Effect of cold ischemia on early acute rejection after orthotopic liver transplantation in rats

Objective To study the mechanism and the impact of prolonged cold ischemia on early acute rejection in rat liver allografts.Methods Thirty cases of isotransplantations from BN to BN rats and 30 cases of allotransplantations from Lewis to BN rats were performed,and donor livers were subjected to 1 or 18 h cold ischemia in 4℃ University of Wisconsin solution before transplantation.Rats were randomly divided into 4 groups (n=15 each):group A:isografts with 1 h cold ischemia transplantation;group B:isografts with 18 h cold isehemia transplantation;group C:allografts with 1 h cold ischemia transplantation;group D:allografts with 18 h cold ischemia transplantation.Recipients were sacrificed at day 2,4 and 6 postoperation (n=3 animals/group/time point for isografts and allografts).Representative specimens were collected for immunohistological assay of MHC-Ⅱand NF-κB or snap frozen in liquid nitrogen for morphological observation.Serum levels of ALT and TBiL were determined.Six recipients of each group were observed for 2-week survival rate postoperatively.Results Immunohistochemical staining of postoperative liver specimens showed stronger MHC-Ⅱ expression on either vascular endothelium or bile duct epithelium in group B than in group A (P＜0.05).In allografts groups,there was a significantly greater expression of MHC-Ⅱ in liver specimens.Prolonged cold ischemia not only up-regulated the expression of NF-κB,but also advanced peak value of the expression of them.There was a significant difference in 2-week survival rate between two allografts groups (P＜0.05).Conclusions Cold ischemia may predispose the liver allograft to the development of acute rejection,in part,not only through the upregulation of the expression of MHC-Ⅱ,but also through the activation of NF-κB.Prolonged cold ischemia can shortern 2-week survival rate postoperatively as well. Key words: Organ preservation; Liver transplantation; Graft reiection; Rats