title: Exercise-induced protection against reperfusion arrhythmia involves stabilization of mitochondrial energetics.
abstract: Mitochondria influence cardiac electrophysiology through energy- and redox-sensitive ion channels in the sarcolemma, with the collapse of energetics believed to be centrally involved in arrhythmogenesis. This study was conducted to determine if preservation of mitochondrial membrane potential (ΔΨm) contributes to the antiarrhythmic effect of exercise. We utilized perfused hearts, isolated myocytes, and isolated mitochondria exposed to metabolic challenge to determine the effects of exercise on cardiac mitochondria. Hearts from sedentary (Sed) and exercised (Ex; 10 days of treadmill running) Sprague-Dawley rats were perfused on a two-photon microscope stage for simultaneous measurement of ΔΨm and ECG. After ischemia-reperfusion, the collapse of ΔΨm was commensurate with the onset of arrhythmia. Exercise preserved ΔΨm and decreased the incidence of fibrillation/tachycardia (P < 0.05). Our findings in intact hearts were corroborated in isolated myocytes exposed to in vitro hypoxia-reoxygenation, with Ex rats demonstrating enhanced redox control and sustained ΔΨm during reoxygenation. Finally, we induced anoxia-reoxygenation in isolated mitochondria using high-resolution respirometry with simultaneous measurement of respiration and H2O2 Mitochondria from Ex rats sustained respiration with lower rates of H2O2 emission than Sed rats. Exercise helps sustain postischemic mitochondrial bioenergetics and redox homeostasis, which is associated with preserved ΔΨm and protection against reperfusion arrhythmia. The reduction of fatal ventricular arrhythmias through exercise-induced mitochondrial adaptations indicates that mitochondrial therapeutics may be an effective target for the treatment of heart disease.
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina; East Carolina Diabetes and Obesity Institute, Brody School of Medicine, East Carolina University, Greenville, North Carolina; and.
authors.forename: Rick J
authors.initials: RJ
authors.lastname: Alleman
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina; East Carolina Diabetes and Obesity Institute, Brody School of Medicine, East Carolina University, Greenville, North Carolina; and.
authors.forename: Alvin M
authors.initials: AM
authors.lastname: Tsang
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina; East Carolina Diabetes and Obesity Institute, Brody School of Medicine, East Carolina University, Greenville, North Carolina; and.
authors.forename: Terence E
authors.initials: TE
authors.lastname: Ryan
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina; East Carolina Diabetes and Obesity Institute, Brody School of Medicine, East Carolina University, Greenville, North Carolina; and.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Patteson
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina; East Carolina Diabetes and Obesity Institute, Brody School of Medicine, East Carolina University, Greenville, North Carolina; and.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McClung
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina; East Carolina Diabetes and Obesity Institute, Brody School of Medicine, East Carolina University, Greenville, North Carolina; and.
authors.forename: Espen E
authors.initials: EE
authors.lastname: Spangenburg
authors.affiliation: East Carolina Diabetes and Obesity Institute, Brody School of Medicine, East Carolina University, Greenville, North Carolina; and Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, Greenville, North Carolina.
authors.forename: Saame Raza
authors.initials: SR
authors.lastname: Shaikh
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina; East Carolina Diabetes and Obesity Institute, Brody School of Medicine, East Carolina University, Greenville, North Carolina; and.
authors.forename: P Darrell
authors.initials: PD
authors.lastname: Neufer
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, North Carolina; East Carolina Diabetes and Obesity Institute, Brody School of Medicine, East Carolina University, Greenville, North Carolina; and brownda@ecu.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
mesh_terms: D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005081:Exercise Therapy / Q000379:methods*; D005978:Glutathione / Q000378:metabolism; D006339:Heart Rate; D000067268:Isolated Heart Preparation; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008929:Mitochondria, Heart / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018384:Oxidative Stress; D005082:Physical Exertion; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012420:Running; D013997:Time Factors
chemical_list: D017382:Reactive Oxygen Species; D005978:Glutathione
keywords: arrhythmia; cardioprotection; exercise; membrane potential; mitochondria