{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T16:49:02Z","timestamp":1769359742684,"version":"3.49.0"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,6,16]],"date-time":"2021-06-16T00:00:00Z","timestamp":1623801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Mechanical ventilation (MV) is a clinical tool providing adequate alveolar ventilation in patients that require respiratory support. Although a life\u2010saving intervention for critically ill patients, prolonged MV results in the rapid development of inspiratory muscle weakness due to both diaphragmatic atrophy and contractile dysfunction; collectively known as \u201cventilator\u2010induced diaphragm dysfunction\u201d (VIDD). VIDD is a severe clinical problem because diaphragmatic weakness is a risk factor for difficulties in weaning patients from MV. Currently, no standard treatment to prevent VIDD exists. Nonetheless, growing evidence reveals that hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) possesses cytoprotective properties capable of protecting skeletal muscles against several hallmarks of VIDD, including oxidative damage, accelerated proteolysis, and mitochondrial damage. Therefore, we used an established animal model of MV to test the hypothesis that treatment with sodium sulfide (H<jats:sub>2<\/jats:sub>S donor) will defend against VIDD. Our results confirm that sodium sulfide was sufficient to protect the diaphragm against both MV\u2010induced fiber atrophy and contractile dysfunction. H<jats:sub>2<\/jats:sub>S prevents MV\u2010induced damage to diaphragmatic mitochondria as evidenced by protection against mitochondrial uncoupling. Moreover, treatment with sodium sulfide prevented the MV\u2010induced activation of the proteases, calpain, and caspase\u20103 in the diaphragm. Taken together, these results support the hypothesis that treatment with a H<jats:sub>2<\/jats:sub>S donor protects the diaphragm against VIDD. These outcomes provide the first evidence that H<jats:sub>2<\/jats:sub>S has therapeutic potential to protect against MV\u2010induced diaphragm weakness and to reduce difficulties in weaning patients from the ventilator.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:boxed-text content-type=\"box\" position=\"anchor\"><jats:caption><jats:title>Study Highlights<\/jats:title><\/jats:caption><jats:p><jats:list list-type=\"simple\"><jats:list-item><jats:p><jats:bold>WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?<\/jats:bold><\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><jats:p>Mechanical ventilation (MV) results in diaphragm atrophy and contractile dysfunction, known as ventilator\u2010induced diaphragm dysfunction (VIDD). VIDD is important because diaphragm weakness is a risk factor for problems in weaning patients from MV. Currently, no accepted treatment exists to protect against VIDD. Growing evidence reveals that hydrogen sulfide (H<jats:sub>2<\/jats:sub>S) donors protect skeletal muscle against ischemia\u2010reperfusion\u2010induced injury. Nonetheless, it is unknown if treatment with a H<jats:sub>2<\/jats:sub>S donor can protect against VIDD.<jats:list list-type=\"simple\"><jats:list-item><jats:p><jats:bold>WHAT QUESTION DID THIS STUDY ADDRESS?<\/jats:bold><\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><jats:p>Can treatment with an H<jats:sub>2<\/jats:sub>S donor protect against VIDD?<jats:list list-type=\"simple\"><jats:list-item><jats:p><jats:bold>WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?<\/jats:bold><\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><jats:p>This study provides the first evidence that treatment with a H<jats:sub>2<\/jats:sub>S donor protects against VIDD.<jats:list list-type=\"simple\"><jats:list-item><jats:p><jats:bold>HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?<\/jats:bold><\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><jats:p>These new findings provide the basis for further exploration of H<jats:sub>2<\/jats:sub>S donors as a therapy to prevent VIDD and reduce the risk of problems in weaning patients from MV.<\/jats:p><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1111\/cts.13081","type":"journal-article","created":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T08:04:37Z","timestamp":1622707477000},"page":"2139-2145","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Hydrogen sulfide donor protects against mechanical ventilation\u2010induced atrophy and contractile dysfunction in the rat diaphragm"],"prefix":"10.1111","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0467-3312","authenticated-orcid":false,"given":"Noriko","family":"Ichinoseki\u2010Sekine","sequence":"first","affiliation":[{"name":"Graduate School of Arts and Sciences The Open University of Japan Chiba Japan"},{"name":"School of Health and Sports Science Juntendo University Inzai Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley J.","family":"Smuder","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology University of Florida Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron B.","family":"Morton","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology University of Florida Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James M.","family":"Hinkley","sequence":"additional","affiliation":[{"name":"AdventHealth Translational Research Institute Orlando Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andres","family":"Mor Huertas","sequence":"additional","affiliation":[{"name":"Department of Applied Physiology and Kinesiology University of Florida Gainesville Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott K.","family":"Powers","sequence":"additional","affiliation":[{"name":"Department 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