The National Heart, Lung, and Blood Institute convened a Workshop on September 20-21, 2010, "New Horizons in Cardioprotection," to identify future research directions for cardioprotection against
ischemia and
reperfusion injury. Since the early 1970s, there has been evidence that the size of a
myocardial infarction could be altered by various interventions. Early coronary artery reperfusion has been an intervention that consistently reduces
myocardial infarct size in animal models as well as humans. Most cardiologists agree that the best way to treat acute
ST-segment elevation myocardial infarction is to reperfuse the
infarct artery as soon as possible and to keep the
infarct artery patent. In general, stenting is superior to angioplasty, which is superior to thrombolysis. There is no accepted adjunctive
therapy to acutely limit
myocardial infarct size along with reperfusion that is routinely used in clinical practice. In the Kloner experimental laboratory, some adjunctive
therapies have reproducibly limited
infarct size (regional
hypothermia, preconditioning,
cariporide, combinations of the above, remote preconditioning, certain
adenosine agonists, and late
sodium current blockade). In clinical trials, a host of pharmacologic adjunctive
therapies have failed to either reduce
infarct size or improve clinical outcome. Potential reasons for the failure of these trials are discussed. However, some adjunctive
therapies have shown promise in data subanalyses or subpopulations of clinical trials (
adenosine,
therapeutic hypothermia, and hyperoxemic reperfusion) or in small clinical trials (
atrial natriuretic peptide,
ischemic postconditioning, and
cyclosporine, the
mitochondrial permeability transition pore inhibitor). A recent clinical trial with remote conditioning induced by repetitive inflation of a brachial artery cuff begun prior to hospitalization showed promise in improving myocardial salvage and there are several reports in the cardiothoracic literature, suggesting that remote preconditioning protects hearts during surgery. Thus, in 2011, there is hope that applying some of the body's own conditioning mechanisms may provide protection against ischemic damage.