Sodium Channel Block and Action Potential Prolongation

Antiarrhythmic drugs have been reported to produce variable effects on defibrillation energy requirements. However, the relation between the in vitro electrophysiologic effects of these agents and the changes in defibrillation energy requirements have not been systematically examined. Therefore, we evaluated the effects of the sodium channel blocking drugs lidocaine and procainamide, the action potential prolonging drugs N-acetyl procainamide and clofilium, and the potassium current blocker cesium in acute canine models with the same internal spring and epicardial patch electrodes used in humans for ventricular defibrillation testing. Ten series of experiments were performed in 78 dogs. Nonlinear regression was used to derive curves of energy dose versus percent successful defibrillation attempts and the 50% and 90% effective energy dose for each experimental condition. Saline control experiments indicated that the preparation was stable throughout the 6-hour duration of the experiments. Lidocaine doubled the defibrillation energy requirement (p<0.001) at a mean plasma concentration of 8.2 jug/ml. The effect of lidocaine on defibrillation energy was reversible, present at therapeutic plasma concentrations, linearly related to plasma concentration (r=0.69, p<0.002), and present even after only 5-second episodes of ventricular fibrillation. In contrast, procainamide had no effect