title: Aerobic interval training reduces inducible ventricular arrhythmias in diabetic mice after myocardial infarction.
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.
authors.affiliation: 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@ntnu.no.
authors.forename: Natale
authors.initials: N
authors.lastname: Rolim
authors.forename: Kristine
authors.initials: K
authors.lastname: Skårdal
authors.forename: Morten
authors.initials: M
authors.lastname: Høydal
authors.forename: Mirta M L
authors.initials: MM
authors.lastname: Sousa
authors.forename: Vegard
authors.initials: V
authors.lastname: Malmo
authors.forename: Guri
authors.initials: G
authors.lastname: Kaurstad
authors.forename: Charlotte B
authors.initials: CB
authors.lastname: Ingul
authors.forename: Harald E M
authors.initials: HE
authors.lastname: Hansen
authors.forename: Marcia N
authors.initials: MN
authors.lastname: Alves
authors.forename: Marte
authors.initials: M
authors.lastname: Thuen
authors.forename: Olav
authors.initials: O
authors.lastname: Haraldseth
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Brum
authors.forename: Geir
authors.initials: G
authors.lastname: Slupphaug
authors.forename: Jan Pål
authors.initials: JP
authors.lastname: Loennechen
authors.forename: Tomas
authors.initials: T
authors.lastname: Stølen
authors.forename: Ulrik
authors.initials: U
authors.lastname: Wisløff
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000150:complications*; D010805:Physical Conditioning, Animal; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000502:physiology; D016277:Ventricular Function, Left
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium