title: Single Sustained Inflation followed by Ventilation Leads to Rapid Cardiorespiratory Recovery but Causes Cerebral Vascular Leakage in Asphyxiated Near-Term Lambs.
abstract: BACKGROUND
  A sustained inflation (SI) rapidly restores cardiac function in asphyxic, bradycardic newborns but its effects on cerebral haemodynamics and brain injury are unknown. We determined the effect of different SI strategies on carotid blood flow (CaBF) and cerebral vascular integrity in asphyxiated near-term lambs.
  
  
  METHODS
  Lambs were instrumented and delivered at 139 ± 2 d gestation and asphyxia was induced by delaying ventilation onset. Lambs were randomised to receive 5 consecutive 3 s SI (multiple SI; n = 6), a single 30 s SI (single SI; n = 6) or conventional ventilation (no SI; n = 6). Ventilation continued for 30 min in all lambs while CaBF and respiratory function parameters were recorded. Brains were assessed for gross histopathology and vascular leakage.
  
  
  RESULTS
  CaBF increased more rapidly and to a greater extent during a single SI (p = 0.01), which then decreased below both other groups by 10 min, due to a higher cerebral oxygen delivery (p = 0.01). Blood brain barrier disruption was increased in single SI lambs as indicated by increased numbers of blood vessel profiles with plasma protein extravasation (p = 0.001) in the cerebral cortex. There were no differences in CaBF or cerebral oxygen delivery between the multiple SI and no SI lambs.
  
  
  CONCLUSIONS
  Ventilation with an initial single 30 s SI improves circulatory recovery, but is associated with greater disruption of blood brain barrier function, which may exacerbate brain injury suffered by asphyxiated newborns. This injury may occur as a direct result of the initial SI or to the higher tidal volumes delivered during subsequent ventilation.
authors.affiliation: The Ritchie Centre, Monash University, Melbourne, Australia.|Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kristina S
authors.initials: KS
authors.lastname: Sobotka
authors.affiliation: The Ritchie Centre, Monash University, Melbourne, Australia.|Department of Obstetrics and Gynaecology, Monash University, Melbourne, Australia.
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Hooper
authors.affiliation: The Ritchie Centre, Monash University, Melbourne, Australia.|Department of Obstetrics and Gynaecology, Monash University, Melbourne, Australia.
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Crossley
authors.affiliation: The Ritchie Centre, Monash University, Melbourne, Australia.
authors.forename: Tracey
authors.initials: T
authors.lastname: Ong
authors.affiliation: Department of Pediatrics, Medical University, Graz, Austria.|Centre for the Studies of Asphyxia and Resuscitation, Neonatal Research Unit, Royal Alexandra Hospital, Edmonton, Canada.|Department of Pediatrics, University of Alberta, Edmonton, Canada.
authors.forename: Georg M
authors.initials: GM
authors.lastname: Schmölzer
authors.affiliation: The Ritchie Centre, Monash University, Melbourne, Australia.
authors.forename: Samantha K
authors.initials: SK
authors.lastname: Barton
authors.affiliation: The Ritchie Centre, Monash University, Melbourne, Australia.
authors.forename: Annie R A
authors.initials: AR
authors.lastname: McDougall
authors.affiliation: The Ritchie Centre, Monash University, Melbourne, Australia.|Department of Obstetrics and Gynaecology, Monash University, Melbourne, Australia.
authors.forename: Suzie L
authors.initials: SL
authors.lastname: Miller
authors.affiliation: The Ritchie Centre, Monash University, Melbourne, Australia.|Department of Obstetrics and Gynaecology, Monash University, Melbourne, Australia.
authors.forename: Mary
authors.initials: M
authors.lastname: Tolcos
authors.affiliation: Department of Paediatrics, University Hospital of North Norway, Tromsø, Norway.|Paediatric Research Group, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
authors.forename: Claus
authors.initials: C
authors.lastname: Klingenberg
authors.affiliation: The Ritchie Centre, Monash University, Melbourne, Australia.|Department of Obstetrics and Gynaecology, Monash University, Melbourne, Australia.
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Polglase
mesh_terms: D000818:Animals; D001238:Asphyxia Neonatorum / Q000503:physiopathology / Q000628:therapy*; D001812:Blood-Brain Barrier / Q000502:physiology; D002339:Carotid Arteries / Q000502:physiology; D002560:Cerebrovascular Circulation; D020300:Intracranial Hemorrhages / Q000209:etiology*; D012121:Respiration, Artificial / Q000009:adverse effects* / Q000379:methods; D012756:Sheep; D014692:Ventilation-Perfusion Ratio