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(Circulation. 1996;94:2542-2550.)
© 1996 American Heart Association, Inc.

Articles

Sympathetic Stimulation Overrides Flow-Mediated Endothelium-Dependent Epicardial Coronary Vasodilation in Transplant Patients

Eduardo Aptecar, MD; Patrick Dupouy, MD; Christophe Benvenuti, MD; Jean-Philippe Mazzucotelli, MD; Emmanuel Teiger, MD; Herbert Geschwind, MD; Alain Castaigne, MD; Daniel Loisance, MD; Jean-Luc Dubois-Rande, MD

the Federation de Cardiologie et Institut National de la Sante et de la Recherche Medicale U400, Unite d'Hemodynamique et de Cardiologie Interventionnelle, Service des Explorations Fonctionnelles, and Service de Chirurgie Thoracique et Cardio-vasculaire et Centre National de la Recherche Scientifique URA 1431, Hopital Henri Mondor (E.A., P.D., C.B., P.M., E.T., H.G., A.C., D.L., J.-L.D.-R.); and the Service de Readaptation Cardiaque, Hopital Albert Chenevier (C.B.), Creteil, France.

Correspondence to E. Aptecar, MD, Federation de Cardiologie, Service du Pr A Castaigne, Hopital Henri Mondor, 51 Av du Marechal de Lattre de Tassigny, 94010 Creteil, France.

Background 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.

Methods and Results 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 µg·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 -blockade with phentolamine (P<.001).

Conclusions These results show that flow-mediated, endothelium-dependent vasodilation is preserved early after transplantation. Sympathetic stimulation, which overrides the endothelium-dependent mechanism, can be related to hypersensitivity to catecholamines due to denervation.

Key Words: transplantation • blood flow • vasodilation

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