The effects of low-dose endotoxin on the umbilicoplacental circulation in preterm sheep.
OBJECTIVE
In the present study we examined the effects of low-dose endotoxin (lipopolysaccharides, LPS) on continuously recorded umbilical blood flow.


METHODS
Twenty fetal sheep were catheterized at a gestational age of 107 +/- 1 days. A flow probe was placed around either the common umbilical artery or one single umbilical artery. Three days later fetuses received either 100 or 500 nanograms of LPS (n = 14) or 2 mL saline (n = 6) intravenously. Six fetuses died within 12 hours after LPS. Fetal heart rate (FHR), mean arterial pressure (MAP), and umbilical blood flow (Q(umb)) were monitored for 3 days.


RESULTS
FHR increased by 25 +/- 4% at 4-5 hours after LPS (P <.01) and was elevated for 15 hours after LPS. MAP increased by 18 +/- 5% 1 hour after LPS (P <.01) and returned to control value 4-5 hours after LPS. Q(umb) began to decrease 1 hour after LPS and was minimal (-30 +/- 7%, P <.001) at 4-5 hours after LPS. Q(umb) slowly returned to the control value at 12 hours after LPS. Placental vascular resistance increased by 73 +/- 37% (P <.01), whereas pH did not appreciably change.


CONCLUSIONS
Intravenous application of endotoxin caused a substantial and long-lasting decrease in umbilical blood flow resulting in fetal hypoxemia without acidemia. These effects may be of significance in the development of fetal brain damage associated with intrauterine infection.
Coumans
A B C
AB
Department of Obstetrics and Gynecology, University of Maastricht, Maastricht, The Netherlands.
Garnier
Y
Y
Supçun
S
S
Jensen
A
A
Berger
R
R
Hasaart
T H M
TH
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001925:Brain Damage, Chronic / Q000196:embryology; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000502:physiology*; D005865:Gestational Age; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D012756:Sheep; D014469:Umbilical Arteries / Q000187:drug effects / Q000473:pathology*; D014472:Umbilicus / Q000098:blood supply*
D004731:Endotoxins; D008070:Lipopolysaccharides