Circulation, Vol 89, 45-51, Copyright © 1994 by American Heart Association
H el-Tamimi, M Mansour, TJ Wargovich, JA Hill, RA Kerensky, CR Conti and CJ Pepine
BACKGROUND: In patients with angiographically detectable atherosclerosis or
in those with risk factors for coronary artery disease, intracoronary
acetylcholine causes coronary constriction instead of endothelium-derived
relaxing factor-mediated dilation. Therefore, it has been hypothesized that
diffuse endothelial dysfunction precedes development of coronary
atherosclerosis. We tested this hypothesis in a systematic investigation of
the effects of ascending doses of acetylcholine on the diameters of
nonstenotic segments of the left coronary artery in patients 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 nonstenotic segments of the left
coronary artery were studied in 28 consecutive patients with chronic stable
angina, positive exercise tests, and angiographic evidence of obstructive
atherosclerosis (> or = 50% 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
observed in all left anterior descending and circumflex artery segments
studied (16 +/- 3%, 19 +/- 4%, and 23 +/- 4%, respectively; P < .01
compared with control). In 7 other patients (group 2), both constriction
and dilation were observed in adjacent segments of the same vessel; maximal
acetylcholine 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, this 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). CONCLUSIONS: In 25% of patients studied with
advanced angiographic coronary atherosclerosis and coronary risk factors,
coronary segments with acetylcholine-inducible dilatation are present. In
these patients, the endothelium is not diffusely dysfunctional as currently
believed but rather shows marked segmental heterogeneity in the response to
acetylcholine reflecting degrees of endothelial dysfunction.
ARTICLES
Constrictor and dilator responses to intracoronary acetylcholine in adjacent segments of the same coronary artery in patients with coronary artery disease. Endothelial function revisited
Division of Cardiology, University of Florida, Gainesville 32610-0277.
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