Immediate effects of milrinone on metabolic and sympathetic responses to exercise in severe congestive heart failure

Abstract

A randomized, double-blind, placebo-controlled protocol was used to determine whether milrinone exerts an immediate effect on exercise performance in patients with severe congestive heart failure. In each of 14 patients with New York Heart Association class III or IV congestive heart failure, intravenous milrinone (mean 57 ± 5 μg/kg) and placebo were randomly administered just before maximal progressive upright cycle ergometry. The duration of exercise was significantly longer with milrinone than with placebo treatment (placebo 11.0 ± 0.6 minutes, milrinone 12.5 ± 0.9 minutes, p = 0.01). Compared with placebo, milrinone caused a higher peak oxygen uptake (placebo 10.8 ± 0.6 ml/kg/ min, milrinone 12.4 ± 0.7 ml/kg/min, p = 0.001) and oxygen uptake at the anaerobic threshold (placebo 7.8 ± 0.4 ml/kg/min, milrinone 9.2 ± 0.4 ml/kg/min, p = 0.001). At peak exercise intensity, systolic blood pressure (placebo 119 ± 5 mm Hg, milrinone 131 ± 5 mm Hg, p = 0.001) and heart rate (placebo 114 ± 5 beats/min, milrinone 126 ± 6 beats/min, p = 0.001) were both increased with milrinone. Likewise, at matched submaximal exercise intensities, heart rate (placebo 111 ± 19 beats/min, milrinone 117 ± 20 beats/min, p < 0.05) and systolic blood pressure (placebo 116 ± 19 mm Hg, milrinone 121 ± 19 mm Hg, p = 0.04) were higher with milrinone; plasma norepinephrine (placebo 1,692 ± 208 mg/liter, milrinone 1,320 ± 216 ng/liter, p = 0.05) and blood lactate concentrations (placebo 2.2 ± 0.2 m M, milrinone 1.9 ± 0.2 m/ M, p < 0.05) were lower. These data indicate that the administration of milrinone acutely causes an improvement in maximal exercise performance and the metabolic response to submaximal exercise.