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Exercise protects against reperfusion arrhythmia by sustaining mitochondrial energetics (881.1)
Author(s) -
Alleman Rick,
Patel Hetal,
Moukdar Fatiha,
Brown David
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.881.1
Subject(s) - cardioprotection , cardiology , medicine , ventricular fibrillation , ventricular tachycardia , reperfusion injury , sudden cardiac death , ischemia
Exercise is known to confer cardioprotection against ventricular arrhythmia and reduce the incidence of sudden cardiac death, yet the underlying mechanisms are not fully understood. We have previously shown that the transition to arrhythmia occurs concomitant with a collapse in mitochondrial energetics, which induces action potential lability via ATP‐ and redox‐sensitive ion channels. In this study, we hypothesized that the cardioprotection observed in exercised (Ex; 10 d of treadmill running) animals would be associated with maintenance of mitochondrial membrane potential (ΔΨ m ) in early reperfusion. We used a novel combination of two‐photon microscopy in intact, perfused hearts, coupled to simultaneous electrocardiogram recording to test our hypothesis. Hearts underwent 40/30 min of ischemia/reperfusion. Consistent with our previous work, hearts that displayed heterogeneous collapses in ΔΨ m transitioned to ventricular arrhythmia. Hearts from Ex animals experienced a much lower incidence of reperfusion arrhythmia than sedentary counterparts, with 7 of 8 Sed hearts experiencing tachycardia or fibrillation compared to 3 of 8 Ex hearts. ΔΨ m , assessed with the fluorescent probe TMRM, was better maintained in Ex hearts during the first 10 minutes of reperfusion. Mitochondrial respiratory control ratios were similar following ischemia/reperfusion in Sed and Ex (9.00±0.92 v. 9.03±0.70, respectively), suggesting that mitochondrial damage was similar across groups. These data provide a definitive link between sustaining mitochondrial energetics and prevention of electrical dysfunction with Ex, and suggest that therapies that preserve ΔΨ m can mitigate sudden cardiac death in patients experiencing acute coronary syndromes.