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Atrial Tachyarrhythmias Induced by the Combined Effects of β1/2-adrenergic Autoantibodies and Thyroid Hormone in the Rabbit

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Abstract

Activating autoantibodies (AAb) to β-adrenergic receptors (βAR) are associated with atrial fibrillation in patients with Graves’ disease. In the present study, we examined the interaction of thyroid hormone with β1/2AR-AAb in inducing atrial tachyarrhythmias in the rabbit. Immunization of rabbits with a β1AR or β2AR second extracellular loop peptide produced high titers of β1AR-AAb or β2AR-AAb. Thyroid hormone in combination with β1AR-AAb or β2AR-AAb induced a significant number of sustained sinus tachycardia and atrial tachycardia, respectively. Both combinations resulted in significantly increased inductions of sustained arrhythmias compared to AAb alone. Thyroid hormone alone induced sustained sinus and junctional tachycardia. Sera from immunized rabbits specifically bound to and activated β1AR or β2AR in transfected cells in vitro. This study demonstrates thyroid hormone qualitatively accentuates the specific arrhythmogenic action of these AAb and quantitatively enhances their rate. Our data support a dual role of AAb and thyroid hormone in Graves’-associated tachyarrhythmias.

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Animal Subjects

This study protocol was approved by the Institutional Animal Care and Use Committee of the Oklahoma City Veterans Affairs Medical Center and Oklahoma University Health Sciences Center, and conforms to international standards for animal safety and comfort.

Human Subjects

No human studies were carried out by the authors for this article.

Funding

This work was supported in part by grants from a Veterans Affairs Merit Review Award (to D.C.K. and X.Y.), National Heart, Lung, and Blood Institute HL56267 (to M.W.C. and D.C.K.), American Heart Association Postdoctoral Fellowship (to H.L.), and the Helen and Will Webster Arrhythmia Research Fund of the University of Oklahoma Foundation (to B.J.S. and D.C.K.).

Conflict of Interest

The authors have no conflict of interest to disclose.

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Authors and Affiliations

  1. Heart Rhythm Institute, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    Hongliang Li, Benjamin J. Scherlag, David C. Kem, Alexandria Benbrook, Ling Zhang, Bing Huang, Ralph Lazzara & Xichun Yu

  2. Endocrinology and the Harold Hamm Diabetes Center, Veterans Affairs Medical Center and University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    Hongliang Li, David C. Kem & Xichun Yu

  3. Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    Madeleine W. Cunningham

  4. Heart Rhythm Institute and Endocrinology, University of Oklahoma Health Sciences Center, TCH 6E103, 1200 Everett Drive, Oklahoma City, OK, 73104, USA

    Xichun Yu

Authors
  1. Hongliang Li
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  2. Benjamin J. Scherlag
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  3. David C. Kem
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  4. Alexandria Benbrook
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  5. Ling Zhang
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  6. Bing Huang
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  7. Madeleine W. Cunningham
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  8. Ralph Lazzara
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  9. Xichun Yu
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Corresponding author

Correspondence to Xichun Yu.

Additional information

Associate Editor Enrique Lara-Pezzi oversaw the review of this article

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Li, H., Scherlag, B.J., Kem, D.C. et al. Atrial Tachyarrhythmias Induced by the Combined Effects of β1/2-adrenergic Autoantibodies and Thyroid Hormone in the Rabbit. J. of Cardiovasc. Trans. Res. 7, 581–589 (2014). https://doi.org/10.1007/s12265-014-9573-5

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  • DOI: https://doi.org/10.1007/s12265-014-9573-5

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