Acetylcholine-induced constriction of angiographically normal coronary arteries is not time dependent in transplant recipients. Effects of stepwise infusion at 1, 6, 12 and more than 24 months after transplantation.
OBJECTIVE
The aim of this study was to evaluate whether acetylcholine may be a useful tool for detection of early angiographically undetectable coronary atherosclerosis in heart transplant recipients.


BACKGROUND
Coronary artery disease is the main determinant of long-term prognosis in transplant recipients. Acetylcholine-induced constriction of angiographically normal coronary arteries in heart transplant recipients could be due to early atherosclerosis, and acetylcholine has been proposed for early detection of coronary artery disease.


METHODS
The responses of large coronary arteries to stepwise intracoronary infusion of acetylcholine (10(-8) to 10(-5) mol/liter) were compared in five control subjects and in four groups of transplant recipients 1, 6, 12 and > 24 months postoperatively (group 1, n = 6; group 2, n = 7; group 3, n = 6; group 4, n = 6, respectively). All patients had normal coronary arteriographic findings. Vessel dimensions were measured in four segments in each patient.


RESULTS
In control subjects, acetylcholine increased diameters significantly at 10(-8), 10(-7) and 10(-6) mol/liter (all p < 0.001 vs. basal value). No significant variation was observed at 10(-5) mol/liter. Intracoronary isosorbide dinitrate increased diameters of all segments (p < 0.001). In transplant recipients, vessel diameters did not vary significantly from baseline at 10(-8) and 10(-7) mol/liter concentrations in groups 1 and 3 and at 10(-8) mol/liter in group 4. Vessels constricted significantly in all the other cases. Comparisons of each group with control subjects showed that responses were significantly different for all concentrations but 10(-8) mol/liter in groups 3 and 4. Intracoronary isosorbide dinitrate elicited coronary vasodilation similar to that of control subjects in all groups of transplant recipients.


CONCLUSIONS
This study indicates that the acetylcholine response is persistently abnormal in transplant recipients compared with that in normal control subjects and that this abnormality may not be related simply to the presence of atherosclerosis. Thus, acetylcholine may not be a useful tool for early detection of coronary atherosclerosis in heart transplant recipients.
Service d'Explorations Fonctionnelles, CHU Xavier-Bichat, Paris, France.
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A
Nitenberg
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Benvenuti
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Aptecar
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I
Antony
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Deleuze
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Loisance
J P
JP
Cachera
D000109:Acetylcholine; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000175:diagnosis*; D003331:Coronary Vessels / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D016027:Heart Transplantation / Q000502:physiology*; D006801:Humans; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects*
D007548:Isosorbide Dinitrate; D000109:Acetylcholine