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Aerobic interval training reduces inducible ventricular arrhythmias in diabetic mice after myocardial infarction

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Abstract

Diabetes mellitus (DM) increases the risk of heart failure after myocardial infarction (MI), and aggravates ventricular arrhythmias in heart failure patients. Although exercise training improves cardiac function in heart failure, it is still unclear how it benefits the diabetic heart after MI. To study the effects of aerobic interval training on cardiac function, susceptibility to inducible ventricular arrhythmias and cardiomyocyte calcium handling in DM mice after MI (DM-MI). Male type 2 DM mice (C57BLKS/J Lepr db /Lepr db) underwent MI or sham surgery. One group of DM-MI mice was submitted to aerobic interval training running sessions during 6 weeks. Cardiac function and structure were assessed by echocardiography and magnetic resonance imaging, respectively. Ventricular arrhythmias were induced by high-frequency cardiac pacing in vivo. Protein expression was measured by Western blot. DM-MI mice displayed increased susceptibility for inducible ventricular arrhythmias and impaired diastolic function when compared to wild type-MI, which was associated with disruption of cardiomyocyte calcium handling and increased calcium leak from the sarcoplasmic reticulum. High-intensity exercise recovered cardiomyocyte function in vitro, reduced sarcoplasmic reticulum diastolic calcium leak and significantly reduced the incidence of inducible ventricular arrhythmias in vivo in DM-MI mice. Exercise training also normalized the expression profile of key proteins involved in cardiomyocyte calcium handling, suggesting a potential molecular mechanism for the benefits of exercise in DM-MI mice. High-intensity aerobic exercise training recovers cardiomyocyte function and reduces inducible ventricular arrhythmias in infarcted diabetic mice.

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Acknowledgments

We thank R. Røsbjørgen for technical assistance, J. Nauman for statistical support, and G. J. J. Silva, and J. B. N. Moreira for very helpful advices. This study was funded by K.G. Jebsen Foundation, The Norwegian Council on Cardiovascular Disease, The Research Council of Norway and Liaison Committee between the Central Norway Regional Health Authority (RHA), the Norwegian University of Science and Technology (NTNU), and the European Commission (FP7-Health-2013; OPTIMEX-602405).

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On behalf of all the authors, the corresponding author states that there is no conflict of interest.

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Authors and Affiliations

  1. Department of Circulation and Medical Imaging, K.G. Jebsen Center of Exercise in Medicine, Norwegian University of Science and Technology-NTNU, Box 8905, 7491, Trondheim, Norway

    Natale Rolim, Morten Høydal, Guri Kaurstad, Charlotte B. Ingul, Harald E. M. Hansen, Marcia N. Alves, Tomas Stølen & Ulrik Wisløff

  2. Department of Circulation and Medical Imaging, MILab, Norwegian University of Science and Technology-NTNU, Trondheim, Norway

    Kristine Skårdal, Vegard Malmo, Marte Thuen, Olav Haraldseth & Jan Pål Loennechen

  3. Department of Cancer Research and Molecular Medicine, Proteomics and Metabolomics Core Facility-PROMEC of the Norwegian University of Science and Technology-NTNU, Trondheim, Norway

    Mirta M. L. Sousa & Geir Slupphaug

  4. Department of Cardiology, St. Olavs University Hospital, Trondheim, Norway

    Vegard Malmo & Jan Pål Loennechen

  5. School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil

    Patricia C. Brum

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  1. Natale Rolim
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Correspondence to Natale Rolim.

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Rolim, N., Skårdal, K., Høydal, M. et al. Aerobic interval training reduces inducible ventricular arrhythmias in diabetic mice after myocardial infarction. Basic Res Cardiol 110, 44 (2015). https://doi.org/10.1007/s00395-015-0502-9

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