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 I(Na) 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 
I(Na) 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 I(Na) after 24 hours (≈ 
-50%) with no further reduction after 120 hours. DT reduced I(Na) (≈ -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 I(Na).
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.