title: Spatiotemporal Aeration and Lung Injury Patterns Are Influenced by the First Inflation Strategy at Birth.
abstract: Ineffective aeration during the first inflations at birth creates regional aeration and ventilation defects, initiating injurious pathways. This study aimed to compare a sustained first inflation at birth or dynamic end-expiratory supported recruitment during tidal inflations against ventilation without intentional recruitment on gas exchange, lung mechanics, spatiotemporal regional aeration and tidal ventilation, and regional lung injury in preterm lambs. Lambs (127 ± 2 d gestation), instrumented at birth, were ventilated for 60 minutes from birth with either lung-protective positive pressure ventilation (control) or as per control after either an initial 30 seconds of 40 cm H2O sustained inflation (SI) or an initial stepwise end-expiratory pressure recruitment maneuver during tidal inflations (duration 180 s; open lung ventilation [OLV]). At study completion, molecular markers of lung injury were analyzed. The initial use of an OLV maneuver, but not SI, at birth resulted in improved lung compliance, oxygenation, end-expiratory lung volume, and reduced ventilatory needs compared with control, persisting throughout the study. These changes were due to more uniform inter- and intrasubject gravity-dependent spatiotemporal patterns of aeration (measured using electrical impedance tomography). Spatial distribution of tidal ventilation was more stable after either recruitment maneuver. All strategies caused regional lung injury patterns that mirrored associated regional volume states. Irrespective of strategy, spatiotemporal volume loss was consistently associated with up-regulation of early growth response-1 expression. Our results show that mechanical and molecular consequences of lung aeration at birth are not simply related to rapidity of fluid clearance; they are also related to spatiotemporal pressure-volume interactions within the lung during inflation and deflation.
authors.affiliation: 1 Neonatal Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia.|2 Neonatology, The Royal Children's Hospital, Parkville, Victoria, Australia.|3 Neonatal Research, The Royal Women's Hospital, Parkville, Victoria, Australia.|4 Departments of Paediatrics and.
authors.forename: David G
authors.initials: DG
authors.lastname: Tingay
authors.affiliation: 1 Neonatal Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
authors.forename: Anushi
authors.initials: A
authors.lastname: Rajapaksa
authors.affiliation: 1 Neonatal Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
authors.forename: C Elroy
authors.initials: CE
authors.lastname: Zonneveld
authors.affiliation: 1 Neonatal Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
authors.forename: Don
authors.initials: D
authors.lastname: Black
authors.affiliation: 1 Neonatal Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Perkins
authors.affiliation: 5 Systems and Computer Engineering, Carleton University, Ottawa, Ontario, Canada.
authors.forename: Andy
authors.initials: A
authors.lastname: Adler
authors.affiliation: 6 Fraunhofer Project Group for Automation in Medicine and Biotechnology, Mannheim, Germany.
authors.forename: Bartłomiej
authors.initials: B
authors.lastname: Grychtol
authors.affiliation: 1 Neonatal Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia.|7 NICU, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico - Università degli Studi di Milano, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Lavizzari
authors.affiliation: 8 Department of Anaesthesiology and Intensive Care Medicine, University Medical Centre Schleswig-Holstein, Campus Kiel, Kiel, Germany; and.
authors.forename: Inéz
authors.initials: I
authors.lastname: Frerichs
authors.affiliation: 9 The Ritchie Centre, MIMR-PHI Institute of Medical Research, and Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia.
authors.forename: Valerie A
authors.initials: VA
authors.lastname: Zahra
authors.affiliation: 1 Neonatal Research, Murdoch Childrens Research Institute, Parkville, Victoria, Australia.|3 Neonatal Research, The Royal Women's Hospital, Parkville, Victoria, Australia.|10 Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Davis
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D008170:Lung Compliance; D008176:Lung Volume Measurements; D011175:Positive-Pressure Respiration / Q000009:adverse effects*; D011312:Pressure; D011659:Pulmonary Gas Exchange; D012123:Pulmonary Ventilation; D012333:RNA, Messenger / Q000378:metabolism; D015656:Respiratory Mechanics; D012307:Risk Factors; D012756:Sheep; D013990:Tidal Volume; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D055397:Ventilator-Induced Lung Injury / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D051766:Early Growth Response Protein 1; D012333:RNA, Messenger
keywords: aeration; electrical impedance tomography; infant, neonate; lung injury; lung mechanics