{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T18:24:27Z","timestamp":1789669467411,"version":"4.0.1"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000050","name":"U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["5R01HL141818"],"award-info":[{"award-number":["5R01HL141818"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["5R01HL141818"],"award-info":[{"award-number":["5R01HL141818"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-19-1-0237"],"award-info":[{"award-number":["W81XWH-19-1-0237"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-19-1-0237"],"award-info":[{"award-number":["W81XWH-19-1-0237"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["W81XWH-19-1-0237"],"award-info":[{"award-number":["W81XWH-19-1-0237"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat. Biomed. Eng"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Acute respiratory failure can cause profound hypoxaemia that leads to organ injury or death within minutes. When conventional interventions are ineffective, the intravenous administration of oxygen can rescue patients from severe hypoxaemia, but at the risk of microvascular obstruction and of toxicity of the carrier material. Here we describe polymeric microbubbles as carriers of high volumes of oxygen (350\u2013500\u2009ml of oxygen per litre of foam) that are stable in storage yet quickly dissolve following intravenous injection, reverting to their soluble and excretable molecular constituents. In swine with profound hypoxaemia owing to acute and temporary (12\u2009min) upper-airway obstruction, the microbubble-mediated delivery of oxygen led to: the maintenance of critical oxygenation, lowered burdens of cardiac arrest, improved survival, and substantially improved neurologic and kidney function in surviving animals. Our findings underscore the importance of maintaining a critical threshold of oxygenation and the promise of injectable oxygen as a viable therapy in acute and temporary hypoxaemic crises.<\/jats:p>","DOI":"10.1038\/s41551-024-01266-8","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T06:02:20Z","timestamp":1729144940000},"page":"1396-1411","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Systemically injected oxygen within rapidly dissolving microbubbles improves the outcomes of severe hypoxaemia in swine"],"prefix":"10.1038","volume":"8","author":[{"given":"Julia Garcia","family":"Mancebo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen","family":"Sack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Hartford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saffron","family":"Dominguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Balcarcel-Monzon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Chartier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tien","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis R.","family":"Cole","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7109-0582","authenticated-orcid":false,"given":"Francesca","family":"Sperotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Harrild","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian D.","family":"Polizzotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen D.","family":"Everett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0906-1021","authenticated-orcid":false,"given":"Alan B.","family":"Packard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Dearling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur G.","family":"Nedder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7659-3880","authenticated-orcid":false,"given":"Simon","family":"Warfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hart G. W.","family":"Lidov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6080-8739","authenticated-orcid":false,"given":"John N.","family":"Kheir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1273-8171","authenticated-orcid":false,"given":"Yifeng","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"1266_CR1","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1001\/jama.2019.1696","volume":"321","author":"LW Andersen","year":"2019","unstructured":"Andersen, L. W., Holmberg, M. J., Berg, K. M., Donnino, M. W. & Granfeldt, A. In-hospital cardiac arrest: a review. JAMA 321, 1200\u20131210 (2019).","journal-title":"JAMA"},{"key":"1266_CR2","doi-asserted-by":"publisher","first-page":"1912","DOI":"10.1056\/NEJMoa1109148","volume":"367","author":"S Girotra","year":"2012","unstructured":"Girotra, S. et al. Trends in survival after in-hospital cardiac arrest. N. Engl. J. Med. 367, 1912\u20131932 (2012).","journal-title":"N. Engl. J. Med."},{"key":"1266_CR3","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1161\/CIR.0b013e31829d8654","volume":"128","author":"PA Meaney","year":"2013","unstructured":"Meaney, P. A. et al. Cardiopulmonary resuscitation quality: improving cardiac resuscitation outcomes both inside and outside the hospital: a consensus statement from the American Heart Association. Circulation 128, 417\u2013435 (2013).","journal-title":"Circulation"},{"key":"1266_CR4","doi-asserted-by":"publisher","first-page":"e31","DOI":"10.1016\/j.resuscitation.2018.07.052","volume":"130","author":"C de Graaf","year":"2018","unstructured":"de Graaf, C., Donders, D. N. V., Beesems, S. G. & Koster, R. W. Time to return of spontaneous circulation (ROSC) and survival in out-of-hospital cardiac arrest (OHCA) patients in the Netherlands. Resuscitation 130, e31\u2013e32 (2018).","journal-title":"Resuscitation"},{"key":"1266_CR5","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-017-1744-8","volume":"21","author":"T Wengenmayer","year":"2017","unstructured":"Wengenmayer, T. et al. Influence of low-flow time on survival after extracorporeal cardiopulmonary resuscitation (eCPR). Crit. Care 21, 157 (2017).","journal-title":"Crit. Care"},{"key":"1266_CR6","doi-asserted-by":"publisher","first-page":"S366","DOI":"10.1161\/CIR.0000000000000916","volume":"142","author":"AR Panchal","year":"2020","unstructured":"Panchal, A. R. et al. Part 3: adult basic and advanced life support: 2020 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 142, S366\u2013S468 (2020).","journal-title":"Circulation"},{"key":"1266_CR7","doi-asserted-by":"publisher","first-page":"18820","DOI":"10.1002\/chem.201802054","volume":"24","author":"Y Peng","year":"2018","unstructured":"Peng, Y., Kheir, J. N. & Polizzotti, B. D. Injectable oxygen: interfacing materials chemistry with resuscitative science. Chem. Eur. J. 24, 18820\u201318829 (2018).","journal-title":"Chem. Eur. J."},{"key":"1266_CR8","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1016\/j.tibtech.2021.01.007","volume":"39","author":"NGA Willemen","year":"2021","unstructured":"Willemen, N. G. A. et al. Oxygen-releasing biomaterials: current challenges and future applications. Trends Biotechnol. 39, 1144\u20131159 (2021).","journal-title":"Trends Biotechnol."},{"key":"1266_CR9","doi-asserted-by":"publisher","first-page":"2797","DOI":"10.1021\/cr970143c","volume":"101","author":"JG Riess","year":"2001","unstructured":"Riess, J. G. Oxygen carriers (\u201cblood substitutes\u201d)\u2013raison d\u2019etre, chemistry, and some physiology. Chem. Rev. 101, 2797\u20132920 (2001).","journal-title":"Chem. Rev."},{"key":"1266_CR10","doi-asserted-by":"publisher","first-page":"R93","DOI":"10.1186\/cc364","volume":"3","author":"DR Spahn","year":"1999","unstructured":"Spahn, D. R. Blood substitutes. Artificial oxygen carriers: perfluorocarbon emulsions. Crit. Care 3, R93\u2013R97 (1999).","journal-title":"Crit. Care"},{"key":"1266_CR11","doi-asserted-by":"publisher","first-page":"100927","DOI":"10.1016\/j.blre.2022.100927","volume":"54","author":"NB Charbe","year":"2022","unstructured":"Charbe, N. B. et al. A new era in oxygen therapeutics? From perfluorocarbon systems to haemoglobin-based oxygen carriers. Blood Rev. 54, 100927 (2022).","journal-title":"Blood Rev."},{"key":"1266_CR12","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1097\/SHK.0000000000001530","volume":"54","author":"AT Williams","year":"2020","unstructured":"Williams, A. T. et al. Resuscitation from hemorrhagic shock with fresh and stored blood and polymerized hemoglobin. Shock 54, 464\u2013473 (2020).","journal-title":"Shock"},{"key":"1266_CR13","doi-asserted-by":"publisher","first-page":"1840","DOI":"10.1182\/blood-2018-10-860809","volume":"133","author":"JW Semple","year":"2019","unstructured":"Semple, J. W., Rebetz, J. & Kapur, R. Transfusion-associated circulatory overload and transfusion-related acute lung injury. Blood 133, 1840\u20131853 (2019).","journal-title":"Blood"},{"key":"1266_CR14","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1038\/s41586-022-05029-w","volume":"608","author":"DP Erdosy","year":"2022","unstructured":"Erdosy, D. P. et al. Microporous water with high gas solubilities. Nature 608, 712\u2013718 (2022).","journal-title":"Nature"},{"key":"1266_CR15","doi-asserted-by":"publisher","first-page":"140ra88","DOI":"10.1126\/scitranslmed.3003679","volume":"4","author":"JN Kheir","year":"2012","unstructured":"Kheir, J. N. et al. Oxygen gas-filled microparticles provide intravenous oxygen delivery. Sci. Transl. Med. 4, 140ra88 (2012).","journal-title":"Sci. Transl. Med."},{"key":"1266_CR16","doi-asserted-by":"publisher","first-page":"12380","DOI":"10.1073\/pnas.1608438113","volume":"113","author":"RP Seekell","year":"2016","unstructured":"Seekell, R. P. et al. Oxygen delivery using engineered microparticles. Proc. Natl Acad. Sci. USA 113, 12380\u201312385 (2016).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1266_CR17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2115276119","volume":"119","author":"AK Vutha","year":"2022","unstructured":"Vutha, A. K. et al. A microfluidic device for real-time on-demand intravenous oxygen delivery. Proc. Natl Acad. Sci. USA 119, e2115276119 (2022).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1266_CR18","doi-asserted-by":"publisher","first-page":"2600","DOI":"10.1016\/j.biomaterials.2013.12.070","volume":"35","author":"JA Feshitan","year":"2014","unstructured":"Feshitan, J. A., Legband, N. D., Borden, M. A. & Terry, B. S. Systemic oxygen delivery by peritoneal perfusion of oxygen microbubbles. Biomaterials 35, 2600\u20132606 (2014).","journal-title":"Biomaterials"},{"key":"1266_CR19","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.7150\/thno.4410","volume":"2","author":"JJ Kwan","year":"2012","unstructured":"Kwan, J. J., Kaya, M., Borden, M. A. & Dayton, P. A. Theranostic oxygen delivery using ultrasound and microbubbles. Theranostics 2, 1174\u20131184 (2012).","journal-title":"Theranostics"},{"key":"1266_CR20","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1002\/anie.201711839","volume":"57","author":"Y Peng","year":"2018","unstructured":"Peng, Y. et al. Interfacial nanoprecipitation toward stable and responsive microbubbles and their use as a resuscitative fluid. Angew. Chem. Int. Ed. 57, 1271\u20131276 (2018).","journal-title":"Angew. Chem. Int. Ed."},{"key":"1266_CR21","doi-asserted-by":"publisher","first-page":"2156","DOI":"10.1007\/s11095-017-2222-3","volume":"34","author":"KJ Black","year":"2017","unstructured":"Black, K. J. et al. Hemodynamic effects of lipid-based oxygen microbubbles via rapid intravenous injection in rodents. Pharm. Res. 34, 2156\u20132162 (2017).","journal-title":"Pharm. Res."},{"key":"1266_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e15500","volume":"9","author":"LFT Pereira","year":"2023","unstructured":"Pereira, L. F. T. et al. Oxygen therapy alternatives in COVID-19: from classical to nanomedicine. Heliyon 9, e15500 (2023).","journal-title":"Heliyon"},{"key":"1266_CR23","doi-asserted-by":"publisher","first-page":"100260","DOI":"10.1016\/j.mtadv.2022.100260","volume":"15","author":"JC Scimeca","year":"2022","unstructured":"Scimeca, J. C. & Verron, E. Nano-engineered biomaterials: safety matters and toxicity evaluation. Mater. Today Adv. 15, 100260 (2022).","journal-title":"Mater. Today Adv."},{"key":"1266_CR24","doi-asserted-by":"publisher","first-page":"15726","DOI":"10.1021\/la1029432","volume":"26","author":"EJ Swanson","year":"2010","unstructured":"Swanson, E. J., Mohan, V., Kheir, J. & Borden, M. A. Phospholipid-stabilized microbubble foam for injectable oxygen delivery. Langmuir 26, 15726\u201315729 (2010).","journal-title":"Langmuir"},{"key":"1266_CR25","doi-asserted-by":"publisher","first-page":"6862","DOI":"10.1016\/j.biomaterials.2013.05.053","volume":"34","author":"S Garg","year":"2013","unstructured":"Garg, S., Thomas, A. A. & Borden, M. A. The effect of lipid monolayer in-plane rigidity on in vivo microbubble circulation persistence. Biomaterials 34, 6862\u20136870 (2013).","journal-title":"Biomaterials"},{"key":"1266_CR26","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1002\/cmmi.414","volume":"6","author":"L Mullin","year":"2011","unstructured":"Mullin, L. et al. Effect of anesthesia carrier gas on in vivo circulation times of ultrasound microbubble contrast agents in rats. Contrast Media Mol. Imaging 6, 126\u2013131 (2011).","journal-title":"Contrast Media Mol. Imaging"},{"key":"1266_CR27","doi-asserted-by":"publisher","first-page":"5283","DOI":"10.1016\/j.polymer.2010.08.022","volume":"51","author":"S Chen","year":"2010","unstructured":"Chen, S., Li, L., Zhao, C. & Zheng, J. Surface hydration: principles and applications toward low-fouling\/nonfouling biomaterials. Polymer 51, 5283\u20135293 (2010).","journal-title":"Polymer"},{"key":"1266_CR28","doi-asserted-by":"publisher","first-page":"3965","DOI":"10.1021\/ja2108905","volume":"134","author":"DF Moyano","year":"2012","unstructured":"Moyano, D. F. et al. Nanoparticle hydrophobicity dictates immune response. J. Am. Chem. Soc. 134, 3965\u20133967 (2012).","journal-title":"J. Am. Chem. Soc."},{"key":"1266_CR29","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.jconrel.2014.03.022","volume":"183","author":"MC Jones","year":"2014","unstructured":"Jones, M. C. et al. Quantitative assessment of nanoparticle surface hydrophobicity and its influence on pulmonary biocompatibility. J. Control. Release 183, 94\u2013104 (2014).","journal-title":"J. Control. Release"},{"key":"1266_CR30","unstructured":"Drug Products, Including Biological Products, that Contain Nanomaterials \u2013 Guidance for Industry (US Food and Drug Administration, 2022)."},{"key":"1266_CR31","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1021\/ma960693x","volume":"30","author":"J Dong","year":"1997","unstructured":"Dong, J., Ozaki, Y. & Nakashima, K. Infrared, Raman, and near-infrared spectrospic evidence for the coexistence of various hydrogen-bond forms in poly(acrylic acid). Macromolecules 30, 1111\u20131117 (1997).","journal-title":"Macromolecules"},{"key":"1266_CR32","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1021\/ar900035f","volume":"42","author":"ME Fox","year":"2009","unstructured":"Fox, M. E., Szoka, F. C. & Fr\u00e9chet, J. M. Soluble polymer carriers for the treatment of cancer: the importance of molecular architecture. Acc. Chem. Res. 42, 1141\u20131151 (2009).","journal-title":"Acc. Chem. Res."},{"key":"1266_CR33","doi-asserted-by":"publisher","first-page":"12369","DOI":"10.1073\/pnas.0913667107","volume":"107","author":"A Ruggiero","year":"2010","unstructured":"Ruggiero, A. et al. Paradoxical glomerular filtration of carbon nanotubes. Proc. Natl Acad. Sci. USA 107, 12369\u201312374 (2010).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1266_CR34","doi-asserted-by":"publisher","first-page":"10173","DOI":"10.1021\/acs.langmuir.8b03779","volume":"35","author":"S Roovers","year":"2019","unstructured":"Roovers, S. et al. The role of ultrasound-driven microbubble dynamics in drug delivery: from microbubble fundamentals to clinical translation. Langmuir 35, 10173\u201310191 (2019).","journal-title":"Langmuir"},{"key":"1266_CR35","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1021\/acsmaterialslett.1c00296","volume":"3","author":"Y Peng","year":"2021","unstructured":"Peng, Y. et al. Engineering caged microbubbles for controlled acoustic cavitation and pressure sensing. ACS Mater. Lett. 3, 978\u2013987 (2021).","journal-title":"ACS Mater. Lett."},{"key":"1266_CR36","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1152\/jappl.1998.85.1.47","volume":"85","author":"RL Conhaim","year":"1985","unstructured":"Conhaim, R. L. & Rodenkirch, L. A. Functional diameters of alveolar microvessels at high lung volume in zone II. J. Appl. Physiol. 85, 47\u201352 (1985).","journal-title":"J. Appl. Physiol."},{"key":"1266_CR37","doi-asserted-by":"publisher","first-page":"163S","DOI":"10.1378\/chest.101.4_Supplement.163S","volume":"101","author":"CG Elliott","year":"1992","unstructured":"Elliott, C. G. Pulmonary physiology during pulmonary embolism. Chest 101, 163S\u2013171S (1992).","journal-title":"Chest"},{"key":"1266_CR38","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1378\/chest.102.2.467","volume":"102","author":"AH Eliasson","year":"1992","unstructured":"Eliasson, A. H., Phillips, Y. Y., Stajduhar, K. C., Carome, M. A. & Cowsar, J. D. Oxygen consumption and ventilation during normal labor. Chest 102, 467\u2013471 (1992).","journal-title":"Chest"},{"key":"1266_CR39","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.1161\/01.CIR.101.14.1743","volume":"101","author":"RA Berg","year":"2000","unstructured":"Berg, R. A., Hilwig, R. W., Kern, K. B. & Ewy, G. A. \u201cBystander\u201d chest compressions and assisted ventilation independently improve outcome from piglet asphyxial pulseless \u201ccardiac arrest\u201d. Circulation 101, 1743\u20131748 (2000).","journal-title":"Circulation"},{"key":"1266_CR40","doi-asserted-by":"publisher","first-page":"251.e1","DOI":"10.1016\/j.ajog.2011.06.025","volume":"205","author":"CS Ennen","year":"2011","unstructured":"Ennen, C. S. et al. Glial fibrillary acidic protein as a biomarker for neonatal hypoxic-ischemic encephalopathy treated with whole-body cooling. Am. J. Obstet. Gynecol. 205, 251.e1\u2013e7 (2011).","journal-title":"Am. J. Obstet. Gynecol."},{"key":"1266_CR41","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1258\/002367798780599802","volume":"32","author":"CL Alem\u00e1n","year":"1998","unstructured":"Alem\u00e1n, C. L. et al. Reference database of the main physiological parameters in Sprague-Dawley rats from 6 to 32 months. Lab. Anim. 32, 457\u2013466 (1998).","journal-title":"Lab. Anim."},{"key":"1266_CR42","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-021-03492-x","volume":"25","author":"D Contou","year":"2021","unstructured":"Contou, D. et al. Causes and timing of death in critically ill COVID-19 patients. Crit. Care 25, 79 (2021).","journal-title":"Crit. Care"},{"key":"1266_CR43","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/S2213-2600(20)30079-5","volume":"8","author":"X Yang","year":"2020","unstructured":"Yang, X. et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir. Med. 8, 475\u2013481 (2020).","journal-title":"Lancet Respir. Med."},{"key":"1266_CR44","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1513\/AnnalsATS.202011-1381RL","volume":"18","author":"SW Ketcham","year":"2021","unstructured":"Ketcham, S. W. et al. Causes and circumstances of death among patients hospitalized with COVID-19: a retrospective cohort study. Ann. Am. Thorac. Soc. 18, 1076\u20131079 (2021).","journal-title":"Ann. Am. Thorac. Soc."},{"key":"1266_CR45","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1097\/PCC.0000000000001766","volume":"20","author":"T Mokhateb-Rafii","year":"2019","unstructured":"Mokhateb-Rafii, T. et al. Hemodynamic impact of oxygen desaturation during tracheal intubation among critically Ill children with cyanotic and noncyanotic heart disease. Pediatr. Crit. Care Med. 20, 19\u201326 (2019).","journal-title":"Pediatr. Crit. Care Med."},{"key":"1266_CR46","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.4187\/respcare.02265","volume":"58","author":"SM Maggiore","year":"2013","unstructured":"Maggiore, S. M. et al. Decreasing the adverse effects of endotracheal suctioning during mechanical ventilation by changing practice. Respir. Care 58, 1588\u20131597 (2013).","journal-title":"Respir. Care"},{"key":"1266_CR47","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/S0022-5223(19)38908-1","volume":"85","author":"AA Conlan","year":"1983","unstructured":"Conlan, A. A., Hurwitz, S. S., Krige, L., Nicolaou, N. & Pool, R. Massive hemoptysis. Review of 123 cases. J. Thorac. Cardiovasc. Surg. 85, 120\u2013124 (1983).","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"1266_CR48","doi-asserted-by":"publisher","first-page":"e41","DOI":"10.1097\/PCC.0000000000001384","volume":"19","author":"S Li","year":"2018","unstructured":"Li, S. et al. Frequency of desaturation and association with hemodynamic adverse events during tracheal intubations in PICUs. Pediatr. Crit. Care Med. 19, e41\u2013e50 (2018).","journal-title":"Pediatr. Crit. Care Med."},{"key":"1266_CR49","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan0117","volume":"9","author":"DA Perry","year":"2017","unstructured":"Perry, D. A. et al. Responsive monitoring of mitochondrial redox states in heart muscle predicts impending cardiac arrest. Sci. Transl. Med. 9, eaan0117 (2017).","journal-title":"Sci. Transl. Med."},{"key":"1266_CR50","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1056\/NEJMcp0903466","volume":"361","author":"GB Young","year":"2009","unstructured":"Young, G. B. Neurologic prognosis after cardiac arrest. N. Engl. J. Med. 361, 605\u2013611 (2009).","journal-title":"N. Engl. J. Med."},{"key":"1266_CR51","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1007\/s00134-021-06548-2","volume":"47","author":"C Sandroni","year":"2021","unstructured":"Sandroni, C., Cronberg, T. & Sekhon, M. Brain injury after cardiac arrest: pathophysiology, treatment, and prognosis. Intensive Care Med. 47, 1393\u20131414 (2021).","journal-title":"Intensive Care Med."},{"key":"1266_CR52","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.jcrc.2016.04.001","volume":"34","author":"R Pana","year":"2016","unstructured":"Pana, R., Hornby, L., Shemie, S. D., Dhanani, S. & Teitelbaum, J. Time to loss of brain function and activity during circulatory arrest. J. Crit. Care 34, 77\u201383 (2016).","journal-title":"J. Crit. Care"},{"key":"1266_CR53","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/S0300-2977(00)00059-0","volume":"57","author":"G Buunk","year":"2000","unstructured":"Buunk, G., van der Hoeven, J. G. & Meinders, A. E. Cerebral blood flow after cardiac arrest. Neth. J. Med. 57, 106\u2013112 (2000).","journal-title":"Neth. J. Med."},{"key":"1266_CR54","first-page":"4143636","volume":"2018","author":"JMD van den Brule","year":"2018","unstructured":"van den Brule, J. M. D., van der Hoeven, J. G. & Hoedemaekers, C. W. E. Cerebral perfusion and cerebral autoregulation after cardiac arrest. BioMed. Res. Int. 2018, 4143636 (2018).","journal-title":"BioMed. Res. Int."},{"key":"1266_CR55","doi-asserted-by":"publisher","first-page":"E517","DOI":"10.1161\/CIR.0000000000000702","volume":"140","author":"RG Geocadin","year":"2019","unstructured":"Geocadin, R. G. et al. Standards for studies of neurological prognostication in comatose survivors of cardiac arrest: a scientific statement from the American Heart Association. Circulation 140, E517\u2013E542 (2019).","journal-title":"Circulation"},{"key":"1266_CR56","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/BF00265110","volume":"13","author":"PT Schumacker","year":"1987","unstructured":"Schumacker, P. T. & Cain, S. M. The concept of a critical oxygen delivery. Intensive Care Med. 13, 223\u2013229 (1987).","journal-title":"Intensive Care Med."},{"key":"1266_CR57","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.resuscitation.2018.03.011","volume":"126","author":"CE Ross","year":"2018","unstructured":"Ross, C. E. et al. Physiologic response to pre-arrest bolus dilute epinephrine in the pediatric intensive care unit. Resuscitation 126, 137\u2013142 (2018).","journal-title":"Resuscitation"},{"key":"1266_CR58","doi-asserted-by":"publisher","first-page":"g3028","DOI":"10.1136\/bmj.g3028","volume":"348","author":"MW Donnino","year":"2014","unstructured":"Donnino, M. W. et al. Time to administration of epinephrine and outcome after in-hospital cardiac arrest with non-shockable rhythms: retrospective analysis of large in-hospital data registry. BMJ 348, g3028 (2014).","journal-title":"BMJ"},{"key":"1266_CR59","first-page":"51467","volume":"87","author":"LM Thomson","year":"2014","unstructured":"Thomson, L. M., Polizzotti, B. D., McGowan, F. X. & Kheir, J. N. Manufacture of concentrated, lipid-based oxygen microbubble emulsions by high shear homogenization and serial concentration. J. Vis. Exp. 87, 51467 (2014).","journal-title":"J. Vis. Exp."},{"key":"1266_CR60","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/s40635-023-00517-3","volume":"11","author":"PA Mountford","year":"2023","unstructured":"Mountford, P. A. et al. Colonic oxygen microbubbles augment systemic oxygenation and CO2 removal in a porcine smoke inhalation model of severe hypoxia. Intensive Care Med. Exp. 11, 35 (2023).","journal-title":"Intensive Care Med. Exp."},{"key":"1266_CR61","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1016\/j.medj.2021.04.004","volume":"2","author":"R Okabe","year":"2021","unstructured":"Okabe, R. et al. Mammalian enteral ventilation ameliorates respiratory failure. Medicine 2, 773\u2013783.e5 (2021).","journal-title":"Medicine"},{"key":"1266_CR62","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1016\/j.ijrobp.2022.12.051","volume":"116","author":"R Patenaude","year":"2023","unstructured":"Patenaude, R. et al. Injectable oxygen microparticles boost radiation-mediated in situ vaccination and systemic antitumor immune responses. Int. J. Radiat. Oncol. Biol. Phys. 116, 906\u2013915 (2023).","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"1266_CR63","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1038\/nm1577","volume":"13","author":"I Ohsawa","year":"2007","unstructured":"Ohsawa, I. et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat. Med. 13, 688\u2013694 (2007).","journal-title":"Nat. Med."},{"key":"1266_CR64","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.jacbts.2018.11.006","volume":"4","author":"AR Cole","year":"2019","unstructured":"Cole, A. R. et al. Perioperatively inhaled hydrogen gas diminishes neurologic injury following experimental circulatory arrest in swine. JACC Basic Transl. Sci. 4, 176\u2013187 (2019).","journal-title":"JACC Basic Transl. Sci."},{"key":"1266_CR65","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/j.ejrad.2016.09.015","volume":"86","author":"L Ebner","year":"2017","unstructured":"Ebner, L. et al. The role of hyperpolarized 129xenon in MR imaging of pulmonary function. Eur. J. Radiol. 86, 343\u2013352 (2017).","journal-title":"Eur. J. Radiol."},{"key":"1266_CR66","first-page":"e60404","volume":"154","author":"S Ribeiro","year":"2019","unstructured":"Ribeiro, S. et al. Echocardiographic assessment of cardiac anatomy and function in adult rats. J. Vis. Exp. 154, e60404(2019).","journal-title":"J. Vis. Exp."},{"key":"1266_CR67","doi-asserted-by":"publisher","first-page":"S494","DOI":"10.1016\/S0003-4975(21)01181-4","volume":"60","author":"JM Forbess","year":"1995","unstructured":"Forbess, J. M. et al. University of Wisconsin cerebroplegia in a piglet survival model of circulatory arrest. Ann. Thorac. Surg. 60, S494\u2013S500 (1995).","journal-title":"Ann. Thorac. Surg."}],"container-title":["Nature Biomedical Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41551-024-01266-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41551-024-01266-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41551-024-01266-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T06:08:39Z","timestamp":1732255719000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41551-024-01266-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,17]]},"references-count":67,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["1266"],"URL":"https:\/\/doi.org\/10.1038\/s41551-024-01266-8","relation":{},"ISSN":["2157-846X"],"issn-type":[{"value":"2157-846X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,17]]},"assertion":[{"value":"12 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"B.D.P., J.N.K. and Y.P. are inventors on a patent (US11147890B2, United States, 2018) related to the technology described in this article. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}