title: Ventricular rate determines early bradycardic electrical remodeling.
abstract: OBJECTIVE
  The purpose of this study was to isolate chronic ventricular rate as the primary determinant of early bradycardic ventricular electrical remodeling.
  
  
  BACKGROUND
  Ventricular repolarization delay predisposing to potentially lethal tachydysrhythmias occurs during chronic bradycardia. Prolonged QT intervals and torsades de pointes are associated with down-regulated ventricular myocyte delayed rectifier potassium (K(+)) currents.
  
  
  METHODS
  Transcatheter AV node ablation in rabbits was followed by chronic right ventricular pacing at either 140 bpm (n = 16) or the near-physiologic rate of 280 bpm (n = 9). ECG QT intervals were assessed in vivo at days 0 and 8 of paced AV block. Repolarizing currents in isolated left and right ventricular myocytes were assessed using whole-cell patch clamp technique.
  
  
  RESULTS
  Bradycardic rabbits had increased steady-state QT intervals (230 +/- 6 ms vs 206 +/- 7 ms [mean +/- SE], day 8 vs day 0; P < .001). Biventricular myocyte expression of the delayed rectifier K(+) currents I(Kr) and I(Ks) was down-regulated in bradycardic rabbits, with no change in the transient outward current I(to) or inwardly rectifying current I(K1). None of these changes were observed in rabbits paced at 280 bpm. Pause-dependent torsades de pointes was documented in one bradycardic animal on day 8. No heart failure or ventricular hypertrophy was apparent.
  
  
  CONCLUSIONS
  Bradycardic ventricular electrical remodeling proceeds independently of structural remodeling, heart failure, or AV synchrony and is prevented by maintenance of near-physiologic ventricular rate.
authors.affiliation: Cardiovascular Research Programme, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Suto
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Sean A
authors.initials: SA
authors.lastname: Cahill
authors.forename: Ilana
authors.initials: I
authors.lastname: Greenwald
authors.forename: André L C
authors.initials: AL
authors.lastname: Navarro
authors.forename: Gil J
authors.initials: GJ
authors.lastname: Gross
mesh_terms: D000818:Animals; D001919:Bradycardia / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D032383:Myocytes, Cardiac / Q000502:physiology; D018408:Patch-Clamp Techniques; D011817:Rabbits