Postconditioning: Reduction of reperfusion-induced injury

Abstract

Reperfusion has the potential to introduce additional injury that is not evident at the end of ischaemia per se, i.e. reperfusion injury. Reperfusion injury is expressed as endothelial and microvascular dysfunction, impaired blood flow, metabolic dysfunction, cellular necrosis, and apoptosis. There is an impressive array of mechanisms contributing to reperfusion injury. Postconditioning, defined as brief periods of reperfusion alternating with re-occlusion applied during the very early minutes of reperfusion, mechanically alters the hydrodynamics of early reperfusion. However, postconditioning also stimulates endogenous mechanisms that attenuate the multiple manifestations of reperfusion injury listed above. These mechanisms include ligands, such as adenosine and opioids, that act as proximal triggers to stimulate molecular pathways involving mediators such as protein kinase C, mitochondrial ATP-sensitive potassium channels, and survival kinases. Postconditioning may also inhibit deleterious pathways such as p38 and JNK mitogen-activated protein (MAP) kinases and attenuate the damage to endothelial cells and cardiomyocytes from oxidants, cytokines, proteases, and inflammatory cells. Postconditioning has been shown to inhibit the mitochondrial permeability transition pore. Hence, postconditioning marshals a variety of endogenous mechanisms that operate at numerous levels and target a broad range of pathological mechanisms. Two clinical studies in patients with acute myocardial infarction have demonstrated that postconditioning was effective in reducing infarct size. Postconditioning indirectly supports the concept of reperfusion injury in animal models of ischaemia-reperfusion and in patients, and exerts cardioprotection that is equivalent to that of ischaemic preconditioning.