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Delayed afterdepolarizations (DADs) induced by the electrogenic Na/Ca exchanger (NCX) play an important role in the genesis of arrhythmias. However, it is not known whether the NCX-induced DADs play any role in the genesis of the repolarization prolonging drug-induced torsades de pointes ventricular tachycardia (TdP). Therefore, the present study examined the effect of the selective inhibition of NCX (by SEA0400) on the occurrence of dofetilide-induced TdP in isolated, Langendorff-perfused, AV-blocked rabbit hearts. A group of hearts was perfused with 100 nM dofetilide, another group was perfused with the combination of 1 μM SEA0400 and 100 nM dofetilide, and a control group of hearts was perfused with the solvent DMSO. Each group contained n=8 hearts. Volume conducted ECG was recorded and the incidence and the onset times of TdPs were analyzed subsequently. The incidence of TdP did not differ between the dofetilide and the SEA0400+dofetilide-perfused hearts, whereas the incidences of TdP were significantly higher in these groups as compared to that in the DMSO control (88% and 100% vs. 13%, respectively, p |
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