Hepatic Venous Occlusion Causes More Impairment After Reperfusion Compared with Portal Clamping in a Murine Model

Abstract

Hepatic ischemia/reperfusion (IR) has been extensively studied, but reperfusion after acute hepatic congestion caused by venous occlusion is poorly understood. Congestion/reperfusion (CR) is not uncommon with the development of partial liver transplantation and liver resection. The purpose of this study was to compare the impairments caused by acute hepatic CR or IR using a murine model. Mice were randomly divided into IR, CR, and a sham operation (SO) group. The portal vein and hepatic artery of the left anterior hepatic lobe (LAHL) were clamped in the IR group, while the hepatic vein of the LAHL was temporarily occluded in the CR Group. This occurred for 75 min followed by reperfusion. The animals were sacrificed at 2, 6, and 24h after reperfusion. Blood and liver samples were collected for hepatic function, histology, myeloperoxidase (MPO), intravital microscopy, and real-time PCR analysis. Both IR and CR groups showed elevated liver function, histologic damage, cellular apoptosis, and microcirculatory dysfunction compared with the SO group. Compared with the IR group, the CR group revealed higher hepatic enzyme activities (ALT: 838.5 ± 155.6 versus 474.6 ± 123.8 P<0.05, AST: 792.5 ± 93.5 versus 574.8 ± 188.4 P<0.05), increased sinusoidal nonperfusion rate at 2h after reperfusion (27.4% ± 1.97% versus 23.8% ± 1.93%, P<0.05), and raised MPO level at 24h (0.34 ± 0.11 versus 0.15 ± 0.04, P<0.01). The mRNA levels of IL-1β at 6h and MCP-1 at 2 and 6h were markedly higher in the CR group than in the IR group. Hepatic reperfusion after acute congestion provokes an increased inflammatory response and causes more severe impairments in the liver compared with ischemia/reperfusion in a murine model.