SYMPATHETIC-STIMULATION OVERRIDES FLOW-MEDIATED ENDOTHELIUM-DEPENDENTEPICARDIAL CORONARY VASODILATION IN TRANSPLANT PATIENTS

Background Abnormal coronary vasomotor responses have been described i n transplant patients. The aim of this study was to evaluate the graft epicardial vasomotor responses to different stimuli that increase cor onary blood flow. Methods and Results Twelve heart transplant recipien ts with angiographically normal epicardial coronary arteries were comp ared 2.7+/-1.2 months after surgery with 6 control subjects. Coronary Bow velocity was measured with a guidewire Doppler. Coronary diameter changes of the proximal and midportion of the left anterior descending coronary artery were assessed by quantitative coronary angiography du ring rapid atrial pacing, cold pressor test, supine exercise, and subs elective infusion of papaverine and after intracoronary injection of l insidomine (SIN-1). Catecholamine plasmatic levels were determined at the different stages of the protocol. In 6 other transplant patients, a cold presser test was performed before and after intracoronary infus ion of phentolamine (10 mu g . kg(-1). min(-1)). Coronary flow velocit y increased significantly in both groups during each phase of the prot ocol. In control subjects, dilation was observed in response to atrial pacing (8.7+/-7.6%; P<.05), CPT (8.8+/-2.3%; P<.01), exercise (14.5+/ -9.4%; P<.001), and papaverine infusion (14.2+/-6.1%; P<.001) and afte r injection of SIN-1 (26.8+/-11.9%; P<.001). In transplant patients, s imilar dilation was observed during atrial pacing (8.2+/-8.3%; P<.05) and papaverine infusion (14.6+/-7.8%; P<.001) and after SIN-1 (25.8+/- 10.8%; P<.001). CPT and exercise caused slight constriction (-3.5+/-4. 5% and -2.7+/-10.5%, respectively; both P<.001 versus control subjects ). Norepinephrine plasmatic levels increased in both groups during CPT and exercise. Slight constriction during the cold pressor test (-4.5/-9.6%) changed to dilation (6.8+/-7.0%) after a blockade with phentol amine (P<.001). Conclusions These results show that flow-mediated, end othelium-dependent vasodilation is preserved early after transplantati on. Sympathetic stimulation, which overrides the endothelium-dependent mechanism, can be related to hypersensitivity to catecholamines due t o denervation.