Publications

We evaluated the effects of isosorbide dinitrate on some of the major determinants of myocardial oxygen demand during upright exercise in ten normal subjects. In addition to heart rate and systolic blood pressure, we assessed left ventricular size and performance by echocardiography. Compared to the control study, heart rate was significantly faster after the nitrate administration at rest (67 +/- 14 versus 83 +/- 21 beats/minute), but there was no difference in heart rate at any stage during exercise. Systolic blood pressure also was significantly lower at rest after nitrate (104 +/- 8 versus 92 +/- 2 mm Hg) but was similar to control after 6 minutes of exercise. Echocardiographic end-diastolic dimension was decreased at rest post-nitrate (45.3 +/- 4.7 versus 40.2 +/- 4.2 mm) and remained significantly reduced during exercise by an analysis of variance. We conclude that a major beneficial effect of nitrates on myocardial oxygen demand during upright exercise is a decrease in left ventricular size which reduces wall tension.

We evaluated a new slow-channel calcium-blocking agent, diltiazem hydrochloride, in 10 patients with documented fixed coronary artery disease who had reproducible angina and greater than or equal to 0.1 mV ST segment depression on ECG treadmill exercise testing after 1 week of single-blind placebo administration. Subsequently, over the next 6 weeks, either diltiazem (30 mg/tablet) or placebo were administered for 1 week each in a randomized double-blind triple crossover design, as one tablet four times a day, two tablets three times a day or two tablets four times a day, for a total diltiazem dose of 120, 180 and 240 mg/day, respectively. Treadmill (electrocardiogram) exercise testing was performed at the end of each week. Only diltiazem at 240 mg/day increased significantly the time to angina pectoris (P less than 0.05), time to ST segment depression (P = 0.01), time to maximal exercise (P less than 0.02), and heart rate at maximal exercise (P less than 0.05) without effecting significantly the maximal rate-pressure product compared to the corresponding placebo values. In addition, using only the diltiazem data, a significant high dose response was observed for time to angina (P less than 0.05), ST segment depression (P less than 0.005), and maximal exercise (P less than 0.025). No adverse reactions were reported during the study. Therefore, we conclude that 240 mg/day of diltiazem improves significantly exercise performance in patients with angina pectoris due to fixed coronary artery disease and adverse effects, rarely, if ever, occur at this dosage.