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Celiprolol: a positive inotropic β‐adrenoceptor blocking agent in conscious dogs
Author(s) -
Nganele David M.,
DeLeonardis V. Maria,
Hintze Thomas H.
Publication year - 1988
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1988.tb10304.x
Subject(s) - celiprolol , inotrope , propranolol , preload , isoprenaline , heart rate , medicine , lusitropy , tachycardia , cardiology , diastole , hemodynamics , blood pressure , stimulation
1 β‐Adrenoceptor blocking agents are used to manage various cardiovascular disorders. A limiting factor in their use is the suppression of the cardiac contractile state. In our study, we examined the cardiac effects of celiprolol, a new β‐adrenoceptor blocking agent with reported positive inotropic effects. 2 Dogs were instrumented by use of sterile surgical techniques for the study of myocardial inotropic state, heart rate and internal left ventricular dimensions. Following complete recovery from surgery, experiments were conducted in the conscious state. 3 Intravenous injection of celiprolol (3 mg kg −1 ) in nine dogs, increased LV dP/dt by 13 ± 2.6%, velocity of shortening (LV dD/dt ) by 9.2 ± 3.4%, and heart rate by 19 ± 4.6% and decreased LV end‐diastolic diameter by 1.8 ± 0.8%, all significantly ( P < 0.05). Celiprolol blocked the inotropic actions of isoprenaline (0.5 μg kg −1 ) but only partially reduced its hypotensive effects. Propranolol, in contrast, reduced LV dP/dt by 17 ± 3.3% and heart rate by 8.1 ± 2.7% ( P < 0.05) while totally abolishing the hypotension, tachycardia and increase in LV dP/dt caused by isoprenaline. Following β‐adrenoceptor blockade with propranolol and with heart rate held constant by electrical pacing, celiprolol increased LV dP/dt by 16 ± 4.0%, LV dD/dt by 12 ± 3.0% and reduced LV end‐diastolic diameter by 3.5 ± 0.5% ( P < 0.05). 4 Thus, in conscious dogs, celiprolol increases inotropic state and reduces preload independently of β‐adrenoceptor mechanisms and the Bowditch phenomenon, while effectively blocking β‐receptors in the heart. These properties would make celiprolol useful in patients where a conventional β‐adrenoceptor blocking agent might lead to pump failure.