Skip Navigation


Europace Advance Access originally published online on March 9, 2007
Europace 2007 9(4):246-251; doi:10.1093/europace/eum018
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
9/4/246    most recent
eum018v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (1)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Hashimoto, N.
Right arrow Articles by Tsuruzoe, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hashimoto, N.
Right arrow Articles by Tsuruzoe, N.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The European Society of Cardiology 2007. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

ANTIARRHYTHMIC DRUGS

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

Biological Research Laboratories, Nissan Chemical Industries Ltd, 1470 Shiraoka, Minamisaitama, Saitama 349-0294, Japan

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.

Key Words: Atrial fibrillation, Antiarrhythmic agents, Electrical remodelling, Na+ channel, Ca2+ channel

* Corresponding author. Tel: +81 480 92 2513; fax: +81 480 90 1014. E-mail address: hashimotot{at}nissanchem.co.jp

Manuscript submitted 20 July 2006. Accepted after revision 18 January 2007.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 EuropaceHome page
I. Savelieva and J. Camm
Anti-arrhythmic drug therapy for atrial fibrillation: current anti-arrhythmic drugs, investigational agents, and innovative approaches
Europace, June 1, 2008; 10(6): 647 - 665.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.