A study of the labetalol-induced changes in conductivity and refractoriness of the dog heart in situ

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Abstract
The effect of labetalol, an a- and β-adrenergic receptor blocking agent, on the electro-physiology of the dog heart in situ was studied. Pentobarbital anaesthesia which is known to increase the sympathetic tone was used. Labetalol in doses of 0.5 to 4.0 mg·kg−1 injected intravenously caused a slight decrease in median heart rate and a slight reduction in the median conduction velocity in the atrioventricular (A-V) node in six dogs. A significant increase in the functional refractory period of the A-V node occurred at doses of 1.0 to 4.0 mg·kg"1. The functional and the effective refractory periods of the right atrium and ventricle were increased by labetalol at all doses tested. The plasma concentrations of labetalol were in the range 0.05 to 0.8 μg·cm−3 in five out of six dogs at the three lowest doses tested which is far below the values which could be expected to cause a membrane-stabilising effect. The a and β adrenoreceptor blocking effects of labetalol on cardiac electrophysiology in vivo are discussed.