Postconditioning for protection of the infarcting heart

Coronary heart disease is set to become the leading worldwide cause of death by 2020.1 Acute myocardial infarction is a major cause of such mortality and the best hope of salvaging viable myocardium is by rapid reperfusion of the ischaemic myocardium, either by thrombolysis or primary percutaneous coronary intervention. Ischaemic post-conditioning was achieved by very short repetitive periods of coronary occlusion and reperfusion in the early minutes of revascularisation of experimental myocardial infarction.5 In a recent landmark clinical study, Patrick Staat and colleagues6, postconditioned the human myocardium in patients undergoing primary percutaneous coronary intervention by repetitively inflating and deflating an angioplasty balloon within minutes of stenting. Studies have identified a signalling pathway that is recruited at the time of reperfusion and which is common to ischaemic preconditioning and postconditioning.5 This pathway consists of the survival kinases PI3K-Akt and Erk1/2, the major components of the reperfusion-injury salvage-kinase pathway, termed the RISK pathway,8 which might influence the mitochondrial permeability transition pore, a non-specific pore of the inner mitochondrial membrane whose opening in the first few minutes of myocardial reperfusion promotes cell death.9,10 Delayed washout of endogenously produced adenosine and activation of the adenosine receptor is also required for postconditioning protection,11 by activating the survival pathway.