{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T15:37:56Z","timestamp":1783957076397,"version":"3.55.0"},"reference-count":58,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,1,14]],"date-time":"2015-01-14T00:00:00Z","timestamp":1421193600000},"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":[[2015,3]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Anterior and posterior cerebral circulations have differential reactivity to changes in arterial blood gases, but the implications for the chemoreflex control of breathing are unclear.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Indomethacin\u2010induced blunting of cerebrovascular flow responsiveness did not affect central or peripheral respiratory chemoreflex magnitude using steady\u2010state end\u2010tidal forcing techniques.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Posterior reactivity was related to hypoxic ventilatory decline, suggesting that CO<jats:sub>2<\/jats:sub> washout from central chemoreceptors modulates hypoxic ventilatory dynamics.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our data indicate that steady\u2010state end\u2010tidal forcing techniques reduce the arterial\u2013venous gradients, attenuating the effect of brain blood flow on ventilatory responses.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our study confirms the importance of measuring posterior cerebrovasculature when investigating the link between cerebral blood flow and the chemical control of breathing.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Cerebrovascular reactivity impacts CO<jats:sub>2<\/jats:sub>\u2013[H<jats:sup>+<\/jats:sup>] washout at the central chemoreceptors and hence has marked influence on the control of ventilation. To date, the integration of cerebral blood flow (CBF) and ventilation has been investigated exclusively with measures of anterior CBF, which has a differential reactivity from the vertebrobasilar system and perfuses the brainstem. We hypothesized that: (1) posterior <jats:italic>versus<\/jats:italic> anterior CBF would have a stronger relationship to central chemoreflex magnitude during hypercapnia, and (2) that higher posterior reactivity would lead to a greater hypoxic ventilatory decline (HVD). End\u2010tidal forcing was used to induce steady\u2010state hyperoxic (300\u00a0mmHg <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp6497-math-0001.png\" xlink:title=\"urn:x-wiley:00223751:tjp6497:equation:tjp6497-math-0001\"\/>) hypercapnia (+3, +6 and +9\u00a0mmHg <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp6497-math-0002.png\" xlink:title=\"urn:x-wiley:00223751:tjp6497:equation:tjp6497-math-0002\"\/>) and isocapnic hypoxia (45\u00a0mmHg <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp6497-math-0003.png\" xlink:title=\"urn:x-wiley:00223751:tjp6497:equation:tjp6497-math-0003\"\/>) before and following pharmacological blunting (indomethacin; INDO; 1.45\u00a0\u00b1\u00a00.17\u00a0mg\u00a0kg<jats:sup>\u22121<\/jats:sup>) of resting CBF and reactivity. In 22 young healthy volunteers, ventilation, intra\u2010cranial arterial blood velocities and extra\u2010cranial blood flows were measured during these challenges. INDO\u2010induced blunting of cerebrovascular flow responsiveness (CVR) to CO<jats:sub>2<\/jats:sub> was unrelated to variability in ventilatory sensitivity during hyperoxic hypercapnia. Further results in a sub\u2010group of volunteers (<jats:italic>n<\/jats:italic>\u00a0=\u00a09) revealed that elevations of <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp6497-math-0004.png\" xlink:title=\"urn:x-wiley:00223751:tjp6497:equation:tjp6497-math-0004\"\/> via end\u2010tidal forcing reduce arterial\u2013jugular venous gradients, attenuating the effect of CBF on chemoreflex responses. During isocapnic hypoxia, vertebral artery CVR was related to the magnitude of HVD (<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a00.27; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.04; <jats:italic>n<\/jats:italic>\u00a0=\u00a016), suggesting that CO<jats:sub>2<\/jats:sub>\u2013[H<jats:sup>+<\/jats:sup>] washout from central chemoreceptors modulates hypoxic ventilatory dynamics. No relationships were apparent with anterior CVR. As higher posterior, but not anterior, CVR was linked to HVD, our study highlights the importance of measuring flow in posterior vessels to investigate CBF and ventilatory integration.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jphysiol.2014.284521","type":"journal-article","created":{"date-parts":[[2014,12,12]],"date-time":"2014-12-12T11:58:30Z","timestamp":1418385510000},"page":"1291-1306","source":"Crossref","is-referenced-by-count":48,"title":["Indomethacin\u2010induced impairment of regional cerebrovascular reactivity: implications for respiratory control"],"prefix":"10.1113","volume":"593","author":[{"given":"Ryan L.","family":"Hoiland","sequence":"first","affiliation":[{"name":"Centre for Heart Lung and Vascular Health School of Health and Exercise Sciences University of British Columbia  Kelowna British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip N.","family":"Ainslie","sequence":"additional","affiliation":[{"name":"Centre for Heart Lung 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