Effects of intravenous dobutamineon coronary vasomotion in humans

Objectives We sought to investigate the vascular mechanisms of dobutamine-induced myocardial ischemia. Background Dobutamine stress is often used as a surrogate for exercise. The effects of dobutamine on the epicardial arteries are incompletely understood and possibly different from those of physical exercise. Methods Intravenous (IV) dobutamine (40 μg/kg per min) was administered in 19 patients with normal, 23 patients with mildly atherosclerotic, and 12 patients with stenotic coronary arteries. In another two groups of patients with stenotic arteries, IV dobutamine was preceded by 1) an intracoronary (IC) bolus of the alpha-adrenergic blocker phentolamine (12 μg/kg, n = 12); and 2) an IC infusion of the nitric oxide substrate l-arginine (150 μmol/l per min for 20 min, n = 11). Intravenous saline instead of dobutamine was infused into eight patients with normal arteries. After dobutamine (or saline), an IC bolus of isosorbide dinitrate (ISDN, 0.2 mg) was given. Coronary vasomotion was evaluated by quantitative coronary angiography on angiograms obtained after each dose of dobutamine, saline, phentolamine, l-arginine, and ISDN. Results Dobutamine increased the rate–pressure product and heart rate similarly in all patients except those who received saline. Dobutamine induced vasodilation in normal (change in luminal diameter [ΔLD] vs. baseline: 19 ± 2%) and in mildly atherosclerotic arteries (ΔLD: 8 ± 2%, p < 0.05 vs. normal). In stenotic arteries, dobutamine did not induce significant vasomotion (ΔLD: −3 ± 3%); the latter was improved by l-arginine (ΔLD: 10 ± 3%, p < 0.05 vs. stenotic arteries) and fully restored by phentolamine (ΔLD: 19 ± 3%, p < 0.05 vs. stenotic arteries). Conclusions Endothelial dysfunction and enhanced alpha-adrenergic tone contribute to the loss of dobutamine-induced vasodilation in coronary atherosclerosis. In contrast to physical exercise, dobutamine does not induce “paradoxical vasoconstriction” of atherosclerotic coronary arteries.