Effect of Simvastatin and Antioxidant Vitamins on Atrial Fibrillation Promotion by Atrial-Tachycardia Remodeling in Dogs

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Abstract
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 (PP2+-channel α-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.