Prolonged Cold Ischemia Does Not Trigger Lethal Rejection or Accelerate the Acute Rejection in Two Allogeneic Rat Liver Transplantation Models

BackgroundProlonged cold ischemia (CI) might induce lethal liver graft rejection and/or accelerate the course of lethal rejection in BN-Lew and ACI-Lew liver transplantation (LT) models, which have been successfully challenged by liver-size reduction.Materials and MethodsSurvival rate of recipients and body weight development after subjecting the grafts to prolonged CI in saline were assessed. Severity of rejection was assessed based on histology and the size of portal infiltration. Hepatic expression of CD25, CD28, CD38, granzyme B, and perforin were assessed to further judge the severity of allogeneic immune response.ResultsAn enhancement of allogeneic immune response after prolonged CI was observed, indicated by up-regulated mRNA expression of CD25, CD28, CD38, granzyme B, and perforin. However, the enhancement of allogeneic immune response did not reverse the BN-Lew spontaneous liver graft acceptance to lethal rejection. Eight-hour CI led to 100% 4 wk survival rate and graft acceptance and did not impair postoperative body weight recovery. Nine-hour CI caused the death of 2/6 rats due to primary non-function (PNF) of the graft within 48 h. Ten-hour CI caused lethal PNF in all rats within 96 h. Histology of surviving recipients revealed an expansion of the portal tract due to an inflammatory infiltrate. In rats dying from PNF, extended centrilobular necrosis was observed, but no sign of rejection. In the ACI-Lew full-size LT model, 8 h CI did not accelerate the course of lethal rejection.ConclusionProlonged CI was associated with an discrete enhancement of allogeneic immune response, but did not trigger lethal rejection in BN-LEW spontaneous liver graft acceptance model and did not accelerate acute rejection in ACI-Lew rejection model.