{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T12:29:29Z","timestamp":1770812969880,"version":"3.50.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T00:00:00Z","timestamp":1601510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Optimal oxygen saturation as measured by pulse oximetry (SpO2) in neonatal lung injury, such as meconium aspiration syndrome (MAS) and persistent pulmonary hypertension of newborn (PPHN), is not known. Our goal was to determine the SpO2 range in lambs with MAS and PPHN that results in the highest brain oxygen delivery (bDO2) and pulmonary blood flow (Qp) and the lowest pulmonary vascular resistance and oxidative stress. Meconium was instilled into endotracheal tubes in 25 near-term gestation lambs, and the umbilical cord was occluded to induce asphyxia and gasping, causing MAS and PPHN. Lambs were randomized into four groups and ventilated for 6 hours with fixed fraction of inspired oxygen (FiO2)\u2009=\u20091.0 irrespective of SpO2, and three groups had FiO2 titrated to keep preductal SpO2 between 85% and 89%, 90% and 94%, and 95% and 99%, respectively. Tissues were collected to measure nitric oxide synthase activity, 3-nitrotyrosine, and 8-isoprostanes. Throughout the 6-hour exposure period, lambs in the 95\u201399% SpO2 target group had the highest Qp, lowest pulmonary vascular resistance, and highest bDO2 but were exposed to higher FiO2 (0.5\u2009\u00b1\u20090.21 vs. 0.29\u2009\u00b1\u20090.17) with higher lung 3-nitrotyrosine (0.67 [interquartile range (IQR), 0.43\u20130.73] ng\/mcg protein vs. 0.1 [IQR, 0.09\u20130.2] ng\/mcg protein) and lower lung nitric oxide synthase activity (196 [IQR, 192\u2013201] mMol nitrite\/mg protein vs. 270 [IQR, 227\u2013280] mMol nitrite\/mg protein) compared with the 90\u201394% target group. Brain 3-nitrotyrosine was lower in the 85\u201389% target group, and brain\/lung 8-isoprostane levels were not significantly different. In term lambs with MAS and PPHN, Qp and bDO2 through the first 6 hours are higher with target SpO2 in the 95\u201399% range. However, the 90\u201394% target range is associated with significantly lower FiO2 and lung oxidative stress. Clinical trials comparing the 90\u201394% versus the 95\u201399% SpO2 target range in term infants with PPHN are warranted.<\/jats:p>","DOI":"10.1165\/rcmb.2019-0449oc","type":"journal-article","created":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T15:02:10Z","timestamp":1593615730000},"page":"510-518","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":22,"title":["Optimal Oxygen Targets in Term Lambs with Meconium Aspiration Syndrome and Pulmonary Hypertension"],"prefix":"10.1093","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9703-9857","authenticated-orcid":false,"given":"Munmun","family":"Rawat","sequence":"first","affiliation":[{"name":"Department of Pediatrics and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8727-3017","authenticated-orcid":false,"given":"Praveen","family":"Chandrasekharan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvia F.","family":"Gugino","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and"},{"name":"Department of Physiology and Biophysics, University at Buffalo, Buffalo, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmon","family":"Koenigsknecht","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lori","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and"},{"name":"Department of Physiology and Biophysics, University at Buffalo, Buffalo, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Wedgwood","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California Davis Medical Center, Sacramento, California; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bobby","family":"Mathew","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayasree","family":"Nair","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Steinhorn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Rady Children\u2019s Hospital, University of California San Diego, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6098-2155","authenticated-orcid":false,"given":"Satyan","family":"Lakshminrusimha","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California Davis Medical Center, Sacramento, California; and"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,10,1]]},"reference":[{"key":"2026021100454464100_bib1","doi-asserted-by":"crossref","DOI":"10.1542\/9781610020275","volume-title":"Textbook of Neonatal Resuscitation (NRP)","author":"Weiner","year":"2016","edition":"7th ed."},{"key":"2026021100454464100_bib2","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/pr.2015.259","article-title":"Neonatal resuscitation adhering to oxygen saturation guidelines in asphyxiated lambs with meconium aspiration","volume":"79","author":"Rawat","year":"2016","journal-title":"Pediatr Res"},{"key":"2026021100454464100_bib3","doi-asserted-by":"crossref","first-page":"243","DOI":"10.3233\/NPM-16915133","article-title":"An international survey on persistent pulmonary hypertension of the newborn: a need for an evidence-based management","volume":"9","author":"Nakwan","year":"2016","journal-title":"J Neonatal Perinatal Med"},{"key":"2026021100454464100_bib4","first-page":"276","article-title":"Management of supplemental oxygen for infants with persistent pulmonary hypertension of newborn: a survey","volume":"34","author":"Alapati","year":"2017","journal-title":"Am J Perinatol"},{"key":"2026021100454464100_bib5","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/j.healun.2019.06.022","article-title":"2019 updated consensus statement on the diagnosis and treatment of pediatric pulmonary hypertension: the European Pediatric Pulmonary Vascular Disease Network (EPPVDN), endorsed by AEPC, ESPR and ISHLT","volume":"38","author":"Hansmann","year":"2019","journal-title":"J Heart Lung Transplant"},{"key":"2026021100454464100_bib6","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.1161\/CIR.0000000000000329","article-title":"Pediatric pulmonary hypertension: guidelines from the American Heart Association and American Thoracic Society","volume":"132","author":"Abman","year":"2015","journal-title":"Circulation"},{"key":"2026021100454464100_bib7","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1203\/PDR.0b013e3181a9eafb","article-title":"Oxygen toxicity and reactive oxygen species: the devil is in the details","volume":"66","author":"Auten","year":"2009","journal-title":"Pediatr Res"},{"key":"2026021100454464100_bib8","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1038\/jp.2008.241","article-title":"Meconium aspiration syndrome remains a significant problem in the NICU: outcomes and treatment patterns in term neonates admitted for intensive care during a ten-year period","volume":"29","author":"Singh","year":"2009","journal-title":"J Perinatol"},{"key":"2026021100454464100_bib9","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.clp.2018.01.014","article-title":"Oxygen therapy in the delivery room: what is the right dose?","volume":"45","author":"Kapadia","year":"2018","journal-title":"Clin Perinatol"},{"key":"2026021100454464100_bib10","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1159\/000499361","article-title":"European consensus guidelines on the management of respiratory distress syndrome - 2019 update","volume":"115","author":"Sweet","year":"2019","journal-title":"Neonatology"},{"key":"2026021100454464100_bib11","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1378\/chest.94.2.227a","article-title":"Routine oximetry: a fifth vital sign?","volume":"94","author":"Neff","year":"1988","journal-title":"Chest"},{"key":"2026021100454464100_bib12","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1203\/PDR.0b013e3181bab0c7","article-title":"Oxygen concentration and pulmonary hemodynamics in newborn lambs with pulmonary hypertension","volume":"66","author":"Lakshminrusimha","year":"2009","journal-title":"Pediatr Res"},{"key":"2026021100454464100_bib13","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1203\/PDR.0b013e3180db29fe","article-title":"Pulmonary hemodynamics in neonatal lambs resuscitated with 21%, 50%, and 100% oxygen","volume":"62","author":"Lakshminrusimha","year":"2007","journal-title":"Pediatr Res"},{"key":"2026021100454464100_bib14","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/pr.2014.186","article-title":"Tracheal suctioning improves gas exchange but not hemodynamics in asphyxiated lambs with meconium aspiration","volume":"77","author":"Lakshminrusimha","year":"2015","journal-title":"Pediatr Res"},{"key":"2026021100454464100_bib15","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1542\/peds.105.1.14","article-title":"Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes","volume":"105","author":"Walsh-Sukys","year":"2000","journal-title":"Pediatrics"},{"key":"2026021100454464100_bib16","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.jpeds.2017.12.055","article-title":"Pulmonary hypertension associated with hypoxic-ischemic encephalopathy-antecedent characteristics and comorbidities","volume":"196","author":"Lakshminrusimha","year":"2018","journal-title":"J Pediatr"},{"key":"2026021100454464100_bib17","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1172\/JCI105355","article-title":"Response of the pulmonary vasculature to hypoxia and H+ ion concentration changes","volume":"45","author":"Rudolph","year":"1966","journal-title":"J Clin Invest"},{"key":"2026021100454464100_bib18","doi-asserted-by":"crossref","first-page":"S12","DOI":"10.1038\/jp.2016.44","article-title":"Considerations in the management of hypoxemic respiratory failure and persistent pulmonary hypertension in term and late preterm neonates","volume":"36","author":"Lakshminrusimha","year":"2016","journal-title":"J Perinatol"},{"key":"2026021100454464100_bib19","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1203\/00006450-198909000-00012","article-title":"The role of oxygen free radicals in postasphyxia cerebral hypoperfusion in newborn lambs","volume":"26","author":"Rosenberg","year":"1989","journal-title":"Pediatr Res"},{"key":"2026021100454464100_bib20","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1097\/00003643-200003000-00004","article-title":"The effect of hyperoxia on cerebral blood flow: a study in healthy volunteers using magnetic resonance phase-contrast angiography","volume":"17","author":"Watson","year":"2000","journal-title":"Eur J Anaesthesiol"},{"key":"2026021100454464100_bib21","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.1152\/japplphysiol.00303.2003","article-title":"Independent cerebral vasoconstrictive effects of hyperoxia and accompanying arterial hypocapnia at 1 ATA","volume":"95","author":"Floyd","year":"2003","journal-title":"J Appl Physiol (1985)"},{"key":"2026021100454464100_bib22","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.jpeds.2013.04.043","article-title":"Perinatal asphyxia with hyperoxemia within the first hour of life is associated with moderate to severe hypoxic-ischemic encephalopathy","volume":"163","author":"Kapadia","year":"2013","journal-title":"J Pediatr"},{"key":"2026021100454464100_bib23","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1152\/japplphysiol.00711.2011","article-title":"Pulmonary hemodynamics and vascular reactivity in asphyxiated term lambs resuscitated with 21 and 100% oxygen","volume":"111","author":"Lakshminrusimha","year":"2011","journal-title":"J Appl Physiol (1985)"},{"key":"2026021100454464100_bib24","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/sj.jp.7210761","article-title":"Inhaled nitric oxide and gentle ventilation in the treatment of pulmonary hypertension of the newborn: a single-center, 5-year experience","volume":"22","author":"Gupta","year":"2002","journal-title":"J Perinatol"},{"key":"2026021100454464100_bib25","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jpeds.2019.06.053","article-title":"Morbidity of persistent pulmonary hypertension of the newborn in the first year of life","volume":"213","author":"Steurer","year":"2019","journal-title":"J Pediatr"},{"key":"2026021100454464100_bib26","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1080\/14767058.2018.1536740","article-title":"An Asian multicenter retrospective study on persistent pulmonary hypertension of the newborn: incidence, etiology, diagnosis, treatment and outcome","volume":"33","author":"Nakwan","year":"2020","journal-title":"J Matern Fetal Neonatal Med"},{"key":"2026021100454464100_bib27","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1203\/00006450-199410000-00015","article-title":"Surfactant therapy and high-frequency jet ventilation in the management of a piglet model of the meconium aspiration syndrome","volume":"36","author":"Wiswell","year":"1994","journal-title":"Pediatr Res"},{"key":"2026021100454464100_bib28","first-page":"1287","article-title":"Management of a piglet model of the meconium aspiration syndrome with high-frequency or conventional ventilation","volume":"146","author":"Wiswell","year":"1992","journal-title":"Am J Dis Child"},{"key":"2026021100454464100_bib29","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1001\/jama.2018.5725","article-title":"Association between oxygen saturation targeting and death or disability in extremely preterm infants in the neonatal oxygenation prospective meta-analysis collaboration","volume":"319","author":"Askie","year":"2018","journal-title":"JAMA"},{"key":"2026021100454464100_bib30","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/jp.2014.199","article-title":"Oxygen targeting in preterm infants: a physiological interpretation","volume":"35","author":"Lakshminrusimha","year":"2015","journal-title":"J Perinatol"}],"container-title":["American Journal of Respiratory Cell and Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/63\/4\/510\/66764577\/ajrcmb_63_4_510.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/63\/4\/510\/66764577\/ajrcmb_63_4_510.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T05:46:02Z","timestamp":1770788762000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article\/63\/4\/510\/8461185"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,1]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2020,10,1]]},"published-print":{"date-parts":[[2020,10,1]]}},"URL":"https:\/\/doi.org\/10.1165\/rcmb.2019-0449oc","relation":{},"ISSN":["1044-1549","1535-4989"],"issn-type":[{"value":"1044-1549","type":"print"},{"value":"1535-4989","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,10]]},"published":{"date-parts":[[2020,10,1]]},"assertion":[{"value":"2019-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}