Why the study?
Does cisapride prolong cardiac action potential duration and induce early afterdepolarizations in rabbit Purkinje fibres?
Does cisapride prolong cardiac action potential duration and induce early afterdepolarizations in rabbit Purkinje fibres?
Cisapride prolongs cardiac action potential duration and induces early afterdepolarizations in rabbit Purkinje fibres, providing an electrophysiological mechanism for its clinical association with Torsades de Pointes.
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May explain cisapride-TdP link via EADs; leaves open translation to human arrhythmias and needs clinical validation.
Cisapride, a gastrointestinal prokinetic agent, has been associated with cases of Torsades de Pointes but its effects on the cardiac action potential have not been described. We investigated its electrophysiological effects on rabbit isolated Purkinje fibres. The results demonstrated that cisapride (0.01-10 microM) lengthened concentration-dependently the action potential duration without modifying other parameters and induced early after depolarizations and subsequent triggered activity. This typical class III antiarrhythmic effect, that showed "reverse" rate-dependence and was reduced by increasing external K concentration, can account for clinical arrhythmogenesis.
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Puisieux et al. (1996) studied this question.
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