{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T15:24:02Z","timestamp":1787757842078,"version":"build-2784847793"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,10]]},"abstract":"\n Background and Aims:<\/jats:title>\n There is a lack of basic science data on the effect of dexmedetomidine on the hypoxic chemosensory reflex with both depression and stimulation suggested. The primary aim of this study was to assess if dexmedetomidine inhibited the cellular response to hypoxia in rat carotid body glomus cells, the cells of the organs mediating acute hypoxic ventilatory response (AHVR). Additionally, we used a small sample of mice to assess if there was any large influence of subsedative doses of dexmedetomidine on AHVR.<\/jats:p>\n <\/jats:sec>\n \n Material and Methods:<\/jats:title>\n \n In the primary study, glomus cells isolated from neonatal rats were used to study the effect of 0.1 nM (\n n<\/jats:italic>\n = 9) and 1 nM (\n n<\/jats:italic>\n = 13) dexmedetomidine on hypoxia-elicited intracellular calcium [Ca\n 2+<\/jats:sup>\n ]i influx using ratiometric fluorimetry. Secondarily, whole animal unrestrained plethysmography was used to study AHVR in a total of 8 age-matched C57BL6 mice, divided on successive days into two groups of four mice randomly assigned to receive sub-sedative doses of 5, 50, or 500 \u03bcg.kg\n -1<\/jats:sup>\n dexmedetomidine versus control in a crossover study design (total\n n<\/jats:italic>\n = 12 exposures to drug with\n n<\/jats:italic>\n = 12 controls).\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n There was no effect of dexmedetomidine on the hypoxia-elicited increase in [Ca\n 2+<\/jats:sup>\n ]i in glomus cells (a mean \u00b1 SEM increase of 95 \u00b1 32 nM from baseline with control hypoxia, 124 \u00b1 41 nM with 0.1 nM dexmedetomidine;\n P<\/jats:italic>\n = 0.514). In intact mice, dexmedetomidine had no effect on baseline ventilation during air-breathing (4.01 \u00b1 0.3 ml.g\n -1<\/jats:sup>\n .min\n -1<\/jats:sup>\n in control and 2.99 \u00b1 0.5 ml.g\n -1<\/jats:sup>\n .min\n -1<\/jats:sup>\n with 500 \u03bcg.kg\n -1<\/jats:sup>\n dexmedetomidine, the highest dose;\n P<\/jats:italic>\n = 0.081) or on AHVR (136 \u00b1 19% increase from baseline in control, 152 \u00b1 46% with 500 \u03bcg.kg\n -1<\/jats:sup>\n dexmedetomidine, the highest dose;\n P<\/jats:italic>\n = 0.536).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n Dexmedetomidine had no effect on the cellular responses to hypoxia. We conclude that it unlikely acts via inhibition of oxygen sensing at the glomus cell. The respiratory chemoreflex effects of this drug remain an open question. In our small sample of intact mice, hypoxic chemoreflex responses and basal breathing were preserved.<\/jats:p>\n <\/jats:sec>","DOI":"10.4103\/joacp.joacp_309_16","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T06:03:51Z","timestamp":1642572231000},"page":"509-516","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Lack of influence of dexmedetomidine on rat glomus cell response to hypoxia, and on mouse acute hypoxic ventilatory response"],"prefix":"10.4103","volume":"37","author":[{"given":"Peadar B.","family":"O\u2019Donohoe","sequence":"first","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, Parks Road, Oxford OX1 3PT, UK"},{"name":"Nuffield Department of Anaesthetics, Oxford University Hospitals, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, Parks Road, Oxford OX1 3PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicky","family":"Huskens","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, Parks Road, Oxford OX1 3PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith J.","family":"Buckler","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, Parks Road, Oxford OX1 3PT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaideep J.","family":"Pandit","sequence":"additional","affiliation":[{"name":"Nuffield Department of Anaesthetics, Oxford University Hospitals, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,1,6]]},"reference":[{"key":"B1-20240828","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1097\/01.aco.0000174958.05383.d5","article-title":"Dexmedetomidine in anaesthesia","volume":"18","author":"Paris","year":"2005","journal-title":"Curr Opinion Anaesthesiol"},{"key":"B2-20240828","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0014-2999(98)00518-4","article-title":"Subtype-specific stimulation of [35S] GTPgammaS binding by recombinant alpha2-adrenoceptors","volume":"355","author":"Peltonen","year":"1998","journal-title":"Eur J Pharmacol"},{"key":"B3-20240828","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1093\/bja\/66.4.454","article-title":"Effect of i.v. midazolam on the ventilatory response to sustained hypoxia in man","volume":"66","author":"Dahan","year":"1991","journal-title":"Br J Anaesth"},{"key":"B4-20240828","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0034-5687(93)90056-G","article-title":"Effects of midazolam and flumazenil on ventilation during sustained hypoxia in humans","volume":"94","author":"Nagyova","year":"1993","journal-title":"Respir Physiol"},{"key":"B5-20240828","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1097\/00000542-199809000-00009","article-title":"Effects of alfentanil on the ventilatory response to sustained hypoxia","volume":"89","author":"Cartwright","year":"1998","journal-title":"Anesthesiology"},{"key":"B6-20240828","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1097\/00000542-197810000-00004","article-title":"Ventilatory responses to hypoxia and hypercapnia during halothane sedation and anesthesia in man","volume":"49","author":"Knill","year":"1978","journal-title":"Anesthesiology"},{"key":"B7-20240828","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1046\/j.1365-2044.2002.02604.x","article-title":"The variable effect of low-dose volatile anaesthetics on the acute ventilatory response to hypoxia in humans:A quantitative review","volume":"57","author":"Pandit","year":"2002","journal-title":"Anaesthesia"},{"key":"B8-20240828","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1097\/00000542-199312000-00007","article-title":"Propofol depresses the hypoxic ventilatory response during conscious sedation and isohypercapnia","volume":"79","author":"Blouin","year":"1993","journal-title":"Anesthesiology"},{"key":"B9-20240828","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1111\/j.1365-2044.2004.04088.x","article-title":"Effect of low dose inhaled anaesthetic agents on the ventilatory response to carbon dioxide in humans:A quantitative review","volume":"60","author":"Pandit","year":"2005","journal-title":"Anaesthesia"},{"key":"B10-20240828","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1007\/s00134-002-1338-y","article-title":"The effects of dexmedetomidine on the ventilatory response to hypercapnia in rabbits","volume":"28","author":"Nishida","year":"2002","journal-title":"Int Care Med"},{"key":"B11-20240828","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.resp.2006.02.002","article-title":"Effects of dexmedetomidine on respiratory mechanics and control of breathing in normal rats","volume":"154","author":"Fernandes","year":"2006","journal-title":"Resp Physiol Neurobiol"},{"key":"B12-20240828","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1097\/00000542-199204000-00014","article-title":"Ventilatory effects of dexmedetomidine, atipamezole, and isoflurane in dogs","volume":"76","author":"Nguyen","year":"1992","journal-title":"Anesthesiology"},{"key":"B13-20240828","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1097\/EJA.0b013e328356fba5","article-title":"Low-dose dexmedetomidine facilitates the carotid body response to low oxygen tension in vitro via alpha2-adrenergic receptor activation in rabbits","volume":"29","author":"Nakatani","year":"2012","journal-title":"Eur J Anaesthesiol"},{"key":"B14-20240828","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/den.12399","article-title":"Dexmedetomidine versus midazolam for gastrointestinal endoscopy:A meta-analysis","volume":"27","author":"Nishizawa","year":"2015","journal-title":"Dig Endosc"},{"key":"B15-20240828","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.2169\/internalmedicine.51.7810","article-title":"Dexmedetomidine versus midazolam for the sedation of patients with non-invasive ventilation failure","volume":"51","author":"Huang","year":"2012","journal-title":"Intern Med"},{"key":"B16-20240828","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1097\/00000542-199212000-00013","article-title":"Effects of intravenous dexmedetomidine in humans: I. Sedation, ventilation, and metabolic rate","volume":"77","author":"Belleville","year":"1992","journal-title":"Anesthesiology"},{"key":"B17-20240828","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1097\/00000542-199608000-00011","article-title":"Acute pain and central nervous system arousal do not restore impaired hypoxic ventilatory response during sevoflurane sedation","volume":"85","author":"Sarton","year":"1996","journal-title":"Anesthesiology"},{"key":"B18-20240828","article-title":"Sedation with dexmedetomidine or propofol impairs control of breathing in healthy male volunteers. A randomized cross-over study, Abstract: Anesthesiology 2014 Conference","author":"Danielson","year":"2014","journal-title":"New Orleans"},{"key":"B19-20240828","first-page":"141","article-title":"Peripheral chemoreceptors:Function and plasticity of the carotid body","volume":"2","author":"Kumar","year":"2011","journal-title":"Comp Physiol"},{"key":"B20-20240828","doi-asserted-by":"crossref","first-page":"3419","DOI":"10.1113\/jphysiol.2013.269829","article-title":"Synaptic and paracrine mechanisms at carotid body arterial chemoreceptors","volume":"592","author":"Nurse","year":"2014","journal-title":"J Physiol"},{"key":"B21-20240828","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1093\/bja\/aep223","article-title":"Differential effects of halothane and sevoflurane on hypoxia-induced intracellular calcium transients of neonatal rat carotid body type I cells","volume":"103","author":"Pandit","year":"2009","journal-title":"Br J Anaesth"},{"key":"B22-20240828","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/978-1-4419-5692-7_41","article-title":"Differential effects of halothane and isoflurane on carotid body glomus cell intracellular Ca2+and background K+channel responses to hypoxia","volume":"669","author":"Pandit","year":"2010","journal-title":"Adv Exp Med Biol"},{"key":"B23-20240828","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1111\/j.1469-7793.2000.00135.x","article-title":"An oxygen-, acid- and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chemoreceptor cells","volume":"525","author":"Buckler","year":"2000","journal-title":"J Physiol"},{"key":"B24-20240828","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/bja\/62.1.41","article-title":"Effect of thiopentone, etomidate and propofol on carotid body chemoreceptor activity in the rabbit and the cat","volume":"62","author":"Ponte","year":"1989","journal-title":"Br J Anaesth"},{"key":"B25-20240828","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1097\/00000542-200501000-00019","article-title":"Effect of propofol on carotid body chemosensitivity and cholinergic chemotransduction","volume":"102","author":"Jonsson","year":"2005","journal-title":"Anesthesiology"},{"key":"B26-20240828","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.resp.2007.10.011","article-title":"Pronounced depression by propofol on carotid body response to CO2 and K+-induced carotid body activation","volume":"160","author":"Akada","year":"2008","journal-title":"Resp Physiol Neurobiol"},{"key":"B27-20240828","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/0034-5687(91)90054-M","article-title":"Role of \u03b12-adrenergic receptors in the carotid body response to isocapnic hypoxia","volume":"83","author":"Kou","year":"1991","journal-title":"Respir Physiol"},{"key":"B28-20240828","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/BF00374499","article-title":"Effects of acidic stimuli on intracellular calcium in isolated type I cells of the neonatal rat carotid body","volume":"425","author":"Buckler","year":"1993","journal-title":"Pfl\u00fcgers Archiv"},{"key":"B29-20240828","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jneumeth.2015.11.002","article-title":"A method for continuous and stable perfusion of tissue and single cell preparations with accurate concentrations of volatile anaesthetics","volume":"258","author":"Huskens","year":"2016","journal-title":"J Neurosci Methods"},{"key":"B30-20240828","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1007\/BF00586988","article-title":"Local oxygen tension field in the glomus caroticum of the cat and its change at changing arterial pO2","volume":"329","author":"Acker","year":"1971","journal-title":"Pfl\u00fcgers Archiv"},{"key":"B31-20240828","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0014-2999(91)90535-X","article-title":"Central alpha 2-adrenoceptors are highly stereoselective for dexmedetomidine, the dextro enantiomer of medetomidine","volume":"195","author":"Savola","year":"1991","journal-title":"Eur J Pharmacol"},{"key":"B32-20240828","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1124\/mol.51.1.36","article-title":"Genetic alteration of alpha 2C-adrenoceptor expression in mice:Influence on locomotor, hypothermic, and neurochemical effects of dexmedetomidine, a subtype-nonselective alpha 2-adrenoceptor agonist","volume":"51","author":"Sallinen","year":"1997","journal-title":"Mol Pharmacol"},{"key":"B33-20240828","doi-asserted-by":"crossref","first-page":"226","DOI":"10.7150\/ijms.7897","article-title":"The antinociceptive effect of dexmedetomidine modulates spleen cell immunity in mice","volume":"11","author":"Jang","year":"2014","journal-title":"Int J Med Sci"},{"key":"B34-20240828","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1152\/jappl.1997.82.2.667","article-title":"Extended models of the ventilatory response to sustained isocapnic hypoxia in humans","volume":"82","author":"Liang","year":"1997","journal-title":"J Appl Physiol"},{"key":"B35-20240828","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1152\/jappl.2000.88.5.1924","article-title":"Methodological and physiological variability within the ventilatory response to hypoxia in humans","volume":"88","author":"Zhang","year":"2000","journal-title":"J Appl Physiol"},{"key":"B36-20240828","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1113\/jphysiol.1994.sp020143","article-title":"Effects of hypoxia on membrane potential and intracellular calcium in rat neonatal carotid body type I cells","volume":"476","author":"Buckler","year":"1994","journal-title":"J Physiol"},{"key":"B37-20240828","first-page":"L36","article-title":"Interactions between hypoxia and hypercapnic acidosis on calcium signaling in carotid body type I cells","volume":"279","author":"Dasso","year":"2000","journal-title":"Am J Physiol"},{"key":"B38-20240828","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0034-5687(01)00271-7","article-title":"Developmental changes in the hypoxic ventilatory response in C57BL\/6 mice","volume":"128","author":"Bissonnette","year":"2001","journal-title":"Respir Physiol"},{"key":"B39-20240828","doi-asserted-by":"crossref","first-page":"91","DOI":"10.33549\/physiolres.930000.50.91","article-title":"Biphasic ventilatory response to hypoxia in unanesthetized rats","volume":"50","author":"Maxova","year":"2001","journal-title":"Physiol Res"},{"key":"B40-20240828","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/0034-5687(92)90004-G","article-title":"Effects of different levels of end-tidal PO2 on ventilation during isocapnia in humans","volume":"88","author":"Bascom","year":"1992","journal-title":"Respir Physiol"},{"key":"B41-20240828","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1152\/jappl.1995.79.2.373","article-title":"Hypoxic ventilatory decline:Site of action","volume":"79","author":"Robbins","year":"1995","journal-title":"J Appl Physiol"},{"key":"B42-20240828","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1152\/jappl.1990.68.3.1107","article-title":"Dynamics of the ventilatory response to central hypoxia in cats","volume":"68","author":"Ward","year":"1990","journal-title":"J Appl Physiol"},{"key":"B43-20240828","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1002\/sim.4780110811","article-title":"Sixteen S-squared over D-squared:A relation for crude sample size estimates","volume":"11","author":"Lehr","year":"1992","journal-title":"Stat Med"},{"key":"B44-20240828","doi-asserted-by":"crossref","first-page":"5977","DOI":"10.1113\/jphysiol.2013.262022","article-title":"Oxygen and mitochondrial inhibitors modulate both monomeric and heteromeric TASK-1 and TASK-3 channels in mouse carotid body type-1 cells","volume":"591","author":"Turner","year":"2013","journal-title":"J Physiol"},{"key":"B45-20240828","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1152\/japplphysiol.00530.2013","article-title":"The von Hippel-Lindau Chuvash mutation in mice causes carotid body hyperplasia and enhanced ventilatory sensitivity to hypoxia","volume":"116","author":"Slingo","year":"2014","journal-title":"J Appl Physiol"},{"key":"B46-20240828","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.resp.2006.01.017","article-title":"Impaired ventilation and metabolism response to hypoxia in histamine H1 receptor-knockout mice","volume":"154","author":"Ishiguro","year":"2006","journal-title":"Respir Physiol Neurobiol"}],"container-title":["Journal of Anaesthesiology Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.4103\/joacp.JOACP_309_16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:54:12Z","timestamp":1787756052000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.4103\/joacp.JOACP_309_16"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":46,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.4103\/joacp.joacp_309_16","relation":{},"ISSN":["2231-2730","0970-9185"],"issn-type":[{"value":"2231-2730","type":"print"},{"value":"0970-9185","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10]]},"assertion":[{"value":"2016-10-11","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-23","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}