Effect of JTV-519 on AF.
INTRODUCTION: 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.
METHODS AND 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).
CONCLUSION: 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.