Cisapride-induced prolongation of cardiac action potential and early afterdepolarizations in rabbit Purkinje fibres

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 mu M) 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.