Selective bowel decontamination of recipients for prevention against liver injury following orthotopic liver transplantation: Evaluation with rat models

Authors

  • Masahiro Arai,

    1. First Department of Internal Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan
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  • Satoshi Mochida,

    1. Third Department of Internal Medicine, Saitama Medical School, Morohongo, Moroyama-cho, Iruma-gun, Saitama 350-04, Japan
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  • Akihiko Ohno,

    1. First Department of Internal Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan
    2. Third Department of Internal Medicine, Saitama Medical School, Morohongo, Moroyama-cho, Iruma-gun, Saitama 350-04, Japan
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  • Shin Arai,

    1. Third Department of Internal Medicine, Saitama Medical School, Morohongo, Moroyama-cho, Iruma-gun, Saitama 350-04, Japan
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  • Kenji Fujiwara M.D., Ph.D.

    Corresponding author
    1. Third Department of Internal Medicine, Saitama Medical School, Morohongo, Moroyama-cho, Iruma-gun, Saitama 350-04, Japan
    • Third Department of Internal Medicine, Saitama Medical School, 38 Morohongo, Moroyama-cho, Iruma-gun, Saitama 350-04, Japan. Fax: 81-492-94-8404
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  • Part of the data was published in Transplantation Proceedings

Abstract

Gut-derived substances can activate Kupffer cells to provoke hepatic necrosis after partial hepatectomy in rats. A similar situation may occur during orthotopic liver transplantation (OLT), as congestion in the intestinal wall, caused by portal vein occlusion, is inevitable during the operation. The contribution of such substances to liver injury following OLT was investigated in rats. Oral administration of polymyxin B sulfate for 7 days significantly altered intestinal bacterial flora in rats; Enterobacteriaceae diminished and anaerobes such as Bifidobacterium, Lactobacillus,Bacteroides, and Eubacterium increased in number, compared with the control rats. Also, this treatment significantly reduced endotoxin concentration in the portal blood 30 minutes after blood reflow following portal vein occlusion. When OLT was performed in rats using the liver preserved in cold University of Wisconsin solution for 18 hours, tissue factor activity in Kupffer cells (KC) isolated from the transplanted liver 1 hour after the operation was significantly higher than in that of normal rats. This increase was significantly reduced by pretreatment of the recipients with polymyxin B sulfate. In these recipients, serum alanine aminotransferase activity, tumor necrosis factor α (TNFα) concentration, and histological extent of liver necrosis were significantly attenuated at 24 hours after the operation compared with those of control rats. We conclude that the substances derived from bacilli sensitive to polymyxin B sulfate in the gut may be a contributing factor to liver injury following OLT in rats; we feel that this probably occurs by entering of the substances into the portal blood during the ahepatic phase of the operation to activate KC. Selective bowel decontamination of recipients with polymyxin B sulfate would be a candidate for protection against early graft failure following OLT.

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