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Circulation, Vol 86, 1864-1871, Copyright © 1992 by American Heart Association
AA Quyyumi, RO Cannon 3d, JA Panza, JG Diodati and SE Epstein
BACKGROUND. A subgroup of patients with chest pain and angiographically
normal epicardial coronary arteries have reduced dilator response to
metabolic or pharmacological stimuli, but the mechanisms responsible for
this reduced dilator response are unknown. In this study, we have
investigated whether microvascular endothelial dysfunction is a cause of
the observed reduced vasodilator reserve. METHODS AND RESULTS. The
functional response of the microvasculature was studied with rapid atrial
pacing at 150 beats per minute. Fifty-one patients, 20 hypertensive and 31
normotensive, with chest pain and normal epicardial coronary arteries (<
10% stenosis) were studied. Endothelial function was tested with
incremental infusions of acetylcholine to achieve estimated intracoronary
concentrations ranging from 10(-7) M to 10(-5) M. Endothelium-independent
smooth muscle vasomotion was measured using intracoronary sodium
nitroprusside. Endothelial dysfunction of epicardial coronary arteries,
demonstrated as severe (> 50%) constriction with < 10(-5) M
acetylcholine concentration, was evident in five patients (10%). In the
remaining 46 patients, coronary blood flow increased with acetylcholine
(mean, 78 +/- 43%) and atrial pacing (mean, 51 +/- 37%), and coronary
vascular resistance decreased by 35 +/- 16% and 29 +/- 14%, respectively,
but the responses were heterogeneous. There was a correlation between the
coronary resistance change with acetylcholine and the change with atrial
pacing: r = 0.68, p < 0.001 in these 46 patients. Thus, patients with
depressed dilation with atrial pacing had reduced endothelium-dependent
dilation with acetylcholine, and vice versa. However, the microvascular
dilation caused by sodium nitroprusside was not significantly different
between patients with and those without reduced dilation with atrial
pacing, indicating that the vasodilator defect was not caused by smooth
muscle dysfunction. There were no differences in the vasodilator responses
with atrial pacing, acetylcholine, or nitroprusside between normotensive
and hypertensive patients. Multivariate regression analysis was performed
to determine whether age, sex, serum cholesterol level, hypertension,
presence of mild epicardial vessel atherosclerosis, resting left
ventricular function, change in left ventricular ejection fraction with
exercise, vasodilation with acetylcholine, and vasodilation with sodium
nitroprusside were independently related to the vasodilator response to
atrial pacing. Only the change in coronary vascular resistance with
acetylcholine was independently correlated with the change in resistance
with atrial pacing: R2 = 0.46, p < 0.0001. CONCLUSIONS. Patients with
chest pain, normal epicardial coronary arteries, and reduced vasodilation
in response to atrial pacing appear to have associated endothelial
dysfunction of the coronary microvasculature. Thus, microvascular
endothelial dysfunction may contribute to the reduced vasodilator reserve
with atrial pacing and anginal chest pain in these patients.
ARTICLES
Endothelial dysfunction in patients with chest pain and normal coronary arteries
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
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