{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T12:52:35Z","timestamp":1789822355817,"version":"4.0.1"},"reference-count":32,"publisher":"American Physiological Society","issue":"5","funder":[{"name":"Peninsula Health Care P\/L"},{"DOI":"10.13039\/501100000038","name":"NSERC","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]},{"name":"CRC"},{"name":"MRU Petro-Canada Young Innovator Award"},{"name":"Lottery Health NZ"},{"DOI":"10.13039\/100008247","name":"University of Otago","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008247","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2018,5,1]]},"abstract":"<jats:p>Earlier studies have indicated an important role for cerebral blood flow in the pathophysiology of central sleep apnea (CSA) at high altitude, but were not decisive. To test the hypothesis that pharmacologically altering cerebral blood flow (CBF) without altering arterial blood gas (ABGs) values would alter the severity of CSA at high altitude, we studied 11 healthy volunteers (8M, 3F; 31\u2009\u00b1\u20097 yr) in a randomized placebo-controlled single-blind study at 5,050 m in Nepal. CBF was increased by intravenous (iv) acetazolamide (Az; 10 mg\/kg) plus intravenous dobutamine (Dob) infusion (2\u20135 \u03bcg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup>) and reduced by oral indomethacin (Indo; 100 mg). ABG samples were collected and ventilatory responses to hypercapnia (HCVR) and hypoxia (HVR) were measured by rebreathing and steady-state techniques before and after drug\/placebo. Duplex ultrasound of blood flow in the internal carotid and vertebral arteries was used to measure global CBF. The initial 3\u20134 h of sleep were recorded by full polysomnography. Intravenous Az + Dob increased global CBF by 37\u2009\u00b1\u200915% compared with placebo ( P &lt; 0.001), whereas it was reduced by 21\u2009\u00b1\u20098% by oral Indo ( P &lt; 0.001). ABGs and HVR were unchanged in both interventions. HCVR was reduced by 28%\u2009\u00b1\u200943% ( P = 0.1) during intravenous Az\u2009\u00b1\u2009Dob administration and was elevated by 23%\u2009\u00b1\u200930% ( P = 0.05) by Indo. During intravenous Az + Dob, the CSA index fell from 140\u2009\u00b1\u200945 (control night) to 48\u2009\u00b1\u200937 events\/h of sleep ( P &lt; 0.001). Oral Indo had no significant effect on CSA. We conclude that increasing cerebral blood flow reduced the severity of CSA at high altitude; the likely mechanism is via a reduction in the background stimulation of central chemoreceptors.<\/jats:p><jats:p>NEW &amp; NOTEWORTHY This work is significant because it shows convincingly for the first time in healthy volunteers that increasing cerebral blood flow will reduce the severity of central sleep apnea in a high-altitude model, without the potentially confounding effects of altering partial pressure of arterial carbon dioxide or the ventilatory response to hypoxia. The proposed mechanism of action is that of increasing the removal of locally produced CO<jats:sub>2<\/jats:sub>from the central chemoreceptors, causing the reduction in hypercapnic ventilatory response, hence reducing loop gain.<\/jats:p>","DOI":"10.1152\/japplphysiol.00799.2017","type":"journal-article","created":{"date-parts":[[2018,2,1]],"date-time":"2018-02-01T14:42:14Z","timestamp":1517496134000},"page":"1341-1348","source":"Crossref","is-referenced-by-count":21,"title":["Increasing cerebral blood flow reduces the severity of central sleep apnea at high altitude"],"prefix":"10.1152","volume":"124","author":[{"given":"Keith R.","family":"Burgess","sequence":"first","affiliation":[{"name":"Peninsula Sleep Clinic, Sydney, New South Wales, Australia"},{"name":"Department of Medicine, University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel J. E.","family":"Lucas","sequence":"additional","affiliation":[{"name":"University of Otago, Dunedin, New Zealand"},{"name":"University of Birmingham, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie M. E.","family":"Burgess","sequence":"additional","affiliation":[{"name":"Peninsula Sleep Clinic, Sydney, New South Wales, Australia"},{"name":"Department of Medicine, University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate E.","family":"Sprecher","sequence":"additional","affiliation":[{"name":"Peninsula Sleep Clinic, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Donnelly","sequence":"additional","affiliation":[{"name":"University of Otago, Dunedin, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aparna S.","family":"Basnet","sequence":"additional","affiliation":[{"name":"Banner Good Samaritan Medical Center, Phoenix, Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9945-339X","authenticated-orcid":false,"given":"Michael 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