title: Endurance exercise attenuates ventilator-induced diaphragm dysfunction.
abstract: Controlled mechanical ventilation (MV) is a life-saving measure for patients in respiratory failure. However, MV renders the diaphragm inactive leading to diaphragm weakness due to both atrophy and contractile dysfunction. It is now established that oxidative stress is a requirement for MV-induced diaphragmatic proteolysis, atrophy, and contractile dysfunction to occur. Given that endurance exercise can elevate diaphragmatic antioxidant capacity and the levels of the cellular stress protein heat shock protein 72 (HSP72), we hypothesized that endurance exercise training before MV would protect the diaphragm against MV-induced oxidative stress, atrophy, and contractile dysfunction in female Sprague-Dawley rats. Our results confirm that endurance exercise training before MV increased both HSP72 and the antioxidant capacity in the diaphragm. Importantly, compared with sedentary animals, exercise training before MV protected the diaphragm against MV-induced oxidative damage, protease activation, myofiber atrophy, and contractile dysfunction. Further, exercise protected diaphragm mitochondria against MV-induced oxidative damage and uncoupling of oxidative phosphorylation. These results provide the first evidence that exercise can provide protection against MV-induced diaphragm weakness. These findings are important and establish the need for future experiments to determine the mechanism(s) responsible for exercise-induced diaphragm protection.
authors.affiliation: Department of Applied Physiology and Kinesiology, Center for Exercise Science, University of Florida, Gainesville, Florida 32611, USA.
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Smuder
authors.forename: Kisuk
authors.initials: K
authors.lastname: Min
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Hudson
authors.forename: Andreas N
authors.initials: AN
authors.lastname: Kavazis
authors.forename: Oh-Sung
authors.initials: OS
authors.lastname: Kwon
authors.forename: W Bradley
authors.initials: WB
authors.lastname: Nelson
authors.forename: Scott K
authors.initials: SK
authors.lastname: Powers
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D019069:Cell Respiration / Q000502:physiology; D003964:Diaphragm / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology; D009133:Muscular Atrophy / Q000378:metabolism / Q000503:physiopathology; D009210:Myofibrils / Q000378:metabolism / Q000502:physiology; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000502:physiology; D010447:Peptide Hydrolases / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010807:Physical Endurance / Q000502:physiology*; D059748:Proteolysis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D050884:HSP72 Heat-Shock Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D010447:Peptide Hydrolases
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