Cardioprotection in ischaemia–reperfusion injury: novel mechanisms and clinical translation

In recent decades, robust successes have been achieved in conquering the acutely lethal manifestations of heart disease. Nevertheless, the prevalence of heart disease, especially heart failure, continues to rise. Among the precipitating aetiologies, ischaemic disease is a leading cause of heart failure. In the context of ischaemia, the myocardium is deprived of oxygen and nutrients, which elicits a cascade of events that provokes cell death. This ischaemic insult is typically coupled with reperfusion, either spontaneous or therapeutically imposed, wherein blood supply is restored to the previously ischaemic tissue. While this intervention limits ischaemic injury, it triggers a new cascade of events that is also harmful, viz. reperfusion injury. In recent years, novel insights have emerged regarding mechanisms of ischaemia-reperfusion injury, and some hold promise as targets of therapeutic relevance. Here, we review a select number of these pathways, focusing on recent discoveries and highlighting prospects for therapeutic manipulation for clinical benefit.