Electrophysiologic effects of a new class III antiarrhythmic agent, E-4031, on atrial flutter, atrial refractoriness, and conduction delay in a canine sterile pericarditis model.
Numerous studies have shown that E-4031 generally prolongs the atrial effective refractory period (AERP) without affecting cardiac conduction. The effects of E-4031 on AERP and cardiac conduction at short cycle lengths (CLs) close to the AERP were measured in 12 dogs with sterile pericarditis. Three pairs of electrodes were sutured at three sites in the atria 4 days after the model was created. We measured AERP and maximum conduction delay (MCD) after 8 beats train at CLs of 400, 300, 200 and 150 ms before and during continuous infusion of E-4031 (0.1 microgram/kg/min) that followed an initial dose of 10 micrograms/kg/min/5 min. E-4031 interrupted sustained atrial flutter (AF) (> or = 10 min) in 4 of 5 episodes and atrial fibrillation (> or = 10 min) in 4 of 4. The CL of AF defined as a rapid atrial rhythm (rate > or = 240 beats/min) in five episodes studied in the sterile pericarditis model was significantly (p < 0.005) prolonged from 120 +/- 8 to 160 +/- 17 ms. There were significant (p < 0.005) increases in AERP at each CL, and prolongation of AERP was 39 +/- 18, 31 +/- 14, 23 +/- 14, and 16 +/- 14 ms at CL 400, 300, 200, and 150 ms, respectively. E-4031 produced less prolongation of AERP at short pacing CLs and had no effect on conduction time during atrial rapid pacing at CLs > 150 ms. E-4031 did not prolong MCD at CL 400 ms, but did prolong MCD at CLs of 300, 200, and 150 ms, despite prolongation of AERP.(ABSTRACT TRUNCATED AT 250 WORDS)
Shimizu
A
A
Third Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Kaibara
M
M
Centurion
O A
OA
Kapuku
G
G
Hirata
T
T
Fukatani
M
M
Yano
K
K
Hashiba
K
K
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D001282:Atrial Flutter / Q000188:drug therapy*; D004285:Dogs; D004558:Electric Stimulation; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006329:Heart Conduction System / Q000187:drug effects*; D008955:Models, Cardiovascular; D010493:Pericarditis / Q000188:drug therapy*; D010880:Piperidines / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D011725:Pyridines; C063968:E 4031