A decrease in plasma noradrenalin-a reflection of sympathetic nervous system activity-by clonidine, a centrally acting u2-agoni8t, could reduce the hyperdynamic circulation oherved in cirrhosis and may thereby decregse portal hypertension. Plasma noradrenaline oonceatration and plasma renin activity as well as systemic and splanchnic hemodynamics were measured in 12 patients with cirrhosis and ascites before and after erlminietration of either 150 pg of clonidine or placebo. Plasma noradrenaline concentration significantly decrefeed in all patients after clonidine administration, whereas plasma renin activity did not change significantly. There were statistically significant reductions of cardiac output (-17.4%), mean arterial pressure (-12.2%). hepatic venous pressure gradient (-19.7%) and assygos blood flow (-26.6%) after administration of clonidine. No significant correlation was found between the reduction of plasma noradrenaline concentration and chmnges in systemic or splanchnic hemodynamics. Heqiatic blood flow was not changed by clonidine. Placebo admidstration had no effect on any laboratory or c meaeurement. We conclude that the reduction in sympathetic nervous system activity by clonidine and the subsequent decrease in the hyperdynamic circulation -eats that sympathetic overactivity contributes to the circulatory derangements in patients with cirrhosis.
Sympathetic nervous system activity is thought to be augmented in patients with cirrhosis, but this is not completely established. Although the weight of evidence points in this direction, the literature is replete with conflicting studies: some have found normal (1, 2) or increased serum catecholamines with hyposensitivity to their effects (3). Baroreflexes may be preserved (4) or attenuated (5, 6), while membrane adrenergic receptors show variable responses (7; Lebrec, D., et al., Heputology 1985; 5972, Abstract). However, amidst this plethora of divergent results, some clinical observations are clear: patients with cirrhosis demonstrate a hyperkinetic circulation with increased cardiac output and decreased systemic vascular resistance (8, 9). Furthermore, direct