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 cause 100% mortality, ischemia of the liver was induced for different lengths of time, starting with 6 hours. If the pig survived, ischemia time was prolonged 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 tightened. SETTING The Laboratory for Hepatopathophysiology, Catholic University, Leuven, Belgium. PARTICIPANTS Female stress-negative Belgian Landrace pigs weighing 18 to 22 kg. INTERVENTIONS During preparatory surgery, all ligaments around the liver and connective tissue around the liver hilum were transected and an end-to-side 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 determined based on neurologic, biochemical, and pathological variables. RESULTS When occluded for 10 hours, all pigs in group 2 (n = 5) [corrected] died between 12 and 17 hours after the induction of ischemia. All pigs developed typical acute liver failure. Tissue specimens showed 90% necrosis of the liver parenchyma. CONCLUSION A highly reproducible and potentially reversible model of acute liver failure in the large animal has been established.