title: Atrial remodeling in an ovine model of anthracycline-induced nonischemic cardiomyopathy: remodeling of the same sort.
abstract: BACKGROUND
  All preclinical studies of atrial remodeling in heart failure (HF) have been confined to a single model of rapid ventricular pacing. To evaluate whether the atrial changes were specific to the model or represented an end result of HF, this study aimed to characterize atrial remodeling in an ovine model of doxorubicin-induced cardiomyopathy.
  
  
  RESULTS
  Fourteen sheep, 7 with cardiomyopathy induced by repeated intracoronary doxorubicin infusions and 7 controls, were studied. The development of HF was monitored by cardiac imaging and hemodynamic parameters. Open chest electrophysiological study was performed using custom-made 128-electrode epicardial plaque assessing effective refractory period (ERP) and conduction velocity. Atrial tissues were harvested for structural analysis. The HF group had demonstrable moderate global HF (left ventricular ejection fraction [LVEF]: 37.1 vs 46.4%; P = 0.003) and showed the following compared to controls: left atrial dilatation (P = 0.02) and dysfunction (P = 0.005); longer P-wave duration (P < 0.05); higher ERP at all cycle lengths (P ≤ 0.002) and locations (P < 0.001); slower conduction velocity (P < 0.001); increased conduction heterogeneity index (P < 0.001); increased atrial fibrosis (right atrial [RA]: 5.9 ± 2.6 vs 2.8 ± 0.9%; P < 0.0001, left atrial [LA]: 3.7 ± 2.2 vs 2.4 ± 1.1%; P = 0.002), and longer induced atrial fibrillation (AF) episodes (16 ± 22 vs 2 ± 3 seconds; P = 0.04).
  
  
  CONCLUSIONS
  In this model of HF, there was significant atrial remodeling characterized by atrial enlargement/dysfunction, increased fibrosis, slowed/heterogeneous conduction, and increased refractoriness associated with more sustained AF. These findings appear the "same sort" to previous models of HF implicating a final common substrate leading to the development of AF in HF.
authors.affiliation: Cardiovascular Research Centre, Departments of Cardiology and Cardiothoracic Surgery, Royal Adelaide Hospital and the Disciplines of Medicine and Physiology, University of Adelaide, Adelaide, Australia.
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Lau
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Psaltis
authors.forename: Lorraine
authors.initials: L
authors.lastname: Mackenzie
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Kelly
authors.forename: Angelo
authors.initials: A
authors.lastname: Carbone
authors.forename: Michael
authors.initials: M
authors.lastname: Worthington
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Nelson
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Pawel
authors.initials: P
authors.lastname: Kuklik
authors.forename: Christopher X
authors.initials: CX
authors.lastname: Wong
authors.forename: James
authors.initials: J
authors.lastname: Edwards
authors.forename: David A
authors.initials: DA
authors.lastname: Saint
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Worthley
authors.forename: Prashanthan
authors.initials: P
authors.lastname: Sanders
mesh_terms: D000818:Animals; D018943:Anthracyclines; D009202:Cardiomyopathies / Q000139:chemically induced / Q000503:physiopathology; D004195:Disease Models, Animal; D004317:Doxorubicin; D006325:Heart Atria / Q000503:physiopathology*; D006329:Heart Conduction System / Q000503:physiopathology*; D006333:Heart Failure / Q000139:chemically induced* / Q000503:physiopathology*; D006801:Humans; D017202:Myocardial Ischemia / Q000139:chemically induced / Q000503:physiopathology; D012756:Sheep
chemical_list: D018943:Anthracyclines; D004317:Doxorubicin