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

  • Natale Rolim
  • Kristine Skårdal
  • Morten Høydal
  • Mirta M. L. Sousa
  • Vegard Malmo
  • Guri Kaurstad
  • Charlotte B. Ingul
  • Harald E. M. Hansen
  • Marcia N. Alves
  • Marte Thuen
  • Olav Haraldseth
  • Patricia C. Brum
  • Geir Slupphaug
  • Jan Pål Loennechen
  • Tomas Stølen
  • Ulrik Wisløff
Original Contribution

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.

Keywords

Diabetes mellitus Myocardial infarction Arrhythmias Calcium Aerobic interval training 

Notes

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).

Conflict of interest

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

Supplementary material

395_2015_502_MOESM1_ESM.docx (30 kb)
Supplementary material 1 (DOCX 30 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Natale Rolim
    • 1
  • Kristine Skårdal
    • 2
  • Morten Høydal
    • 1
  • Mirta M. L. Sousa
    • 3
  • Vegard Malmo
    • 2
    • 4
  • Guri Kaurstad
    • 1
  • Charlotte B. Ingul
    • 1
  • Harald E. M. Hansen
    • 1
  • Marcia N. Alves
    • 1
  • Marte Thuen
    • 2
  • Olav Haraldseth
    • 2
  • Patricia C. Brum
    • 5
  • Geir Slupphaug
    • 3
  • Jan Pål Loennechen
    • 2
    • 4
  • Tomas Stølen
    • 1
  • Ulrik Wisløff
    • 1
  1. 1.Department of Circulation and Medical Imaging, K.G. Jebsen Center of Exercise in MedicineNorwegian University of Science and Technology-NTNUTrondheimNorway
  2. 2.Department of Circulation and Medical Imaging, MILabNorwegian University of Science and Technology-NTNUTrondheimNorway
  3. 3.Department of Cancer Research and Molecular MedicineProteomics and Metabolomics Core Facility-PROMEC of the Norwegian University of Science and Technology-NTNUTrondheimNorway
  4. 4.Department of CardiologySt. Olavs University HospitalTrondheimNorway
  5. 5.School of Physical Education and SportUniversity of São PauloSão PauloBrazil

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