Health & body · 1988
Can celiprolol increase heart contraction strength while still blocking cardiac in conscious dogs?
Yes. In conscious dogs, celiprolol increased measures of heart contraction strength while blocking cardiac beta-1 receptors; the researchers concluded that its contraction-strengthening and -reducing effects were independent of beta-1 mechanisms and the Bowditch phenomenon.
Details
Beta-adrenoceptor blocking agents are used to manage various cardiovascular disorders, but suppression of heart contraction strength limits their use. This study examined the cardiac effects of celiprolol, a new beta-adrenoceptor blocker reported to have positive inotropic effects—that is, to increase contraction strength.
In this pharmacological animal experiment, dogs were instrumented using sterile surgical techniques to measure myocardial inotropic state, heart rate and internal left ventricular dimensions. Experiments were conducted while the dogs were conscious, after complete recovery from surgery.
In nine dogs, intravenous celiprolol at 3 mg/kg increased the rate of left ventricular pressure rise (LV dP/dt) by 13 ± 2.6%, the velocity of shortening (LV dD/dt) by 9.2 ± 3.4%, and heart rate by 19 ± 4.6%. It decreased left ventricular end-diastolic diameter by 1.8 ± 0.8%. All these changes were statistically significant (P < 0.05).
Celiprolol blocked the contraction-strengthening actions of isoprenaline at 0.5 micrograms/kg, but only partially reduced its blood-pressure-lowering effects. In contrast, propranolol reduced LV dP/dt by 17 ± 3.3% and heart rate by 8.1 ± 2.7% (P < 0.05), while completely abolishing the low blood pressure, increased heart rate and increase in LV dP/dt caused by isoprenaline.
After beta-adrenoceptor blockade with propranolol, and with heart rate held constant by electrical pacing, celiprolol increased LV dP/dt by 16 ± 4.0% and LV dD/dt by 12 ± 3.0%, and reduced left ventricular end-diastolic diameter by 3.5 ± 0.5% (P < 0.05).
The researchers concluded that, in conscious dogs, celiprolol increases myocardial contraction strength and reduces preload independently of beta-1-adrenoceptor mechanisms and the Bowditch phenomenon, while effectively blocking beta-1 receptors in the heart. They suggested that these properties could make celiprolol useful in patients for whom a conventional beta-adrenoceptor blocker might lead to cardiac pump failure.
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