SELECTIVE BOWEL DECONTAMINATION OF RECIPIENTS FOR PREVENTION AGAINST LIVER-INJURY FOLLOWING ORTHOTOPIC LIVER-TRANSPLANTATION - EVALUATION WITH RAT MODELS

Gut-derived substances can activate Kupffer cells to provoke hepatic n ecrosis after partial hepatectomy in rats. A similar situation may occ ur during orthotopic liver transplantation (OLT), as congestion in the intestinal wall, caused by portal vein occlusion, is inevitable durin g the operation, The contribution of such substances to liver injury f ollowing OLT was investigated in rats. Oral administration of polymyxi n B sulfate for 7 days significantly altered intestinal bacterial flor a in rats; Enterobacteriaceae diminished and anaerobes such as Bifidob acterium, Lactobacillus, Bacteroides, and Eubacterium increased in num ber, compared with the control rats, Also, this treatment significantl y 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 solu tion for 18 hours, tissue factor activity in Kupffer cells (KC) isolat ed from the transplanted liver 1 hour after the operation was signific antly higher than in that of normal rats. This increase was significan tly reduced by pretreatment of the recipients with polymyxin B sulfate . In these recipients, serum alanine aminotransferase activity, tumor necrosis factor alpha (TNF alpha) concentration, and histological exte nt of liver necrosis were significantly attenuated at 24 hours after t he operation compared with those of control rats, We conclude that the substances derived from bacilli sensitive to polymyxin B sulfate in t he gut may be a contributing factor to liver injury following OLT in r ats; we feel that this probably occurs by entering of the substances i nto the portal blood during the ahepatic phase of the operation to act ivate KC, Selective bowel decontamination of recipients with polymyxin B sulfate would be a candidate for protection against early graft fai lure following OLT.