SINUSOIDAL FLOW BLOCK AFTER WARM ISCHEMIA IN RATS WITH DIET-INDUCED FATTY LIVER

Donor livers with massive fatty infiltration reportedly are susceptibl e to ischemia/reperfusion injury after transplantation, which contribu tes 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 par tial hepatic warm ischemia for 30, 60, or 90 min. In a second study, a n anti-ICAM-1 monoclonal antibody was injected intraportally 2 min aft er a 60-min ischemic period. In both studies, injury was assessed by l iver histology 6 hr after vascular clamp release and by animal surviva l. 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 fat ty livers showed marked sinusoidal congestion, especially in the midzo ne of the acinus, while control rats showed no disturbance in microcir culation. In rats with fatty livers treated with intraportal injection of an anti-ICAM-1 antibody, sinusoidal microcirculation was well pres erved and the 7-day survival rate after warm ischemia was improved (50 % vs no antibody 10%; P = 0.0112). In fatty livers, midzonal sinusoida l flow block occurs after hepatic warm ischemia and reperfusion. Altho ugh intraportal injection of an anti-ICAM-1 monoclonal antibody correc ted this microcirculatory failure, animal survival was not as good as for controls without fatty livers. These results suggest that both sin usoidal microcirculatory failure and ischemic hepatocellular damage co ntribute to warm ischemia/reperfusion injury in fatty livers. (C) 1997 Academic Press.