Myocardial Ischemia/Reperfusion injury: novel strategies for an old problem

Ischemic heart disease remains the leading cause of death and disability in Europe and worldwide. Thrombolytic therapy and angioplasty, by allowing the recovery of coronary blood flow (reperfusion) after ischemia, greatly improved clinical outcomes and reduced the infarct size in patients.  Reperfusion per se, however, can cause serious and fatal cardiac dysfunctions, mainly due to the sudden entry of oxygen, ionic and metabolic disorders that, by overwhelming the endogenous cellular defences, can lead to the death of cardiomyocytes and trigger myocardial injury and dysfunction. Preclinical animal studies have identified and characterized many endogenous pathways that have the potential to protect cardiomyocytes and reduce the infarct size if activated before the ischemic event or early after the onset of reperfusion. However, the improvement in our knowledge and the implementation of adjuvant strategies to provide cardioprotection against short– and long–term ischemia‑reperfusion (I/R) induced damage are of great importance and remain a major unmet clinical need. The present review summarizes our current comprehension on the pathophysiology of I/R injury and analyze recent progress in pharmacological and non-pharmacological strategies of cardioprotection. Future perspectives of preclinical research on this field and its role in addressing important open questions, improving translation into the clinical setting included, are also presented.