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AIM: Ischemic preconditioning (IP) is a brief ischemic episode,which confers a state of protection against the subsequent long-term ischemia-reperfusion injuries. However, little is known regarding the use of IP before the sustained cold storage and liver transplantation. The present study was designed to evaluate the protective effect of IP on the long-term preservation of liver graft and the prolonged anhepatic-phase injury.METHODS: Male Sprague-Dawley rats were used as donors and recipients of orthotopic liver transplantation. All livers underwent 10 min of ischemia followed by 10 min of reperfusion before harvest. Rat liver transplantation was performed with the portal vein clamped for 25 min. Tolerance of transplanted liver to the reperfusion injury and liverdamage were investigated. The changes in adenosineconcentration in hepatic tissue and those of nitric oxide (NO)and tumor necrosis factor (TNF) in serum were also assessed.RESULTS: Recipients with IP significantly improved theirone-week survival rate and liver function, they had increasedlevels of circulating NO and hepatic adenosine, and a reducedlevel of serum TNF, as compared to controls. Histologicalchanges indicating hepatic injuries appeared improved in theIP group compared with those in control group. The protectiveeffect of IP was also obtained by administration of adenosine,while blockage of the NO pathway using Nω-nitro-L-argininemethyl ester abolished the protective effect of IRCONCLUSION: IP appears to have a protective effect onthe long-term preservation of liver graft and the prolongedanhepatic-phase injuries. NO may be involved in this process.