Reperfusion Injury: How Can We Reduce It by Pre-, Per-, and Postconditioning

While early coronary reperfusion via primary percutaneous coronary intervention (pPCI) is established as the most efficacious therapy for minimizing infarct size (IS) in acute ST-elevation myocardial infarction (STEMI), the restoration of blood flow also introduces myocardial ischemia-reperfusion injury (IRI), leading to cardiomyocyte death. Among diverse methods, ischemic conditioning (IC), achieved through repetitive cycles of ischemia and reperfusion, has emerged as the most promising method to mitigate IRI. IC can be performed by applying the protective stimulus directly to the affected myocardium or indirectly to non-affected tissue, which is known as remote ischemic conditioning (RIC). In clinical practice, RIC is often applied by serial inflations and deflations of a blood pressure cuff on a limb. Despite encouraging preclinical studies, as well as clinical studies demonstrating reductions in enzymatic IS and myocardial injury on imaging, the observed impact on clinical outcome has been disappointing so far. Nevertheless, previous studies indicate a potential benefit of IC in high-risk STEMI patients. Additional research is needed to evaluate the impact of IC in such high-risk cohorts. The objective of this review is to summarize the pathophysiological background and preclinical and clinical data of IRI reduction by IC.