LOCAL AND NEUROHUMORAL CONTROL OF CORONARY BLOOD-FLOW

The powerful local metabolic regulation adjusting coronary blood flow to myocardial oxygen consumption under normal conditions is beyond dou bt. However, despite substantial experimental efforts the responsible mediators are still largely unknown. Adenosine, a purported mediator o f local metabolic control of coronary blood flow, is probably only inv olved in transient flow adaptations, but not in steady-state coronary autoregulation. Even below the autoregulatory range a substantial vaso dilator reserve persists. Recruitment of such vasodilator reserve resu lts in improved regional myocardial blood flow and attenuated regional ischemic dysfunction. Beta-adrenergic coronary dilation is of minor f unctional importance. Alpha-adrenergic coronary constriction acts to a ttenuate increases in coronary blood flow during sympathetic activatio n under normal conditions, such that myocardial oxygen extraction incr eases to match the increased oxygen consumption. Alpha-adrenergic coro nary constriction remains operative in ischemic myocardium, thus preci pitating or contributing to acute myocardial ischemia during sympathet ic activation and exercise in experimental animals as well as in patie nts with stable angina. The vagal transmitter acetylcholine - upon exo genous intracoronary infusion - induces critical constriction of epica rdial coronary arteries with endothelial dysfunction and atheroscleros is. However, a vagal initiation of coronary spasm or myocardial ischem ia has not been documented so far. Similarly, peptide hormones/transmi tters such as NPY, vasopressin, and angiotensin can induce myocardial ischemia upon exogenous administration. Their pathophysiological role in myocardial ischemia and reperfusion, however, remains to be establi shed.