Circulation, Vol 89, 1615-1623, Copyright © 1994 by American Heart Association
H Drexler, TA Fischell, FJ Pinto, A Chenzbraun, J Botas, JP Cooke and EL Alderman
BACKGROUND: Coronary endothelial vasodilator dysfunction is a common
finding in cardiac transplant recipients and may represent an early marker
for the development of intimal thickening and graft atherosclerosis. The
present study tested the hypothesis that endothelial dysfunction precedes
intimal thickening and that administration of L-arginine, the precursor of
endothelium-derived relaxing factor, improves endothelial vasodilator
function of coronary conduit and resistance vessels if given at an early
stage of graft atherosclerosis. METHODS AND RESULTS: Acetylcholine (10(-6),
10(-5), 10(-4) mol/L) was infused into the left anterior descending or
circumflex artery and repeated after intravenous infusion of L-arginine (10
mg.kg-1.min-1 over 20 minutes) in 18 cardiac transplant recipients.
Epicardial responses were evaluated by quantitative angiography, and the
microcirculation was studied by determination of coronary blood flow with a
Doppler flow velocity wire. Intimal thickening was assessed by
intravascular ultrasound (n = 14). In epicardial coronary arteries,
acetylcholine tended to elicit vasoconstriction. Epicardial coronary
vasoconstriction elicited by acetylcholine was attenuated by infusion of
L-arginine (10(-4) mol/L, -6.8% versus -2.8%; P < .01); this beneficial
effect was observed predominantly in patients with normal intravascular
ultrasound characteristics. In coronary resistance vessels, acetylcholine
induced vasodilation, reflected by increases in coronary blood flow. The
acetylcholine-induced increase in blood flow was significantly enhanced
with L-arginine (at a dose of 10(-4) mol/L, + 121% versus 176%; before
versus after L-arginine, P < .002). CONCLUSIONS: The coronary
vasculature of cardiac transplant recipients exhibits a generalized
endothelial dysfunction of conduit and resistance vessels. L-Arginine
improves endothelial dysfunction of both coronary microvasculature and
epicardial coronary arteries. The reversibility of epicardial endothelial
dysfunction by L-arginine is more likely in vessels with normal wall
morphology.
ARTICLES
Effect of L-arginine on coronary endothelial function in cardiac transplant recipients. Relation to vessel wall morphology
Stanford University School of Medicine, Division of Cardiovascular Medicine, Calif.
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