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Antiarrhythmic Effects of JTV‐519, a Novel Cardioprotective Drug, on Atrial Fibrillation/Flutter in a Canine Sterile Pericarditis Model
Author(s) -
Kumagai Koichiro,
Nakashima Hideko,
Gondo Naoki,
Saku Keijiro
Publication year - 2003
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1046/j.1540-8167.2003.03050.x
Subject(s) - atrial flutter , medicine , atrial fibrillation , effective refractory period , cardiology , pericarditis , refractory period , anesthesia
A new cardioprotective drug, JTV‐519, blocks Na + current and inwardly rectifying K + current and inhibits Ca 2+ 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. (J Cardiovasc Electrophysiol, Vol. 14, pp. 880‐884, August 2003)