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

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 ␣ (TNF␣) 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. (HEPATOLOGY 1998;27:123-127.)

Role of ischemic preconditioning and the portosystemic shunt in the prevention of liver and lung damage after rat liver transplantation1

“…Along this line, studies have reported an increase in TNF levels after rat liver transplantation, whereas no increase in plasma TNF was detected in recipient rats, in which intestine was resected, or in splanchnic rats (5). In addition, it has also been reported that the intestine, as a consequence of splanchnic congestion, could indirectly contribute to the increase in plasma TNF levels after liver transplantation (7,41). Thus, these authors suggest that the intestinal release of some proinflammatory mediators could stimulate TNF production in Kupffer cells.…”

Anti-Endotoxin Monoclonal Antibodies are Protective against Hepatic Ischemia/Reperfusion Injury in Steatotic Mice

“…The heterogenicity of endotoxin delivered to the liver as a consequence of portal occlusion is well known (11). Consequently, two monoclonal antibodies (mAb) whose antigen binding sites are directed against a common epitope of the LPS molecule were used.…”

The Microbiome, Systemic Immune Function, and Allotransplantation

“…Germfree mice lack MAMPs in the portal circulation, and this absence of MAMPs appears to correlate with lower levels of hepatic leukocyte adhesion molecule expression and reduced numbers of Kupffer cells. Consistent with these studies, treatment of rats with polymyxin B prior to liver transplantation reduced intestinal levels of Enterobacteriaceae; this reduction was correlated with decreased portal circulation endotoxin levels, decreased hepatic Kupffer cell tissue factor activity, and decreased posttransplant hepatonecrosis (87). Thus, after ischemia-reperfusion, MAMPs may participate in recruitment of Kupffer cells to the liver allograft, contributing to graft injury after liver transplantation (88).…”