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Pharmacodynamics of propranolol on left ventricular function: Assessment by Doppler echocardiography
Author(s) -
Clifton G Dennis,
Pennell Andrew T,
Harrison Michael R
Publication year - 1990
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1990.172
Subject(s) - propranolol , chronotropic , heart rate , medicine , inotrope , placebo , cardiology , pharmacodynamics , crossover study , anesthesia , blood pressure , pharmacokinetics , alternative medicine , pathology
The relationship of left ventricular systolic function and heart rate to serum 1‐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 E max 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 < 0.05) more potent in reducing heart rate (EC 50 , 10.6 ± 9.2 ng/ml) compared with ACL (EC 50 , 19.2 ± 8.9 ng/ml). However, E max of propranolol for reducing ACL was significantly greater than that for reducing heart rate (−46.7% ± 6.9% versus −29.5% ± 15.9%; p < 0.05). These data indicate that the concentration‐effect relationship for 1‐propranolol and its negative inotropic effect differ from its negative chronotropic effect. Clinical Pharmacology and Therapeutics (1990) 48, 431–438; doi: 10.1038/clpt.1990.172