Pulmonary perfusion during lipopolysaccharide (LPS) induced fetal endotoxemia in the preterm fetal sheep.
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.
Garnier
Yves
Y
Department of Obstetrics and Gynecology, University Hospital at Cologne, Kerpenerstrasse 62, 50924 Cologne, Germany. yves.garnier@uk-koeln.de
Coumans
Audrey B C
AB
Berger
Richard
R
Hasaart
Tom H M
TH
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
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