The experimental promise and clinical reality of myocardial conditioning for prevention of myocardial ischemia and reperfusion injury: an umbrella review of systematic reviews

Abstract

Introduction: Experimental research sequentially identified reperfusion (in 1972) and conditioning (in 1986) as the two most powerful interventions for reducing acute myocardial infarct (AMI) size following acute coronary occlusion. These discoveries led to further experimental studies on optimal myocardial salvage and intensive clinical efforts to translate these interventions into the management of patients. This umbrella review of systematic reviews addresses the state of research on the effectiveness of pharmacological and interventional conditioning protocols to modulate the impact of ischemia and reperfusion in experimental animals and patients and the comparability of results in experimental animals and humans. This umbrella review documents the paradox of the experimental success of conditioning strategies in the experimental arena and equivocal clinical results of the application of the same conditioning strategies in patients.

Evidence acquisition: The review was conducted using the reporting guideline for overviews of reviews of healthcare interventions codified in the PRIOR statement (https://www.equator-network.org/reporting-guidelines/reporting-guideline-for-overviews-of-reviews-of-healthcare-interventions-development-of-the-prior-statement/).

Evidence synthesis: The results are summarized in the PRISMA format. A discussion is provided of known and unknown factors responsible for the lack of progress in identifying and implementing interventions to further reduce morbidity and mortality from ischemic heart disease, as well as a practical strategy to achieve timely reperfusion in a larger number of patients experiencing acute coronary syndrome.

Conclusions: While awaiting further research to develop a third window of cardioprotection, the most practical approach today is to reduce the morbidity and mortality from IHD is to mount a public education campaign to get the 50% of acute coronary syndrome (ACS) patients with prodromal AMI to the hospital to institute timely reperfusion therapy which has a proven to be the most effective therapy to limit the extend of myocardial damage in patients with IHD. However, the possibility has been raised that the human myocardium may have a genetically determined, primordial non-responsiveness to cardioprotective interventions that exists beyond the established recognized confounding factors. Primordial genetic factors may be particularly difficult to overcome.