Document Detail

Responses of coronary arteries of cardiac transplant patients to acetylcholine.
MedLine Citation:
PMID:  3121675     Owner:  NLM     Status:  MEDLINE    
Accelerated coronary atherosclerosis is a major cause of graft failure after heart transplantation. Graft atherosclerosis is typically diffuse and difficult to detect even with coronary arteriography. Recently, acetylcholine was shown to dilate blood vessels by releasing a vasorelaxant substance from the endothelium (endothelium-derived relaxing factor). We have demonstrated paradoxical vasoconstriction induced by acetylcholine both early and late in the course of coronary atherosclerosis in patients, suggesting an association of endothelial dysfunction and atherosclerosis. In this report, we tested the hypothesis that coronary arteries of heart transplant patients can show endothelial dysfunction before or in the early stages of angiographically evident coronary atherosclerosis. Acetylcholine was infused into the left anterior descending artery of 13 heart transplant patients at 12 (n = 9) and 24 (n = 4) mo after transplantation. Vascular responses were evaluated by quantitative angiography. Among patients with angiographically smooth coronary arteries, relatively few (6/25) arterial segments had preserved vasodilator responses, while the majority failed to dilate (10/25) or paradoxically constricted (9/25). Angiographically irregular coronary arteries were present in three patients, in whom 8/10 segments showed marked paradoxical constriction and the remaining 2/10 failed to dilate. Only 1 of 13 patients retained appropriate dilation to acetylcholine in all segments. Nitroglycerin, which acts directly on vascular smooth muscle, dilated nearly all segments. No clinical features of the patients, including myocardial rejection appeared to correlate with the impaired functional response of vessels. Thus impaired response to acetylcholine is a common early finding in heart transplant patients and emphasizes the potential importance of endothelial dysfunction in the development of atherosclerosis.
R D Fish; E G Nabel; A P Selwyn; P L Ludmer; G H Mudge; J M Kirshenbaum; F J Schoen; R W Alexander; P Ganz
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  81     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1988 Jan 
Date Detail:
Created Date:  1988-02-09     Completed Date:  1988-02-09     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  21-31     Citation Subset:  AIM; IM    
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
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MeSH Terms
Acetylcholine / pharmacology*
Coronary Angiography
Coronary Artery Disease / etiology,  physiopathology,  radiography
Coronary Vessels / drug effects*,  physiopathology
Heart Transplantation*
Hemodynamics / drug effects
Middle Aged
Nitroglycerin / pharmacology
Transplantation, Homologous / adverse effects
Vasodilator Agents / pharmacology*
Grant Support
Reg. No./Substance:
0/Vasodilator Agents; 51-84-3/Acetylcholine; 55-63-0/Nitroglycerin

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