title: Repolarization abnormalities and their arrhythmogenic consequences in porcine tachycardia-induced cardiomyopathy.
abstract: OBJECTIVE
  Action potential prolongation related to the alteration of several membrane currents is constantly reported in heart failure (HF) but reports about its role in arrhythmogenesis are sparse. Our aim was to determine, by analogy with long QT syndromes, whether prolonged repolarization is associated with increased dispersion or linked to bradycardia-dependent ventricular arrhythmias in pacing-induced cardiomyopathy.
  
  
  METHODS
  QT intervals, action potentials and transmural activation-to-recovery intervals (ARIs) along with whole-cell delayed rectifier (I(K)) and transient outward (I(to1)) K+ currents were recorded in left ventricle from pigs with HF and controls. HF was obtained after 14 days of rapid pacing at 250 ms.
  
  
  RESULTS
  Repolarization was delayed as indexed by corrected QT intervals (13.7% increase, P<0.01) or ARIs (252+/-4 to 340+/-7 ms, P<0.01). ARIs were uniformly prolonged with disappearance of the transmural gradient, spatial dispersion of repolarization decreased by 50% (P<0.05). I(to1) density was reduced in HF from 1.35+/-0.1 to 0.57+/-0.04 pA/pF subepicardially, from 1.05+/-0.19 to 0.55+/-0.08 pA/pF midmyocardially and from 1.04+/-0.1 to 0.48+/-0.04 pA/pF subendocardially. I(K) density was significantly decreased in HF pigs vs. controls: subepicardially from 0.46+/-0.04 to 0.22+/-0.02 pA/pF; midmyocardially from 0.46+/-0.05 to 0.25+/-0.03 pA/pF; and subendocardially from 0.49+/-0.04 to 0.20+/-0.04 pA/pF following depolarization at +50 mV. Electrocardiogram (ECG) monitoring at the time of death did not disclose any polymorphic ventricular tachyarrhythmia.
  
  
  CONCLUSIONS
  Despite a profound alteration in K+ currents, repolarization is uniformly prolonged in this model with no proclivity to develop bradycardia-dependent arrhythmias.
authors.affiliation: Department of Cardiology, University of Lille, France. dlacroix@chru_lille.fr
authors.forename: Dominique
authors.initials: D
authors.lastname: Lacroix
authors.forename: Pascale
authors.initials: P
authors.lastname: Gluais
authors.forename: Christelle
authors.initials: C
authors.lastname: Marquié
authors.forename: Christine
authors.initials: C
authors.lastname: D'Hoinne
authors.forename: Monique
authors.initials: M
authors.lastname: Adamantidis
authors.forename: Michèle
authors.initials: M
authors.lastname: Bastide
mesh_terms: D000200:Action Potentials; D000704:Analysis of Variance; D000818:Animals; D002304:Cardiac Pacing, Artificial; D004562:Electrocardiography; D006333:Heart Failure / Q000503:physiopathology*; D066298:In Vitro Techniques; D008133:Long QT Syndrome / Q000503:physiopathology*; D023421:Models, Animal; D018408:Patch-Clamp Techniques; D010477:Perfusion; D024661:Potassium Channels, Inwardly Rectifying; D013552:Swine; D020257:Ventricular Remodeling
chemical_list: D024661:Potassium Channels, Inwardly Rectifying