RESPONSE OF HUMAN CORONARY-ARTERIES TO ACETYLCHOLINE AFTER INJURY BY CORONARY ANGIOPLASTY

Objectives. The aim of this study was to investigate the effect of intracoronary administration of acetylcholine on large epicardial vessels 8 days after successful coronary angioplasty. Background. Intracoronary infusion of acetylcholine causes vessel dilation in patients without angiographic evidence of coronary atherosclerosis, whereas it causes constriction of stenotic coronary branches. These findings were interpreted as evidence of endothelial dysfunction in patients with coronary atherosclerosis. Methods. Eight patients who underwent successful single-vessel coronary angioplasty of the proximal left anterior descending artery were studied. Eight days after coronary angioplasty at the time of follow-up coronary angiography, intracoronary acetylcholine was infused (1 nl/min for 2 min) at concentrations ranging from 10(-7) to 10(-4) mol/liter. The diameter of the angioplasty and distal segments of the left anterior descending artery and that of the proximal and distal segments of the circumflex artery (control artery) were measured using computerized edge detection angiography. Results. All patients showed a dose-dependent constriction in response to acetylcholine and experienced chest pain and ST segment changes. Intracoronary nitroglycerin (300 mug) relieved the effects of acetylcholine. The maximal tolerated dose of acetylcholine (10(-6) mol/liter in three patients, 10(-5) mol/liter in three patients and 10(-4) mol/liter in two patients) induced a mild constriction of the angioplasty segment from 1.84 +/- 0.11 mm to 1.52 +/- 0.13 mm (p < 0.02) similar to that of the proximal segment of the control artery (from 2.42 +/- 0.23 to 2.07 +/- 0.19 mm, p < 0.02). However, the degree of constriction of the vascular segments distal to the angioplasty site (from 1.24 +/- 0.09 to 0.62 +/-0.13 mm, p < 0.01) was significantly greater (p < 0.05) than that observed in the distal segments of the control artery (from 1.23 +/-0.03 to 0.71 +/- 0.01 mm, p < 0.01) and resulted in transient total occlusion in two patients. Conclusions. Eight days after coronary angioplasty, coronary segments distal to the dilated site but not at the dilated site are hyperreactive to acetylcholine. The response of epicardial coronary arteries to acetylcholine is influenced not only by the dose of acetylcholine and the endothelial function (as currently believed) but also by the location of the coronary segment considered, confirming the presence of a profound alteration of distal coronary vessels.