Journal Article

NIP-141, a multiple ion channel blocker, terminates aconitine-induced atrial fibrillation and prevents the rapid pacing-induced atrial effective refractory period shortening in dogs

Norio Hashimoto, Toru Yamashita, Naoki Fujikura and Nobutomo Tsuruzoe

in EP Europace

Published on behalf of European Heart Rhythm Association of the European Society of Cardiology (ESC)

Volume 9, issue 4, pages 246-251
Published in print April 2007 | ISSN: 1099-5129
Published online March 2007 | e-ISSN: 1532-2092 | DOI: http://dx.doi.org/10.1093/europace/eum018
NIP-141, a multiple ion channel blocker, terminates aconitine-induced atrial fibrillation and prevents the rapid pacing-induced atrial effective refractory period shortening in dogs

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Aims NIP-141 is a novel multiple ion channel blocker with atrial selective effects. In this study, we examined the effects of NIP-141 on aconitine-induced atrial fibrillation (AF) and rapid atrial pacing-induced atrial effective refractory period (ERP) shortening in dogs.

Methods and results Aconitine AF was induced by the application of aconitine on the right appendage. NIP-141 (10 mg/kg) converted AF to sinus rhythm in 5 of 6 dogs. The Na+ channel blockers disopyramide (1 mg/kg) and phenytoin (10 mg/kg) also terminated AF, but the IKr blocker (d-sotalol; 4 mg/kg) and a Ca2+ channel blocker (verapamil; 0.3 mg/kg) did not terminate AF in this model. To clarify the mechanism of AF termination, we examined the effects on ERP and conduction time, but NIP-141 (10 mg/kg) had no significant effects. In a short-term rapid atrial pacing model, NIP-141 (2.5 mg/kg/10 min, followed by 0.033 mg/kg/min) prevented atrial ERP shortening. We also found NIP-141 bound to Na+ channel site 2 receptor and L-type Ca2+ channel, but not to Na+ channel site 1 receptor using radioligands binding assay.

Conclusion NIP-141 terminated AF in aconitine-induced AF and prevented the atrial remodelling by short-term rapid pacing in dogs, possibly via the blocking of Na+ and Ca2+ channels.

Keywords: Atrial fibrillation; Antiarrhythmic agents; Electrical remodelling; Na+ channel; Ca2+ channel

Journal Article.  3427 words.  Illustrated.

Subjects: Cardiovascular Medicine

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