期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 310, 期 10, 页码 H1360-H1370出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00858.2015
关键词
exercise; cardioprotection; mitochondria; arrhythmia; membrane potential
资金
- National Institutes of Health [R01 HL-123647-01, R15 HL-12292201, R01 DK-096907, R00 HL-103797]
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 (Delta Psi(m)) 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 Delta Psi(m) and ECG. After ischemia-reperfusion, the collapse of Delta Psi(m) was commensurate with the onset of arrhythmia. Exercise preserved Delta Psi(m) 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 Delta Psi(m) 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 Delta Psi(m) 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.
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