{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T03:57:51Z","timestamp":1771041471769,"version":"3.50.1"},"reference-count":49,"publisher":"American Physiological Society","issue":"12","funder":[{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)","doi-asserted-by":"publisher","award":["R01NS053934"],"award-info":[{"award-number":["R01NS053934"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)","doi-asserted-by":"publisher","award":["R21NS075812"],"award-info":[{"award-number":["R21NS075812"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)","doi-asserted-by":"publisher","award":["R01NS036722"],"award-info":[{"award-number":["R01NS036722"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2015,12,15]]},"abstract":"<jats:p> Low doses of the carbonic anhydrase inhibitor acetazolamide provides accelerated acclimatization to high-altitude hypoxia and prevention of cerebral and other symptoms of acute mountain sickness. We previously observed increases in cerebral O<jats:sub>2<\/jats:sub> metabolism (CMR<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub>) during hypoxia. In this study, we investigate whether low-dose oral acetazolamide (250 mg) reduces this elevated CMR<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub> and in turn might improve cerebral tissue oxygenation (Pti<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub>) during acute hypoxia. Six normal human subjects were exposed to 6 h of normobaric hypoxia with and without acetazolamide prophylaxis. We determined CMR<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub> and cerebral Pti<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub> from MRI measurements of cerebral blood flow (CBF) and cerebral venous O<jats:sub>2<\/jats:sub> saturation. During normoxia, low-dose acetazolamide resulted in no significant change in CBF, CMR<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub>, or Pti<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub>. During hypoxia, we observed increases in CBF [48.5 (SD 12.4) (normoxia) to 65.5 (20.4) ml\u00b7100 ml<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup> (hypoxia), P &lt; 0.05] and CMR<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub> [1.54 (0.19) to 1.79 (0.25) \u03bcmol\u00b7ml<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup>, P &lt; 0.05] and a dramatic decline in Pti<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub> [25.0 to 11.4 (2.7) mmHg, P &lt; 0.05]. Acetazolamide prophylaxis mitigated these rises in CBF [53.7 (20.7) ml\u00b7100 ml<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup> (hypoxia + acetazolamide)] and CMR<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub> [1.41 (0.09) \u03bcmol\u00b7ml<jats:sup>\u22121<\/jats:sup>\u00b7min<jats:sup>\u22121<\/jats:sup> (hypoxia + acetazolamide)] associated with acute hypoxia but also reduced O<jats:sub>2<\/jats:sub> delivery [6.92 (1.45) (hypoxia) to 5.60 (1.14) mmol\/min (hypoxia + acetazolamide), P &lt; 0.05]. The net effect was improved cerebral tissue Pti<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub> during acute hypoxia [11.4 (2.7) (hypoxia) to 16.5 (3.0) mmHg (hypoxia + acetazolamide), P &lt; 0.05]. In addition to its renal effect, low-dose acetazolamide is effective at the capillary endothelium, and we hypothesize that local interruption in cerebral CO<jats:sub>2<\/jats:sub> excretion accounts for the improvements in CMR<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub> and ultimately in cerebral tissue oxygenation during hypoxia. This study suggests a potentially pivotal role of cerebral CO<jats:sub>2<\/jats:sub> and pH in modulating CMR<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub> and Pti<jats:sub>O<jats:sub>2<\/jats:sub><\/jats:sub> during acute hypoxia. <\/jats:p>","DOI":"10.1152\/japplphysiol.00117.2015","type":"journal-article","created":{"date-parts":[[2015,10,15]],"date-time":"2015-10-15T22:08:31Z","timestamp":1444946911000},"page":"1494-1500","source":"Crossref","is-referenced-by-count":22,"title":["Acetazolamide during acute hypoxia improves tissue oxygenation in the human brain"],"prefix":"10.1152","volume":"119","author":[{"given":"Kang","family":"Wang","sequence":"first","affiliation":[{"name":"Center for Functional MRI, Department of Radiology, University of California, San Diego, California;"},{"name":"School of Medicine, University of California, San Diego, California; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zachary 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