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

Lau, Dennis H., Shipp, Nicholas J., Kelly, Darren J., Thanigaimani, Shivshankar, Neo, Melissa, Kuklik, Pawel, Lim, Han S., Zhang, Yuan, Drury, Karen, Wong, Christopher X., Chia, Nicholas H., Brooks, Anthony G., Dimitri, Hany, Saint, David A., Brown, Lindsay, and Sanders, Prashanthan (2013) Atrial arrhythmia in ageing spontaneously hypertensive rats: unraveling the substrate in hypertension and ageing. PLoS ONE, 8 (8). e72416.

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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.

Item ID: 62534
Item Type: Article (Research - C1)
ISSN: 1932-6203
Copyright Information: (C) 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.
Funders: National Heart Foundation of Australia (NHF), National Health and Medical Research Council (NHMRC), University of Adelaide, Cardiac Society of Australian and New Zealand
Projects and Grants: NHF Grant-in-Aid G08A3653
Date Deposited: 18 Mar 2020 02:37
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1102 Cardiovascular Medicine and Haematology > 110201 Cardiology (incl Cardiovascular Diseases) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 100%
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