Mouse livers with macrosteatosis are more susceptible to normothermic ischemic injury than those with microsteatosis

BACKGROUND/AIMS: Fatty livers are increasingly used for transplantation due to the dramatic organ shortage. While steatosis is an established risk factor for post-operative complications, the impact of macro- vs. microvesicular steatosis on ischemic injury is unclear. METHODS: The effects of ischemia and reperfusion were tested in two different models of steatotic mice: ob/ob as a model disclosing predominantly macrovesicular steatosis and choline deficient diet having mainly microvesicular steatosis. Steatotic and lean livers were subjected to 45 min of ischemia. Serial markers of hepatocellular injury, animal survival were measured. Hepatic tissue blood flow and portal vein perfusion were assessed. RESULTS: Ob/ob mice had a significantly lower tolerance to hepatic ischemia. with increased AST release and decreased survival in comparison to the choline deficient mice. No difference in ATP content was found between both steatosis models, but hepatic perfusion and portal vein flow were significantly lower after reperfusion in the ob/ob mice when compared to the choline deficient animals. Ischemic pre-conditioning significantly improved liver reperfusion and injury in both models of steatosis. CONCLUSIONS: Livers with macrovesicular steatosis have a lower tolerance to ischemic injury than those with microvesicular steatosis. Low intrahepatic and portal vein perfusion in macrovesicular fatty livers is, at least partially, responsible for the poorer outcome.