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Effect of beta-adrenergic blockade with alprenolol on ST-segment depression and circulatory dynamics during exercise
Abstract:
1. Nine subjects with severe coronary artery disease were studied during graded "sprint" and "steady-state" exercise before and after intravenous administration of the beta-receptor antagonist alprenolol. During "sprint" workload was increased every minute until maximum work capacity (Wmax) was reached. "Steady-state" exercise was performed at work rates of 0.250, 0.50, and 0.75 of each subject's sprint Wmax. Variables measured included ST-segment depression, changes in heart rate, blood pressure, respiratory gas exchange, and arterial blood composition. Cardiac output (indirect Fick) was measured during "steady-state" exercise. 2. Alprenolol did not alter Wmax during "sprint" but reduced the incidence of angina in both types of exercise. After the drug work capacity was limited by symptoms and signs suggestive of mild left ventricular failure. 3. The relationship between workload (normalized in terms of Wmax) and ST-segment depression was curvilinear. Under control conditions a given rate of work during "steady-state" exercise was assocaited with more marked ST-segment depression than during "sprint". Alprenolol displaced the work-ST-depression curve to the right in each type of exercise; now a given rate of work produced similar ST-depressing during "steady-state" and "sprint" exercise. 4. Alprenolol attentuated the exercise tachycardia during both types of exercise. Cardiac output was lower in "steady-state" exercise after the drug than under control conditions. Metabolic effects included significant reduction in body oxygen consumption after alpreprenolol at 0.25 Wmax and diminished arterial lactate at 0.75 Wmax. The beneficial effects of the drug thus appeared to involve not only cardiac but peripheral effects on beta receptors. 5. Before alprenolol cardiac output was relatively fixed at all workloads, but after the drug there was a work-related rise in output in five out of nine subjects. Comparison with data in normal subjects suggested that in anginal subjects cardiac output at low "steady-state" workloads was inappropriately high.