Alpha-adrenergic mechanisms in myocardial ischemia.

Abstract

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

Anaesthesia for coronary artery bypass surgery supplemented with subarachnoid bupivacaine and morphine: a report of 18 cases

“…These agents may have detrimental effects on the coronary circulation, bypass grafts, and other organs. [30][31][32] Studies using somatosensory-evoked potentials are underway to determine the extent and duration of the subarachnoid block. Given the small number of eligible patients at this institution, a multi-centre randomized trial of spinal anaesthesia for cardiac surgery may be warranted.…”

Comparison of the effects of EXP3174, an angiotensin II antagonist and enalaprilat on myocardial infarct size in anaesthetized dogs

“…Among the numerous factors contributing to ischaemiainduced myocardial damage during coronary artery occlusion, the increase in sympathetic tone and the release of catecholamines are known to play a major role (Schomig et al, 1984;Heusch, 1990). However, ischaemia-induced activation of the renin-angiotensin system may also contribute (Ertl, 1987;Ambrosioni & Borghi, 1989).…”

α-Adrenergic Coronary Vasoconstriction and Myocardial Ischemia in Humans

“…When the coronary circulation, however, is impaired by hypercholesterolemia, 3 endothelial dysfunction, 4 exhaustion of autoregulation, 5 or severe coronary stenosis, 6,7 ␣-adrenergic vasoconstriction becomes unrestrained and powerful enough to reduce coronary blood flow and initiate myocardial ischemia. 8 Both ␣ 1 -and ␣ 2 -adrenoceptors mediate coronary vasoconstriction, and there is a gradient with ␣ 1 -adrenoceptors more predominant in larger vessels and a reverse gradient with ␣ 2 -adrenoceptors more predominant in the microcirculation. 5,9 Surprisingly, isolated coronary arterioles of a size that constricts in vivo to ␣ 1 -adrenoceptor activation are unresponsive in vitro, 10 and cardiomyocytes on ␣ 1 -adrenergic activation release endothelin, which causes arteriolar constriction.…”