Pharmacodynamics of propranolol on left ventricular function: assessment by Doppler echocardiography.
The relationship of left ventricular systolic function and heart rate to serum l-propranolol concentrations was determined in 10 healthy male volunteers during maximal exercise treadmill testing. Peak aortic blood flow acceleration (ACL), measured by Doppler ultrasonography, was used to evaluate left ventricular systolic function. Repeated exercise testing was performed on two separate days after long-term oral administration of 40 mg propranolol or placebo every 6 hours in a randomized, double-blind, crossover fashion. Pharmacodynamic relationships were determined by fitting percent change in ACL and heart rate at maximal exertion with 1-propranolol with the Emax model (maximal effect) and nonlinear regression. Reductions in systolic function and heart rate during exercise were related directly to 1-propranolol. Propranolol was significantly (p less than 0.05) more potent in reducing heart rate (EC50, 10.6 +/- 9.2 ng/ml) compared with ACL (EC50, 19.2 +/- 8.9 ng/ml). However, Emax of propranolol for reducing ACL was significantly greater than that for reducing heart rate (-46.7% +/- 6.9% versus -29.5% +/- 15.9%; p less than 0.05). These data indicate that the concentration-effect relationship for 1-propranolol and its negative inotropic effect differ from its negative chronotropic effect.
Clifton, GD; Pennell, AT; Harrison, MR
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