{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T23:24:20Z","timestamp":1779924260330,"version":"3.53.1"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["R21ES029657"],"award-info":[{"award-number":["R21ES029657"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Lung"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Anesthetics are required for procedures that deliver drugs\/biologics, infectious\/inflammatory agents, and toxicants directly to the lungs. However, the possible confounding effects of anesthesia on lung inflammation and injury are underreported. Here, we evaluated the effects of two commonly used anesthetic regimens on lung inflammatory responses to ozone in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We tested the effects of brief isoflurane (Iso) or ketamine\/xylazine\/atipamezole (K\/X\/A) anesthesia prior to ozone exposure (4\u00a0h, 3\u00a0ppm) on lung inflammatory responses in mice. Anesthesia regimens modeled those used for non-surgical intratracheal instillations and were administered 1\u20132\u00a0h or 24\u00a0h prior to initiating ozone exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that Iso given 1\u20132\u00a0h prior to ozone inhibited inflammatory responses in the lung, and this effect was absent when Iso was given 23\u201324\u00a0h prior to ozone. In contrast, K\/X\/A given 1\u20132\u00a0h prior to ozone increased lung and systemic inflammation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results highlight the need to comprehensively evaluate anesthesia as an experimental variable in the assessment of lung inflammation in response to ozone and other inflammatory stimuli.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00408-022-00514-5","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T13:03:25Z","timestamp":1645621405000},"page":"269-275","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of Anesthesia on Ozone-Induced Lung and Systemic Inflammation"],"prefix":"10.1007","volume":"200","author":[{"given":"Miranda L.","family":"Wilson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarl A.","family":"Thysell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen K.","family":"Baumann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danny V.","family":"Quaranta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Sandy","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2575-1594","authenticated-orcid":false,"given":"Michelle A.","family":"Erickson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"key":"514_CR1","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1093\/toxsci\/55.1.24","volume":"55","author":"KE Driscoll","year":"2000","unstructured":"Driscoll KE et al (2000) Intratracheal instillation as an exposure technique for the evaluation of respiratory tract toxicity: uses and limitations. Toxicol Sci 55:24\u201335. https:\/\/doi.org\/10.1093\/toxsci\/55.1.24","journal-title":"Toxicol Sci"},{"key":"514_CR2","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.jviromet.2014.09.004","volume":"209","author":"L Morales-Nebreda","year":"2014","unstructured":"Morales-Nebreda L et al (2014) Intratracheal administration of influenza virus is superior to intranasal administration as a model of acute lung injury. J Virol Methods 209:116\u2013120. https:\/\/doi.org\/10.1016\/j.jviromet.2014.09.004","journal-title":"J Virol Methods"},{"key":"514_CR3","doi-asserted-by":"publisher","DOI":"10.3791\/52261","author":"MB Lawrenz","year":"2014","unstructured":"Lawrenz MB, Fodah RA, Gutierrez MG, Warawa J (2014) Intubation-mediated intratracheal (IMIT) instillation: a noninvasive, lung-specific delivery system. J Vis Exp. https:\/\/doi.org\/10.3791\/52261","journal-title":"J Vis Exp"},{"key":"514_CR4","doi-asserted-by":"publisher","first-page":"242709","DOI":"10.1155\/2015\/242709","volume":"2015","author":"YM Lee","year":"2015","unstructured":"Lee YM, Song BC, Yeum KJ (2015) Impact of volatile anesthetics on oxidative stress and inflammation. Biomed Res Int 2015:242709. https:\/\/doi.org\/10.1155\/2015\/242709","journal-title":"Biomed Res Int"},{"key":"514_CR5","doi-asserted-by":"publisher","first-page":"77","DOI":"10.3109\/08958370902929969","volume":"22","author":"SE Lacher","year":"2010","unstructured":"Lacher SE, Johnson C, Jessop F, Holian A, Migliaccio CT (2010) Murine pulmonary inflammation model: a comparative study of anesthesia and instillation methods. Inhalation Toxicol 22:77\u201383. https:\/\/doi.org\/10.3109\/08958370902929969","journal-title":"Inhalation Toxicol"},{"key":"514_CR6","doi-asserted-by":"publisher","DOI":"10.3791\/1941","author":"MN Helms","year":"2010","unstructured":"Helms MN, Torres-Gonzalez E, Goodson P, Rojas M (2010) Direct tracheal instillation of solutes into mouse lung. J Vis Exp. https:\/\/doi.org\/10.3791\/1941","journal-title":"J Vis Exp"},{"key":"514_CR7","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1248\/bpb.b17-00131","volume":"40","author":"S Tan","year":"2017","unstructured":"Tan S, Wang Y, Chen K, Long Z, Zou J (2017) Ketamine alleviates depressive-like behaviors via down-regulating inflammatory cytokines induced by chronic restraint stress in mice. Biol Pharm Bull 40:1260\u20131267. https:\/\/doi.org\/10.1248\/bpb.b17-00131","journal-title":"Biol Pharm Bull"},{"key":"514_CR8","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.psychres.2018.08.078","volume":"269","author":"MH Chen","year":"2018","unstructured":"Chen MH et al (2018) Rapid inflammation modulation and antidepressant efficacy of a low-dose ketamine infusion in treatment-resistant depression: a randomized, double-blind control study. Psychiatry Res 269:207\u2013211. https:\/\/doi.org\/10.1016\/j.psychres.2018.08.078","journal-title":"Psychiatry Res"},{"key":"514_CR9","doi-asserted-by":"publisher","first-page":"343","DOI":"10.17219\/acem\/37124","volume":"23","author":"MK Erdem","year":"2014","unstructured":"Erdem MK, Yurdakan G, Yilmaz-Sipahi E (2014) The effects of ketamine, midazolam and ketamine\/xylazine on acute lung injury induced by alpha-naphthylthiourea in rats. Adv Clin Exp Med 23:343\u2013351. https:\/\/doi.org\/10.17219\/acem\/37124","journal-title":"Adv Clin Exp Med"},{"key":"514_CR10","doi-asserted-by":"publisher","first-page":"3565","DOI":"10.1097\/00001756-200011090-00032","volume":"11","author":"J Szelenyi","year":"2000","unstructured":"Szelenyi J et al (2000) Opposite role of alpha2- and beta-adrenoceptors in the modulation of interleukin-10 production in endotoxaemic mice. NeuroReport 11:3565\u20133568. https:\/\/doi.org\/10.1097\/00001756-200011090-00032","journal-title":"NeuroReport"},{"key":"514_CR11","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1111\/j.1398-9995.2007.01587.x","volume":"63","author":"S Kierstein","year":"2008","unstructured":"Kierstein S et al (2008) Ozone inhalation induces exacerbation of eosinophilic airway inflammation and hyperresponsiveness in allergen-sensitized mice. Allergy 63:438\u2013446. https:\/\/doi.org\/10.1111\/j.1398-9995.2007.01587.x","journal-title":"Allergy"},{"key":"514_CR12","doi-asserted-by":"publisher","first-page":"3950","DOI":"10.1096\/fj.201600857RRR","volume":"31","author":"MA Erickson","year":"2017","unstructured":"Erickson MA et al (2017) Serum amyloid A: an ozone-induced circulating factor with potentially important functions in the lung-brain axis. FASEB J 31:3950\u20133965. https:\/\/doi.org\/10.1096\/fj.201600857RRR","journal-title":"FASEB J"},{"key":"514_CR13","doi-asserted-by":"publisher","first-page":"2232","DOI":"10.1152\/jn.00299.2018","volume":"120","author":"NJ Michelson","year":"2018","unstructured":"Michelson NJ, Kozai TDY (2018) Isoflurane and ketamine differentially influence spontaneous and evoked laminar electrophysiology in mouse V1. J Neurophysiol 120:2232\u20132245. https:\/\/doi.org\/10.1152\/jn.00299.2018","journal-title":"J Neurophysiol"},{"key":"514_CR14","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.jneuroim.2007.05.013","volume":"188","author":"MG Reyes-Garcia","year":"2007","unstructured":"Reyes-Garcia MG, Hernandez-Hernandez F, Hernandez-Tellez B, Garcia-Tamayo F (2007) GABA (A) receptor subunits RNA expression in mice peritoneal macrophages modulate their IL-6\/IL-12 production. J Neuroimmunol 188:64\u201368. https:\/\/doi.org\/10.1016\/j.jneuroim.2007.05.013","journal-title":"J Neuroimmunol"},{"key":"514_CR15","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.ebiom.2018.03.019","volume":"30","author":"AK Bhandage","year":"2018","unstructured":"Bhandage AK et al (2018) GABA regulates release of inflammatory cytokines from peripheral blood mononuclear cells and CD4(+) T cells and is immunosuppressive in type 1 diabetes. EBioMedicine 30:283\u2013294. https:\/\/doi.org\/10.1016\/j.ebiom.2018.03.019","journal-title":"EBioMedicine"},{"key":"514_CR16","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1186\/s12931-016-0453-1","volume":"17","author":"Y Wang","year":"2016","unstructured":"Wang Y et al (2016) N-methyl-d-aspartate receptor activation mediates lung fibroblast proliferation and differentiation in hyperoxia-induced chronic lung disease in newborn rats. Respir Res 17:136. https:\/\/doi.org\/10.1186\/s12931-016-0453-1","journal-title":"Respir Res"},{"key":"514_CR17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0199087","volume":"13","author":"L Mees","year":"2018","unstructured":"Mees L et al (2018) Faster emergence behavior from ketamine\/xylazine anesthesia with atipamezole versus yohimbine. PLoS ONE 13:e0199087. https:\/\/doi.org\/10.1371\/journal.pone.0199087","journal-title":"PLoS ONE"},{"key":"514_CR18","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1097\/ALN.0000000000002038","volume":"128","author":"J Hu","year":"2018","unstructured":"Hu J et al (2018) Dexmedetomidine prevents cognitive decline by enhancing resolution of high mobility group box 1 protein-induced inflammation through a vagomimetic action in mice. Anesthesiology 128:921\u2013931. https:\/\/doi.org\/10.1097\/ALN.0000000000002038","journal-title":"Anesthesiology"},{"key":"514_CR19","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1093\/toxsci\/kfz219","volume":"173","author":"A Tovar","year":"2020","unstructured":"Tovar A et al (2020) Transcriptional profiling of the murine airway response to acute ozone exposure. Toxicol Sci 173:114\u2013130. https:\/\/doi.org\/10.1093\/toxsci\/kfz219","journal-title":"Toxicol Sci"},{"key":"514_CR20","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1093\/toxsci\/69.2.400","volume":"69","author":"DK Bhalla","year":"2002","unstructured":"Bhalla DK, Reinhart PG, Bai C, Gupta SK (2002) Amelioration of ozone-induced lung injury by anti-tumor necrosis factor-alpha. Toxicol Sci 69:400\u2013408. https:\/\/doi.org\/10.1093\/toxsci\/69.2.400","journal-title":"Toxicol Sci"},{"key":"514_CR21","doi-asserted-by":"publisher","first-page":"L537","DOI":"10.1152\/ajplung.2001.280.3.L537","volume":"280","author":"HY Cho","year":"2001","unstructured":"Cho HY, Zhang LY, Kleeberger SR (2001) Ozone-induced lung inflammation and hyperreactivity are mediated via tumor necrosis factor-alpha receptors. Am J Physiol Lung Cell Mol Physiol 280:L537-546. https:\/\/doi.org\/10.1152\/ajplung.2001.280.3.L537","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"514_CR22","doi-asserted-by":"publisher","first-page":"L390","DOI":"10.1152\/ajplung.00007.2004","volume":"288","author":"RA Johnston","year":"2005","unstructured":"Johnston RA, Schwartzman IN, Flynt L, Shore SA (2005) Role of interleukin-6 in murine airway responses to ozone. Am J Physiol Lung Cell Mol Physiol 288:L390-397. https:\/\/doi.org\/10.1152\/ajplung.00007.2004","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"514_CR23","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1165\/rcmb.2003-0373OC","volume":"30","author":"JW Park","year":"2004","unstructured":"Park JW et al (2004) Interleukin-1 receptor antagonist attenuates airway hyperresponsiveness following exposure to ozone. Am J Respir Cell Mol Biol 30:830\u2013836. https:\/\/doi.org\/10.1165\/rcmb.2003-0373OC","journal-title":"Am J Respir Cell Mol Biol"},{"key":"514_CR24","doi-asserted-by":"publisher","first-page":"846","DOI":"10.4049\/jimmunol.168.2.846","volume":"168","author":"L Michalec","year":"2002","unstructured":"Michalec L et al (2002) CCL7 and CXCL10 orchestrate oxidative stress-induced neutrophilic lung inflammation. J Immunol 168:846\u2013852. https:\/\/doi.org\/10.4049\/jimmunol.168.2.846","journal-title":"J Immunol"},{"key":"514_CR25","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1093\/toxsci\/kfw226","volume":"155","author":"M Francis","year":"2017","unstructured":"Francis M et al (2017) Editor\u2019s highlight: CCR2 regulates inflammatory cell accumulation in the lung and tissue injury following ozone exposure. Toxicol Sci 155:474\u2013484. https:\/\/doi.org\/10.1093\/toxsci\/kfw226","journal-title":"Toxicol Sci"},{"key":"514_CR26","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.bbrc.2021.04.045","volume":"557","author":"K Yuki","year":"2021","unstructured":"Yuki K et al (2021) Anesthetics isoflurane and sevoflurane attenuate flagellin-mediated inflammation in the lung. Biochem Biophys Res Commun 557:254\u2013260. https:\/\/doi.org\/10.1016\/j.bbrc.2021.04.045","journal-title":"Biochem Biophys Res Commun"},{"key":"514_CR27","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1165\/rcmb.2017-0357OC","volume":"59","author":"RM Tighe","year":"2018","unstructured":"Tighe RM, Birukova A, Yaeger MJ, Reece SW, Gowdy KM (2018) Euthanasia- and lavage-mediated effects on bronchoalveolar measures of lung injury and inflammation. Am J Respir Cell Mol Biol 59:257\u2013266. https:\/\/doi.org\/10.1165\/rcmb.2017-0357OC","journal-title":"Am J Respir Cell Mol Biol"}],"container-title":["Lung"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00408-022-00514-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00408-022-00514-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00408-022-00514-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,25]],"date-time":"2022-04-25T07:10:31Z","timestamp":1650870631000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00408-022-00514-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,23]]},"references-count":27,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["514"],"URL":"https:\/\/doi.org\/10.1007\/s00408-022-00514-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-1179142\/v1","asserted-by":"object"},{"id-type":"doi","id":"10.1101\/2021.12.16.472860","asserted-by":"object"}]},"ISSN":["0341-2040","1432-1750"],"issn-type":[{"value":"0341-2040","type":"print"},{"value":"1432-1750","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,23]]},"assertion":[{"value":"16 December 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 January 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 February 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors have no relevant financial or non-financial interests to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The use of mice on this study was approved by the VA Puget Sound Healthcare System IACUC, protocol 0924. Human subjects were not used on this study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}}]}}