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

To explore the hypothesis that class III antiarrhythmics reduce defibrillation threshold (DFT) by prolonging postshock refractoriness.

The effect of a new selective potassium channel blocker, dofetilide (DOFlow 2.5 micrograms/kg bolus plus 0.9 microgram/kg/h; DOFmed 10 micrograms/kg bolus plus 3.6 micrograms/kg/h; and DOFhigh 25 micrograms/kg bolus plus 9 micrograms/kg/h), on DFT was compared with that of placebo in anesthetized open chest dogs (n = 6 per group). The effects of dofetilide on refractory period extension (RPE) were assessed by using DFT strength shocks delivered at various stages of repolarization.

DFT was significantly decreased in the DOFhigh group, whether expressed as shock peak voltage or energy (P < 0.05 compared with changes in placebo). At baseline, a shock timing of ventricular effective refractory period of 25 ms resulted in RPE of 100 +/- 24 ms, 80 +/- 11 ms, 91 +/- 14 ms and 90 +/- 20 ms in the placebo, DOFlow, DOFmed, and DOFhigh groups, respectively. After infusion, these RPE values were unchanged in the placebo group but tended to increase in the dofetilide treatment groups. DOFhigh significantly increased RPE by 20 +/- 18 ms (P < 0.05 compared with baseline values and changes in placebo). Dofetilide-induced changes in RPE and DFT were significantly correlated when expressed as voltage (r2 = 0.78, P < 0.01), current (r2 = 0.80, P < 0.01) and energy (r2 = 0.53, P < 0.01).

These results show that dofetilide prolonged RPE at a plasma level that reduced DFT, thus providing support for the hypothesis that selective prolongation of refractoriness may synergize with shock-induced RPE to decrease the energy requirements for defibrillation.