Exploring the mechanisms of exercise-induced cardioprotection against myocardial stunning

Brief periods of ischemia followed by reperfusion results in stunning of the myocardium that is reversible within hours to days. This insult leads to contractile dysfunction and is associated with an increase in reactive oxygen species and calcium overload. Exercise has been shown to be cardioprotective against a stunning insult. The mechanisms behind this cardioprotection are unclear and are the focus of this experiment. These experiments tested the hypothesis that exercise-induced increases in manganese superoxide dismutase (MnSOD) activity and glutathione (GSH) levels in the heart are essential to achieve exercise-induced cardioprotection against myocardial stunning. To test this hypothesis, adult male rats were randomly assigned to 1 of 4 experimental groups: (1) sedentary, control with no treatment (S-C); (2) exercise trained, control no treatment (E-C); (3) exercise trained, treated with antisense oligonucleotide against MnSOD (E-AS); and (4) exercise trained, treated with mismatch oligonucleotide (E-MM). Groups were further subdivided into two surgery groups: sham or an in vitro working heart ischemia-reperfusion (I-R) group to evaluate cardiac performance and contractile dysfunction. Exercise trained animals performed 60 minutes of treadmill running at ∼70% VO2max for 3 consecutive days. Exercise-induced increases in myocardial MnSOD content and activity were inhibited using an AS oligonucleotide against MnSOD. A mismatch oligonucleotide was employed as a control to test the specificity of the AS oliogonucleotide against MnSOD. Exercise training increased MnSOD activity in the E-C and E-MM as compared to the S-C and E-AS groups (p < 0.05). In contrast, exercise did not alter (p > 0.05) myocardial GSH content in any experimental group. When hearts were subjected to an I-R insult of 25 minutes ischemia followed by 30 minutes of reperfusion, all trained groups showed significant recovery of pre-ischemic cardiac work (SP x CO) versus S-C. Additionally, the release of LDH, a marker of cellular damage, was significantly elevated in the S-C group as compared to the trained groups (p < 0.05). In conclusion, our results indicate that increases in myocardial GSH levels and MnSOD activity are not essential to achieve exercise-induced cardioprotection against stunning; therefore, exercise-induced cardioprotection must occur via other mechanisms.