Atrial arrhythmia in ageing spontaneously hypertensive rats: unraveling the substrate in hypertension and ageing

Lau, Dennis H. and Shipp, Nicholas J. and Kelly, Darren J. and Thanigaimani, Shivshankar and Neo, Melissa and Kuklik, Pawel and Lim, Han S. and Zhang, Yuan and Drury, Karen and Wong, Christopher X. and Chia, Nicholas H. and Brooks, Anthony G. and Dimitri, Hany and Saint, David A. and Brown, Lindsay and Sanders, Prashanthan (2013) Atrial arrhythmia in ageing spontaneously hypertensive rats: unraveling the substrate in hypertension and ageing. PLoS One, 8 (8). pp. 1-9. ISSN 1544-9173

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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.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: © 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.
Faculty / Department / School: Historic - Faculty of Health, Engineering and Sciences - School of Health, Nursing and Midwifery
Date Deposited: 09 Sep 2013 00:04
Last Modified: 15 May 2017 02:26
Fields of Research : 06 Biological Sciences > 0601 Biochemistry and Cell Biology > 060112 Structural Biology (incl. Macromolecular Modelling)
06 Biological Sciences > 0606 Physiology > 060602 Animal Physiology - Cell
11 Medical and Health Sciences > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl. Cardiovascular Diseases)
Socio-Economic Objective: E Expanding Knowledge > 97 Expanding Knowledge > 970106 Expanding Knowledge in the Biological Sciences
Identification Number or DOI: 10.1371/journal.pone.0072416
URI: http://eprints.usq.edu.au/id/eprint/24029

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