Copyright © 2005, European Society of Cardiology
Prednisone prevents atrial fibrillation promotion by atrial tachycardia remodeling in dogs
aDepartment of Medicine and Research Center, Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada
bDepartment of Clinical Chemistry, Montreal Heart Institute, Montreal, Quebec, Canada
cDepartment of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
dDepartment of Radiation and Stress Cell Biology, University of Groningen, The Netherlands
* Corresponding author. Montreal Heart Institute, 5000 Belanger Street East, Montreal, Quebec, Canada H1T 1C8. Tel.: +1 514 376 3330; fax: +1 514 376 1355. Email address: stanley.nattel{at}icm-mhi.org
Background: There is evidence suggesting involvement of oxidative stress, inflammation, and calcineurin/nuclear factor of activated T cell pathways in atrial fibrillation. This study evaluated the efficacy of anti-inflammatory and calcineurin-inhibitory drugs on promotion of atrial fibrillation by atrial tachycardia-induced remodeling in dogs.
Methods and results: Dogs were subjected to atrial tachypacing at 400 bpm in the absence and presence of treatment with prednisone (15 or 50 mg/day) or ibuprofen (anti-inflammatory) or cyclosporine-A (calcineurin inhibitor). Serial closed-chest electrophysiological studies were performed in each dog at baseline and 2, 4, and 7 days after tachypacing onset. A final open-chest study was performed on day 8. Serum C-reactive protein was measured by ELISA and nitric oxide synthase by Western blotting. The mean duration of induced atrial fibrillation was markedly increased by tachypacing alone, from 26 ± 8 to 962 ± 317 s (p<0.01), and the atrial effective refractory period was decreased from 117 ± 4 to 73 ± 7 ms (p<0.001; cycle-length 300 ms). Tachypacing-induced effective refractory period shortening and atrial fibrillation promotion were unaffected by ibuprofen or cyclosporine-A; however, both doses of prednisone suppressed tachypacing-remodeling effects (atrial fibrillation duration to 96 ± 60 s and 28 ± 11 s at higher and lower doses, respectively; effective refractory period to 101 ± 6 ms for higher-dose and 105 ± 3 ms for lower-dose group). In addition, prednisone (but not ibuprofen or cyclosporine) significantly decreased C-reactive protein concentrations and attenuated the increase in endothelial nitric oxide synthase expression caused by atrial tachypacing.
Conclusions: Prednisone prevents the electrophysiological and atrial fibrillation-promoting effects of atrial tachycardia-remodeling, possibly by an anti-inflammatory action, whereas the less potent anti-inflammatory ibuprofen and the calcineurin inhibitor cyclosporine-A are without effect.
KEYWORDS Antiarrhythmic agents; Arrhythmia (mechanisms); Infection/inflammation; Remodeling
Time for primary review 7 days
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