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Is it time to translate ischemic preconditioning's mechanism of cardioprotection into clinical practice?
Michael V Cohen1, James M Downey
1Department of Physiology, University of South Alabama, College of Medicine, Mobile, AL 36688, USA. mcohen@usouthal.edu
Insights
Ischemic preconditioning (IPC) is the most potent anti-infarct intervention. New strategies can activate IPC
Area of Science:
- Cardiology
- Cardioprotection
- Translational Medicine
Background:
- Despite decades of research, no approved interventions limit infarct size in acute myocardial infarction (AMI) beyond reperfusion therapy.
- Excessive myocardial necrosis post-reperfusion places 25% of AMI patients at risk for heart failure.
- Ischemic preconditioning (IPC) remains the most potent anti-infarct intervention described.
Purpose of the Study:
- To advocate for the clinical testing of Ischemic Preconditioning (IPC)-based interventions for acute myocardial infarction (AMI).
- To highlight the potential of IPC-targeting drugs and interventions for clinical application.
Main Methods:
- Elucidation of IPC mechanisms over 25 years, identifying targets for reperfusion injury.
- Identification of drugs and interventions that activate IPC signaling pathways during reperfusion.
- Review of small clinical trials suggesting efficacy of IPC-based interventions.
Main Results:
- IPC's mechanism is well-understood, targeting reperfusion injury.
- Numerous drugs and interventions can activate IPC pathways at reperfusion.
- Small clinical trials indicate significant efficacy, yet industry interest is lacking.
Conclusions:
- IPC-based interventions are ready for large-scale clinical trials in acute myocardial infarction (AMI).
- There is a critical need to translate basic science discoveries into clinical practice for cardioprotection.
- Translating IPC-based strategies could significantly reduce heart failure risk in AMI patients.
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.
