{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T08:22:50Z","timestamp":1740126170266,"version":"3.37.3"},"reference-count":33,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,8,26]],"date-time":"2015-08-26T00:00:00Z","timestamp":1440547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Australian National Health and Medical Research Council","award":["APP1010665","1045824"],"award-info":[{"award-number":["APP1010665","1045824"]}]},{"DOI":"10.13039\/501100001069","name":"Women and Infants Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001069","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Sylvia and Charles Viertel Senior Medical Research Fellowship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Respirology"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and objective<\/jats:title><jats:p><jats:italic>In utero<\/jats:italic> infection may critically influence diaphragm development and predispose preterm infants to postnatal respiratory failure. We aimed to determine how frequency and gestational age (<jats:styled-content style=\"fixed-case\">GA<\/jats:styled-content>) at time of intra\u2010amniotic (<jats:styled-content style=\"fixed-case\">IA<\/jats:styled-content>) lipopolysaccharide (<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>) exposure affects preterm diaphragm function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pregnant ewes received <jats:styled-content style=\"fixed-case\">IA<\/jats:styled-content> injections of saline or 10\u2010mg <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> at 7 days or 21 days or weekly injections 21, 14 and 7 days before delivery at 121\u2010day <jats:styled-content style=\"fixed-case\">GA<\/jats:styled-content>. Foetal lambs were killed with pentobarbitone (150\u2009mg\/kg; intravenous). Diaphragm contractile function was measured <jats:italic>in vitro<\/jats:italic>. Muscle fibre type, activation of protein synthesis and degradation pathways, pro\u2010inflammatory signalling and oxidative stress were evaluated using immunofluorescence staining, <jats:styled-content style=\"fixed-case\">RT\u2010qPCR, ELISA<\/jats:styled-content>, Western blotting and biochemical assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>In utero<\/jats:italic>\u2005<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> exposure significantly impaired diaphragm contractile function. <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> exposure 7 days before delivery caused maximum specific twitch and tetanic forces 30% lower than controls. When the initial <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> exposure occurred 21 days before delivery maximum specific forces were 40% lower than controls. Earlier <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> exposure also prolonged twitch contraction time, increased fatigue resistance and elevated protein carbonyl content. Despite increased white blood cell counts and interleukin\u20106 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression following weekly <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> exposure, there were no significant differences in contractile properties between exposure 21 days before delivery and repeated <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> groups suggesting that frequency of inflammatory exposure does not influence the severity of contractile dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">GA<\/jats:styled-content> at time of initial <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> exposure, rather than frequency of exposure, determines the extent of inflammation\u2010induced diaphragm dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1111\/resp.12615","type":"journal-article","created":{"date-parts":[[2015,8,27]],"date-time":"2015-08-27T03:04:03Z","timestamp":1440644643000},"page":"1255-1262","source":"Crossref","is-referenced-by-count":5,"title":["Gestational age at initial exposure to <i>in utero<\/i> inflammation influences the extent of diaphragm dysfunction in preterm lambs"],"prefix":"10.1111","volume":"20","author":[{"given":"Kanakeswary","family":"Karisnan","sequence":"first","affiliation":[{"name":"School of Anatomy, Physiology and Human Biology University of Western Australia  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony J.","family":"Bakker","sequence":"additional","affiliation":[{"name":"School of Anatomy, Physiology and Human Biology University of Western Australia  Perth Western Australia Australia"},{"name":"Centre for Neonatal Research and Education School of Paediatrics and Child Health University of Western Australia  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Song","sequence":"additional","affiliation":[{"name":"School of Anatomy, Physiology and Human Biology University of Western Australia  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter B.","family":"Noble","sequence":"additional","affiliation":[{"name":"School of Anatomy, Physiology and Human Biology University of Western Australia  Perth Western Australia Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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