Is It Time to Translate Ischemic Preconditioning’s Mechanism of Cardioprotection into Clinical Practice?

Abstract

After three decades of intense research on cardioprotection, we still do not have an approved intervention for limiting infarct size in the patient with acute myocardial infarction (AMI) aside from reperfusion therapy. Yet approximately 25% of patients with AMI that are reperfused are still at risk for heart failure because of excessive muscle necrosis. This article will try to make the case that ischemic preconditioning (IPC), still the most potent anti-infarct intervention ever described, is ready for serious clinical testing now. Over the past 25 years, IPC’s mechanism has been largely elucidated and targets a reperfusion injury. Ischemic preconditioning was never considered an intervention for AMI because of its need for pretreatment. However, knowledge of IPC’s mechanism has revealed a large number of drugs and interventions that will activate IPC’s signaling pathway at the time of reperfusion. Several small clinical trials suggest that they can be quite effective, but so far industry seems to have little interest in developing them. So, while basic scientists are in a continuous cycle of discovery and publication for new and novel cardioprotectants, there has been little effort devoted to translating these interventions into clinical practice. We believe that there are suitable IPC-based interventions that are ready for clinical testing today and the time has come for large-scale clinical trials.