Electrophysiological effects of labetalol on canine atrial, cardiac Purkinje fibres and ventricular muscle

Abstract

1 Using conventional microelectrode techniques for the intracellular recordings of the membrane potential, the effects of labetalol were studied on cardiac Purkinje, atrial and ventricular muscle fibres of the dog. 2 Labetalol (1-101M) reduced, in a concentration-dependent manner, the action potential amplitude (APA) and the maximum rate of rise of the action potential (V. ) in Purkinje fibres.3 The action potential duration (APD) was decreased in Purkinje fibres but significantly increased in ventricular fibres after small concentrations of labetalol (1-3 jIM). The atrial fibres were not very sensitive to labetalol. 4 Depolarization of the cardiac Purkinje fibres by increasing the external potassium concentration (8-12mM), potentiated the labetalol effects on APA and V,",. but blocked its effects on the APD. 5 The effects of labetalol on V,,, of Purkinje fibres were dependent on the frequency of stimulation.

Antiarrhythmic efficacy of labetalol as assessed by programmed electrical stimulation

“…an increase in ventricular refractory periods and in intraventricular conduction time. These alterations reflect, at least partially, the proposed class I and III activity of this drug (Vaughan Williams et al, 1982;Mill-& Neto, 1987). Class III activity is also indicated by the increase in the rate corrected QT interval (QTc) which cannot be expected to occur afteradrenoceptor blockade (Edvardsson & Olsson, 1981).…”

“…From this comparison one might speculate that in our model f6adrenoceptor blockade induces a certain antiarrhythmic effect which, as shown in the present study with labetalol, might be enhanced by direct membrane stabilizing qualities. In the case of labetalol such qualities are reported to be present in the therapeutic range (Vaughan Williams et al, 1982;Mill & Neto, 1987;Venditti et al, 1987).…”

“…Experimentally, labetalol has been shown to have local anaesthetic properties (Vaughan Williams et al, 1982) with class I and III antiarrythmic activity (Vaughan Williams, 1970) in rabbit isolated Purkinje fibres (Vaughan Williams et al, 1982) and dog ventricular muscle cells (Mill & Neto, 1987). Furthermore the drug exhibited activity against electricallyinduced ventricular fibrillation in anaesthetized dogs (Anderson et al, 1983), ouabain-and noradrenaline-induced arrhythmias in anaesthetized dogs (Farmer et al, 1972) and coronary occlusionand reperfusion-induced arrhythmias in anaesthetized cats (Pogwizd et al, 1982).…”