Exercise Training Prevents Diaphragm Contractile Dysfunction in Heart Failure

NORMAN MANGNER, T. SCOTT BOWEN, SARAH WERNER, TINA FISCHER, YVONNE KULLNICK, ANDREAS OBERBACH, AXEL LINKE, LEIF STEIL, GERHARD SCHULER, VOLKER ADAMS
2016 Medicine & Science in Sports & Exercise  
26 Purpose: Patient studies have demonstrated the efficacy of exercise training in attenuating 27 respiratory muscle weakness in chronic heart failure (HF), yet direct assessment of muscle fiber 28 contractile function together with data on the underlying intracellular mechanisms remain 29 elusive. The present study, therefore, used a mouse model of HF to assess whether exercise 30 training could prevent diaphragm contractile fiber dysfunction, by potentially mediating the 31 complex interplay
more » ... complex interplay between intracellular oxidative stress and proteolysis. 32 Methods: Mice underwent sham operation (n=10) or a ligation of the left coronary artery and 33 were randomized to sedentary HF (n=10) or HF with aerobic exercise training (HF+AET; n=10). 34 Ten weeks later, echocardiography and histological analyses confirmed HF. 35 Results: In vitro diaphragm fiber bundles demonstrated contractile dysfunction in sedentary HF 36 compared to sham mice that was prevented by AET, with maximal force 21.0±0.7 vs. 26.7±1.4 37 and 25.4±1.4 N/cm 2 , respectively (P<0.05). Xanthine oxidase enzyme activity and MuRF1 38 protein expression, markers of oxidative stress and protein degradation, were ~20 and ~70 % 39 higher in sedentary HF compared to sham mice (P<0.05), but were not different when compared 40 to the HF+AET group. Oxidative modifications to numerous contractile proteins (i.e., actin and 41 creatine kinase) and markers of proteolysis (i.e. proteasome and calpain activity) were elevated in 42 sedentary HF compared to HF+AET mice (P<0.05), however these indices were not significantly 43 different between sedentary HF and sham mice. Anti-oxidative enzyme activities were also not 44 different between groups. 45 Conclusion: Our findings demonstrate that aerobic exercise training can protect against 46 diaphragm contractile fiber dysfunction induced by HF, but it remains unclear whether alterations 47 323 Alexander von Humboldt Foundation. 324 325 Conflict of interest: The authors declare no professional relationships. The results of the present 326 study do not constitute endorsement by ACSM, and are presented clearly, honestly, and without 327 fabrication, falsification, or inappropriate data manipulation. 328 329 330
doi:10.1249/mss.0000000000001016 pmid:27327028 fatcat:7uqdqrnodndrrex7lmgg5xca2i