title: Endurance exercise training normalizes repolarization and calcium-handling abnormalities, preventing ventricular fibrillation in a model of sudden cardiac death.
abstract: The risk of sudden cardiac death is increased following myocardial infarction. Exercise training reduces arrhythmia susceptibility, but the mechanism is unknown. We used a canine model of sudden cardiac death (healed infarction, with ventricular tachyarrhythmias induced by an exercise plus ischemia test, VF+); we previously reported that endurance exercise training was antiarrhythmic in this model (Billman GE. Am J Physiol Heart Circ Physiol 297: H1171-H1193, 2009). A total of 41 VF+ animals were studied, after random assignment to 10 wk of endurance exercise training (EET; n = 21) or a matched sedentary period (n = 20). Following (>1 wk) the final attempted arrhythmia induction, isolated myocytes were used to test the hypotheses that the endurance exercise-induced antiarrhythmic effects resulted from normalization of cellular electrophysiology and/or normalization of calcium handling. EET prevented VF and shortened in vivo repolarization (P < 0.05). EET normalized action potential duration and variability compared with the sedentary group. EET resulted in a further decrement in transient outward current compared with the sedentary VF+ group (P < 0.05). Sedentary VF+ dogs had a significant reduction in repolarizing K(+) current, which was restored by exercise training (P < 0.05). Compared with controls, myocytes from the sedentary VF+ group displayed calcium alternans, increased calcium spark frequency, and increased phosphorylation of S2814 on ryanodine receptor 2. These abnormalities in intracellular calcium handling were attenuated by exercise training (P < 0.05). Exercise training prevented ischemically induced VF, in association with a combination of beneficial effects on cellular electrophysiology and calcium handling.
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Bonilla
authors.forename: Andriy E
authors.initials: AE
authors.lastname: Belevych
authors.forename: Arun
authors.initials: A
authors.lastname: Sridhar
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nishijima
authors.forename: Hsiang-Ting
authors.initials: HT
authors.lastname: Ho
authors.forename: Quanhua
authors.initials: Q
authors.lastname: He
authors.forename: Monica
authors.initials: M
authors.lastname: Kukielka
authors.forename: Dmitry
authors.initials: D
authors.lastname: Terentyev
authors.forename: Radmila
authors.initials: R
authors.lastname: Terentyeva
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Victor P
authors.initials: VP
authors.lastname: Long
authors.forename: Sandor
authors.initials: S
authors.lastname: Györke
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Carnes
authors.forename: George E
authors.initials: GE
authors.lastname: Billman
mesh_terms: D000200:Action Potentials; D000818:Animals; D020013:Calcium Signaling; D016757:Death, Sudden, Cardiac / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D005081:Exercise Therapy; D006339:Heart Rate; D009203:Myocardial Infarction / Q000150:complications; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D010807:Physical Endurance; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D015221:Potassium Channels; D019837:Ryanodine Receptor Calcium Release Channel; D011188:Potassium