Importance of the Functional Integrity of the Endothelium in Coronary Vasomotion in Humans

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Abstract
Summary: Although our understanding of endothelial function has been substantially expanded by numerous experimental studies since the discovery of endothelium-derived relaxing factor (EDRF), the functional significance of endothelial function in humans, in particular in the coronary circulation, remained elusive. Recently, the application of new interventional catheter technology and accurate quantitative coronary angiography has set the stage for evaluating the potential functional importance of the endothelium of coronary arteries in humans. Intracoronary application of acetylcholine has been shown to provide a useful tool for identifying coronary endothelial dysfunction, i.e., modest coronary vasodilatation in normal subjects but paradoxical vasoconstriction in atherosclerosis. Sympathetic stimulation by cold pressor test exactly mirrors the response to acetylcholine in normal and atherosclerotic coronary arteries but not in hypercholesterolemia. Flow-dependent dilation can be demonstrated in human coronary arteries in vivo and may play a modulatory role in coronary vasomotor tone; however, this dilation in response to increased flow is impaired in angiographically visible atherosclerosis. By measuring the blood flow response to acetylcholine (and papaverine as a nonspecific dilator), the endothelial function of the coronary microvasculature can be assessed, demonstrating that endothelial function of the coronary microvas-culature is substantially depressed in hypercholesterolemia. This may impair coronary perfusion and could facilitate platelet aggregation in the microcirculation. Thus, evaluation of endothelial function provides a useful tool for identification of early functional vascular abnormalities (both of epicardial coronary arteries and the microcirculation) at a stage not detectable by coronary angiography. This should allow the elucidation of therapeutic interventions that are able to prevent the progression of atherosclerosis at an early stage rather than late, when the efficacy of such a treatment appears to be limited.

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