ELECTROPHYSIOLOGICAL EFFECTS OF A NEW CLASS-III ANTIARRHYTHMIC AGENT (E-4031) ON THE CONDUCTION AND REFRACTORINESS OF THE IN-VIVO HUMAN ATRIUM

Objective: The aim was to test the efficacy of a new class III drug, E -4031, on human atrial muscle in vivo. Methods: Electrophysiological m easurements were performed in 10 patients, age 54(SD 11) years, before and during the continuous infusion of E-4031 (0.15 mug.kg-1.min-1) wh ich followed an initial dose of 9 mug-kg-1.5 min-1. Extrastimuli at 50 0 ms were delivered from the right atrial appendage, high lateral righ t atrium, and low lateral right atrium. The effective refractory perio d, repetitive atrial firing zone, and fragmented atrial activity zone were assessed at three sites in the right atrium. The conduction delay zone from the stimulus artefact to the distal electrode pair at the c oronary sinus was also measured. Results: E-4031 caused a significant increase in overall right atrial effective refractory period from 210( SD 29) to 232(26) ms (p<0.001, n=30 sites). There were significant dec reases in the incidence of repetitive atrial firing (67% to 37%: p<0.0 05), in the repetitive atrial firing zone [23(20) to 11(22) ms: p<0.01 ], and in the fragmented atrial activity zone [15(22) to 3(8) ms: p<0. 005], but no significant change in the conduction delay zone. However, E-4031 significantly prolonged the longest coupling interval that eli cited conduction delay, from 249(31) ms to 267(28) ms (p<0.01). E-4031 had no effect on the conduction time except at coupling intervals clo se to the atrial effective refractory period. Conclusion: These result s suggest that E-4031 has a potential effect in the treatment of human paroxysmal atrial fibrillation.