Circulation. 2004;110:2313-2319
Published online before print October 11, 2004, doi: 10.1161/01.CIR.0000145163.56529.D1
Published online before print October 11, 2004, doi: 10.1161/01.CIR.0000145163.56529.D1
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(Circulation. 2004;110:2313-2319.)
© 2004 American Heart Association, Inc.
Arrhythmia/Electrophysiology |
Effect of Simvastatin and Antioxidant Vitamins on Atrial Fibrillation Promotion by Atrial-Tachycardia Remodeling in Dogs
From the Department of Medicine (S.N., A.S.-T., G.S.), Clinical Chemistry (J.L.), and Research Center (A.S.-T., G.S., S.N.), Montreal Heart Institute and University of Montreal, Montreal, Quebec, Canada.
Correspondence to Stanley Nattel, 5000 Belanger St E, Montreal, Quebec H1T 1C8, Canada. E-mail stanley.nattel{at}icm-mhi.org
Received March 16, 2004; revision received May 26, 2004; accepted May 28, 2004.
Background— There is evidence for a role of oxidant stress and inflammation in atrial fibrillation (AF). Statins have both antioxidant and antiinflammatory properties. We compared the effects of simvastatin with those of antioxidant vitamins on AF promotion by atrial tachycardia in dogs.
Methods and Results— We studied dogs subjected to atrial tachypacing (ATP) at 400 bpm in the absence and presence of treatment with simvastatin, vitamin C, and combined vitamins C and E. Serial closed-chest electrophysiological studies were performed in each dog at baseline and 2, 4, and 7 days after tachypacing onset. Atrioventricular block was performed to control ventricular rate. Mean duration of induced AF was increased from 42±18 to 1079±341 seconds at terminal open-chest study after tachypacing alone (P<0.01), and atrial effective refractory period (ERP) at a cycle length of 300 ms was decreased from 117±5 to 76±6 ms (P<0.01). Tachypacing-induced ERP shortening and AF promotion were unaffected by vitamin C or vitamins C and E; however, simvastatin suppressed tachypacing-induced remodeling effects significantly, with AF duration and ERP averaging 41±15 seconds and 103±4 ms, respectively, after tachypacing with simvastatin therapy. Tachypacing downregulated L-type Ca2+-channel 
-subunit expression (Western blot), an effect that was unaltered by antioxidant vitamins but greatly attenuated by simvastatin.
Conclusions— Simvastatin attenuates AF promotion by atrial tachycardia in dogs, an effect not shared by antioxidant vitamins, and constitutes a potentially interesting new pharmacological approach to preventing the consequences of atrial tachycardia remodeling.
Key Words: antioxidants • antiarrhythmia agents • electrophysiology
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