Cardiac electrophysiological effects of two class III antiarrhythmic agents, tedisamil and D-sotalol: DISCUSSION (part 1)


Because Cardiac Arrhythmia Suppression Trial (CAST) data have justified the concerns for the safety of class I antiarrhythmic, class III antiarrhythmic drugs are increasingly favoured for treatment of patients with serious arrhythmias . The benefit of the racemic compound sota-lol against ventricular arrhythmias is well documented . This beneficial effect could not be shown for D-sotalol, the substance with pure class III action . The problem with class III antiarrhythmic agents is that they exhibit a reverse use-dependent effect, which means that prolongation of the repolarization period is low at high rates and is high at low rates . Thus, when the action of the drug on the cardiac conduction system is needed, it is attenuated by a high rate of activity. On the other hand, during sinus rhythm the repolarization period is prolonged, which could lead to torsade de pointes.However, potassium channel blockade has been described as a mechanism for suppressing ventricular fibrillation, and class III agents are pharmacologically heterogeneous, particularly in their selectivity for different potassium currents.

In the present study, basic electrophysiological effects of the two class III antiarrhythmic agents tedisamil and D-sota-lol on intact isolated guinea pig hearts were evaluated. Both drugsinduced a significant prolongation of the AV nodal conduction interval and reduced the spontaneous sinus rate. The effect on the sinus rate was more marked with tedisamil than with D-sotalol. Tedisamil additionally influenced His bundle and intraventricular conduction. At a constant stimulation rate, tedisamil more markedly prolonged the repolarization period (JT interval) than D-sotalol. Atrial refractoriness was significantly prolonged by tedisamil, whereas this parameter was not influenced by D-sotalol. On the other hand, tedisamil caused a marginal prolongation of the AV-ERP, while D-sotalol significantly affected this parameter. The V-ERP was minimally affected by both drugs.
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Category: Cardiology

Tags: Conduction, D-sotalol, Guinea pig, Refractoriness, Repolarization, Tedisamil

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