Protection of the Liver by Ischemic Preconditioning: A Review of Mechanisms and Clinical Applications

Abstract

Ischemic preconditioning refers to the endogenous mechanism of protection against a sustained ischemic insult following an initial, brief ischemic stimulus. Ischemia-reperfusion injury of the liver is a major cause of morbidity and mortality in liver surgery and transplantation and ischemic preconditioning is a promising strategy for improving the outcome of liver surgery. The preconditioning phenomenon was first described in a canine model of myocardial ischemia-reperfusion injury in 1986 and since then has been shown to exist in other organs including skeletal muscle, brain, kidneys, retina and liver. In the liver, the preconditioning effect has been demonstrated in rodents and a recent study has demonstrated human clinical benefits of preconditioning during hemihepatectomies. Ischemic preconditioning has been described as an adaptive response and although the precise mechanism of hepatoprotection from preconditioning is unknown it is likely to be a receptor-mediated process. Several hypotheses have been proposed and this review assesses possible mechanisms of ischemic preconditioning and its role in hepatic surgery and liver transplantation. The future lies in defining the mechanisms of the ischemic preconditioning effect to allow drug targeting to induce the preconditioning response.