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Electrical and structural remodeling contribute to atrial fibrillation in type 2 diabetic db/db mice

  • Loryn J. Bohne
    Affiliations
    Libin Cardiovascular Institute, Department of Cardiac Sciences, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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  • Hailey J. Jansen
    Affiliations
    Libin Cardiovascular Institute, Department of Cardiac Sciences, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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  • Irene Daniel
    Affiliations
    Libin Cardiovascular Institute, Department of Cardiac Sciences, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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  • Tristan W. Dorey
    Affiliations
    Libin Cardiovascular Institute, Department of Cardiac Sciences, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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  • Motahareh Moghtadaei
    Affiliations
    Libin Cardiovascular Institute, Department of Cardiac Sciences, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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  • Darrell D. Belke
    Affiliations
    Libin Cardiovascular Institute, Department of Cardiac Sciences, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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  • Martin Ezeani
    Affiliations
    Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada
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  • Robert A. Rose
    Correspondence
    Address reprint requests and correspondence: Dr Robert A. Rose, Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, GAC66, Health Research Innovation Centre, 3280 Hospital Drive NW, Calgary, Alberta, Canada T2N 4Z6.
    Affiliations
    Libin Cardiovascular Institute, Department of Cardiac Sciences, Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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Published:September 07, 2020DOI:https://doi.org/10.1016/j.hrthm.2020.08.019

      Background

      Atrial fibrillation (AF) is highly prevalent in diabetes mellitus (DM), yet the basis for this finding is poorly understood. Type 2 DM may be associated with unique patterns of atrial electrical and structural remodeling; however, this has not been investigated in detail.

      Objective

      The purpose of this study was to investigate AF susceptibility and atrial electrical and structural remodeling in type 2 diabetic db/db mice.

      Methods

      AF susceptibility and atrial function were assessed in male and female db/db mice and age-matched wildtype littermates. Electrophysiological studies were conducted in vivo using intracardiac electrophysiology and programmed stimulation. Atrial electrophysiology was also investigated in isolated atrial preparations using high-resolution optical mapping and in isolated atrial myocytes using patch-clamping. Molecular biology studies were performed using quantitative polymerase chain reaction and western blotting. Atrial fibrosis was assessed using histology.

      Results

      db/db mice were highly susceptible to AF in association with reduced atrial conduction velocity, action potential duration prolongation, and increased heterogeneity in repolarization in left and right atria. In db/db mice, atrial K+ currents, including the transient outward current (Ito) and the ultrarapid delayed rectifier current (IKur), were reduced. The reduction in Ito occurred in association with reductions in Kcnd2 mRNA expression and KV4.2 protein levels. The reduction in IKur was not related to gene or protein expression changes. Interstitial atrial fibrosis was increased in db/db mice.

      Conclusion

      Our study demonstrates that increased susceptibility to AF in db/db mice occurs in association with impaired electrical conduction as well as electrical and structural remodeling of the atria.

      Keywords

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