Circulation, Vol 83, 391-401, Copyright © 1991 by American Heart Association
AM Zeiher, H Drexler, H Wollschlager and H Just
The endothelium plays a critical role in the control of vasomotor tone by
the release of vasoactive substances. Because endothelial injury or
dysfunction is considered important very early in atherogenesis, we
hypothesized that abnormal endothelial function precedes the angiographic
detection of coronary atherosclerosis in the human coronary circulation.
The coronary vasomotor responses to three different endothelium-mediated
stimuli (intracoronary infusion of acetylcholine 10(-8) to 10(-6) M,
increase in blood flow to induce flow- dependent dilation, and sympathetic
stimulation by cold pressor testing) were assessed by quantitative
angiography and subselective intracoronary Doppler flow velocity
measurements within the left anterior descending coronary artery in 38
patients. All three stimuli elicited epicardial artery dilation in all 11
patients with smooth coronary arteries and absence of risk factors for
coronary artery disease (group 1). All nine patients with smooth coronary
arteries but with hypercholesterolemia (group 2) demonstrated a selective
impairment in endothelial function with vasoconstriction (35 +/- 12.7%
decrease in mean luminal area) in response to acetylcholine but showed a
preserved flow-dependent dilation (15.5 +/- 4.4% increase in mean luminal
area) and vasodilation in response to cold pressor testing (14.2 +/- 4.6%
increase in mean luminal area). In all nine patients with an
angiographically defined smooth coronary artery segment but with evidence
of atherosclerosis elsewhere in the coronary system (group 3), both
acetylcholine and cold pressor testing induced vasoconstriction (26.2 +/-
8.7% and 18.7 +/- 7.9% decrease in mean luminal area, respectively),
whereas flow-dependent dilation was preserved (20.4 +/- 8.7% increase in
mean luminal area). In the nine patients with angiographic evidence of wall
irregularities (group 4), flow-dependent dilation was also abolished and
vasoconstriction occurred in response to acetylcholine and cold pressor
testing (34.5 +/- 10.7% and 19.9 +/- 6.3% decrease in mean luminal area,
respectively). All coronary artery segments dilated in response to
nitroglycerin, suggesting preserved function of vascular smooth muscle.
Despite similar reductions in coronary vascular resistance in response to
the smooth muscle relaxant papaverin, patients with hypercholesterolemia
demonstrated a selective impairment of vasodilation of the resistance
vasculature in response to acetylcholine (p less than 0.05 versus groups 1,
3, and 4). Thus, there is a progressive impairment of endothelial
vasoactive functioning in coronary arteries of patients with different
early stages of atherosclerosis, beginning with a selective endothelial
dysfunction in angiographically defined normal arteries in patients with
hypercholesterolemia and progressively worsening to a complete loss of
endothelium-mediated vasodilation in angiographically defined
atherosclerotic coronary arteries.(ABSTRACT TRUNCATED AT 400 WORDS)
ARTICLES
Modulation of coronary vasomotor tone in humans. Progressive endothelial dysfunction with different early stages of coronary atherosclerosis
Department of Cardiology, University of Freiburg, FRG.
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