CLINICAL RESEARCH: ATRIAL FIBRILLATION/FLUTTER, TACHYCARDIA
Effects of angiotensin II type 1 receptor antagonist on electrical and structural remodeling in atrial fibrillation
Koichiro Kumagai, MD*,*,
Hideko Nakashima, MD*,
Hidenori Urata, MD*,
Naoki Gondo, MD*,
Kikuo Arakawa, MD, FACC* and
Keijiro Saku, MD, FACC*
* Department of Cardiology, School of Medicine, Fukuoka University, Fukuoka, Japan
Manuscript received July 26, 2002;
revised manuscript received November 15, 2002,
accepted December 26, 2002.
* Reprint requests and correspondence: Dr. Koichiro Kumagai, Department of Cardiology, School of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, Fukuoka, 814-0180 Japan.
kxk{at}fukuoka-u.ac.jp
OBJECTIVES: The purpose of the present study was to evaluate the effect of angiotensin II type 1 receptor (AT1R) antagonist on chronic structural remodeling in atrial fibrillation (AF).
BACKGROUND: We previously reported that an AT1R antagonist, candesartan, prevents acute electrical remodeling in a rapid pacing model. However, the effect of candesartan on chronic structural remodeling in AF is unclear.
METHODS: Sustained AF was induced in 20 dogs (10 in a control group and 10 in a candesartan group) by rapid pacing of the right atrium (RA) at 400 beats/min for five weeks. Candesartan was administered orally (10 mg/kg/day) for one week before rapid pacing and was continued for five weeks. The AF duration, atrial effective refractory period (AERP) at four sites in the RA, and intra-atrial conduction time (CT) from the RA appendage to the other three sites were measured every week.
RESULTS: The mean AF duration in the control group after five weeks was significantly longer than that with candesartan (1,333 ± 725 vs. 411 ± 301 s, p < 0.01). The degree of AERP shortening after five weeks was not significantly different between the two groups. The CT from the RA appendage to the low RA after five weeks with candesartan was significantly shorter than that in the control (43 ± 14 vs. 68 ± 10 ms, p < 0.05). The candesartan group had a significantly lower percentage of interstitial fibrosis than the control group (7 ± 2% vs. 16 ± 1% at the RA appendage, p < 0.001).
CONCLUSIONS: Candesartan can prevent the promotion of AF by suppressing the development of structural remodeling.
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Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme | | AERP | = atrial effective refractory period | | AF | = atrial fibrillation | | Ang II | = angiotensin II | | AT1R | = angiotensin II type 1 receptor | | CT | = conduction time | | Erk | = extracellular signal-regulated kinases |
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P. L. L'Allier, A. Ducharme, P.-F. Keller, H. Yu, M.-C. Guertin, and J.-C. Tardif
Angiotensin-converting enzyme inhibition in hypertensive patients is associated with a reduction in the occurrence of atrial fibrillation
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[Abstract]
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A. Boldt, J. Garbade, J. F. Gummert, and S. Dhein
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S. Cardin, D. Li, N. Thorin-Trescases, T.-K. Leung, E. Thorin, and S. Nattel
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Cardiovasc Res,
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[Abstract]
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H. U. Klein and A. Goette
Blockade of atrial angiotensin II type 1 receptors: A novel antiarrhythmic strategy to prevent atrial fibrillation?
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I. Savelieva and A. John Camm
Atrial fibrillation and heart failure: natural history and pharmacological treatment
Europace,
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