Sinusoidal Flow Block after Warm Ischemia in Rats with Diet-Induced Fatty Liver

Abstract

Donor livers with massive fatty infiltration reportedly are susceptible to ischemia/reperfusion injury after transplantation, which contributes to risk of primary nonfunction. We investigated the effect of warm ischemia and reperfusion on sinusoidal microcirculation in rats with fatty livers from a choline-deficient diet. Rats were subjected to partial hepatic warm ischemia for 30, 60, or 90 min. In a second study, an anti-ICAM-1 monoclonal antibody was injected intraportally 2 min after a 60-min ischemic period. In both studies, injury was assessed by liver histology 6 hr after vascular clamp release and by animal survival. After 30 min of hepatic warm ischemia, almost all control and fatty-liver rats survived 7 days. After 60-min ischemia, however, survival was significantly less in rats with fatty livers than in controls with normal livers (10% vs 90%,P< 0.0001). Histologically, rats with fatty livers showed marked sinusoidal congestion, especially in the midzone of the acinus, while control rats showed no disturbance in microcirculation. In rats with fatty livers treated with intraportal injection of an anti-ICAM-1 antibody, sinusoidal microcirculation was well preserved and the 7-day survival rate after warm ischemia was improved (50% vs no antibody 10%;P= 0.0112). In fatty livers, midzonal sinusoidal flow block occurs after hepatic warm ischemia and reperfusion. Although intraportal injection of an anti-ICAM-1 monoclonal antibody corrected this microcirculatory failure, animal survival was not as good as for controls without fatty livers. These results suggest that both sinusoidal microcirculatory failure and ischemic hepatocellular damage contribute to warm ischemia/reperfusion injury in fatty livers.