Hepatosplanchnic haemodynamics and renal blood flow and function in rats with liver failure

Abstract

Background - Massive liver necrosis, characteristic of acute liver failure, may affect hepatosplanchnic haemodynamics, and contribute to the alterations in renal haemodynamics and function. Aims - To investigate the relation between hepatosplanchnic haemodynamics, including portal systemic shunting, and renal blood flow and function in rats with acute liver failure. Methods - Liver failure was induced in male Wistar rats by intraperitoneal injection of 1.1 g/kg of D(+)-galactosamine hydrochloride. The parameters assessed included: systemic, hepatosplanchnic, and renal blood flow (57Co microsphere method); portal-systemic shunting and intrarenal shunting (consecutive intrasplenic, intraportal, or renal arterial injections of 99mTc methylene diphosphonate and 99mTc albumin microspheres); arterial blood pressure and portal pressure; renal function; and liver function (liver function tests and 14C aminopyrine breath test). Results - Progressive liver dysfunction was accompanied by the development of a hyperdynamic circulation, a highly significant decrease in renal blood flow and function, and an increase in intrarenal shunting 367 427 and 48 hours after administration of D-galactosamine. The alterations in renal blood flow and function were accompanied by significant increases in portal pressure, portal venous inflow, and intrahepatic portal systemic shunting in galactosamine treated rats compared with controls. There was a significant correlation between changes in renal blood flow and changes in portal pressure, intrahepatic portal systemic shunting, and deterioration in liver function (r = 0.8, p < 0.0001). Conclusions - The results of this study suggest that both increased intrahepatic portal systemic shunting and hepatocyte impairment may contribute to alterations in renal haemodynamics and function.