Background: Coronary vasomotor responses to sympathetic stimulation vary with endothelial-layer integrity or presence of atherosclerosis. Our study objective was to assess the effects of phenylephrine-induced alpha-adrenergic stimulation on coronary vasomotion in heart transplant recipients with and without graft atherosclerosis.
Methods: Intracoronary phenylephrine (alpha(1)-selective agonist) was injected in 6 control subjects, 9 recipients with angiographically normal coronary arteries and 8 recipients with mild or moderate atherosclerosis. Coronary flow velocity was measured using a Doppler guide-wire. The diameters of 3 epicardial segments of the left coronary artery and coronary blood flow and resistance were assessed at baseline, after infusion of increasing acetylcholine doses (10(-7) and 10(-6) mol/liter) and after phenylephrine (150- to 200-microg bolus). Systemic and coronary hemodynamic parameters were measured immediately after acetylcholine and 1, 3, 5, 7, 10 and 15 minutes after phenylephrine.
Results: Phenylephrine induced similar significant increases in rate pressure product in the 3 groups. Acetylcholine induced epicardial vasodilation in controls and vasoconstriction in transplant recipients. Phenylephrine induced epicardial vasodilation in controls and in angiographically normal recipients; subsequent vasoconstriction occurred in this last group. In the recipients with angiographic abnormalities, sustained vasoconstriction occurred. At peak phenylephrine effect, coronary blood flow (CBF) increased significantly (p < 0.001 vs baseline) in all 3 groups. Coronary resistance decreased in the 3 groups but the decrease was smaller in the recipients with angiographic abnormalities (p < 0.05 vs controls).
Conclusions: In heart transplant patients, graft atherosclerosis unmasks the direct coronary vasoconstricting effects of pharmacologic alpha-adrenergic stimulation.