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HANDBOOK OF I'llVMOI.DCV 



CIRCULATION II 



also much more impressive than that of the adrenal 

 medulla. Stimulation of the constrictor nerve fibers to 

 i In- spleen, for example, causes marked contraction at 

 rates as low as one impulse every other second, 

 whereas large doses (5 /ug/kg/min) of the medullary 

 amines fail to cause more than 40 per cent contraction 

 of the denervated spleen and an even smaller maximal 

 response is produced by stimulation of the adrenal 

 medullae. Celander (79) has concluded therefore that 

 motor control of smooth muscle in blood vessels is 

 dominated by the neural component. A corresponding 

 predominance of the adrenal medullary hormones 

 might apply to the sympathetic control of various 

 metabolic processes. In emergency situations, more- 

 over, it is possible that circulating hormones may have 

 greater importance in determining vascular responses. 

 Both epinephrine and norepinephrine are clearly 

 vasoconstrictor at all dosage levels in the perfused 

 liver (12, 13, 25, 81, 132). In the early work adren- 

 aline, known to be a mixture of /-epinephrine and 

 /-norepinephrine, was used. Fortunately, the effect of 

 epinephrine appears to dominate the vascular re- 

 sponse to the mixture and the findings of the earlier 

 studies do not differ substantially from those carried 

 out more recently with /-epinephrine alone. The 

 published data are often difficult to evaluate owing to 

 the rapidity with which a succession of shifts occurs 

 after introduction of the drugs. In part, the changes 

 may be attributed to the rearrangements involved in 

 passing from one state to another. Thus hepatic 

 venous outflow may increase transiently as the liver 

 shrinks with a reduction in intrahepatic blood volume, 

 although inflow may fall and remain depressed. 

 Differences in dosage are also obviously responsible 

 for certain variants and may indeed give rise to ir- 

 regularities in response pattern as the plasma con- 

 centration of the amine rises abruptly and then tails 

 off following injection, reaching some parts of the 

 vasculature early in high concentration, others later 

 after dilution within the vessels. Finally, the physio- 

 logic state of the organ, whether liver, spleen, or in- 

 testine, is especially important. Congestion and in- 

 creased resistance to perfusion arising from various 

 causes, chiefly on deterioration with time, may greatly 

 modify the response. With due allowance for all these 

 considerations, however, both drugs appear to in- 

 crease resistance to flow through the perfused hepatic 

 (12, 13, 25, 81, 132), mesenteric (132, 269), and 

 splenic (132) arterioles and to diminish the vascular 

 capacity by venoconstriction and splenic contraction 

 in all species. The facts are consistent with the pres- 

 ence of a-receptors mediated by norepinephrine (161). 



The moderate vasodilation that may occur in the 

 perfused mesenteric circuit, but not in the hepatic 

 vessels, following the vasoconstrictive response to 

 epinephrine may be regarded as evidence that [1- 

 receptors occur in the former and not in the latter, 

 though the role of secondary changes with gut activity 

 or of balanced shifts within the liver is not easily 

 determined. Little information regarding the dis- 

 tribution of resistance and volume changes and the 

 relative intensities of smooth muscle contraction be- 

 tween the different beds or even within the same one 

 may be gleaned from these data. 



In the intact animal, the responses are even more 

 varied and complex, but the interplay of local circuits, 

 pressures, and over-all cardiovascular adjustments 

 may be made out more readily. The early work (132) 

 on mammals yielded data generally consistent with 

 the conclusion that epinephrine gives rise to an eleva- 

 tion in arterial and portal venous pressure in asso- 

 tion with a reduction in splenic and hepatic volume, 

 and diminished hepatic venous outflow. All these 

 changes are in accord with those observed in the 

 isolated systems and suggest, furthermore, that a more 

 marked increase may develop in the hepatic vascular 

 resistances than in mesenteric or splenic to account 

 for the rise in portal venous pressure (1, 29, 47, 68, 

 104, 125, 142, 157, 159, 160, 163, 203, 2io, 223, 281). 

 Recent studies (1, 29, 47, 68, 125, 142, 157, 159, 160, 

 223, 281) indicate that norepinephrine may behave 

 similarly. With greater detail and precision, however, 

 interpretation has become somewhat more dubious. 

 In the first place, it is now clear that epinephrine is 

 essentially vasodilator in its total systemic effect, 

 physiologic doses producing no change or even a fall 

 in arterial mean pressure. Changes in flow must be 

 equated with mean pressures and cannot be taken 

 alone as evidence for vasodilation or vasoconstriction. 

 Furthermore, much of the published material relates 

 to the pattern of response observed after a single dose 

 of the drug that induces a succession of conflicting 

 local and reflex adjustments in which the assignment 

 of cause and effect may be quite impossible. With 

 constant infusion of epinephrine in unoperated, 

 unanesthetized man (47), dog (142), and rat (157), 

 hepatic venous outflow has been found to increase. 

 Since the increment in flow exceeded or was out of 

 phase with the increment in arterial mean pressure 

 in the studies of man (0.10 jug epinephrine kg min 

 for 30 min — BSP method) and dog (0.25 /ug/kg/min 

 for 1 min — blood flow velocity measured by implanted 

 "thermistorsonde") it may be concluded that over-all 

 splanchnic vascular resistance decreased during these 



