Refractoriness and Conduction Interaction during Modulation of Non-Ischemic Ventricular Fibrillation by Flecainide

Purpose: To study refractoriness and conduction interaction during modulation of non-ischemic ventricular fibrillation (VF) by flecainide. Methods: Isolated feline and rabbit hearts were used. (a) In the feline hearts (n = 8), electrophysiological parameters were measured before and after flecainide administration (0.6, 1.2 × 10^-6 M). During pacing the parameters were: epicardial conduction time, refractoriness and 1:1 pacing/response capture. During 8 min of electrically-induced tachyarrhythmias they included heart rate and normalized entropy reflecting the degree of organization. (b) In rabbit hearts (n = 4), three-dimensional mapping was performed before and after flecainide administration (2 × 10^-6 M). To follow changes in organization, local RR-intervals and differences in activation time between adjacent epicardial electrodes were measured immediately and 80 sec after VF induction. Results: In feline hearts with flecainide, fibrillation was more difficult to induce, more frequently terminated spontaneously and was slower and more organized; conduction time was markedly lengthened, and refractoriness less than 1:1 capture, was moderately prolonged. An inverse correlation was observed between arrhythmia properties, rate and organization, and changes in refractoriness and conduction time. In rabbit, the number of wave fronts was reduced, RR-intervals were prolonged but at the same time activation time differences between adjacent electrodes were smaller following flecainide administration. Conclusions: It is suggested that flecainide modulation of VF properties is associated with conduction suppression and refractoriness prolongation, which act in a synergistic, additive way.