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 of 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 mg 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 at 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.
The Kasumigaura Branch Hospital, Tokyo Medical and Dental University, Ohyama, Miho, Inashiki-gun, Ibaraki 300-04, JAPAN; Hokushin General Hospital, Nakano-shi, Nagano 383, JAPAN; and the Second Department of Internal Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113, JAPAN
Submitted for publication July 1996.
Accepted for publication January 1997.
This work was supported in part by a grant-in-aid for Scientific Research of the Ministry of Education, Science, and Culture of Japan.
This study was presented in part at the 68th annual meeting of the American Heart Association, Anaheim, CA, November 15, 1995.
Address for correspondence: Akira Koike, M.D., Second Department of Internal Medicine, Tokyo Medical and Dental University, 5-45, Yushima 1-chome, Bunkyo-ku, Tokyo 113, Japan.