Beyond Preconditioning: Postconditioning as an Alternative Technique in the Prevention of Liver Ischemia-Reperfusion Injury

Kassiani Theodoraki,Aliki Tympa,Nikolaos Arkadopoulos,Constantinos Nastos,Marios-Konstantinos Tasoulis,Vassilios Smyrniotis,Iosifina Karmaniolou,Ioannis Vassiliou

doi:10.1155/2016/8235921

Abstract

Liver ischemia/reperfusion injury may significantly compromise hepatic postoperative function. Various hepatoprotective methods have been improvised, aiming at attenuating IR injury. With ischemic preconditioning (IPC), the liver is conditioned with a brief ischemic period followed by reperfusion, prior to sustained ischemia. Ischemic postconditioning (IPostC), consisting of intermittent sequential interruptions of blood flow in the early phase of reperfusion, seems to be a more feasible alternative than IPC, since the onset of reperfusion is more predictable. Regarding the potential mechanisms involved, it has been postulated that the slow intermittent oxygenation through controlled reperfusion decreases the burst production of oxygen free radicals, increases antioxidant activity, suppresses neutrophil accumulation, and modulates the apoptotic cascade. Additionally, favorable effects on mitochondrial ultrastructure and function, and upregulation of the cytoprotective properties of nitric oxide, leading to preservation of sinusoidal structure and maintenance of blood flow through the hepatic circulation could also underlie the protection afforded by postconditioning. Clinical studies are required to show whether biochemical and histological improvements afforded by the reperfusion/reocclusion cycles of postconditioning during early reperfusion can be translated to a substantial clinical benefit in liver resection and transplantation settings or to highlight more aspects of its molecular mechanisms.

Highlights

Prevention of major hemorrhage during hepatic resection is crucial because of the unfavorable short- and long-term outcomes associated with blood transfusion [1]
Despite the favorable effects of ischemic preconditioning (IPC), documented in a variety of experimental and some clinical settings, it has an obvious disadvantage: it must be initiated before the ischemic event, which is not always a feasible option
The protection afforded by Ischemic postconditioning (IPostC), which could be seen as an attempt for slow intermittent oxygenation through several cycles of on/off flow before permanent reperfusion, could be considered as a more appropriate choice with a theoretical clinical application value

Summary

Introduction

Prevention of major hemorrhage during hepatic resection is crucial because of the unfavorable short- and long-term outcomes associated with blood transfusion [1] In this context, techniques involving some type of vascular control are favored by many surgeons since they can ensure a less hemorrhagic surgical field by taking advantage of liver tolerance to normothermic warm ischemia [2, 3]. Hepatic IR injury can occur in other clinical contexts, such as liver donor preservation and transplantation and hypovolemia [6, 7] Both warm and cold ischemia, with the accompanying reduction of blood flow, cause depletion of hepatocyte energy reserves, accumulation of intracellular sodium, calcium, and reactive oxygen species (ROS), and the activation of multiple enzyme systems leading to cell damage [8]. The ensuing microcirculatory derangement can culminate in hepatocellular apoptosis and necrosis with untoward consequences for the liver and for distant organs [16,17,18]

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