Cited by 255Muscle Physiology and DisordersRespiratory Support and MechanismsMitochondrial Function and Pathology

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Mitochondria-targeted antioxidants protect against mechanical ventilation-induced diaphragm weakness*

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Powers, Scott K., Hudson, Matthew B., Nelson, W. Bradley, Talbert, Erin E., Min, Kisuk, Szeto, Hazel H., Kavazis, Andreas N., Smuder, Ashley J.·2011·Critical Care Medicine

DOI 10.1097/ccm.0b013e3182190b62PMC PMC4995067

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Abstract

BACKGROUND: Mechanical ventilation is a life-saving intervention used to provide adequate pulmonary ventilation in patients suffering from respiratory failure. However, prolonged mechanical ventilation is associated with significant diaphragmatic weakness resulting from both myofiber atrophy and contractile dysfunction. Although several signaling pathways contribute to diaphragm weakness during mechanical ventilation, it is established that oxidative stress is required for diaphragmatic weakness to occur. Therefore, identifying the site(s) of mechanical ventilation- induced reactive oxygen species production in the diaphragm is important. OBJECTIVE: These experiments tested the hypothesis that elevated mitochondrial reactive oxygen species emission is required for mechanical ventilation-induced oxidative stress, atrophy, and contractile dysfunction in the diaphragm. DESIGN: Cause and effect was determined by preventing mechanical ventilation-induced mitochondrial reactive oxygen species emission in the diaphragm of rats using a novel mitochondria-targeted antioxidant (SS-31). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Compared to mechanically ventilated animals treated with saline, animals treated with SS-31 were protected against mechanical ventilation-induced mitochondrial dysfunction, oxidative stress, and protease activation in the diaphragm. Importantly, treatment of animals with the mitochondrial antioxidant also protected the diaphragm against mechanical ventilation-induced myofiber atrophy and contractile dysfunction. CONCLUSIONS: These results reveal that prevention of mechanical ventilation-induced increases in diaphragmatic mitochondrial reactive oxygen species emission protects the diaphragm from mechanical ventilation-induced diaphragmatic weakness. This important new finding indicates that mitochondria are a primary source of reactive oxygen species production in the diaphragm during prolonged mechanical ventilation. These results could lead to the development of a therapeutic intervention to impede mechanical ventilation-induced diaphragmatic weakness.

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Authors: Powers, S. K., Hudson, M. B., Nelson, W. B., Talbert, E. E., Min, K., Szeto, H. H., Kavazis, A. N., & Smuder, A. J.
Affiliations: University of Florida (US)
ORCID: Powers, Scott K.
Hudson, Matthew B.
Nelson, W. Bradley
Talbert, Erin E.
Min, Kisuk
Szeto, Hazel H.
Kavazis, Andreas N.
Smuder, Ashley J.
Venue: Critical Care Medicine
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2011-07
Volume: 39
Issue: 7
Pages: 1749-1759
ISSN: 0090-3493 (ISSN-L)
DOI: 10.1097/ccm.0b013e3182190b62
PMC: PMC4995067
OpenAlex: W2059026617
Cited by: 255
References: 38
Citations by year: 2026: 6 · 2025: 10 · 2024: 16 · 2023: 9 · 2022: 11 · 2021: 23 · 2020: 21 · 2019: 16 · 2018: 21 · 2017: 15 · 2016: 22 · 2015: 22 · 2014: 19 · 2013: 20 · 2012: 16
FWCI: 8.19
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Critical Care Medicine (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Heart, Lung, and Blood Institute (R01HL087839)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Respiratory Support and Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords: mechanical ventilation, diaphragmatic weakness, mitochondria-targeted antioxidants, SS-31, mitochondrial reactive oxygen species, oxidative stress, diaphragm atrophy, contractile dysfunction, protease activation, mitochondrial dysfunction, respiratory failure
MeSH terms: Tripartite Motif Proteins, Actins, Animals, Calpain, Diaphragm, Female, Hydrogen Peroxide, Mitochondria, Muscle, Muscle Contraction, Muscle Proteins, Muscular Atrophy, Oligopeptides, Respiration, Artificial, Rats, Sprague-Dawley, Oxidative Stress, Muscle Fibers, Skeletal, Muscle Weakness, Ubiquitin-Protein Ligases, SKP Cullin F-Box Protein Ligases, Rats, Caspase 3

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Mitochondria-targeted antioxidants protect against mechanical ventilation-induced diaphragm weakness*

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