Sympathetic stimulation overrides flow-mediated endothelium-dependent epicardial coronary vasodilation in transplant patients.

Abstract

Abnormal coronary vasomotor responses have been described in transplant patients. The aim of this study was to evaluate the graft epicardial vasomotor responses to different stimuli that increase coronary blood flow. Twelve heart transplant recipients with angiographically normal epicardial coronary arteries were compared 2.7 +/- 1.2 months after surgery with 6 control subjects. Coronary flow 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 during rapid atrial pacing, cold pressor test, supine exercise, and subselective infusion of papaverine and after intracoronary injection of linsidomine (SIN-1). Catecholamine plasmatic levels were determined at the different stages of the protocol. In 6 other transplant patients, a cold pressor test was performed before and after intracoronary infusion of phentolamine (10 micrograms.kg-1.min-1). Coronary flow velocity increased significantly in both groups during each phase of the protocol. 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 after injection of SIN-1 (26.8 +/- 11.9%; P < .001). In transplant patients, similar 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 alpha-blockade with phentolamine (P < .001). These results show that flow-mediated, endothelium-dependent vasodilation is preserved early after trans-plantation. Sympathetic stimulation, which overrides the endothelium-dependent mechanism, can be related to hypersensitivity to catecholamines due to denervation.