Regulation of coronary blood flow: coordination of heterogeneous control mechanisms in vascular microdomains
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The technology is available for the study of the coronary microcirculation in vivo and in vitro. Coronary microvascular resistance depends continually upon intrinsic and extrinsic regulatory influences operating on different vascular microdomains. These regulatory influences are (1) a predominant metabolic influence of multifactorial aetiology (this mechanism is poorly understood); (2) myogenic responsiveness to pressure; (3) endothelium dependent dilatation in response to flow and agonists; and (4) neurohumoral factors. The diameter of a microvessel, and thus the resistance it poses to flow, depends upon local interactions between regulatory mechanisms and also on distant interactions mediated by the effects of transmitted flow and pressure. Distant interactions occur mainly because of a strong capacity for autoregulatory adjustments in the diameter of microvessels of less than 100 m in diameter. The coronary circulation matches blood flow with oxygen demands by coordinating the resistances within various vascular microdomains, each governed by distinct regulatory mechanisms. Such integration appears advantageous, because the system does not rely on a single mechanism for control.Functional abnormalities of the coronary microcirculation are recognised in disease states including hypercholesterolaemia, atherosclerosis, hypertension, and heart failure. Endothelial dysfunction, marked by reduced release of EDRF, has been described in each of these conditions. The overall consequence of coronary vascular pathology seems likely to be inadequate matching of oxygen and nutrient supply to changing myocardial metabolic demand. One possible reason for the pathophysiological sequelae associated with ischaemic heart disease may be a loss of regulatory mechanisms involved in coronary vasomotor adjustments. As stated above, it appears advantageous to have multiple control mechanisms involved in the regulation of coronary vascular resistance, but if a pathological process renders a mechanism dysfunctional, there is a reduction in "regulatory mechanism reserve." The potential consequence would be that fewer mechanisms could be recruited for an adjustment of coronary vasomotor tone during physiological and pathophysiological stresses. Perhaps a loss of vasoactive compensatory mechanisms accounts in part for the vulnerability of the coronary circulation in disease states. Finally, we are compelled to emphasise that adjustments in microvascular tone have a significant impact on vasodilator reserve of coronary resistance vessels. It appears that interventions that normally reduce coronary blood flow and oxygen delivery (reductions in perfusion pressure, for example, coronary stenosis; vasoconstrictors, for example, adrenergic agonists, NO synthase inhibitors) are compensated for by "vasodilator escape" of coronary arterioles. The consequence of this compensatory mechanism is a reduction in the remaining vasodilator reserve, that is, blunting of the remaining mechanisms. Perhaps also this contributes to the augmented effects of constrictors in patients with ischaemic heart disease.
