Cardiovascular Research Advance Access [Accepted Manuscript] published online on September 17, 2008
Cardiovascular Research, doi:10.1093/cvr/cvn249
Rate-dependence of atrial tachycardia effects on atrial refractoriness and atrial fibrillation maintenance
1 Department of Medicine and Research Center, Montreal Heart Institute and Université de Montréal, 5000 Belanger Street, Montreal, Quebec, Canada, H1T 1C8
2 Department of Emergency and Critical Care Medicine, Keio University School of Medicine, Tokyo, Japan
3 Cardiology Department, Saiseikai Central Hospital, Tokyo, Japan
4 Cardiology Division, Keio University School of Medicine, Tokyo, Japan
* Corresponding author. Tel: 514 376 3330; Fax: 514 376 1355 E-mail address: stanley.nattel{at}icm-mhi.org
Aims: Although atrial-tachycardia remodeling is a significant atrial fibrillation (AF)-promoting factor, little information is available about how atrial-tachycardia rate determines remodeling effects. This study assessed the effects of atrial tachypacing (ATP) over a range of clinically-relevant rates on atrial electrophysiology and AF.
Methods and results: Chronically-instrumented dogs underwent sequential 7-day ATP at 400, 300, 200, and 160 bpm in random order with 2-day recovery intervals between periods of ATP. ATP at 400, 300 and 200 bpm significantly decreased atrial effective refractory period (ERP) by 41±2, 37±3, 7±1 ms, respectively, with no significant effects at 160 bpm. Mean duration of induced AF was increased by 400 and 300 bpm ATP (404±284 s and 410±283 s on day 4 respectively, vs. 12±4 s at baseline, P<0.01), but not by 200 or 160 bpm ATP. ATP effects developed slowly with 200-bpm pacing, so we studied 5-week ATP at 200 and 160 bpm in additional dogs. ERP shortened gradually over 3 weeks at 200 bpm (131±5 ms baseline vs. 112±4 and 105±4 ms at 2 and 3 weeks respectively) but no decrease occurred thereafter (5-week value: 104±3 ms) and AF-duration was not significantly affected. No change in ERP or AF-duration occurred at 160 bpm. Because of the limited effects of 200-bpm ATP on AF-duration despite significant effects on ERP, we tested 200-bpm ATP effects in the presence of AF substrates. When 200-bpm ATP was induced in the presence of a fibrotic AF substrate induced by 2 weeks of ventricular tachypacing followed by one-week recovery, no change in AF-duration or atrial vulnerability occurred. However, when 200-bpm ATP was followed by 400-bpm ATP, the onset of remodeling and AF-duration increases was accelerated.
Conclusions: There is a nonlinear relationship between atrial rate and the extent of atrial electrical remodeling. Remodeling at rates equivalent to paroxysmal supraventricular tachycardias in man are insufficient to promote AF alone or in the presence of an atrial fibrotic substrate, but can accelerate the remodeling and stabilization of AF when followed by faster atrial tachyarrhythmias.
KEYWORDS arrhythmia (mechanisms); remodeling; supraventricular arrhythmia
Time for primary review: 19 Days
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  K. Nishida, G. Michael, D. Dobrev, and S. Nattel Animal models for atrial fibrillation: clinical insights and scientific opportunities Europace, October 29, 2009; (2009) eup328v1. [Abstract] [Full Text] [PDF]
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