{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:31:45Z","timestamp":1789965105738,"version":"4.0.1"},"reference-count":73,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,2,28]],"date-time":"2013-02-28T00:00:00Z","timestamp":1362009600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>Key points<\/jats:title>\n                  <jats:p>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>Central sleep apnoea is a condition characterized by oscillations between apnoea and hyperpnoea during sleep, which can have many serous health implications.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Each ventilatory overshoot following an apnoea attenuates peripheral chemoreceptor input which, in turn, has the potential to cause a further apnoea.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          In a decerebrate, vagotomized,\n                          <jats:italic>in situ<\/jats:italic>\n                          rat preparation, we show that central apnoeas can be overcome both physiologically (with high peripheral CO\n                          <jats:sub>2<\/jats:sub>\n                          ) and pharmacologically (with peripheral pituitary adenylate cyclase\u2010activating peptide).\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>\n                          We also show that the central apnoeic threshold, i.e. the CO\n                          <jats:sub>2<\/jats:sub>\n                          level at which the animal stops breathing, can be lowered by increasing peripheral chemoreceptor stimulation.\n                        <\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>These data suggest that stimulation of peripheral chemoreceptors may prevent central apnoeas, re\u2010affirming the peripheral chemoreceptors as possible therapeutic targets for some sleep apnea phenotypes.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Abstract\u2002<\/jats:bold>\n                    Central sleep apnoea is a condition characterized by oscillations between apnoea and hyperpnoea during sleep. Studies in sleeping dogs suggest that withdrawal of peripheral chemoreceptor (carotid body) activation following transient ventilatory overshoots plays an essential role in causing apnoea, raising the possibility that sustaining carotid body activity during ventilatory overshoots may prevent apnoea. To test whether sustained peripheral chemoreceptor activation is sufficient to drive breathing, even in the absence of central chemoreceptor stimulation and vagal feedback, we used a vagotomized, decerebrate dual\u2010perfused\n                    <jats:italic>in situ<\/jats:italic>\n                    rat preparation in which the central and peripheral chemoreceptors are independently and artificially perfused with gas\u2010equilibrated medium. At varying levels of carotid body stimulation (CB\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>O2<\/jats:sub>\n                    \/\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>CO2<\/jats:sub>\n                    : 40\/60, 100\/40, 200\/15, 500\/15\u00a0Torr), we decreased the brainstem perfusate\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>CO2<\/jats:sub>\n                    in 5\u00a0Torr steps while recording phrenic nerve activity to determine the central apnoeic thresholds. The central apnoeic thresholds decreased with increased carotid body stimulation. When the carotid bodies were strongly stimulated (CB 40\/60), the apnoeic threshold was 3.6\u00a0\u00b1\u00a01.4\u00a0Torr\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>CO2<\/jats:sub>\n                    (mean\u00a0\u00b1\u00a0SEM,\n                    <jats:italic>n\u00a0<\/jats:italic>\n                    =\u00a07). Stimulating carotid body afferent activity with either hypercapnia (60\u00a0Torr\n                    <jats:italic>P<\/jats:italic>\n                    <jats:sub>CO2<\/jats:sub>\n                    ) or the neuropeptide pituitary adenylate cyclase\u2010activating peptide restored phrenic activity during central apnoea. We conclude that peripheral stimulation shifts the central apnoeic threshold to very hypocapnic levels that would likely increase the CO\n                    <jats:sub>2<\/jats:sub>\n                    reserve and have a protective effect on breathing. These data demonstrate that peripheral respiratory chemoreceptors are sufficient to stave off central apnoeas when the brainstem is perfused with low to no CO\n                    <jats:sub>2<\/jats:sub>\n                    .\n                  <\/jats:p>","DOI":"10.1113\/jphysiol.2012.247304","type":"journal-article","created":{"date-parts":[[2013,1,29]],"date-time":"2013-01-29T05:52:25Z","timestamp":1359438745000},"page":"1507-1521","source":"Crossref","is-referenced-by-count":30,"title":["The essential role of peripheral respiratory chemoreceptor inputs in maintaining breathing revealed when CO\n                    <sub>2<\/sub>\n                    stimulation of central chemoreceptors is diminished"],"prefix":"10.1113","volume":"591","author":[{"given":"Marie\u2010No\u00eblle","family":"Fiamma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward T.","family":"O\u2019Connor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arijit","family":"Roy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Zuna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J. 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