Cardioprotection: nitric oxide, protein kinases, and mitochondria.

Over the past 2 to 3 decades, several phenomena have been identified that provide powerful protection against myocardial infarction and other sequelae of ischemia/reperfusion1: myocardial hibernation that is related to stunning,2 ischemic preconditioning,3 delayed or second-window ischemic preconditioning,4 ischemic postconditioning,5 and their pharmacological recruitment. Stunning and hibernation share contractile function as an end point. In stunning, reduced postischemic contractile function is viewed as reversible injury, whereas in hibernation dysfunction is viewed as an adaptive response. Ischemic preconditioning is characterized by infarct size reduction as its most robust end point but shares with hibernation the underlying idea of a regulated protective response. These phenomena have been confirmed in patients with coronary artery disease.2,6–8 Nitric oxide (NO) and mitochondria also are important in patients with coronary artery disease. Nitroglycerin induces delayed protection against periinterventional ischemic ECG alterations, contractile dysfunction, and pain sensation,7 and cyclosporin A, which inhibits opening of the mitochondrial permeability transition pore (MPTP), attenuates reperfusion injury in patients with acute myocardial infarction.9