Different ischemic preconditioning for rat liver graft: protection and mechanism

Hepatobiliary Pancreat Dis Int. 2003 Nov;2(4):509-12.

Abstract

Objective: To investigate the protective mechanism of different ischemic preconditioning (IPC) to ischemia/reperfusion (I/R) injury of rat liver graft.

Methods: 192 Wistar rats were randomly divided into 4 groups (48 rats in each group): control group (group C), experimental group 1 (group E1), experimental group 2 (group E2), and experimental group 3 (group E3). IPC was not carried out in group C. In the experimental groups, IPC was carried out by blocking blood flow of the portal vein and hepatic artery and then reperfusion by removal of the clamp before donor liver was resected. Group E1: 5-minute ischemia and 10-minute reperfusion; Group E2: 5-minute ischemia and 5-minute reperfusion and one more the same procedure; Group E3: 10-minute ischemia and 15-minute reperfusion. Four hours after IPC, liver transplantations were performed. Recipient blood and graft samples were obtained to determine the levels of ALT, AST, TNF-alpha and apoptosis index at 0.5, 2, 6, 24 hours after portal vein reperfusion.

Results: At 0.5, 2 hours after portal vein reperfusion, the levels of TNF-alpha in the experimental groups E1, E2, and E3 were significantly lower than in the control group (P<0.05), and the levels in group E2 were significantly lower than in groups E1 and E3 (P<0.05). At 24 hours, the levels of TNF-alpha in group E2 were significantly lower than in groups C, E1 and E3 (P<0.05). At 2 and 6 hours, apoptosis index in the experimental groups E1, E2, and E3 was significantly less than in the control group (P<0.05). Apoptosis index in group E2 was significantly less than groups E1 and E3 (P<0.05). At 24 hours apoptosis index in the experimental groups E1, E2, and E3 was significantly less than in the control group (P<0.05).

Conclusions: Ischemic preconditioning could attenuate liver graft injury by decreasing apoptosis of hepatocytes and production of TNF-alpha. The method of IPC with 5-minute ischemia, 5-minute reperfusion and one more the same procedure is a better way to protect liver graft from ischemia-reperfusion injury.

Publication types

  • Comparative Study

MeSH terms

  • Analysis of Variance
  • Animals
  • Aspartate Aminotransferases / analysis
  • Disease Models, Animal
  • Female
  • Graft Rejection
  • Graft Survival
  • In Situ Nick-End Labeling
  • Ischemic Preconditioning / methods*
  • Liver / blood supply*
  • Liver Function Tests
  • Liver Transplantation / adverse effects
  • Liver Transplantation / methods*
  • Male
  • Probability
  • Random Allocation
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Sensitivity and Specificity
  • Tumor Necrosis Factor-alpha / analysis

Substances

  • Tumor Necrosis Factor-alpha
  • Aspartate Aminotransferases