Verapamil favorably influences hepatic microvascular exchange and function in rats with cirrhosis of the liver

Abstract

The effect of the calcium channel blocking agent, verapamil, on microcirculatory patterns and hepatic function was investigated in the perfused liver of cirrhotic rats. Compared with controls, cirrhotic livers had higher vascular resistance, increased intrahepatic shunting, and smaller extravascular albumin space and larger extravascular sucrose space, as determined by a multiple-indicator dilution technique. Hepatic function, estimated by determining propranolol and antipyrine extraction, was markedly reduced in cirrhotic livers. Portal pressure was then reduced 25% either pharmacologically by verapamil or hydrodynamically by lowering inflow. Verapamil decreased vascular resistance by 22%. This was associated with a 38% reduction in intrahepatic shunting and a 62% increase in extravascular albumin space. Hydrodynamically lowering pressure had no or adverse effects. The verapamil-induced improvement in microcirculatory characteristics was associated with a significant improvement in oxygen consumption (+21%) and antipyrine clearance (+20%). We conclude that the microvascular distortions of liver cirrhosis in the rat are partially reversible by vasodilators like verapamil.