Dedicated to Prof Dr. Franz Loogen on the occasion of his 70th birthday c-Adrenoceptor-mediated effects of sympathetic activation on the heart and coronary circulation are reviewed with emphasis on the pathophysiology of myocardial ischemia. A classification of a-adrenoceptor subtypes is presented, and the effects of a-adrenoceptor activation on presynaptic sympathetic nerve terminals, cardiomyocytes, endothelium, platelets, and coronary smooth muscle cells are discussed. av-Adrenergic coronary vasoconstriction at rest and during situations of sympathetic activation such as exercise and excitement is analyzed for the segmental, transmural, and regional distribution of coronary blood flow. Evidence for a significant contribution of av-adrenergic coronary vasoconstriction to experimental and clinical myocardial ischemia is provided. Cardiomyocyte a-adrenoceptor activation may be involved in ischemic and reperfusion arrhythmias. The participation of presynaptic and postsynaptic aadrenoceptors, as well as of ael-and a2-adrenoceptors, in experimental and clinical myocardial ischemia will require further investigation. (Circulation 1990;81:1-13) D uring the sympathetic activation induced by exercise or excitement, the activity of cardiac sympathetic nerves, as well as the release of circulating catecholamines, is enhanced. The resultant activation of cardiac 83-adrenoceptors by neuronal and humoral catecholamines mediates an increase in heart rate and myocardial inotropic state, thereby increasing myocardial oxygen demand. Increased oxygen demand is adequately matched by an augmented oxygen supply after metabolic dilation of the coronary vasculature under normal conditions.' However, the direct effect of the sympathetic neurotransmitter norepinephrine on coronary vascular smooth muscle cells is vasoconstriction through activation of a-adrenoceptors. Even when under normal conditions a substantial coronary dilator reserve is present, a-adrenergic constriction acts to limit metabolic coronary dilation by about 30%, such that myocardial oxygen extraction increases together with coronary blood flow during sympathetic activation to match oxygen supply to the increased myocardial oxygen demand.2-4