TY - JOUR
T1 - Atrial Arrhythmia in Ageing Spontaneously Hypertensive Rats
T2 - Unraveling the Substrate in Hypertension and Ageing
AU - Lau, Dennis H.
AU - Shipp, Nicholas J.
AU - Kelly, Darren J.
AU - Thanigaimani, Shivshankar
AU - Neo, Melissa
AU - Kuklik, Pawel
AU - Lim, Han S.
AU - Zhang, Yuan
AU - Drury, Karen
AU - Wong, Christopher X.
AU - Chia, Nicholas H.
AU - Brooks, Anthony G.
AU - Dimitri, Hany
AU - Saint, David A.
AU - Brown, Lindsay
AU - Sanders, Prashanthan
N1 - Funding Information:
Dr. Sanders reports having served on the advisory board of St. Jude Medical, Bard Electrophysiology, Biosense-Webster, Medtronic, Sanofi- Aventis, and Merck. Dr. Sanders reports having received lecture fees from St. Jude Medical, Bard Electrophysiology, Biosense-Webster, Medtronic and Merck. Dr. Sanders reports having received research funding from St. Jude Medical, Bard Electrophysiology, Biosense-Webster and Medtronic. However, this does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.
PY - 2013/8/27
Y1 - 2013/8/27
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84883177220
U2 - 10.1371/journal.pone.0072416
DO - 10.1371/journal.pone.0072416
M3 - Article
C2 - 24013508
AN - SCOPUS:84883177220
SN - 1932-6203
VL - 8
JO - PloS one
JF - PloS one
IS - 8
M1 - e72416
ER -