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Functional Characterization of Atrial Electrograms in a Pacing-Induced Heart Failure Model of Atrial Fibrillation: Importance of Regional Atrial Connexin40 Remodeling

Authors

  • MING-HSIUNG HSIEH M.D.,

    1. Division of Cardiology, Taipei Wang-Fan Hospital and Taipei Medical University, Taipei, Taiwan
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  • YENN-JIANG LIN M.D., Ph.D.,

    1. Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital
    2. Faculty of Medicine, Institute of Clinical Medicine, and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan
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  • HSUEH-HSIAO WANG Ph.D.,

    1. Departments of Internal Medicine and Medical Research, Mackay Memorial Hospital, Mackay Medical College, New Taipei City, Taiwan
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  • LI-WEI LO M.D.,

    1. Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital
    2. Faculty of Medicine, Institute of Clinical Medicine, and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan
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  • SHIH-LIN CHANG M.D.,

    1. Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital
    2. Faculty of Medicine, Institute of Clinical Medicine, and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan
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  • YI-LING YAN M.S.,

    1. Departments of Internal Medicine and Medical Research, Mackay Memorial Hospital, Mackay Medical College, New Taipei City, Taiwan
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  • THE-YING CHOU M.D., Ph.D.,

    1. Division of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan
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  • SHIH-ANN CHEN M.D.,

    1. Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital
    2. Faculty of Medicine, Institute of Clinical Medicine, and Cardiovascular Research Center, National Yang-Ming University, Taipei, Taiwan
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  • HUNG-I YEH M.D., Ph.D.

    Corresponding author
    • Departments of Internal Medicine and Medical Research, Mackay Memorial Hospital, Mackay Medical College, New Taipei City, Taiwan
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  • M.-H. Hsieh and Y.-J. Lin contributed equally to this manuscript.

  • This study was supported by research grants from the Taipei Veterans General Hospital (V100C-109), National Scientific Council (NSC98-2314-B-010-031-MY3, NSC99-2628-B-075-007-MY3), and Mackay Memorial Hospital (MMH-E-98003).

  • No disclosures.

Address for correspondence: Hung-I Yeh, M.D., Ph.D., Departments of Internal Medicine, Mackay Memorial Hospital, 92, Sector 2, Chung San North Road, Taipei 10449, Taiwan. Fax: 886-2-2543-3642; E-mail: hiyeh@ms1.mmh.org.tw

Cx40 Remodeling in Atrial Fibrillation

Introduction

Heart failure (HF) increases the susceptibility to atrial fibrillation (AF) and is associated with altered cardiomyocyte connexin. The regional remodeling of connexin(s) may contribute to the spatiotemporal organization of AF. This study sought to investigate the regional differences in connexin(s) and fibrosis in specific atrial regions and correlate that with the electrogram properties.

Methods and Results

Biatrial electroanatomic mapping during sinus rhythm (electrogram voltage and velocity) and AF (dominant frequency, DF) was performed in 6 ventricular pacing-induced HF dogs (at 252 beats/minute for 6 weeks) and 6 controls. Atrial tissues were sampled from 7 specific sites for analysis of the connexin and fibrosis. HF caused marked atrial dilatation, and increased the induced AF duration (P < 0.001). Remodeled connexins, including a lower expression and more lateralization of both connexin40 (Cx40) and Cx43 as well as increased regional dispersion of Cx40, in the presence of diffuse enhanced atrial fibrosis, characterized the atrial substrate of the HF dogs (P < 0.01). Regional analysis showed abnormal velocity and low electrogram voltage in the areas with downregulated Cx40 and Cx43 was enhanced in the presence of marked atrial fibrosis (>30% of area, P < 0.01). During AF, lower expression of the Cx40 was associated with higher DF in areas of less and more fibrosis, respectively (R = 0.67 and 0.58, P < 0.01).

Conclusions

An altered expression of connexins correlated with the electrogram properties in the existence of diffuse enhanced atrial fibrosis associated with HF. The regional remodeling of Cx40 is likely an important factor in the maintenance of AF in HF.

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