EFFECTS OF DEXAMETHASONE AND ATORVASTATIN ON ATRIAL SODIUM CURRENT AND ITS EARLY TACHYCARDIA-INDUCED ELECTRICAL REMODELING IN RABBITS

Abstract

ABSTRACT Purpose: Atrial fibrillation (AF) results in tachycardia-induced ionic remodeling. Pharmacological prevention of tachycardia-induced ionic remodeling not only with “classical” antiarrhythmics but also with drugs which provide a basis for some of the pillars of the so-called “upstream” therapy of AF like corticosteroids or statins has been proposed as a therapeutic strategy. Amongst other ion currents, atrial sodium current INa and its tachycardia-induced alterations play an important role in AF pathophysiology. Thus, effects of a dexamethasone (DT) and atorvastatin treatment (AT) on atrial sodium current INa and its tachycardia-induced remodeling were studied in a rabbit model. Methods: 9 groups with 4 animals were examined. Atrial pacemaker leads were implanted in all animals. No rapid atrial pacing (600/min) was performed in the control group but for 24 or 120 hours in the respective pacing groups. Instrumentation and pacing did not differ from the respective drug groups but an additional treatment with dexamethasone or atorvastatin (7 days) was performed. Results: Rapid atrial pacing (RAP, 600/min) reduced INa after 24 hours (≈ -50%) with no further reduction after 120 hours. DT reduced INa (≈ -20%), current densities in consecutively tachypaced animals did not differ from those in untreated animals. AT reduced INa similar as RAP, subsequent RAP did not further diminish INa. Conclusions: Impact of corticosteroids and statins on INa and its tachycardia-induced alterations also contribute to the mode of action of these substances in upstream treatment of atrial fibrillation.