Amelioration of hepatic ischemia/reperfusion injury by ischemic preconditioning

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[Background]Ischemic preconditioning, i.e. preparatory brief ischemia before subsequent long ischemia, protects canine heart from myocardial injury caused by long ischemia (Circulation 1986). We have reported the protective effect of ischemic preconditioning in the liver. To our knowledge, however, little has known about the mechanisms of ischemic preconditioning.[Purpose]The prupose of this study was to clarify the mechanisms of ischemic preconditioning in rat hepatic warm ischemia/reperfusion model and demonstrate the same phenomenon in rat liver transplantation.[results](1) Murry et al. proposed that the mechanism for protection of the myocardium in ischemic preconditioning includes reduced myocardial energy demand which results in reduced utilization of high-energy phosphate and preservation of ATP, In this study, at 120 min after reperfusion following 40min of warm ischemia, the livers with 10 min of ischemic preconditioning had a significantly higher ATP level than the control livers (78*13% versus 61*11%, p<0.05). (2) Next, we performed orthotopic liver transplantation in rats. In this setting, liver grafts were preserved in UW solution for 1, 12, or 24 hr at 4ﾟC with or without 10 min of ischemic preconditioning. Liver grafts with ischemic preconditioning had no significant improvement in AST or ALT at 4 hr after reperfusion. Survival study and histological examination had also no significant change in both groups. We could not demonstrate the same phenomenon in our transplantation model.[discussion]This study has demonstrated for the first time the advantage of ischemic preconditioning on hepatic warm ischemia/reperfusion injury in rats. The recovery of tissue ATP may be associated with the protective effect of ischemic preconditioning. What seems to be a paradoxical phenomenon may be useful for the amelioration of hepatic ischemia/reperfusion injury in liver surgery.