Abstract | BACKGROUND: OBJECTIVE: The purpose of this study was to test the validity of 5/6 nephrectomy (5.6Nx) as an appropriate model of AF associated with CKD and to investigate the role of oxidative stress. METHODS: RESULTS: We observed 5 main findings. (1) 5.6Nx induced renal dysfunction with elevation of systolic blood pressure and impaired glucose tolerance. (2) In the left atrium (LA), expressions of α-smooth muscle action and collagen type I, the compositional proteins of nicotinamide adenine dinucleotide phosphate ( NADPH) oxidase, and malondialdehyde were increased by 5.6Nx, which was reversed by DHLHZn treatment. (3) In the LA, the tissue content of angiotensin II was elevated by 5.6Nx, which was also reversed by DHLHZn. (4) Masson trichrome staining revealed that heterogeneous LA interstitial fibrosis was induced by 5.6Nx, which was attenuated by DHLHZn. (5) In isolated perfused heart experiments, 5.6Nx caused slowing of interatrial conduction. In the hearts of rats of the 5.6Nxgroup, right atrial extrastimuli invariably induced AF (8/8 [100%]), which were suppressed by DHLHZn (3/8 [38%], P <.05). CONCLUSION: We successfully established an appropriate model of AF associated with CKD in rats. Because the amount of NADPH oxidase was increased and the potent antioxidant agent DHLHZn was effective, oxidative stress may be involved in the pathogenesis of LA fibrosis and enhanced AF vulnerability in our model.
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Authors | Naoya Fukunaga, Naohiko Takahashi, Satoshi Hagiwara, Osamu Kume, Akira Fukui, Yasushi Teshima, Tetsuji Shinohara, Tomoko Nawata, Masahide Hara, Takayuki Noguchi, Tetsunori Saikawa |
Journal | Heart rhythm
(Heart Rhythm)
Vol. 9
Issue 12
Pg. 2023-31
(Dec 2012)
ISSN: 1556-3871 [Electronic] United States |
PMID | 22906534
(Publication Type: Comparative Study, Journal Article)
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Copyright | Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved. |
Topics |
- Animals
- Atrial Fibrillation
(etiology, metabolism, physiopathology)
- Blood Pressure
- Disease Models, Animal
- Male
- Oxidative Stress
(physiology)
- Rats
- Rats, Sprague-Dawley
- Renal Insufficiency, Chronic
(complications, metabolism)
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