{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:37:46Z","timestamp":1789562266638,"version":"build-2803163510"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The aim of this study was to assess the association between regional tidal volume (Vt), regional functional residual capacity (FRC), and the expression of genes linked with ventilator-induced lung injury. Two groups of BALB\/c mice (n\u2009=\u20098 per group) were ventilated for 2 hours using a protective or injurious ventilation strategy, with free-breathing mice used as control animals. Regional Vt and FRC of the ventilated mice was determined by analysis of high-resolution four-dimensional computed tomographic images taken at baseline and after 2 hours of ventilation and corrected for the volume of the region (i.e., specific [s]Vt and specific [s]FRC). RNA concentrations of 21 genes in 10 different lung regions were quantified using a quantitative PCR array. sFRC at baseline varied regionally, independent of ventilation strategy, whereas sVt varied regionally depending on ventilation strategy. The expression of IL-6 (P\u2009=\u20090.04), Ccl2 (P\u2009&amp;lt;\u20090.01), and Ang-2 (P\u2009&amp;lt;\u20090.05) was associated with sVt but not sFRC. The expression of seven other genes varied regionally (IL-1\u03b2 and RAGE [receptor for advanced glycation end products]) or depended on ventilation strategy (Nfe2l2 [nuclear factor erythroid-derived 2 factor 2], c-fos, and Wnt1) or both (TNF-\u03b1 and Cxcl2), but it was not associated with regional sFRC or sVt. These observations suggest that regional inflammatory responses to mechanical ventilation are driven primarily by tidal stretch.<\/jats:p>","DOI":"10.1165\/rcmb.2018-0143oc","type":"journal-article","created":{"date-parts":[[2018,11,14]],"date-time":"2018-11-14T17:07:47Z","timestamp":1542215267000},"page":"569-577","source":"Crossref","is-referenced-by-count":27,"title":["The Link between Regional Tidal Stretch and Lung Injury during Mechanical Ventilation"],"prefix":"10.1093","volume":"60","author":[{"given":"Seiha","family":"Yen","sequence":"first","affiliation":[{"name":"School of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Preissner","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Aerospace Engineering, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Bennett","sequence":"additional","affiliation":[{"name":"School of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Dubsky","sequence":"additional","affiliation":[{"name":"Department of Mechanical and Aerospace Engineering, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Carnibella","sequence":"additional","affiliation":[{"name":"4Dx Limited, Melbourne, Victoria, Australia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronan","family":"O\u2019Toole","sequence":"additional","affiliation":[{"name":"School of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Roddam","sequence":"additional","affiliation":[{"name":"School of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Jones","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Research Institute"},{"name":"Department of Medicine, and"},{"name":"Women\u2019s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Dargaville","sequence":"additional","affiliation":[{"name":"Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, Tasmania, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Fouras","sequence":"additional","affiliation":[{"name":"4Dx Limited, Melbourne, Victoria, Australia; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9039-0302","authenticated-orcid":false,"given":"Graeme R.","family":"Zosky","sequence":"additional","affiliation":[{"name":"School of Medicine and"},{"name":"Menzies Institute for Medical Research, College of Health and Medicine, University of Tasmania, Hobart, Tasmania, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,5,1]]},"reference":[{"key":"2026012222071023000_bib1","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1164\/rccm.200805-722OC","article-title":"Has mortality from acute respiratory distress syndrome decreased over time? a systematic review","volume":"179","author":"Phua","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012222071023000_bib2","first-page":"1","article-title":"Current incidence and outcome of the acute respiratory distress syndrome","volume":"22","author":"Villar","year":"2016","journal-title":"Curr Opin Crit Care"},{"key":"2026012222071023000_bib3","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1001\/jama.2016.0291","article-title":"Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries","volume":"315","author":"Bellani","year":"2016","journal-title":"JAMA"},{"key":"2026012222071023000_bib4","first-page":"2526","article-title":"Acute respiratory distress syndrome: the Berlin Definition","volume":"307","author":"Ranieri","year":"2012","journal-title":"JAMA"},{"key":"2026012222071023000_bib5","first-page":"485","article-title":"Causes of mortality in patients with the adult respiratory distress syndrome","volume":"132","author":"Montgomery","year":"1985","journal-title":"Am Rev Respir Dis"},{"key":"2026012222071023000_bib6","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1164\/rccm.201503-0421PP","article-title":"History of mechanical ventilation: from Vesalius to ventilator-induced lung injury","volume":"191","author":"Slutsky","year":"2015","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012222071023000_bib7","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1001\/jama.289.16.2104","article-title":"Injurious mechanical ventilation and end-organ epithelial cell apoptosis and organ dysfunction in an experimental model of acute respiratory distress syndrome","volume":"289","author":"Imai","year":"2003","journal-title":"JAMA"},{"key":"2026012222071023000_bib8","doi-asserted-by":"crossref","first-page":"112","DOI":"10.2174\/1874306401509010112","article-title":"Ventilator-induced lung injury (VILI) in acute respiratory distress syndrome (ARDS): volutrauma and molecular effects","volume":"9","author":"Carrasco Loza","year":"2015","journal-title":"Open Respir Med J"},{"key":"2026012222071023000_bib9","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1097\/CCM.0b013e318180b65c","article-title":"The effects of long-term conventional mechanical ventilation on the lungs of adult rats","volume":"36","author":"Bailey","year":"2008","journal-title":"Crit Care Med"},{"key":"2026012222071023000_bib10","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1164\/ajrccm.157.1.9604014","article-title":"Ventilator-induced lung injury: lessons from experimental studies","volume":"157","author":"Dreyfuss","year":"1998","journal-title":"Am J Respir Crit Care Med"},{"key":"2026012222071023000_bib11","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1056\/NEJM200005043421801","article-title":"Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome","volume":"342","author":"Brower","year":"2000","journal-title":"N Engl J Med"},{"key":"2026012222071023000_bib12","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1056\/NEJMoa1214103","article-title":"Prone positioning in severe acute respiratory distress syndrome","volume":"368","author":"Gu\u00e9rin","year":"2013","journal-title":"N Engl J Med"},{"key":"2026012222071023000_bib13","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1001\/jama.2017.14171","article-title":"Effect of lung recruitment and titrated positive end-expiratory pressure (PEEP) vs low PEEP on mortality in patients with acute respiratory distress syndrome: a randomized clinical trial","volume":"318","author":"Cavalcanti","year":"2017","journal-title":"JAMA"},{"key":"2026012222071023000_bib14","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s00134-015-4200-8","article-title":"The \u201cbaby lung\u201d became an adult","volume":"42","author":"Gattinoni","year":"2016","journal-title":"Intensive Care Med"},{"key":"2026012222071023000_bib15","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1097\/ALN.0000000000000727","article-title":"Lung inhomogeneities and time course of ventilator-induced mechanical injuries","volume":"123","author":"Cressoni","year":"2015","journal-title":"Anesthesiology"},{"key":"2026012222071023000_bib16","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1007\/s00134-010-1995-1","article-title":"Regional tidal ventilation and compliance during a stepwise vital capacity manoeuvre","volume":"36","author":"Dargaville","year":"2010","journal-title":"Intensive Care Med"},{"key":"2026012222071023000_bib17","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1172\/JCI119259","article-title":"Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model","volume":"99","author":"Tremblay","year":"1997","journal-title":"J Clin Invest"},{"issue":"4","key":"2026012222071023000_bib18","doi-asserted-by":"crossref","first-page":"S200","DOI":"10.1097\/01.CCM.0000057844.31307.ED","article-title":"Molecular mechanisms of lung cell activation induced by cyclic stretch","volume":"31","author":"Pugin","year":"2003","journal-title":"Crit Care Med"},{"key":"2026012222071023000_bib19","first-page":"L167","article-title":"Stretch induces cytokine release by alveolar epithelial cells in vitro","volume":"277","author":"Vlahakis","year":"1999","journal-title":"Am J Physiol"},{"key":"2026012222071023000_bib20","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1007\/s00134-002-1321-7","article-title":"Kinetic and reversibility of mechanical ventilation-associated pulmonary and systemic inflammatory response in patients with acute lung injury","volume":"28","author":"St\u00fcber","year":"2002","journal-title":"Intensive Care Med"},{"key":"2026012222071023000_bib21","doi-asserted-by":"crossref","first-page":"L112","DOI":"10.1152\/ajplung.00158.2010","article-title":"Linking lung function and inflammatory responses in ventilator-induced lung injury","volume":"300","author":"Cannizzaro","year":"2011","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026012222071023000_bib22","doi-asserted-by":"crossref","first-page":"e491","DOI":"10.1097\/CCM.0000000000000346","article-title":"Effect of local tidal lung strain on inflammation in normal and lipopolysaccharide-exposed sheep","volume":"42","author":"Wellman","year":"2014","journal-title":"Crit Care Med"},{"key":"2026012222071023000_bib23","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1152\/japplphysiol.00861.2015","article-title":"Regional tidal lung strain in mechanically ventilated normal lungs","volume":"121","author":"Paula","year":"2016","journal-title":"J Appl Physiol (1985)"},{"key":"2026012222071023000_bib24","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1098\/rsif.2012.0116","article-title":"Synchrotron-based dynamic computed tomography of tissue motion for regional lung function measurement","volume":"9","author":"Dubsky","year":"2012","journal-title":"J R Soc Interface"},{"key":"2026012222071023000_bib25","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1152\/japplphysiol.00393.2009","article-title":"Protective mechanical ventilation does not exacerbate lung function impairment or lung inflammation following influenza A infection","volume":"107","author":"Zosky","year":"2009","journal-title":"J Appl Physiol (1985)"},{"key":"2026012222071023000_bib26","doi-asserted-by":"crossref","first-page":"123701","DOI":"10.1063\/1.3664870","article-title":"A 24 keV liquid-metal-jet x-ray source for biomedical applications","volume":"82","author":"Larsson","year":"2011","journal-title":"Rev Sci Instrum"},{"key":"2026012222071023000_bib27","doi-asserted-by":"crossref","first-page":"6017","DOI":"10.1118\/1.4964794","article-title":"Technical note: contrast free angiography of the pulmonary vasculature in live mice using a laboratory x-ray source","volume":"43","author":"Samarage","year":"2016","journal-title":"Med Phys"},{"key":"2026012222071023000_bib28","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1152\/japplphysiol.00903.2016","article-title":"Novel analysis of 4DCT imaging quantifies progressive increases in anatomic dead space during mechanical ventilation in mice","volume":"123","author":"Kim","year":"2017","journal-title":"J Appl Physiol (1985)"},{"key":"2026012222071023000_bib29","doi-asserted-by":"crossref","first-page":"29438","DOI":"10.1038\/srep29438","article-title":"Quantification of heterogeneity in lung disease with image-based pulmonary function testing","volume":"6","author":"Stahr","year":"2016","journal-title":"Sci Rep"},{"key":"2026012222071023000_bib30","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1152\/japplphysiol.00476.2016","article-title":"Assessment of airway response distribution and paradoxical airway dilation in mice during methacholine challenge","volume":"122","author":"Dubsky","year":"2017","journal-title":"J Appl Physiol (1985)"},{"key":"2026012222071023000_bib31","first-page":"130","article-title":"Multiscale vessel enhancement filtering","author":"Frangi","year":"1998"},{"key":"2026012222071023000_bib32","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1172\/JCI1368","article-title":"IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses","volume":"101","author":"Xing","year":"1998","journal-title":"J Clin Invest"},{"key":"2026012222071023000_bib33","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1046\/j.1523-1755.1999.00514.x","article-title":"Synergistic effect of interleukin-1 and CD40L on the activation of human renal tubular epithelial cells","volume":"56","author":"van Kooten","year":"1999","journal-title":"Kidney Int"},{"key":"2026012222071023000_bib34","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1038\/ki.1995.437","article-title":"Production and cytokine-mediated regulation of monocyte chemoattractant protein-1 by human proximal tubular epithelial cells","volume":"48","author":"Prodjosudjadi","year":"1995","journal-title":"Kidney Int"},{"key":"2026012222071023000_bib35","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1161\/STROKEAHA.116.015590","article-title":"Monocyte chemotactic protein-1-interleukin-6-osteopontin pathway of intra-aneurysmal tissue healing","volume":"48","author":"Hosaka","year":"2017","journal-title":"Stroke"},{"key":"2026012222071023000_bib36","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1182\/blood.V91.1.258","article-title":"Interleukin-6 induces monocyte chemotactic protein-1 in peripheral blood mononuclear cells and in the U937 cell line","volume":"91","author":"Biswas","year":"1998","journal-title":"Blood"},{"key":"2026012222071023000_bib37","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1097\/01.ASN.0000015609.31253.7F","article-title":"MCP-1 induces inflammatory activation of human tubular epithelial cells: involvement of the transcription factors, nuclear factor-\u03baB and activating protein-1","volume":"13","author":"Viedt","year":"2002","journal-title":"J Am Soc Nephrol"},{"key":"2026012222071023000_bib38","doi-asserted-by":"crossref","first-page":"L533","DOI":"10.1152\/ajplung.00004.2004","article-title":"Mechanical ventilation with moderate tidal volumes synergistically increases lung cytokine response to systemic endotoxin","volume":"287","author":"Altemeier","year":"2004","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026012222071023000_bib39","doi-asserted-by":"crossref","first-page":"L224","DOI":"10.1152\/ajplung.00336.2015","article-title":"Plasma angiopoietin-2 outperforms other markers of endothelial injury in prognosticating pediatric ARDS mortality","volume":"310","author":"Zinter","year":"2016","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"2026012222071023000_bib40","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1172\/JCI4876","article-title":"Monocyte chemoattractant protein-1 promotes macrophage-mediated tubular injury, but not glomerular injury, in nephrotoxic serum nephritis","volume":"103","author":"Tesch","year":"1999","journal-title":"J Clin Invest"},{"key":"2026012222071023000_bib41","first-page":"91","article-title":"Synergistic effect of hyperoxia and biotrauma on ventilator-induced lung injury","volume":"38","author":"Shosholcheva","year":"2017","journal-title":"Pril (Makedon Akad Nauk Umet Odd Med Nauki)"},{"key":"2026012222071023000_bib42","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1089\/ars.2014.5987","article-title":"ATF3 protects pulmonary resident cells from acute and ventilator-induced lung injury by preventing Nrf2 degradation","volume":"22","author":"Shan","year":"2015","journal-title":"Antioxid Redox Signal"},{"key":"2026012222071023000_bib43","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.bpa.2015.08.004","article-title":"Mechanisms of ventilator-induced lung injury in healthy lungs","volume":"29","author":"Silva","year":"2015","journal-title":"Best Pract Res Clin Anaesthesiol"},{"key":"2026012222071023000_bib44","doi-asserted-by":"crossref","first-page":"4930","DOI":"10.1182\/blood-2013-02-486217","article-title":"Mast cell and macrophage chemokines CXCL1\/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation","volume":"121","author":"De Filippo","year":"2013","journal-title":"Blood"},{"key":"2026012222071023000_bib45","doi-asserted-by":"crossref","first-page":"994","DOI":"10.3390\/cancers3010994","article-title":"Role of p53 in cell death and human cancers","volume":"3","author":"Ozaki","year":"2011","journal-title":"Cancers (Basel)"},{"key":"2026012222071023000_bib46","doi-asserted-by":"crossref","first-page":"929","DOI":"10.2174\/156652412802480844","article-title":"p53 is an important regulator of CCL2 gene expression","volume":"12","author":"Tang","year":"2012","journal-title":"Curr Mol Med"},{"key":"2026012222071023000_bib47","doi-asserted-by":"crossref","first-page":"8056","DOI":"10.4049\/jimmunol.0801323","article-title":"Neutrophil-derived IL-6 limits alveolar barrier disruption in experimental ventilator-induced lung injury","volume":"182","author":"Wolters","year":"2009","journal-title":"J Immunol"},{"key":"2026012222071023000_bib48","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1038\/nm1494","article-title":"Hyperoxia causes angiopoietin 2-mediated acute lung injury and necrotic cell death","volume":"12","author":"Bhandari","year":"2006","journal-title":"Nat Med"}],"container-title":["American Journal of Respiratory Cell and Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/60\/5\/569\/66465289\/ajrcmb_60_5_569.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article-pdf\/60\/5\/569\/66465289\/ajrcmb_60_5_569.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T03:11:35Z","timestamp":1769137895000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrcmb\/article\/60\/5\/569\/8430394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,1]]},"references-count":48,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,5,1]]},"published-print":{"date-parts":[[2019,5,1]]}},"URL":"https:\/\/doi.org\/10.1165\/rcmb.2018-0143oc","relation":{},"ISSN":["1044-1549","1535-4989"],"issn-type":[{"value":"1044-1549","type":"print"},{"value":"1535-4989","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,5]]},"published":{"date-parts":[[2019,5,1]]}}}