Coronary artery blood how: Physiologic and pathophysiologic regulation

Abstract

Summary: Acute myocardial ischemia, which results from a significant imbalance between myocardial oxygen demands and myocardial oxygen supply, occurs in as many as six million persons with atherosclerotic coronary artery disease in the United States. Accordingly, a clear understanding of the physiologic and pathophysiologic factors that influence coronary artery blood flow is important to the clinician and provides the basis for the judicious use of medications for the treatment of patients with atherosclerotic coronary artery disease. This review discusses the endothelial, metablic, myogenic, and neurohumoral mechanisms of coronary blood flow regulation and the interaction of the different mechanisms in the regulation of coronary blood flow. The importance of nitric oxide in coronary blood flow regulation is emphasized. We also discuss the common clinical problems of hyperlipidemia and coronary atherosclerosis, coronary artery spasm, and systemic arterial hypertension that result in coronary artery endothelial dysfunction, the impaired production and increased inactivation of nitric oxide, and impairment in coronary blood flow regulation. This information is important to clinicians because more than forty million people in the United States have atherosclerotic or hypertensive heart disease and therefore are at risk for significant myocardial complications due to impairment of coronary blood flow regulation.

Nitric oxide and coronary vascular endothelium adaptations in hypertension

“…As might be expected from the known dependency of vasomotor control mechanisms on the position of a given vessel type in the vascular tree, 2,5,6 the distribution of the eNOS protein is likewise not uniform throughout the coronary vasculature of normal healthy hearts. Laughlin and colleagues demonstrated a reduced eNOS protein content per mg total vessel protein in the smallest porcine coronary resistance arteries (50 µM) compared to larger coronary arteries, despite a large reduction in the smooth muscle cell-to-endothelial cell ratio as coronary artery diameter decreases.…”

“…104 The reported expression pattern for eNOS is consistent with a greater dependence on NO-mediated, endothelium-dependent dilation in larger arteries compared to the smallest arterioles. 2,5,6 The coronary artery is characterized by asynchronous hemodynamics, wherein the wall shear stress from blood flow is out of phase with the circumferential strain from blood pressure 105 and this may play a role in determining the heterogeneous eNOS expression in the coronary arterial tree. 106,107 Further support for the role of hemodynamics in eNOS protein expression comes from studies in miniature swine following prolonged aerobic exercise training.…”

“…Several reports have suggested that altered NO bioavailability contributes to altered vasomotion seen in hypertension 38,47,48 and NO is the primary dilator of large epicardial coronary arteries 3,6,49 as well as a mediator of flowinduced dilation in the coronary microcirculation. 2,5,6 Given the potential importance of the NO system in the etiology of hypertensive large artery disease, and given the fact that studies in other vascular beds have revealed a number of patterns of regulation of the NO system, the importance of which is not known in the coronary bed and in hypertension, it is important to bring attention to these factors as they may be important clinically and therapeutically.…”

“…2,5,6 Given the potential importance of the NO system in the etiology of hypertensive large artery disease, and given the fact that studies in other vascular beds have revealed a number of patterns of regulation of the NO system, the importance of which is not known in the coronary bed and in hypertension, it is important to bring attention to these factors as they may be important clinically and therapeutically. Thus, this review attempts to highlight a number of factors that influence NO function and which may be relevant from both basic science and clinical perspectives of understanding the function of the coronary circulation in hypertension.…”

The imbalance between coronary reserve and wall stress explains the severity of ventricular dysfunction in hypertension

“…The underestimation of coronary reserve that might have resulted seems of little magnitude, since major coronary arteries make only a minor contribution to coronary resistance. 36 Also, continuous intravenous adenosine appears not to be associated with a substantial flow-mediated increase in the luminal diameter of epicardial coronary arteries. 37 Apart from not controlling for coronary epicardial diameter, the assessment of coronary dynamics by transesophageal Doppler echocardiography precludes the examination of endothelial function in the coronary bed, for which intracoronary studies are required.…”