Effects of isosorbide dinitrate on oxygen uptake kinetics in cardiac patients

Purpose: Although nitrates are known to improve indices of exercise capacity in patients with coronary artery disease, their effects on oxygen uptake kinetics during the onset of exercise have not been clarified. We evaluated the acute effects of isosorbide dinitrate on the kinetics or oxygen uptake during the onset of exercise at a constant work rate in patients with coronary artery disease. Methods: We studied 14 patients with coronary artery disease who performed 6 min of low-intensity exercise at a constant work rate on a cycle ergometer 30 min after oral administration of 10 mp of isosorbide dinitrate or placebo in a double-blind, crossover manner. Oxygen uptake was calculated from breath-by-breath analysis of respired gases. The time constant of oxygen uptake kinetics during the onset of exercise was determined by fitting a single exponential function to the oxygen uptake response. Results: Heart rate was significantly increased al rest, and systolic blood pressure was significantly decreased both at rest and during exercise after administration of isosorbide dinitrate. The time constant of oxygen uptake was significantly shorter (the kinetics were faster) after administration of isosorbide dinitrate (39.4 +/- 10.1 vs 44.5 +/- 10.5 s, P = 0.038). Conclusions: Isosorbide dinitrate was found to speed the kinetics of the increase in oxygen uptake during constant work-rate exercise. The time constant of oxygen uptake. which reflects the rapidity of cardiovascular adaptation at the onset of exercise, seems to be a useful parameter of the effectiveness of therapy in patients with coronary artery disease.