title: Digoxin delays recovery from tachycardia-induced electrical remodeling of the atria.
abstract: BACKGROUND
  Atrial fibrillation (AF) induces electrical remodeling, which is thought to be responsible for the low success rate of antiarrhythmic treatment in AF of longer duration. Electrical remodeling seems to be related to tachycardia-induced intracellular calcium overload. Due to its vagomimetic action, digoxin is widely used to control the ventricular rate during AF, but it also increases intracellular calcium. On the basis of these characteristics, we hypothesized that digoxin would aggravate tachycardia-induced electrical remodeling.
  
  
  RESULTS
  We analyzed the atrial effective refractory period (AERP) at cycle lengths of 430, 300, and 200 ms during 24 hours of rapid atrio/ventricular (300/150 bpm) pacing in 7 chronically instrumented conscious goats treated with digoxin or saline. Digoxin decreased the spontaneous heart rate but had no other effects on baseline electrophysiological characteristics. In addition to a moderate increase in the rate of electrical remodeling during rapid pacing, digoxin significantly delayed the recovery from electrical remodeling after cessation of pacing (at 430, 300, and 200 ms: P=0. 001, P=0.0015, and P=0.007, respectively). This was paralleled by an increased inducibility and duration of AF during digoxin. Multivariate analysis revealed that both a short AERP and treatment with digoxin were independent predictors of inducibility (P=0.001 and P=0.03, respectively) and duration (P=0.001 for both) of AF.
  
  
  CONCLUSIONS
  Dioxin aggravates tachycardia-induced atrial electrical remodeling and delays recovery from electrical remodeling in the goat, which increases the inducibility and duration of AF.
authors.affiliation: Department of Cardiology, Thoraxcenter, University of Groningen, Netherlands.
authors.forename: R G
authors.initials: RG
authors.lastname: Tieleman
authors.forename: Y
authors.initials: Y
authors.lastname: Blaauw
authors.forename: I C
authors.initials: IC
authors.lastname: Van Gelder
authors.forename: C D
authors.initials: CD
authors.lastname: De Langen
authors.forename: P J
authors.initials: PJ
authors.lastname: de Kam
authors.forename: J G
authors.initials: JG
authors.lastname: Grandjean
authors.forename: K W
authors.initials: KW
authors.lastname: Patberg
authors.forename: K J
authors.initials: KJ
authors.lastname: Bel
authors.forename: M A
authors.initials: MA
authors.lastname: Allessie
authors.forename: H J
authors.initials: HJ
authors.lastname: Crijns
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001016:Aortic Bodies / Q000187:drug effects; D001281:Atrial Fibrillation / Q000503:physiopathology; D016275:Atrial Function / Q000187:drug effects*; D004077:Digoxin / Q000494:pharmacology*; D004594:Electrophysiology; D006041:Goats; D006339:Heart Rate; D012032:Refractory Period, Electrophysiological; D013612:Tachycardia, Ectopic Atrial / Q000503:physiopathology*
chemical_list: D000889:Anti-Arrhythmia Agents; D004077:Digoxin