Myocardial protection from ischemia-reperfusion injury post coronary revascularization

Abstract

Effective primary and secondary prevention and advances in cardiac surgery have significantly improved the care and outcomes of patients with myocardial ischemia. While timely reperfusion has proved to be an invaluable tool, ischemia–reperfusion injury represents a mechanism that may limit its effectiveness. Numerous experimental studies have shown effective protection from ischemia–reperfusion injury in animal models, but translation into clinical practice has been less successful. This article summarizes the role of ischemia–reperfusion injury in the pathophysiology of ischemic heart disease and gives an overview of the various modalities that have been developed in order to provide myocardial protection from reperfusion injury in clinical practice.

Keywords:

• acute myocardial infarction
• cardiac surgery
• ischemia–reperfusion injury
• myocardial protection
• percutaneous coronary intervention
• postconditioning
• preconditioning

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Reperfusion of an occluded coronary artery is the standard of care to salvage the myocardial tissue from ischemic death. However, ischemia–reperfusion injury continues to be a barrier from reaping full benefits of such efforts. Ischemia–reperfusion injury also occurs during cardiac surgery because of the artificially induced ischemia by aortic cross-clamping as a result of incompletely or inconsistently delivered cardioplegia.

• Ischemia–reperfusion injury encompasses the sequence of cellular mechanisms that take place after the ischemic tissue gets reperfused contributing to further tissue damage.

• In the past couple of decades, many modalities of myocardial protection, including non-pharmacologic intervention and pharmacologic intervention, have been studied.

• Some of the non-pharmacologic interventions include hypothermia, mechanical ischemic preconditioning and mechanical postconditioning.

• Some of the pharmacologic interventions include caspase inhibitors (suppressing apoptosis), cariporide (sodium–hydrogen exchange inhibitors), adenosine, cyclosporine, phosphodiesterase-5 inhibitors, erythropoietin and protein kinase C inhibitors.

• Many of these therapies have shown success in minimizing the damage from ischemia–reperfusion injury either in animal models or in small clinical trials.

• However, larger multicenter studies have failed to consistently confirm the encouraging preliminary results and none of the interventions are routinely used in clinical practice, with the exception of hypothermia in cardiac surgery.

• The reasons for this are unclear and various explanations are offered.