Dofetilide enhances shock-induced extension of refractoriness and lowers defibrillation threshold

OBJECTIVE: To explore the hypothesis that class III antiarrhythmics reduce defibrillation threshold (DFT) by prolonging postshock refractoriness. ANIMALS AND METHODS: The effect of a new selective potassium channel blocke r, dofetilide (DOFlow 2.5 mu g/kg bolus plus 0.9 mu g/kg/h; DOFmed 10 mu g/ kg bolus plus 3.6 mu g/kg/h; and DOFhigh 25 mu g/kg bolus plus 9 mu g/kg/h) , on DFT was compared with that of placebo in anesthetized open chest clogs (n = 6 per group). The effects of dofetilide on refractory period extensio n (RPE) were assessed by using DFT strength shocks delivered at various sta ges of repolarization. RESULTS: DFT was significantly decreased in the DOFhigh group, whether expr essed as shock peak voltage or energy (P < 0.05 compared with changes in pl acebo). At baseline, a shock timing of ventricular effective refractory per iod of 25 ms resulted in RPE of 1001 +/- 24 ms, 80 +/- 11 ms, 91 +/- 14 ms and 90 +/- 20 ms in the placebo, DOFlow, DOFmed, and DOFhigh groups, respec tively. After infusion, these RPE values were unchanged in the placebo grou p but tended to increase in the dofetilide treatment groups. DOFhigh signif icantly increased RPE by 20 +/- 18 ms (P < 0.05 compared with baseline valu es and changes in placebo). Dofetilide-induced changes in RPE and DFT were significantly correlated when ex pressed as voltage (r(2) = 0.78, P < 0.01) , current (r(2) = 0.80, P < 0.01) and energy (r(2) = 0.53, P < 0.01). CONCLUSIONS: These results show that dofetilide prolonged RPE at a plasma l evel that reduced DFT, thus providing support for the hypothesis that selec tive prolongation of refractoriness may synergize with shock-induced RPE to decrease the energy requirements for defibrillation.