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A surgical model of fulminant hepatic failure in rabbits

Authors

  • Kuo-Chen Hung,

    1. Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung Hsien, Chang Gung University College of Medicine, Taiwan
    2. Department of Surgery, E-Da Hospital and I-Shou University, Kaohsiung, Taiwan
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  • Chee-Chien Yong,

    1. Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung Hsien, Chang Gung University College of Medicine, Taiwan
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  • Yaw-Sen Chen,

    1. Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung Hsien, Chang Gung University College of Medicine, Taiwan
    2. Department of Surgery, E-Da Hospital and I-Shou University, Kaohsiung, Taiwan
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  • Hock-Liew Eng,

    1. Department of Pathology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung Hsien, Chang Gung University College of Medicine, Taiwan
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  • Fang-Ying Kuo,

    1. Department of Pathology, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung Hsien, Chang Gung University College of Medicine, Taiwan
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  • Chi-Chang Lin,

    1. Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung Hsien, Chang Gung University College of Medicine, Taiwan
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  • Tai-Horng Young,

    1. Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan
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  • Eiji Kobayashi,

    1. Division of Organ Replacement Research and Animal Transgenic Research Center for Molecular Medicine, JiChi Medical School, Tochigi, Japan
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  • Chao-Long Chen,

    1. Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung Hsien, Chang Gung University College of Medicine, Taiwan
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  • Chih-Chi Wang

    1. Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung Medical Center, Kaohsiung Hsien, Chang Gung University College of Medicine, Taiwan
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Correspondence
Chih-Chi Wang, MD, Department of Surgery, Chang Gung Memorial Hospital, Kaohsiung Medical Centre, Chang Gung University College of Medicine, 123, Ta-Pei Road, Niao Sung Hsiang, Kaohsiung Hsien, Taiwan.
Tel: +886 7 7317123, ext: 8093
Fax: 886 7 3790719
e-mail: ufel4996@ms26.hinet.net

Abstract

Aim: 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.

Materials and 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.

Conclusion: 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.

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