Reperfusion-induced coronary endothelial injury: A new target for ischemic preconditioning.

Although cardiac ischemia-reperfusion is well known as a disease of the myocytes, it is now clear that the consequences of this disease also extend to the vascular wall and especially to the endothelium. A rat model of ischemia-reperfusion in vivo was used to detect severe endothelial dysfunction characterized by a decreased nitric oxide (NO)-dependent relaxation to acetylcholine in isolated coronary arteries. Given the essential role of the endothelium and NO in the regulation of vascular tone, protection of the coronary endothelial cells is an important therapeutic target. For this purpose, a focus on the concept of endogenous protection against ischemia, ie, preconditioning, showed that endothelial dysfunction could be reversed by both the early and the delayed phase of preconditioning. With regard to the mechanisms of the coronaroprotective effects of preconditioning, it was shown that both free radicals and NO seem to have an important triggering role, leading to a delayed increase in NO production and decreased adhesion of neutrophils to endothelial cells. Identification of the precise triggers and mediators of this protection will allow the development of new therapeutic agents targeting both the myocardium and the coronary vasculature.