title: Effects of dexamethasone and atorvastatin on atrial sodium current and its early tachycardia-induced electrical remodeling in rabbits.
abstract: OBJECTIVE
  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.
authors.affiliation: Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard Karls Universität Tuebingen, Otfried-Mueller-Strasse 10, D-72076 Tuebingen, Germany. roman.laszlo@gmx.de
authors.forename: Roman
authors.initials: R
authors.lastname: Laszlo
authors.forename: Mareike
authors.initials: M
authors.lastname: Schwiebert
authors.forename: Karen Anna
authors.initials: KA
authors.lastname: Menzel
authors.forename: Christian
authors.initials: C
authors.lastname: Eick
authors.forename: Birgit
authors.initials: B
authors.lastname: Schreiner
authors.forename: Juergen
authors.initials: J
authors.lastname: Schreieck
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D002304:Cardiac Pacing, Artificial / Q000379:methods; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D006325:Heart Atria / Q000187:drug effects* / Q000503:physiopathology; D006538:Heptanoic Acids / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology; D013610:Tachycardia / Q000503:physiopathology*
chemical_list: D002316:Cardiotonic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D015222:Sodium Channels; D003907:Dexamethasone; D000069059:Atorvastatin