Effects of nicorandil on kinetics of oxygen uptake at the onset of exercise in patients with coronary artery disease

Abstract

The beneficial effects of coronary vasodilators on exercise capacity in patients with angina pectoris are well known. However, their effects on oxygen uptake (VO 2) kinetics at the onset of exercise have not been elucidated. The present study was undertaken to determine the acute effects of nicorandil, a newer coronary vasodilator, on the kinetics of VO 2 at the onset of exercise in patients with ischemic heart disease. Ten patients with significant coronary stenosis performed constant mild-intensity cycle exercise (32 ± 3 W) for 6 minutes after oral administration of 10 mg of nicorandil or an identical placebo in a double-blind, crossover manner. Nicorandil had no effect on resting heart rate, blood pressure, or VO 2. However, the time constant for the increase in VO 2 during constant work rate exercise was significantly shorter (the kinetics of VO 2 were faster) after administration of nicorandil than after placebo (46.5 ± 13.3 vs 51.1 ± 11.9 seconds; p = 0.039). The increase in VO 2 at 6 minutes compared with 3 minutes of constant work, which reflects the VO 2 kinetics, also was reduced with nicorandil (3.8 ± 37.9 vs 27.5 ± 27.1 ml/min; p = 0.022). Nicorandil was found to increase the rate of VO 2 increase during the onset of constant work rate exercise, probably as a result of an improved response in cardiac output. Analysis of VO 2 kinetics provides new and useful parameters for the evaluation of circulatory adjustments at the onset of exercise in patients with ischemic heart disease.