in each 

 coupled system. It is also difficult to be certain whether 

 dilation is an active or passive process or whether it 

 involves the participation of other substances pro- 

 duced locally in response to epinephrine. There is no 

 doubt that general blockade at any level is associated 

 with a much more marked interference with vascular 

 responses than is evident in the reversal of responses to 

 epinephrine. Although the hemodynamic pattern at 

 rest is not materially affected, any shift in position, 

 imposition of stress, or environmental change unmasks 

 a serious loss of capacity to make corrective adjust- 

 ments. Tilting into the upright position, for example, 

 results in a sharp drop in arterial pressure without 

 eliciting the normal compensatory change in splanch- 

 nic vascular resistance. Pooling of blood within the 

 splanchnic veins actually enhances the tendency to 

 circulatory collapse (42). Neural and neurohumoral 

 mechanisms may not be essential to maintenance of 

 the resting state but they are clearly necessary for 

 coordination in systemic responses. 



Local Biochemical Determinants 



Changes in blood flow result in corresponding 

 changes in the delivery of oxygen and essential nu- 

 trients to, and in the removal of metabolites from, the 

 tissues. Moreover, the associated activity of smooth 

 muscle, the distention or deflation of capillaries, the 

 alterations in interstitial pressure and in lymphatic 

 drainage all impinge directly upon the cells. Meta- 

 bolic processes are certainly affected by the secondary 

 shifts in exchange and in the milieu interieur and by 

 the neurohumoral agents themselves concerned in 

 these responses. In consequence, vasoactive materials 



