{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T04:41:53Z","timestamp":1775968913527,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2002,11,1]],"date-time":"2002-11-01T00:00:00Z","timestamp":1036108800000},"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":[[2002,11]]},"abstract":"<jats:p>We studied the effect of the antioxidants (AOX) ascorbic acid (2 g, I.V.) and \u03b1\u2010tocopherol (200 mg, P.O.) on the depressant effect of subanaesthetic doses of halothane (0.11 % end\u2010tidal concentration) on the acute isocapnic hypoxic ventilatory response (AHR), i.e. the ventilatory response upon inhalation of a hypoxic gas mixture for 3 min (leading to a haemoglobin saturation of 82 \u00b1 1.8 %) in healthy male volunteers. In the first set of protocols, two groups of eight subjects each underwent a control hypoxic study, a halothane hypoxic study and finally a halothane hypoxic study after pretreatment with AOX (study 1) or placebo (study 2). Halothane reduced the AHR by more than 50 %, from 0.79 \u00b1 0.31 to 0.36 \u00b1 0.14 l min<jats:sup>\u22121<\/jats:sup> %<jats:sup>\u22121<\/jats:sup> in study 1 and from 0.79 \u00b1 0.40 to 0.36 \u00b1 0.19 l min<jats:sup>\u22121<\/jats:sup> %<jats:sup>\u22121<\/jats:sup> in study 2, <jats:styled-content><jats:italic>P<\/jats:italic> &lt; 0.01<\/jats:styled-content> for both. Pretreatment with AOX prevented this depressant effect of halothane in the subjects of study 1 (AHR returning to 0.77 \u00b1 0.32 l min<jats:sup>\u22121<\/jats:sup> %<jats:sup>\u22121<\/jats:sup>, n.s. from control), whereas placebo (study 2) had no effect (AHR remaining depressed at 0.36 \u00b1 0.27 l min<jats:sup>\u22121<\/jats:sup> %<jats:sup>\u22121<\/jats:sup>, <jats:styled-content><jats:italic>P<\/jats:italic> &lt; 0.01<\/jats:styled-content> from control). In a second set of protocols, two separate groups of eight subjects each underwent a control hypoxic study, a sham halothane hypoxic study and finally a sham halothane hypoxic study after pretreatment with AOX (study 3) or placebo (study 4). In studies 3 and 4, sham halothane did not modify the control hypoxic response, nor did AOX (study 3) or placebo (study 4). The 95 % confidence intervals for the ratio of hypoxic sensitivities, (AOX + halothane) : halothane in study 1 and (AOX \u2010 sham halothane) : sham halothane in study 3, were [1.7, 2.6] and [1.0, 1.2], respectively. Because the antioxidants prevented the reduction of the acute hypoxic response by halothane, we suggest that this depressant effect may be caused by reactive species produced by a reductive metabolism of halothane during hypoxia or that a change in redox state of carotid body cells by the antioxidants prevented or changed the binding of halothane to its effect site. Our findings may also suggest that reactive species have an inhibiting effect on the acute hypoxic ventilatory response.<\/jats:p>","DOI":"10.1113\/jphysiol.2002.025999","type":"journal-article","created":{"date-parts":[[2002,11,1]],"date-time":"2002-11-01T00:42:52Z","timestamp":1036111372000},"page":"931-938","source":"Crossref","is-referenced-by-count":32,"title":["Antioxidants prevent depression of the acute hypoxic ventilatory response by subanaesthetic halothane in men"],"prefix":"10.1113","volume":"544","author":[{"given":"Luc J.","family":"Teppema","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diederik","family":"Nieuwenhuijs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elise","family":"Sarton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymonda","family":"Romberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cees N.","family":"Olievier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denham S.","family":"Ward","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"Dahan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,11]]},"reference":[{"key":"e_1_2_5_2_1","first-page":"174","article-title":"Protective effect of alpha\u2010tocopherol and l\u2010ascorbic acid against the ischemic\u2010reperfusion injury in patients during open\u2010heart surgery","volume":"92","author":"Barta E.","year":"1991","journal-title":"Bratislavske Lekarske Listy"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-2397-0_14"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.00135.x"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(83)90145-5"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1995.sp021012"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199607000-00009"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199404000-00004"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-198209000-00002"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840030421"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.3109\/03602538909103543"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000539-199910000-00043"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.16.6377"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1994.74.4.829"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-196905000-00003"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010357200"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1996.271.1.C85"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(00)00320-8"},{"key":"e_1_2_5_19_1","first-page":"202","article-title":"Oxygen radicals as messengers in oxygen\u2010dependent gene expression","volume":"15","author":"Kietzmann T.","year":"2000","journal-title":"News in Physiological Sciences"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-198408000-00002"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi001292j"},{"key":"e_1_2_5_22_1","first-page":"10","article-title":"Characteristics and implications of desflurane metabolism and toxicity","volume":"75","author":"Koblin D. 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