Ischemia reperfusion injury and ischemic preconditioning of the liver: From molecular basis to clinical application

Ischemia-reperfusion (IR) injury is an inevitable consequence of major liver surgeryand liver transplantation. It occurs when the blood flow to an organ is stopped (ischemia)and then restored (reperfusion). Liver ischemia-reperfusion injury (IRI) raises morbidityand mortality rates due to parenchymal cell injury and liver dysfunction, and in certaincircumstances may inflict irreversible damage on the organ. Various therapeuticstrategies have been used to reduce the severity of this damage. One of them is known asischemic preconditioning (IPC), which involves the application of brief periods of IR,followed by a prolonged session of IR. In the liver, IPC has focused on normothermic IRmodels (liver resection) and on cold ischemia (liver transplantation). Liver IPC is knownto protect the organ from the detrimental effects of ischemia-reperfusion. Recent studieshave shown the role of IPC in liver regeneration, and even in stimulating the outgrowth of colorectal micrometastases. Other studies have shown that IPC increases the toleranceof fatty liver to hepatic IRI, achieving significantly better results than intermittentclamping. Furthermore, IPC with intermittent pedicle clamping has been reported toimprove the postoperative clinical course of patients undergoing major hepatectomy.Recent results suggest that the protective effect of IPC is mediated by the modulation ofcertain mechanisms involved in local and systemic inflammation responses. Here wereview the molecular mechanisms through which ischemic preconditioning confersprotection against ischemia-reperfusion injury. © 2009 by Nova Science Publishers, Inc. All rights reserved.