BACKGROUND: Acute myocardial infarction can cause cardiac remodeling and heart failure, as well as skeletal myopathy, affecting patients' quality of life. Exercise therapy is an important rehabilitation method for patients with heart failure; however, the optimal exercise prescription has not been clarified.
OBJECTIVE: To compare the effects of different exercise modes (aerobic exercise, resistance exercise) on skeletal muscle remodeling in rats with acute myocardial infarction induced heart failure and to explore the possible mechanism, so as to provide a basis for optimizing the exercise rehabilitation program.
METHODS: Forty-eight Sprague-Dawley rats were randomly divided into sham operation group, myocardial infarction group, aerobic exercise group and resistance exercise group. Coronary artery ligation was used to create model of heart failure. After 3 months, animals in the aerobic exercise group and resistance exercise group underwent 12 weeks of corresponding exercise mode interventions, while those in the sham operation group and myocardial infarction group were kept quietly in mouse cages. After the experiment, maximal running speed and maximal weight-bearing load were measured by graded treadmill exercise test and ladder-climbing test respectively, and heart structure and function were evaluated by echocardiography. The heart was isolated, and hematoxylin-eosin staining and Sirius red staining were performed to detect cardiac remodeling. For the gstrocnemius muscle, ATPase staining was performed to observe changes in muscle fiber type and cell cross-sectional area, dihydroethidium method was used to evaluate reactive oxygen species levels, enzyme-linked immunosorbent method was used to determine malondialdehyde content and antioxidant enzyme activity, western blot was used to determine the expression of ubiquitin-proteasome system proteins, and the number of activated satellite cells (Pax7+/MyoD+) were detected by double immunofluorescence staining.
RESULTS AND CONCLUSION: (1) Exercise performance: Compared with the sham operation group, maximal running speed and maximal weight-bearing load in the myocardial infarction group decreased (P < 0.05); compared with the myocardial infarction group, the maximal running speed of the aerobic exercise group and the maximal weight-bearing load of the resistance exercise group increased (P < 0.05). (2) Cardiac remodeling: Compared with the sham operation group, infarction area, myocardial cell cross-sectional area, and collagen content in the myocardial infarction group increased (P < 0.05), while left ventricular ejection fraction and shortening fraction decreased (P < 0.05); compared with the myocardial infarction group, there was no statistical difference in the above parameters in both aerobic exercise resistance exercise groups (P > 0.05). (3) Skeletal muscle remodeling: Compared with the sham operation group, gastrocnemius muscle mass, gastrocnemius muscle mass index, cell cross-sectional area, superoxide dismutase activity, glutathione peroxidase activity, and the number of activated satellite cells decreased in myocardial infarction group (P < 0.05), while reactive oxygen species content, malondialdehyde content, and the protein expression of ubiquitin, MuRF1 and MAFbx increased (P < 0.05); compared with the myocardial infarction group, gastrocnemius muscle mass index, superoxide dismutase activity, the number of activated satellite cells increased in both aerobic exercise and resistance exercise groups (P < 0.05), while reactive oxygen species content and the protein expression of ubiquitin, MuRF1, and MAFbx decreased (P < 0.05); compared with the aerobic exercise group, gastrocnemius muscle mass, gastrocnemius muscle mass index, cell cross-sectional area, reactive oxygen species content, malondialdehyde content, the number of activated satellite cells increased in resistance exercise group (P < 0.05), while superoxide dismutase activity, glutathione peroxidase activity down-regulated (P < 0.05). To conclude, aerobic exercise and resistance exercise can both improve exercise performance of rats with heart failure, and the mechanism is related to reducing oxidative stress, inhibiting ubiquitin-proteasome system activity and activating satellite cells to improve skeletal muscle remodeling. Aerobic exercise has a better effect on improving skeletal muscle oxidative stress, while resistance exercise has a more significant effect on promoting skeletal muscle regeneration.