Tedisamil increases coherence during ventricular fibrillation and decreases defibrillation energy requirements

Introduction: Drugs which primarily prolong cardiac refractoriness decrease defibrillation voltage and energy requirements in animals and man. The effect of such drugs on ventricular fibrillation itself is not well understood. We hypothesized that tedisamil, an investigational antiarrhythmic drug which blocks I,, and !, repolarizing potassium channels, would increase organization of epicardial electrograms during ventricular fibrillation while it lowered defibrillation energy requirements. Methods: We measured magnitude-squared coherence, a measure of spatial organization, and ventricular fibrillation (VF) cycle length, ventricular effective refractory period (VERP), and monophasic action potential duration (APD(90)) as well as defibrillation energy threshold (E(50)) at baseline and after 150 mu g/kg of tedisamil (n = 13) or saline control (n = 6) in an open chest dog model. Results: After tedisamil, mean magnitude-squared coherence increased by 132 +/- 133%, from 0.15 +/- 0.08 to 0.31 +/- 0.16 (P < 0.001); VF cycle length increased from 121 +/- 24 to 190 +/- 63 ms (P < 0.001) and became more regular, with the coefficient of variation between adjacent VF intervals decreasing from 14.1 +/- 6.9 to 3.9 +/- 2.2% (P < 0.001). Mean E(50) decreased from 8.9 +/- 3.8 to 6.1 +/- 2.7 joules (P < 0.001); VERP increased from 158 +/- 30 to 201 +/- 31 ms (P < 0.001), and APD(90) increased from 177 +/- 25 to 244 +/- 45 ms (P < 0.001) after tedisamil. No electrophysiologic parameter was changed after saline infusion. Conclusions: Tedisamil increases both spatial coherence and temporal regularity of ventricular fibrillation, These effects on 'order' during VF may be in part responsible for the observed reduction in defibrillation energy requirements.