title: Hypertension and atrial fibrillation: evidence of progressive atrial remodeling with electrostructural correlate in a conscious chronically instrumented ovine model.
abstract: BACKGROUND
  Hypertension accounts for more atrial fibrillation (AF) than any other predisposing factor.
  
  
  OBJECTIVE
  The purpose of this study was to characterize the time course, extent, and electrostructural correlation of atrial remodeling in chronic hypertension.
  
  
  METHODS
  Thirty-two sheep were studied: 21 with induced "one-kidney, one-clip" hypertension and 11 controls. Sequential closed-chest electrophysiologic studies were performed in 12 conscious animals (6 hypertensive, 6 controls) to evaluate progressive remodeling over 15 weeks. Additional atrial structural/functional analyses were performed in 5 controls and at 5, 10, and 15 weeks of hypertension (five per time point) via histology/cardiac magnetic resonance imaging to correlate with open-chest electrophysiologic parameters.
  
  
  RESULTS
  The hypertensive group developed a progressive increase in mean arterial pressure (P <.001). Mean effective refractory periods were uniformly higher at all time points (P <.001). Progressive biatrial hypertrophy (P = .003), left atrial dysfunction (P <.05) and greater AF inducibility were seen early with increased inflammation from 5 weeks of hypertension. In contrast, significant conduction slowing (P <.001) with increased heterogeneity (P <.001) along with increased interstitial fibrosis resulted in longer and more fractionated AF episodes only from 10 weeks of hypertension. Significant electrostructural correlation was seen in conduction abnormalities and AF inducibility with both atrial inflammation and fibrosis.
  
  
  CONCLUSIONS
  Hypertension is associated with early and progressive changes in atrial remodeling. Atrial remodeling occurs at different time domains in chronic hypertension with significant electrostructural correlation of the remodeling cascade. Early institution of antihypertensive treatment may prevent formation of substrate capable of maintaining AF.
authors.affiliation: Cardiovascular Research Centre, Department of Cardiology, Royal Adelaide Hospital and Discipline of Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Lau
authors.forename: Lorraine
authors.initials: L
authors.lastname: Mackenzie
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Kelly
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Psaltis
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Michael
authors.initials: M
authors.lastname: Worthington
authors.forename: Arumuga
authors.initials: A
authors.lastname: Rajendram
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Kelly
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Pawel
authors.initials: P
authors.lastname: Kuklik
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Nelson
authors.forename: Christopher X
authors.initials: CX
authors.lastname: Wong
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Worthley
authors.forename: Mohan
authors.initials: M
authors.lastname: Rao
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Faull
authors.forename: James
authors.initials: J
authors.lastname: Edwards
authors.forename: David A
authors.initials: DA
authors.lastname: Saint
authors.forename: Prashanthan
authors.initials: P
authors.lastname: Sanders
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D016275:Atrial Function / Q000502:physiology*; D002908:Chronic Disease; D003243:Consciousness; D004195:Disease Models, Animal; D018450:Disease Progression; D022062:Electrophysiologic Techniques, Cardiac; D006325:Heart Atria / Q000473:pathology / Q000503:physiopathology*; D006329:Heart Conduction System / Q000503:physiopathology*; D006973:Hypertension / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D034561:Sheep, Domestic