CONSTRICTOR AND DILATOR RESPONSES TO INTRACORONARY ACETYLCHOLINE IN ADJACENT SEGMENTS OF THE SAME CORONARY-ARTERY IN PATIENTS WITH CORONARY-ARTERY DISEASE - ENDOTHELIAL FUNCTION REVISITED

Background In patients with angiographically detectable atherosclerosi s or in those with risk factors for coronary artery disease, intracoro nary acetylcholine causes coronary constriction instead of endothelium -derived relaxing factor-mediated dilation. Therefore, it has been hyp othesized that diffuse endothelial dysfunction precedes development of coronary atherosclerosis. We tested this hypothesis in a systematic i nvestigation of the effects of ascending doses of acetylcholine on the diameters of nonstenotic segments of the left coronary artery in pati ents with advanced atherosclerosis and coronary risk factors. Methods and Results Effects of intracoronary infusion of acetylcholine (10(-6) to 10(-4) mol/L) on diameters of proximal, middle, and distal nonsten otic segments of the left coronary artery were studied in 28 consecuti ve patients with chronic stable angina, positive exercise tests, and a ngiographic evidence of obstructive atherosclerosis (greater than or e qual to 150% reduction in lumen diameter in at least one vessel). Two patterns of response to the maximal acetylcholine dose (10(-4) mol/L) were observed. In 21 patients (group 1), only constriction was observe d in ah left anterior descending and circumflex artery segments studie d (16+/-3%, 19+/-4%, and 23+/-4%, respectively; P<.01 compared with co ntrol). In 7 other patients (group 2), both constriction and dilation were observed in adjacent segments of the same vessel; maximal acetylc holine dose caused constriction in 14 left anterior descending artery segments from a control diameter of 1.94+/-0.19 to 1.33+/-0.26 mm (37% reduction, P<.01) and dilation in 16 other segments from 1.63+/-0.22 to 1.93+/-0.21 mm (25% increase, P<.01). In the circumflex artery, thi s dose caused constriction in 16 segments from a control diameter of 1 .88+/-0.14 to 1.33+/-0.17 mm (31% reduction, P<.01) and dilation in 12 segments from 1.37+/-0.12 to 1.71+/-0.09 mm (34% increase, P<.01). Co nclusions In 25% of patients studied with advanced angiographic corona ry atherosclerosis and coronary risk factors, coronary segments with a cetylcholine-inducible dilatation are present. In these patients, the endothelium is not diffusely dysfunctional as currently believed but r ather shows marked segmental heterogeneity in the response to acetylch oline reflecting degrees of endothelial dysfunction.