Antiarrhythmic effects of JTV-519, a novel cardioprotective drug, on atrial fibrillation/flutter in a canine sterile pericarditis model.
Effect of JTV-519 on AF.


BACKGROUND
A new cardioprotective drug, JTV-519, blocks Na+ current and inwardly rectifying K+ current and inhibits Ca2+ current. However, its role in atrial electrophysiology is unknown. We investigated the antiarrhythmic effects of JTV-519 on atrial fibrillation/flutter in the canine sterile pericarditis model.


RESULTS
In nine dogs with sterile pericarditis, 38 episodes of sustained (>30 sec) atrial fibrillation (8 dogs) and 24 episodes of sustained atrial flutter (7 dogs) were induced by rapid atrial pacing. When atrial fibrillation or atrial flutter was sustained >15 minutes, it was cardioverted and reinduced. The inducibility of atrial fibrillation/flutter, the atrial effective refractory period, and the intra-atrial conduction time were compared before and after the continuous infusion of JTV-519 (0.03 mg/kg/min). JTV-519 significantly decreased the mean number of sustained atrial fibrillation episodes (from 4.2 +/- 2.9 to 0 +/- 0, P < 0.01). In contrast, atrial flutter was still inducible in 4 dogs after JTV-519 (from 2.7 +/- 2.5 to 1.6 +/- 2.1, P = NS). JTV-519 significantly prolonged effective refractory period (from 123 +/- 18 to 143 +/- 14 msec, from 127 +/- 18 to 151 +/- 12 msec, and from 132 +/- 13 to 159 +/- 9 msec at basic cycle lengths of 200, 300, and 400 msec, respectively, P < 0.01), but it did not affect the intra-atrial conduction time (from 47 +/- 11 msec to 48 +/- 11 msec, P = NS).


CONCLUSIONS
JTV-519 had significant protective effects on atrial fibrillation in the canine sterile pericarditis model, mainly by increasing effective refractory period, suggesting that it may have potential as a novel antiarrhythmic agent for atrial fibrillation.
Kumagai
Koichiro
K
Department of Cardiology, School of Medicine, Fukuoka University, Fukuoka, Japan. kxk@fukuoka-u.ac.jp
Nakashima
Hideko
H
Gondo
Naoki
N
Saku
Keijiro
K
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage; D001281:Atrial Fibrillation / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control*; D001282:Atrial Flutter / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000008:administration & dosage; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004562:Electrocardiography; D005260:Female; D008297:Male; D010493:Pericarditis / Q000150:complications; D013841:Thiazepines / Q000008:administration & dosage*; D016896:Treatment Outcome
D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D013841:Thiazepines; C109183:K201 compound