Establishment of a model of atrial fibrillation associated with chronic kidney disease in rats and the role of oxidative stress

被引：47

作者：

Fukunaga, Naoya ^{[2
]}

Takahashi, Naohiko ^{[1
]}

Hagiwara, Satoshi ^{[3
]}

Kume, Osamu ^{[2
]}

Fukui, Akira ^{[1
]}

Teshima, Yasushi ^{[1
]}

Shinohara, Tetsuji ^{[2
]}

Nawata, Tomoko ^{[2
]}

Hara, Masahide ^{[2
]}

Noguchi, Takayuki ^{[3
]}

Saikawa, Tetsunori ^{[1
]}

机构：

[1] Oita Univ, Fac Med, Dept Lab Examinat & Diagnost, Hasama, Oita 8795593, Japan

[2] Oita Univ, Fac Med, Dept Internal Med 1, Hasama, Oita 8795593, Japan

[3] Oita Univ, Fac Med, Dept Anesthesia, Hasama, Oita 8795593, Japan

来源：

HEART RHYTHM | 2012年 / 9卷 / 12期

基金：

日本学术振兴会;

关键词：

Atrial fibrillation; Chronic kidney disease; Nephrectomy; Oxidative stress; NADPH OXIDASE; ANGIOTENSIN-II; RENAL-INSUFFICIENCY; REPERFUSION INJURY; FIBROSIS; RISK; HYPERTENSION; NOX4;

D O I：

10.1016/j.hrthm.2012.08.019

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND An animal model of atrial fibrillation (AF) associated with chronic kidney disease (CKD) has not been available. 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 Male Sprague-Dawley rats were subjected to 5.6Nx. A novel derivative of lipoic acid, sodium zinc dihydrolipoylhistidinate (DHLHZn), was subcutaneously infused. Four weeks later, hearts were isolated. 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 alpha-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.

引用

页码：2023 / 2031

页数：9

共 27 条

[1] Upregulation of Nox4 by Hypertrophic Stimuli Promotes Apoptosis and Mitochondrial Dysfunction in Cardiac Myocytes [J].

Ago, Tetsuro ;

Kuroda, Junya ;

Pain, Jayashree ;

Fu, Cexiong ;

Li, Hong ;

Sadoshima, Junichi .

CIRCULATION RESEARCH, 2010, 106 (07) :1253-U183

[2] Association of Chronic Kidney Disease With Atrial Fibrillation Among Adults in the United States REasons for Geographic and Racial Differences in Stroke (REGARDS) Study [J].

Baber, Usman ;

Howard, Virginia J. ;

Halperin, Jonathan L. ;

Soliman, Elsayed Z. ;

Zhang, Xiao ;

McClellan, William ;

Warnock, David G. ;

Muntner, Paul .

CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY, 2011, 4 (01) :26-32

[3] Effect of Exercise on Cardiac Tissue Oxidative and Inflammatory Mediators in Chronic Kidney Disease [J].

Bai, Y. ;

Sigala, W. ;

Adams, G. R. ;

Vaziri, N. D. .

AMERICAN JOURNAL OF NEPHROLOGY, 2009, 29 (03) :213-221

[4] NADPH oxidase signal transduces angiotensin II in hepatic stellate cells and is critical in hepatic fibrosis [J].

Bataller, R ;

Schwabe, RF ;

Choi, YH ;

Yang, L ;

Paik, YH ;

Lindquist, J ;

Qian, T ;

Schoonhoven, R ;

Hagedorn, CH ;

Lemasters, JJ ;

Brenner, DA .

JOURNAL OF CLINICAL INVESTIGATION, 2003, 112 (09) :1383-1394

[5] Pivotal role of a gp91phox-containing NADPH oxidase in angiotensin II-induced cardiac hypertrophy in mice [J].

Bendall, JK ;

Cave, AC ;

Heymes, C ;

Gall, N ;

Shah, AM .

CIRCULATION, 2002, 105 (03) :293-296

[6] Impact of atrial fibrillation on the risk of death [J].

Benjamin, EJ ;

Wolf, PA ;

D'Agostino, RB ;

Silbershatz, H ;

Kannel, WB ;

Levy, D .

CIRCULATION, 1998, 98 (10) :946-952

[7]

Campese VM, 1997, J NEPHROL, V10, P184

[8] A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress [J].

Del Rio, D ;

Stewart, AJ ;

Pellegrini, N .

NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES, 2005, 15 (04) :316-328

[9] Marinobufagenin stimulates fibroblast collagen production and causes fibrosis in experimental uremic cardiomyopathy [J].

Elkareh, Jihad ;

Kennedy, David J. ;

Yashaswi, Belvadi ;

Vetteth, Sandeep ;

Shidyak, Amjad ;

Kim, Eric G. R. ;

Smaili, Sleiman ;

Periyasamy, Sankaridrug M. ;

Hariri, Imad M. ;

Fedorova, Larisa ;

Liu, Jiang ;

Wu, Liang ;

Kahaleh, M. Bashar ;

Xie, Zijian ;

Malhotra, Deepak ;

Fedorova, Olga V. ;

Kashkin, Vladimir A. ;

Bagrov, Alexei Y. ;

Shapiro, Joseph I. .

HYPERTENSION, 2007, 49 (01) :215-224

[10] Prevalence of diagnosed atrial fibrillation in adults - National implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study [J].

Go, AS ;

Hylek, EM ;

Phillips, KA ;

Chang, YC ;

Henault, LE ;

Selby, JV ;

Singer, DE .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2001, 285 (18) :2370-2375

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