The DOI matches its Crossref record; 37 of the 38 references it cites were found in a registry or an index.
Mitochondria-targeted antioxidants protect against mechanical ventilation-induced diaphragm weakness*
Open accessAbstract
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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“the use of a mitochondrial-targeted antioxidant peptide (SS-31) has been shown to inhibit ROS production and skeletal muscle atrophy in a variety of experimental animal models of inactivity (Min, Smuder, Kwon, Kavazis, Szeto, and Powers 2011;Powers, Hudson, Nelson, Talbert, Min, Szeto, Kavazis, and Smuder 2011)”
From Successful aging: Advancing the science of physical independence in older adults (2015) · cites this paper as Powers et al. 2011
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Cites
[7] Mitochondrial respiratory control and the polarographic measurement of ADP : O ratios
Estabrook, R. W. (1967) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(67)10010-4 · Cited by 1,781
Rapid Disuse Atrophy of Diaphragm Fibers in Mechanically Ventilated Humans
Levine, S., Nguyen, T., Taylor, N. E., Friscia, M. E., Budak, M. T., Rothenberg, P., Zhu, J., Sachdeva, R., Sonnad, S. S., Kaiser, L. R., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa070447 · Cited by 1,580
A Comparison of Four Methods of Weaning Patients from Mechanical Ventilation
Esteban, A., Frutos–Vivar, F., Tobin, M. J., Alía, I., Solsona, J. F., Valverdu, V., Fernández, R., de la Cal, M. A., Benito, S., Tomás, R., et al. (1995) · New England Journal of Medicine · doi:10.1056/nejm199502093320601 · Cited by 1,542
Anderson, E. J., Lustig, M. E., Boyle, K. E., Woodlief, T. L., Kane, D. A., Lin, C.-T., Price, J. W., Kang, L., Rabinovitch, P. S., Szeto, H. H., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci37048 · Cited by 1,253
Zhao, K., Zhao, G.-M., Wu, D., Soong, Y., Birk, A. V., Schiller, P. W., & Szeto, H. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402999200 · Cited by 782
Self-citationThe Machinery of Mitochondrial Inheritance and Behavior
Yaffe, M. P. (1999) · Science · doi:10.1126/science.283.5407.1493 · Cited by 496
Is Weaning Failure Caused by Low-Frequency Fatigue of the Diaphragm?
Laghi, F. A., Cattapan, S. E., Jubran, A., Parthasarathy, S., Warshawsky, P. J., Choi, Y.-S. A., & Tobin, M. J. (2003) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200210-1246oc · Cited by 359
Shanely, R. A., Zergeroğlu, A. M., Lennon, S. L., Sugiura, T., Yimlamai, T., Enns, D., BELCASTRO, A. N., & Powers, S. K. (2002) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200202-088oc · Cited by 348
Type II skeletal myofibers possess unique properties that potentiate mitochondrial H2O2 generation
Anderson, E. J., & Neufer, P. D. (2005) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00402.2005 · Cited by 339
Mechanical ventilation results in progressive contractile dysfunction in the diaphragm
Powers, S. K., Shanely, R. A., Coombes, J. S., Koesterer, T. J., McKenzie, M., Gammeren, D. V., Cicale, M. J., & DODD, S. L. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00881.2001 · Cited by 319
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Items 201–254 of 254
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Zhu, E., & Sassoon, C. S. H. (2012) · Critical Care Medicine · doi:10.1097/ccm.0b013e318263236e · Cited by 8
[Diaphragm dysfunction : Facts for clinicians].
Bruells, C. S., & Marx, G. (2018) · PubMed · doi:10.1007/s00063-016-0226-0 · Cited by 7
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Powers, S. K., & Gómez‐Cabrera, M. C. (2026) · Sports Medicine and Health Science · doi:10.1016/j.smhs.2026.03.006 · Cited by 7
Li, L., Tien, M.-L., Leung, S., & Lin, M. (2011) · Intensive Care Medicine · doi:10.1007/s00134-011-2350-x · Cited by 7
Mechanical ventilation preserves diaphragm mitochondrial function in a rat sepsis model
Eyenga, P., Roussel, D., Rey, B., Ndille, P., Teulier, L., Eyenga, F., Romestaing, C., Morel, J., Gueguen‐Chaignon, V., & Sheu, S. S. (2021) · Intensive Care Medicine Experimental · doi:10.1186/s40635-021-00384-w · Cited by 7
Graham, Z., DeBerry, J. J., Cardozo, C. P., & Bamman, M. M. (2021) · Physiological Reports · doi:10.14814/phy2.14751 · Cited by 6
Sigurtà, A., Zambelli, V., & Bellani, G. (2016) · Medical Hypotheses · doi:10.1016/j.mehy.2016.07.013 · Cited by 6
Hall, S. E., Ahn, B., Smuder, A. J., Morton, A. B., Hinkley, J. M., Wiggs, M. P., Sollanek, K. J., Hyatt, H. W., & Powers, S. K. (2020) · Clinical and Translational Science · doi:10.1111/cts.12916 · Cited by 6
Rossetti, M. L., Dunlap, K. R., Salazar, G., Hickner, R. C., Kim, J., Chase, P. B., Miller, B. F., & Gordon, B. S. (2021) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2021.111391 · Cited by 6
Levine, S., Budak, M. T., Dierov, J. K., & Singhal, S. K. (2011) · Critical Care Medicine · doi:10.1097/ccm.0b013e31821e85ca · Cited by 8
SS-31: A promising therapeutic agent against bleomycin-induced pulmonary fibrosis in Mice
Gu, Q., Wang, Y., Zhang, H., Yang, W., Meng, X., & Zhao, M. (2025) · PLoS ONE · doi:10.1371/journal.pone.0315473 · Cited by 4
Mitochondrial bioenergetics are not associated with myofibrillar protein synthesis rates
Holwerda, A. M., Dirks, M. L., Barbeau, P., Goessens, J. P. B., Gijsen, A. P., van Loon, L. J. C., & Holloway, G. P. (2024) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1002/jcsm.13532 · Cited by 4
Bruells, C. S., Duschner, P., Marx, G., Gayan‐Ramirez, G., Frank, N., Breuer, T., Krenkel, O., Tacke, F., & Mossanen, J. C. (2021) · Scientific Reports · doi:10.1038/s41598-021-85859-2 · Cited by 5
When Does Nutrition Impact Respiratory Function?
Allen, K. S., Mehta, I., & Cavallazzi, R. (2013) · Current Gastroenterology Reports · doi:10.1007/s11894-013-0327-3 · Cited by 5
Yasul, Y., Yılmaz, B., YASUL, M. E., Şenel, Ö., & Çınar, V. (2024) · Turkish Journal of Kinesiology · doi:10.31459/turkjkin.1429014 · Cited by 4
Skeletal Muscle Dysfunction in Critical Illness
Iida, Y., & Sakuma, K. (2017) · InTech eBooks · doi:10.5772/intechopen.69051 · Cited by 5
Aldh1a1 and Scl25a30 in diaphragmatic dysfunction
Zhang, D., Hao, W., Li, X., Han, P., & Niu, Q. (2022) · Experimental Biology and Medicine · doi:10.1177/15353702221085201 · Cited by 3
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Hailiang, B., Xiafen, B., Hao, X., Jiake, C., & Hongjie, D. (2024) · Journal of Burn Care & Research · doi:10.1093/jbcr/irae009 · Cited by 3
Relevance of Ventilator-induced Diaphragm Dysfunction in ICU Patients
Demoule, A., Coirault, C., Jaber, S., & Similowski, T. (2012) · Clinical Pulmonary Medicine · doi:10.1097/cpm.0b013e318272cf2e · Cited by 3
Pardo, P. S., Lopez, M. A., Mohamed, J. S., & Boriek, A. M. (2017) · Journal of Muscle Research and Cell Motility · doi:10.1007/s10974-017-9483-7 · Cited by 3
Mitochondrial dysfunction in sepsis
Schroder, E. A., Callahan, L. A., Wang, L., & Supinski, G. S. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-85666-9.00016-4 · Cited by 2
Noor, R. A. M., Shah, N. S. M., Zin, A. A. M., & Sulaiman, W. A. W. (2025) · Tissue and Cell · doi:10.1016/j.tice.2025.102887 · Cited by 2
Ran, Y., Wang, Y., Lv, C., Zhao, Y., & Zheng, L. (2025) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2025.118281 · Cited by 2
Diaphragm Function in Health and Disease
Powers, S. K. (2025) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-88361-3_25 · Cited by 2
Effect of Long-Term Polytrauma on Ventilator-Induced Diaphragmatic Dysfunction in a Piglet Model
Breuer, T., Bruells, C. S., Horst, K., Thiele, C., Hildebrand, F., Linnartz, S., Siegberg, T., Frank, N., Gayan‐Ramirez, G., Märtin, L., et al. (2018) · Shock · doi:10.1097/shk.0000000000001272 · Cited by 2
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Claassen, W. J., van den Berg, M., Shi, Z., Baelde, R., Bogaards, S. J. P., Bonis, L., Hakkeling, H., Bamyani, A., Schaaf, G., Beishuizen, A., et al. (2024) · medRxiv · doi:10.1101/2024.07.23.24310792 · Cited by 1
González-Seguel, F., Gustafson, O. D., Robinson, C. M., Villablanca, C., Olave, C., Muñoz-Muñoz, F., Cáceres-Parra, C., Parry, S. M., Wen, Y., Dupont‐Versteegden, E. E., et al. (2026) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01125.2025 · Cited by 1
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Martone, M., Irving, B. A., Spielmann, G., Johannsen, N. M., Robinson, M. M., Chancellor, J. C., & Allaway, H. C. M. (2026) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00014.2026 · Cited by 1
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Pryor, E. K., Wachsmuth, H. R., & McCully, K. K. (2020) · Medical Research Archives · doi:10.18103/mra.v8i8.2198 · Cited by 1
Bai, H., Duan, H., Chen, C., Liu, L. Y., Wu, Y., Han, S., & Wang, X. T. (2021) · PubMed Central · doi:10.3760/cma.j.cn501120-20200120-00030 · Cited by 1
王, 茜. (2023) · Advances in Clinical Medicine · doi:10.12677/acm.2023.13112559 · Cited by 1
Jackson, M. J. (2024) · Proceedings of The Nutrition Society · doi:10.1017/s0029665124004877 · Cited by 1
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Travis, S. K., Skinner, S. K., Thome, T., Fitzgerald, L. F., Cohen, M. S., Wolan, D. W., Toth, M. J., RYAN, T. E., & Hepple, R. T. (2022) · Preprints.org · doi:10.20944/preprints202203.0225.v1 · Cited by 1
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Bickenbach, J., Brülls, C. S., & Marx, G. (2014) · Springer eBooks · doi:10.1007/978-3-319-03746-2_12
Georges, M. (2013) · Revue des Maladies Respiratoires Actualités · doi:10.1016/s1877-1203(13)70475-0
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Demoule, A. (2014) · Revue des Maladies Respiratoires Actualités · doi:10.1016/s1877-1203(14)70509-9
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Bruells, C. S., Goetzenich, A., & Rossaint, R. (2013) · Zeitschrift für Herz- Thorax- und Gefäßchirurgie · doi:10.1007/s00398-013-1028-9
Siegel, M. P. (2012) · ResearchWorks at the University of Washington (University of Washington)
Is diaphragmatic dysfunction a major problem following mechanical ventilation?
Goligher, E. C., & Dres, M. (2020) · Elsevier eBooks · doi:10.1016/b978-0-323-64068-8.00021-3
Ventilator-Induced Diaphragm Dysfunction
Li, H.-L. (2021) · Springer eBooks · doi:10.1007/978-981-15-9770-1_11
Kavazis, A. N., & Smuder, A. J. (2012) · Springer eBooks · doi:10.1007/978-3-540-29807-6_203
Trinity, J. D., Drummond, M. J., Fermoyle, C. C., McKenzie, A. I., Supiano, M. A., & Richardson, R. S. (2022) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00339.2022
Liu, H., Chai, D., Lyu, X., Zhao, B., Zhi, N., Yang, Y., Zhou, X., Dong, H., Liao, Y., Zhang, W., et al. (2024) · Research Square · doi:10.21203/rs.3.rs-4539738/v1
Meneses‐Valdés, R., Gallero, S., Hentze, J., Nielsen, S. F., Nielsen, J., Jaimovich, E., Henríquez‐Olguín, C., & Jensen, T. E. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.08.19.671046
Mitophagy in Botulinum Toxin Type A ‐Induced Muscle Atrophy
Mao, Q., Chen, Z., Xie, S., Xiang, R., & Cai, Z. (2025) · Oral Diseases · doi:10.1111/odi.70168
Additional file 1 of Energetic dysfunction in sepsis: a narrative review
Preau, S., Vodovar, D., Jung, B., Lancel, S., Zafrani, L., Flatres, A., Oualha, M., Voiriot, G., Jouan, Y., Joffre, J., et al. (2021) · Figshare · doi:10.6084/m9.figshare.14905992
Semel, M. G., Lukasiewicz, C. J., Skinner, S. K., Viggars, M. R., Noh, S. G., Picard, M., Mannings, A.-G., Cohen, M. S., Wolan, D. W., RYAN, T. E., et al. (2026) · The Journal of Physiology · doi:10.1113/jp291213
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Cussonneau, L. (2022) · theses.fr (ABES) · doi:10.70675/1a11a81bzf829z4ba2zba9az6f3f4841c773
Kavazis, A. N., & Smuder, A. J. (2026) · Springer eBooks · doi:10.1007/978-3-032-05988-8_203
Metadata
- 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
- Venue
- Critical Care Medicine
- Published
- 2011-07
- Volume
- 39
- Issue
- 7
- Pages
- 1749-1759
- ISSN
- 0090-3493 (ISSN-L)
- 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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