Exercise training in coronary artery disease and coronary vasomotion

Exercise training has assumed a major role in cardiac rehabilitation, mostl y because of its positive effects on myocardial perfusion in patients with coronary artery disease. The mechanisms involved in mediating this key effe ct have long been debated: both regression of coronary artery stenosis and improvement of collateralization have been suggested as potential adaptatio ns. However, the comparatively minute changes in luminal diameter and myoca rdial contrast staining do not fully explain the significant changes in myo cardial perfusion. During the last decade, endothelial dysfunction was iden tified as a trigger of myocardial ischemia. The impaired production of endo thelium-derived nitric oxide (NO) in response to acetylcholine and flow lea ds to paradoxic vasoconstriction and exercise-induced ischemia. Recently, i t was confirmed in humans that training attenuates paradoxic vasoconstricti on in coronary artery disease and increases coronary blood flow in response to acetylcholine. Data from cell-culture and animal experiments suggest th at shear stress acts as a stimulus for the endothelium to increase the tran sport capacity for L-arginine (the precursor molecule for NO), to enhance N O synthase activity and expression, and to increase the production of extra cellular superoxide dismutase, which prevents premature breakdown of NO. Ex ercise also affects the microcirculation, where it sensitizes resistance ar teries for the vasodilatory effects of adenosine. These novel findings prov ide a pathophysiological framework to explain the improvement of myocardial perfusion in the absence of changes in baseline coronary artery diameter. Because endothelial dysfunction has been identified as a predictor of coron ary events, exercise may contribute to the long-term reduction of cardiovas cular morbidity and mortality.