Ischemic preconditioning in hepatic ischemia and reperfusion

Abstract

Ischemic preconditioning that consists of a short period of hepatic inflow occlusion followed by reperfusion has the potential to increase tolerance to a subsequent prolonged ischemic insult. This review outlines current insight into ischemic preconditioning for hepatic ischemia and reperfusion injury in experimental and clinical settings. Experimental evidence suggests that interleukin-6 signaling and increased phosphorylation of STAT3 (signal transducer and activator of transcription-3) are involved in the protective effects of ischemic preconditioning. The benefit of ischemic preconditioning is restricted, however, by old liver and prolonged ischemic time (>60 min). To overcome this, ascorbic acid or glucose administration combined with ischemic preconditioning potentially can maintain the integrity of hepatic mitochondrial function through signal transduction pathways. The influence of ischemic preconditioning on hepatic regeneration varies with partial hepatectomy or small-for-size liver graft models, and remains controversial. Clinically, ischemic preconditioning in deceased donors protects against ischemia and reperfusion injury, as demonstrated by lowered liver enzyme levels, reduced incidence of primary nonfunction, and increased hepatic hypoxia-induced factor-1alpha concentrations. Enhanced understanding of the mechanisms of organ tolerance induced by ischemic preconditioning would strengthen the significance of this potential therapeutic strategy in liver transplantation.