The purpose of this study was to determine if exercise (Ex) protects hearts from arrhythmias induced by
glutathione oxidation or
ischemia-reperfusion (I/R). Female Sprague-Dawley rats were divided into two experimental groups: sedentary controls (Sed) or short-term Ex (10 days of treadmill running). Twenty-four hours after the last session, hearts were excised and exposed to either perfusion with the
thiol oxidant diamide (200 μM) or global I/R. Ex significantly delayed the time to the onset of ventricular
arrhythmia after irreversible
diamide perfusion. During a shorter
diamide perfusion protocol with washout, Ex significantly decreased the incidence of
arrhythmia, as evidenced by a delayed time to the first observed
arrhythmia, lower
arrhythmia scores, and lower incidence of
ventricular fibrillation. Ex hearts exposed to I/R (30-min
ischemia/30-min reperfusion) also showed lower
arrhythmia scores and incidence of
ventricular fibrillation compared with Sed counterparts. Our finding that Ex protected intact hearts from
thiol oxidation was corroborated in isolated ventricular myocytes. In myocytes from Ex animals, both the increase in H(2)O(2) fluorescence and incidence of cell death were delayed after
diamide. Although there were no baseline differences in reduced-to-
oxidized glutathione ratios (GSH/
GSSG) between the Sed and Ex groups, GSH/
GSSG was better preserved in Ex groups after
diamide perfusion and I/R. Myocardial
glutathione reductase activity was significantly enhanced after Ex, and this was preserved in the Ex group after
diamide perfusion. Our results show that Ex protects the heart from arrhythmias after two different oxidative stressors and support the hypothesis that sustaining the GSH/
GSSG pool stabilizes cardiac electrical function during conditions of oxidative stress.