Developing class III antiarrhythmic agents with normal use-dependent prolongation of refractoriness could improve efficacy and reduce proarrhythmic risks during tachycardias.
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May warrant caution in tachycardias; supports development of use-dependent class III agents.
With regard to currently available class III agents, although their class III effect may reduce the likelihood of tachycardia initiation, their reverse use-dependent prolongation of action potential duration reduces their effectiveness during tachycardias and may even render them proarrhythmic, especially after long diastolic intervals. In contrast, agents that exhibit normal use-dependent prolongation of refractoriness hold great promise: While having relatively less effects on the normal heart beat, they could induce self-termination of a tachycardia. Prolongation of refractoriness can be achieved by lengthening of action potential duration and delaying recovery of excitability. Combination of these drug actions may yield important clinical applications.
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Hondeghem et al. (1990) studied this question.
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