The Influence of Specific and Nonspecific Potassium Current Blockade on the Defibrillation Energy Requirement of Biphasic Shock

UNLABELLED: Block of delayed rectifier potassium current (IK) is known to decrease defibrillation energy requirements (DERs). We tested the hypothesis that there would be no difference in DER reduction with a nonspecific IK (IKr + IKs) blocker, ambasilide, and a specific IKr blocker, dofetilide. METHODS: An anesthetized canine model (n = 30) of internal transvenous defibrillation with biphasic shocks was used. Ambasilide (n = 9; dose: 4.8 mg/kg, then 9.6 mg/kg/hour), dofetilide (n = 10; dose: 10 (micrograms/kg, then 3.6 (micrograms/kg/hour), or matched placebo (n = 11) were administered. DERs (J) were determined in triplicate using an increment-decrement protocol at baseline and during each treatment. ECG intervals were measured at baseline and during each treatment. ANOVA with post-hoc Bonferroni test was used for statistical analysis. RESULTS: Ambasilide resulted in a +23.5 +/- 4.06% prolongation of the QTc interval, while dofetilide resulted in a +20.5% +/- 3.76% prolongation of the QTc interval. Thus, the two drugs resulted in comparable prolongation of the QTc interval (P < 0.05 compared to placebo). Both drugs significantly reduced the DER (-17.7% +/- 5.33% reduction by ambasilide, and -21.9% +/- 5.21% reduction by dofetilide, P < 0.05 compared to placebo). There was no difference in the magnitude of DER reduction between the two treatments. CONCLUSIONS: Administration of equipotent doses (as indicated by QTc changes) of ambasilide or dofetilide had comparable effects on DERs. Selectivity of IK blockade has no significant effect on the magnitude of reduction in DERs.