An improved model of acute liver failure based on transient ischemia of the liver

Hypothesis: A reproducible and potentially reversible model of acute liver failure in the pig is feasible based on transient ischemia of the liver. Design: To determine the shortest period of liver ischemia sufficient to ca use 100% mortality, ischemia of the liver was induced for different lengths of time, starting with 6 hours. If the pig survived, ischemia time was pro longed for 2 hours in the next animal. In the first group, the common bile duct was not tightened. In the second group, the common bile duct was tight ened. Setting: The Laboratory for Hepatopathophysiology, Catholic University, Leu ven, Belgium. Participants: Female stress-negative Belgian Landrace pigs weighing 18 to 2 2 kg. Interventions: During preparatory surgery, all ligaments around the liver a nd connective tissue around the liver hilum were transected and an end-to-s ide portacaval shunt was made. Vessel loops were placed around the branches of the hepatic artery and bile duct. Three days later, in fully awake pigs , the loops were tightened. Main Outcome Measures: Mortality. Development of acute Liver failure was de termined based on neurologic, biochemical, and pathological variables. Results: When occluded for 10 hours, 5 of 6 pigs in group 2 died between 12 and 17 hours after the induction of ischemia. All pigs developed typical a cute liver failure. Tissue specimens showed 90% necrosis of the liver paren chyma. Conclusion: A highly reproducible and potentially reversible model of acute liver failure in the large animal has been established.