The Influence of Vasoactive Agents on Metabolic Activity of the Liver in Cirrhosis: A Study of the Effects of Posterior Pituitary Extract, Vasopressin, and Somatostatin

Abstract

We studied the influence of posterior pituitary extract, vasopressin, and somatostatin on hepatic elimination function. Hepatic clearance and its two biological determinants, hepatic blood flow and metabolic activity (clearance V_max/K_m), were determined from hepatic indocyanine green elimination at steady-state in cirrhotic patients. Intravenous infusion of posterior pituitary extract (oxytocin, 59%; vasopressin, 41%) at the constant rate of 0.3 unit per kg per hr decreased hepatic clearance (p < 0.05) and V_max/K_m (p < 0.05) but did not change hepatic blood flow. Intravenous infusion of vasopressin (0.3 unit per kg per hr) decreased hepatic clearance (p < 0.05), V_max/K_m (p < 0.05) and hepatic blood flow (p < 0.05). Intravenous infusion of somatostatin (250 μg per hr following a bolus i.v. injection of 250 μg) decreased hepatic clearance (p < 0.05), V_max/K_m (p < 0.05), and hepatic blood flow (p < 0.05). This study shows that the vasoactive agents used in the management of upper digestive bleeding in cirrhotic patients may have deleterious effects on the metabolic activity of the liver in addition to their effects on hemodynamics. The results suggest that the vasoactive substances either increased the fraction of total hepatic blood which bypassed intact hepatocytes or directly impaired metabolic activity of hepatocytes. Reduction in the metabolic activity of the liver produced by vasoactive agents may have important implications in therapy of portal hypertension.