{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T02:21:05Z","timestamp":1789611665956,"version":"build-2803163510"},"reference-count":71,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,1,17]],"date-time":"2014-01-17T00:00:00Z","timestamp":1389916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Health Research Board Ireland"},{"name":"School of Medicine and Medical Science"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>The effects of chronic intermittent hypoxia (CIH) on respiratory muscles are relatively underexplored. It is speculated that muscle dysfunction and other key morbidities associated with sleep apnoea are the result of CIH\u2010induced oxidative stress. We sought to investigate the putative role of CIH\u2010induced reactive oxygen species in the development of respiratory muscle dysfunction.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>The CIH\u2010induced diaphragm muscle fatigue is time and intensity dependent and is associated with a modest oxidative stress. Supplementation with <jats:italic>N<\/jats:italic>\u2010acetyl cysteine prevents CIH\u2010induced diaphragm muscle dysfunction, suggesting that antioxidant supplementation may have therapeutic value in respiratory muscle disorders characterized by CIH, such as obstructive sleep apnoea.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>Respiratory muscle dysfunction documented in sleep apnoea patients is perhaps due to oxidative stress secondary to chronic intermittent hypoxia (CIH). We sought to explore the effects of different CIH protocols on respiratory muscle form and function in a rodent model. Adult male Wistar rats were exposed to CIH (<jats:italic>n<\/jats:italic>\u00a0=\u00a032) consisting of 90\u00a0s normoxia\u201390\u00a0s hypoxia (either 10 or 5% oxygen at the nadir; arterial O<jats:sub>2<\/jats:sub> saturation \u223c90 or 80%, respectively] for 8\u00a0h per day or to sham treatment (air\u2013air, <jats:italic>n<\/jats:italic>\u00a0=\u00a032) for 1 or 2\u00a0weeks. Three additional groups of CIH\u2010treated rats (5% O<jats:sub>2<\/jats:sub> for 2\u00a0weeks) had free access to water containing <jats:italic>N<\/jats:italic>\u2010acetyl cysteine (1% NAC, <jats:italic>n<\/jats:italic>\u00a0=\u00a08), tempol (1\u00a0m<jats:sc>m<\/jats:sc>, <jats:italic>n<\/jats:italic>\u00a0=\u00a08) or apocynin (2\u00a0m<jats:sc>m<\/jats:sc>, <jats:italic>n<\/jats:italic>\u00a0=\u00a08). Functional properties of the diaphragm muscle were examined <jats:italic>ex vivo<\/jats:italic> at 35\u00b0C. The myosin heavy chain and sarco(endo)plasmic reticulum Ca<jats:sup>2+<\/jats:sup>\u2010ATPase isoform distribution, succinate dehydrogenase and glyercol phosphate dehydrogenase enzyme activities, Na<jats:sup>+<\/jats:sup>\u2013K<jats:sup>+<\/jats:sup>\u2010ATPase pump content, concentration of thiobarbituric acid reactive substances, DNA oxidation and antioxidant capacity were determined. Chronic intermittent hypoxia (5% oxygen at the nadir; 2\u00a0weeks) decreased diaphragm muscle force and endurance. All three drugs reversed the deleterious effects of CIH on diaphragm endurance, but only NAC prevented CIH\u2010induced diaphragm weakness. Chronic intermittent hypoxia increased diaphragm muscle myosin heavy chain\u00a02B areal density and oxidized glutathione\/reduced glutathione (GSSG\/GSH) ratio. We conclude that CIH\u2010induced diaphragm dysfunction is reactive oxygen species dependent. <jats:italic>N<\/jats:italic>\u2010Acetyl cysteine was most effective in reversing CIH\u2010induced effects on diaphragm. Our results suggest that respiratory muscle dysfunction in sleep apnoea may be the result of oxidative stress and, as such, antioxidant treatment could prove a useful adjunctive therapy for the disorder.<\/jats:p><\/jats:sec>","DOI":"10.1113\/expphysiol.2013.076828","type":"journal-article","created":{"date-parts":[[2014,1,18]],"date-time":"2014-01-18T01:16:29Z","timestamp":1390007789000},"page":"688-700","source":"Crossref","is-referenced-by-count":43,"title":["Reactive oxygen species mediated diaphragm fatigue in a rat model of chronic intermittent hypoxia"],"prefix":"10.1113","volume":"99","author":[{"given":"Christine M.","family":"Shortt","sequence":"first","affiliation":[{"name":"UCD School of Medicine and Medical Science University College Dublin  Dublin Ireland"},{"name":"Department of Physiology School of Medicine University College Cork  Cork Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Fredsted","sequence":"additional","affiliation":[{"name":"Department of Biomedicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han Bing","family":"Chow","sequence":"additional","affiliation":[{"name":"UCD School of Medicine and Medical Science University College Dublin  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Physiology School of Medicine University College Cork  Cork Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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