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Am J Physiol Heart Circ Physiol (January 4, 2008). doi:10.1152/ajpheart.00999.2007
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Submitted on August 29, 2007
Accepted on January 3, 2008

Experimental studies of atrial fibrillation: Comparison of two pacing models

Gabriel Laurent1, Gordon W Moe2, Xudong Hu1, Howard Leong-Poi3, Kim A Connelly4, Petsy Pui-Sze So5, Andrew Ramadeen5, Liia Doumanovskaia1, Andrea Konig1, Judy Trogadis6, David W Courtman7, Bradley Strauss8, and Paul Dorian9*

1 Keenan Research Center, Li Ka Shing Knowledge Institute, Toronto, Canada; Cardiology, St Michael's Hospital, Toronto, Canada
2 Keenan Research Center, Li Ka Shing Knowledge Institute, Toronto, Canada; Cardiology, St Michael's Hospital, 30 Bond Street, Toronto, M5B1W8, Canada; Medicine, University of Toronto, Toronto, Canada
3 Cardiology, St Michael's Hospital, Toronto, Canada; Medicine, University of Toronto, Toronto, Canada
4 Medicine, University of Melbourne, PO Box 2900, Fitzroy, Victoria, 3065, Australia; Cardiology, St Michael's Hospital, Toronto, Canada; Medicine, University of Toronto, Toronto, Canada
5 Pharmacology, University of Toronto, Toronto, Canada
6 Bio-imaging, St Michael's Hospital, Toronto, Canada
7 St. Michael's Hospital, 30 Bond Street, Toronto, M5B 1W8, Canada; Surgery, University of Toronto, Toronto, Canada
8 Schulich Heart Centre, Sunnybrook Health Sciences Centre, Toronto, Canada
9 Keenan Research Center, Li Ka Shing Knowledge Institute, Toronto, Canada; Cardiology, St. Michael's Hospital, St. Michael's Hospital, Toronto, M5B 1W8, Canada; Medicine, University of Toronto, Toronto, Canada; Pharmacology, University of Toronto, Toronto, Canada

* To whom correspondence should be addressed. E-mail: dorianp{at}smh.toronto.on.ca.

Background: Rapid ventricular pacing (RVP) is a well-established animal model of atrial fibrillation (AF). However, this model is limited by a high mortality rate and severe heart failure. The purpose of our study was to assess a new canine model of inducible AF. Methods and Results: We performed acute, short-term, simultaneous atrio-ventricular pacing (SAVP) and RVP (in random order) in 14 dogs for 30 seconds. SAVP produced more echocardiographic pulmonary venous flow reversal, a greater increase in mean pulmonary capillary wedge pressure and a significantly greater decrease in left atrial emptying function (-84.4 ± 38.6% vs. -23.7 ± 27.1%, p < 0.05), than RVP. Thirty dogs were randomized to three, longer-term, study groups: eight control (no pacing; CTRL), eight to RVP (2 weeks at 240 bpm followed by 3 weeks at 220 bpm), and fourteen to SAVP (2 weeks at 220 bpm). SAVP induced less left ventricular dysfunction, but more left atrial dysfunction, than RVP. SAVP dogs had similar atrial effective refractory periods as RVP dogs, but more heterogeneity in conduction and more AF inducibility (83% vs. 40%, p < 0.05), and maintenance (median 1660 s vs. 710 s, p < 0.05) than RVP dogs. SAVP induced more collagen turnover and was associated with a significantly greater increase in type III collagen in the atria compared to RVP dogs (6.9 ± 1.5 vs. 4.8 ± 1.6 respectively, p < 0.05 vs. 1.1 ± 0.7 in unpaced controls). Conclusion: The SAVP model induced profound mechanical and substrate atrial remodeling and reproducible sustained AF. This new model is clinically relevant and may be useful for testing AF interventions.







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