With the use of equilibrium radionuclide ventriculography the effects on left ventricular (LV) function of 160 mg oral propranolol daily and 360 mg verapamil daily alone and in combination were compared in 18 patients with chronic exertional angina. A randomized, double-blind, placebocontrolled, crossover protocol was used. The reduction in exercise rate-pressure product induced by the combination (1 18 ± 28 mm Hg/min) was significantly greater (p < .05) than that by propranolol (135 + 27 mm Hg/min) or verapamil alone (163 ± 28 mm Hg/min). In patients at rest, neither single nor combined therapy altered global or regional left ventricular ejection fractions (EFs). Verapamil, but not propranolol, increased (p < .05) cardiac volumes of resting subjects; used in combination, no further increase in LV volume occurred. With placebo, exercise global EF did not decrease from the level at rest and therefore no drug effect could be demonstrated for this parameter of LV function. By an evaluation of normalized regional EF measurements the combination was shown to reduce exerciseinduced hypokinesis (placebo 52 ± 20%, combination 61 + 23%; p < .01). No significant improvement was noted with propranolol or verapamil alone; only the combination prevented a significant increase in end-systolic and end-diastolic volumes during exercise. Thus, propranolol and verapamil, used alone in moderate doses, exert no beneficial effect on exercise LV function as measured by EF and volume changes, and resting function deteriorates slightly with verapamil. Compared with single-drug therapy, the combination causes no further change in LV function of resting subjects and improves exercise function. This improvement was most likely due to a reduction in myocardial oxygen demand. Circulation 68, No. 6, 1280No. 6, -1289No. 6, , 1983 COMBINATION THERAPY with /8-adrenergic-receptor antagonists and nitrates is a well-established part of the treatment of chronic exertional angina. Recently, reports have shown that calcium-channel antagonists such as verapamil have antianginal properties comparable to those of propranolol.'-1 Moreover, in selected patients, the combination of propranolol and

As an agent potentially capable of inducing ischemia in patients with coronary artery disease, dopamine administered intravenously was evaluated as a pharmacologic stress agent by supine radionuclide angiography, and the results were compared with ergometer exercise. In a preliminary group of 11 subjects (4 normal subjects and 7 patients with coronary disease), dopamine alone was administered in increments of 2.5 micrograms/kg per min to a maximum of 15 micrograms/kg per min. There were significant differences between exercise and dopamine in maximal stress heart rates, 129.3 +/- 30.0 versus 88.0 +/- 35.8 beats/min (p less than 0.05) in normal subjects and 118.9 +/- 21.1 versus 87.6 +/- 22.6 beats/min (p less than 0.05) in patients with coronary disease, as well as in maximal stress rate-pressure products, 213.3 +/- 51.4 versus 155.0 +/- 52.5 mm Hg/min X 10(2) (p less than 0.02) in normal subjects and 216.0 +/- 45.6 versus 161.0 +/- 48.6 mm Hg/min X 10(2) (p less than 0.003) in patients with coronary disease. As a result, in these patients the ejection fraction response was significantly different: -3.3 +/- 4.5% with exercise versus + 6.3 +/- 4.6% with dopamine (p less than 0.05). In a second group of 41 subjects (9 normal subjects and 32 patients with coronary disease), atropine (0.6 mg) was administered intravenously before and after every second dopamine dose increment. This produced statistically similar maximal stress heart rates as compared with exercise in all subjects, rate-pressure products in normal subjects and slightly higher values with dopamine in patients with coronary disease: 200.3 +/- 47.2 versus 183.1 +/- 43.0 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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