A surgical model of fulminant hepatic failure in rabbits

Abstract

Animal models of fulminant hepatic failure (FHF) have been developed for characterization of disease progression and to evaluate the effectiveness of liver-assist devices, some by treatment with hepatotoxic drugs, viral hepatitis or surgical procedures. We have developed a model in the rabbit by combining resection of the three anterior lobes with ligation of the pedicle of the right lateral lobes, resulting in liver necrosis; the remnant quadrate lobes are left intact. Adult male New Zealand white rabbits (n=16) were used. Six animals were killed to measure the weight of the separate liver lobes. The others (n=10) underwent left neck central line placement to monitor continuous blood pressure and collect blood for laboratory analysis, and a burr hole on the right parietal bone to monitor the intracranial pressure (ICP). Blood laboratory analysis, clinical hepatic encephalopathy and ICP levels were measured in FHF animals (n=6). Animals (n=4) undergoing a sham operation served as controls. All FHF animals died between 12 and 26 h after liver surgery from FHF characterized by a progressive increase in liver enzymes, ammonia, total bilirubin, coagulopathy, hepatic encephalopathy and intracranial hypertension. Histological features of the ischaemic lobes showed coagulative necrosis of hepatocytes with absence of nuclei and collapse of cell plates. Brain histology revealed hypoxic cell damage. We have developed a simple, reproducible model of FHF in rabbits that has a number of features comparable with clinical FHF patients and is well suited for testing experimental bioartificial liver systems and investigating the pathogenesis of FHF.