{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T03:40:34Z","timestamp":1777520434223,"version":"3.51.4"},"reference-count":57,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2018,5,27]],"date-time":"2018-05-27T00:00:00Z","timestamp":1527379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["RT731289"],"award-info":[{"award-number":["RT731289"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\"><jats:list-item><jats:p>Evidence obtained at whole animal, organ\u2010system, and cellular and molecular levels suggests that afferent volume feedback is critical for the establishment of adequate ventilation at birth.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>As a result of the irreversible nature of the vagal ablation studies performed to date, it was difficult to quantify the roles of afferent volume input, arousal and changes in blood gas tensions on neonatal respiratory control.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>During reversible perineural vagal block, profound apnoeas and hypoxaemia and hypercarbia were observed, necessitating the termination of perineural blockade.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Respiratory depression and apnoeas were independent of sleep state. We demonstrate that profound apnoeas and life\u2010threatening respiratory failure in vagally denervated animals do not result from a lack of arousal or hypoxaemia.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>A change in sleep state and concomitant respiratory depression result from a lack of afferent volume feedback, which appears to be critical for the maintenance of normal breathing patterns and adequate gas exchange during the early postnatal period.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Afferent volume feedback plays a vital role in neonatal respiratory control. Mechanisms for the profound respiratory depression and life\u2010threatening apnoeas observed in vagally denervated neonatal animals remain unclear. We investigated the roles of sleep states, hypoxic\u2010hypercapnia and afferent volume feedback on respiratory depression using reversible perineural vagal block during the early postnatal period. Seven lambs were instrumented during the first 48\u00a0h of life to record\/analyse sleep states, diaphragmatic electromyograph, arterial blood gas tensions, systemic arterial blood pressure and rectal temperature. Perineural cuffs were placed around the vagi to attain reversible blockade. Postoperatively, during the awake state, both vagi were blocked using 2% xylocaine for up to 30\u00a0min. Compared to baseline values, pH<jats:sub>a<\/jats:sub>,<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp12978-math-0001.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp12978:tjp12978-math-0001\"\/>and<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp12978-math-0002.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp12978:tjp12978-math-0002\"\/>decreased and<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp12978-math-0003.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp12978:tjp12978-math-0003\"\/>increased during perineural blockade (<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.05). Four of seven animals exhibited apnoeas of \u226520\u00a0s requiring the immediate termination of perineural blockade. Breathing rates decreased from the baseline value of 53\u00a0\u00b1\u00a012 to 24\u00a0\u00b1\u00a020\u00a0breaths\u00a0min<jats:sup>\u20131<\/jats:sup>during blockade despite an increased<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp12978-math-0004.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp12978:tjp12978-math-0004\"\/>(<jats:italic>P\u00a0<\/jats:italic>&lt;\u00a00.001). Following blockade, breathing patterns returned to baseline values despite marked hypocapnia (<jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp12978-math-0005.png\" xlink:title=\"urn:x-wiley:00223751:media:tjp12978:tjp12978-math-0005\"\/>33\u00a0\u00b1\u00a03\u00a0torr;<jats:italic>P\u00a0<\/jats:italic>=\u00a00.03). Respiratory depression and apnoeas were independent of sleep states. The present study provides the much needed physiological evidence indicating that profound apnoeas and life\u2010threatening respiratory failure in vagally denervated animals do not result from a lack of arousal or hypoxaemia. Rather, a change in sleep state and concomitant respiratory depression result from a lack of afferent volume feedback, which appears to be critical for the maintenance of normal breathing patterns and adequate gas exchange during the early postnatal period.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp275682","type":"journal-article","created":{"date-parts":[[2018,4,20]],"date-time":"2018-04-20T15:24:45Z","timestamp":1524237885000},"page":"6009-6019","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Afferent neural feedback overrides the modulating effects of arousal, hypercapnia and hypoxaemia on neonatal cardiorespiratory control"],"prefix":"10.1113","volume":"596","author":[{"given":"Kathleen J.","family":"Lumb","sequence":"first","affiliation":[{"name":"Department of Pediatrics Alberta Children's Hospital Research Institute, Faculty of Medicine University of Calgary Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer M.","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Alberta Children's Hospital Research Institute, Faculty of Medicine University of Calgary Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thowfique","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Alberta Children's Hospital Research Institute, Faculty of Medicine University of Calgary Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Rigaux","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Alberta Children's Hospital Research Institute, Faculty of Medicine University of Calgary Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3824-9293","authenticated-orcid":false,"given":"Shabih U.","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Alberta Children's Hospital Research Institute, Faculty of Medicine University of Calgary Calgary Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,5,27]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-017-2649-1"},{"key":"e_1_2_5_3_1","first-page":"1541","article-title":"Influence of hypoxia and hypercapnia on sleep state\u2010dependent heart rate variability behavior in newborn lambs","volume":"35","author":"Beuchee A","year":"2012","journal-title":"Sleep"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193270"},{"key":"e_1_2_5_5_1","first-page":"425","volume-title":"The Human Nervous System","author":"Counts SE","year":"2011"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1951.sp004620"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1991.sp018693"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2010.07.002"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0034-5687(94)00078-E"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2993"},{"key":"e_1_2_5_11_1","first-page":"236","article-title":"Sleep\u2010induced breathing instability. 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