Ischemic conditioning: the challenge of protecting the diabetic heart

Cardiovascular disease (CVD) remains the leading cause of death in the United States and globally, with acute myocardial infarction (AMI) accounting for a substantial portion of CVD-associated mortality (1). Timely reperfusion is the standard clinical therapy for AMI and, although necessary to rescue ischemic tissue, restoration of blood flow can paradoxically exacerbate cell death (rather than initiate salvage) in populations of ischemic myocytes, a phenomenon termed lethal ischemia-reperfusion (I/R) injury (2-6). The volume of myocardium rendered necrotic following I/R (i.e., myocardial infarct size) is a primary determinant of mortality and morbidity associated with AMI (6-8). Indeed, decades of preclinical and clinical investigation have been devoted to: (I) elucidating the mechanisms of I/R injury, and (II) developing mechanisms-based therapies to augment the benefits of early reperfusion and reduce myocardial infarct size. Despite this substantial investment of time and resources, no advances have, to date, been successfully translated into clinical practice (8-10)