Patterns of regional sympathetic nerve traffic in preascitic and ascitic cirrhosis

Abstract

Overactivity of the sympathetic nervous system and portal hypertension are key factors in the development of ascites in cirrhosis. The sympathoexcitation that characterizes the more advanced stages of liver diseases is less clearly defined in preascitic cirrhosis. We measured sympathetic nerve traffic to skeletal muscle (peroneal nerve) and to skin districts by microneurography in (1) 12 Child class A cirrhotic patients with clinically significant portal hypertension (portal pressure gradient > 10 mm Hg, 14.8 ؎ 1.2 mm Hg, mean ؎ SEM) but without actual or previous ascites, (2) 16 Child class C cirrhotic patients with tense ascites, and (3) 10 patients with mild congestive heart failure, a condition paradigmatic of a marked sympathetic activation. Muscle sympathetic nerve traffic was markedly increased in Child class C subjects as compared with controls (23.9 ؎ 1.6 bursts/min, P < .01) and superimposable to that recorded in heart failure patients (52.9 ؎ 4.7 vs. 60.3 ؎ 2 bursts/min, P ‫؍‬ not significant). Muscle sympathetic nerve traffic was also increased in Child class A subjects (41.6 ؎ 2 bursts/min, P < .01 vs. controls) although to a lesser extent (P < .05 vs. Child class C patients). Skin sympathetic nerve traffic was within the normal range in all patients. Neurohormones were all markedly increased in Child class C subjects. Only norepinephrine was increased in Child class A patients. Our data show that sympathetic nerve traffic activation (1) is already detectable in Child class A cirrhosis when clinically significant portal hypertension is present but ascites never developed and (2) Cirrhosis is accompanied by an increase in sympathetic activity 1 as shown by the observation that in this condition plasma norepinephrine, 2-5 norepinephrine spillover from neuroeffector junctions, 6 and muscle sympathetic nerve traffic as directly quantified by microneurography 7-9 are all increased. The sympathoactivation accompanying cirrhosis has not yet been thoroughly characterized, however. For example, it is not yet clear whether the sympathoactivation is a pathophysiologic feature of cirrhosis throughout its course or if it just appears when fluid retention, ascites, or the hepatorenal syndrome dramatically alter circulating blood volume. 10 It is also not clear whether the sympathoactivation is generalized to the entire cardiovascular system or if it involves some vascular beds but not others.The aim of the present study has been to provide information on these two issues; that is, whether sympathetic activity is increased in earlier stages of cirrhosis in which portal pressure is increased but ascites has never developed and whether in either preascitic and more advanced cirrhosis the sympathetic activation has a generalized or more regional distribution. PATIENTS AND METHODSStudy Population. This study was performed on a total of 48 subjects. Twenty-eight patients had cirrhosis and portal hypertension with different degrees of liver impairment as assessed by the ChildPugh classification. Twelve patients were Ch...

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