A surgical model of fulminant hepatic failure in rabbits.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Hung
Kuo-Chen
KC
Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung Hsien, Chang Gung University College of Medicine, Taiwan.
Yong
Chee-Chien
CC
Chen
Yaw-Sen
YS
Eng
Hock-Liew
HL
Kuo
Fang-Ying
FY
Lin
Chi-Chang
CC
Young
Tai-Horng
TH
Kobayashi
Eiji
E
Chen
Chao-Long
CL
Wang
Chih-Chi
CC
D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D006498:Hepatectomy / Q000379:methods*; D006501:Hepatic Encephalopathy / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D007427:Intracranial Pressure; D017114:Liver Failure, Acute / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy*; D008297:Male; D009336:Necrosis; D009929:Organ Size; D011817:Rabbits