The winding road to cardioprotection

Over the past two decades, the mortality from acute myocardial infarction (AMI) has been reduced dramatically. Timely reperfusion is the most powerful intervention for limiting infarct size, alongside antiplatelet, antithrombotic and anti-ischemic therapies. Paradoxically, reperfusion itself can also exacerbate myocardial injury, so called ‘‘reperfusion injury’’, which can cause additional cardiomyocyte death or microvascular obstruction. This may partially explain why the rate of death after an AMI still approaches 10%, despite optimal reperfusion. ‘‘Postconditioning’’ describes the exciting phenomenon whereby a pharmacological agent or a repeated brief ischemic stimulus can provide cardioprotection, despite administration after the lethal ischemic event. Furthermore, cardioprotection has also been demonstrated when ischemic stimuli are applied in a distant organ, so called ‘‘remote’’ postconditioning. Basic laboratory and animal studies have demonstrated significant reductions in infarct size with both pharmacological and ischemic postconditioning. Despite further promising results from proof of concept clinical studies, subsequent larger randomised controlled trials (RCTs) have failed to confirm beneficial effects with pharmacological agents. However, ongoing clinical trials using novel pharmacological agents, alongside RCTs investigating ischemic postconditioning and additional trials investigating ‘‘remote’’ postconditioning, all hold promise. Heart Metab. 2010;46:25–33.