title: Pulmonary perfusion during lipopolysaccharide (LPS) induced fetal endotoxemia in the preterm fetal sheep.
abstract: OBJECTIVE
  To study endotoxin induced changes in pulmonary blood flow during normoxia and hypoxia and analyzed the role of nitric oxide (NO) and endothelin (ET) in this process.
  
  
  METHODS
  Twenty-seven fetal sheep were chronically instrumented at 107+/-1 days (term is 147 days). Experiments were performed 3 days after surgery. Fetuses were randomized into four groups. Group 1: control group (n=5); Group 2: LPS group (n=6) with lipopolysaccharide (LPS) injection at t -60min; Group 3: L-NAME (n=6) with nitro-l-arginine methyl ester (l-NAME) treatment at t -75min; Group 4: l-NAME+LPS group (n=6) with nitro-l-arginine methyl ester (l-NAME) pre-treatment at t -75min and LPS administration at t -60min as described above; Group 5: BQ123+LPS group (n=4) with BQ123 pre-treatment at t -75min and LPS injection at t -60min as described above.
  
  
  RESULTS
  Unlike in control fetuses, there was a marked elevation in pulmonary perfusion in response to LPS induced endotoxemia during normoxia (+112%; p<0.01), which was even further increased during hypoxia (+434%; p<0.001). This increase was partially blocked by BQ123 (p<0.05) and completely abolished by pre-treatment with l-NAME (p<0.001).
  
  
  CONCLUSIONS
  During fetal endotoxemia, pulmonary perfusion is increased by LPS induced production of nitric oxide. This may have a significant impact in the fetal inflammatory response syndrome, particularly in the inflammation of the fetal lungs observed in response to intrauterine infection.
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital at Cologne, Kerpenerstrasse 62, 50924 Cologne, Germany. yves.garnier@uk-koeln.de
authors.forename: Yves
authors.initials: Y
authors.lastname: Garnier
authors.forename: Audrey B C
authors.initials: AB
authors.lastname: Coumans
authors.forename: Richard
authors.initials: R
authors.lastname: Berger
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Hasaart
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D016232:Endothelins / Q000502:physiology*; D019446:Endotoxemia / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005311:Fetal Hypoxia / Q000503:physiopathology*; D005333:Fetus / Q000098:blood supply; D006340:Heart Rate, Fetal / Q000187:drug effects; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000196:embryology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D011897:Random Allocation; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep
chemical_list: D000959:Antihypertensive Agents; D016232:Endothelins; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D010456:Peptides, Cyclic; D009569:Nitric Oxide; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D019331:NG-Nitroarginine Methyl Ester