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Type: Journal article
Title: Atrial arrhythmia in ageing spontaneously hypertensive rats: Unraveling the substrate in hypertension and ageing
Author: Lau, D.
Shipp, N.
Kelly, D.
Thanigaimani, S.
Neo, M.
Kuklik, P.
Lim, H.
Zhang, Y.
Drury, K.
Wong, C.
Chia, N.
Brooks, A.
Dimitri, H.
Saint, D.
Brown, L.
Sanders, P.
Citation: PLoS One, 2013; 8(8):1-10
Publisher: Public Library of Science
Issue Date: 2013
ISSN: 1932-6203
Statement of
Dennis H. Lau, Nicholas J. Shipp, Darren J. Kelly, Shivshankar Thanigaimani, Melissa Neo, Pawel Kuklik, Han S. Lim, Yuan Zhang, Karen Drury, Christopher X. Wong, Nicholas H. Chia, Anthony G. Brooks, Hany Dimitri, David A. Saint, Lindsay Brown, Prashanthan Sanders
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.
Keywords: Myocardium
Heart Atria
Heart Conduction System
Rats, Inbred SHR
Rats, Inbred WKY
Atrial Fibrillation
Hypertrophy, Left Ventricular
Risk Factors
Myocardial Contraction
Refractory Period, Electrophysiological
Atrial Remodeling
In Vitro Techniques
Rights: © 2013 Lau et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI: 10.1371/journal.pone.0072416
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