title: Atrial arrhythmia in ageing spontaneously hypertensive rats: unraveling the substrate in hypertension and ageing.
abstract: BACKGROUND
  Both ageing and hypertension are known risk factors for atrial fibrillation (AF) although the pathophysiological contribution or interaction of the individual factors remains poorly understood. Here we aim to delineate the arrhythmogenic atrial substrate in mature spontaneously hypertensive rats (SHR).
  
  
  METHODS
  SHR were studied at 12 and 15 months of age (n = 8 per group) together with equal numbers of age-matched normotensive Wistar-Kyoto control rats (WKY). Electrophysiologic study was performed on superfused isolated right and left atrial preparations using a custom built high-density multiple-electrode array to determine effective refractory periods (ERP), atrial conduction and atrial arrhythmia inducibility. Tissue specimens were harvested for structural analysis.
  
  
  RESULTS
  COMPARED TO WKY CONTROLS, THE SHR DEMONSTRATED: Higher systolic blood pressure (p<0.0001), bi-atrial enlargement (p<0.05), bi-ventricular hypertrophy (p<0.05), lower atrial ERP (p = 0.008), increased atrial conduction heterogeneity (p = 0.001) and increased atrial interstitial fibrosis (p = 0.006) & CD68-positive macrophages infiltration (p<0.0001). These changes resulted in higher atrial arrhythmia inducibility (p = 0.01) and longer induced AF episodes (p = 0.02) in 15-month old SHR. Ageing contributed to incremental bi-atrial hypertrophy (p<0.01) and atrial conduction heterogeneity (p<0.01) without affecting atrial ERP, fibrosis and arrhythmia inducibility. The limited effect of ageing on the atrial substrate may be secondary to the reduction in CD68-positive macrophages.
  
  
  CONCLUSIONS
  Significant atrial electrical and structural remodeling is evident in the ageing spontaneously hypertensive rat atria. Concomitant hypertension appears to play a greater pathophysiological role than ageing despite their compounding effect on the atrial substrate. Inflammation is pathophysiologically linked to the pro-fibrotic changes in the hypertensive atria.
authors.affiliation: Centre for Heart Rhythm Disorders (CHRD), University of Adelaide and Royal Adelaide Hospital, Adelaide, Australia.
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Lau
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Shipp
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Kelly
authors.forename: Shivshankar
authors.initials: S
authors.lastname: Thanigaimani
authors.forename: Melissa
authors.initials: M
authors.lastname: Neo
authors.forename: Pawel
authors.initials: P
authors.lastname: Kuklik
authors.forename: Han S
authors.initials: HS
authors.lastname: Lim
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Karen
authors.initials: K
authors.lastname: Drury
authors.forename: Christopher X
authors.initials: CX
authors.lastname: Wong
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Chia
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Hany
authors.initials: H
authors.lastname: Dimitri
authors.forename: David A
authors.initials: DA
authors.lastname: Saint
authors.forename: Lindsay
authors.initials: L
authors.lastname: Brown
authors.forename: Prashanthan
authors.initials: P
authors.lastname: Sanders
mesh_terms: D000375:Aging; D000818:Animals; D001281:Atrial Fibrillation / Q000209:etiology* / Q000503:physiopathology; D064752:Atrial Remodeling; D006325:Heart Atria / Q000473:pathology / Q000503:physiopathology; D006329:Heart Conduction System; D006973:Hypertension / Q000150:complications*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012032:Refractory Period, Electrophysiological; D012307:Risk Factors