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 measurements were performed in 10 patients, age 54(SD 11) years, before and during the continuous infusion of E-4031 (0.15 microgram.kg-1.min-1) which followed an initial dose of 9 micrograms.kg-1 x 5 min-1. Extrastimuli at 500 ms were delivered from the right atrial appendage, high lateral right atrium, and low lateral right atrium. The effective refractory period, 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 coronary 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 decreases in the incidence of repetitive atrial firing (67% to 37%: p < 0.005), 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 elicited 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 close to the atrial effective refractory period.


CONCLUSIONS
These results suggest that E-4031 has a potential effect in the treatment of human paroxysmal atrial fibrillation.
Shimizu
A
A
Third Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Fukatani
M
M
Konoe
A
A
Isomoto
S
S
Centurion
O A
OA
Yano
K
K
D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001281:Atrial Fibrillation / Q000188:drug therapy; D004341:Drug Evaluation; D004594:Electrophysiology; D006321:Heart / Q000502:physiology*; D006325:Heart Atria; D006801:Humans; D008875:Middle Aged; D010880:Piperidines / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D011725:Pyridines; C063968:E 4031