title: Altered cardiovascular function at birth in growth-restricted preterm lambs.
abstract: Cardiovascular dysfunction at birth may underlie poor outcomes after fetal growth restriction (FGR) in neonates. We compared the cardiovascular transition between FGR and appropriately grown (AG) preterm lambs and examined possible mechanisms underlying any cardiovascular dysfunction in FGR lambs.
  
  
  
  FGR was induced in ewes bearing twins at 0.7 gestation; the twin was used as an internal control (AG). At 0.8 gestation, lambs were delivered and either euthanized with their arteries isolated for in vitro wire myography, or ventilated for 2 h. At 60 min, inhaled nitric oxide (iNO) was administered in a subgroup for 30 min. Molecular assessment of the nitric oxide (NO) pathway within lung tissue was conducted.
  
  
  
  FGR lambs had lower left ventricular output and cerebral blood flow (CBF) and higher systemic vascular resistance compared with AG lambs. INO administration to FGR lambs rapidly improved cardiovascular and systemic hemodynamics but resulted in decreased CBF in AG lambs. Isolated arteries from FGR lambs showed impaired sensitivity to NO donors, but enhanced vasodilation to Sildenafil and Sodium nitroprusside, and altered expression of components of the NO pathway.
  
  
  
  Cardiovascular dysfunction at birth may underlie the increased morbidity and mortality observed in preterm FGR newborns. Impaired NO signaling likely underlies the abnormal vascular reactivity.
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.|Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia.
authors.forename: Graeme R
authors.initials: GR
authors.lastname: Polglase
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.|Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia.
authors.forename: Beth J
authors.initials: BJ
authors.lastname: Allison
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
authors.forename: Elise
authors.initials: E
authors.lastname: Coia
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.
authors.forename: Anqi
authors.initials: A
authors.lastname: Li
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.|Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia.
authors.forename: Graham
authors.initials: G
authors.lastname: Jenkin
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.|Monash Newborn, Monash Medical Centre, and Department of Pediatrics, Monash University, Melbourne, Victoria, Australia.
authors.forename: Atul
authors.initials: A
authors.lastname: Malhotra
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.|Monash Newborn, Monash Medical Centre, and Department of Pediatrics, Monash University, Melbourne, Victoria, Australia.
authors.forename: Arvind
authors.initials: A
authors.lastname: Sehgal
authors.affiliation: Department of Neonatology, Royal North Shore Hospital and University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Martin
authors.initials: M
authors.lastname: Kluckow
authors.affiliation: Centre for Neonatal Research and Education, The University of Western Australia, Perth, Western Australia, Australia.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Gill
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.|Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia.
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Hooper
authors.affiliation: The Ritchie Centre, Hudson Institute of Medical Research, Clayton, Victoria, Australia.|Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Miller
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D015150:Echocardiography, Doppler; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D008098:Litter Size; D008168:Lung / Q000187:drug effects; D009569:Nitric Oxide / Q000008:administration & dosage; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009599:Nitroprusside / Q000627:therapeutic use; D010100:Oxygen / Q000378:metabolism; D012756:Sheep; D034561:Sheep, Domestic; D000068677:Sildenafil Citrate / Q000627:therapeutic use; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D009599:Nitroprusside; D009569:Nitric Oxide; D000068677:Sildenafil Citrate; D052250:Nitric Oxide Synthase Type III; D010100:Oxygen