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

Objectives. 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.