Fetal responses to intra-amniotic endotoxin in sheep.
OBJECTIVE
Our aim was to determine the acute physiologic effects of intra-amniotic endotoxin administration in fetal sheep, and in particular, to determine whether intra-amniotic endotoxin causes an increase in fetal cortisol that could underlie the functional maturation of the fetal lungs previously reported in this model.


METHODS
As in our previous experiments, ewes were randomly assigned to receive a single intra-amniotic injection of either endotoxin (20 mg, Escherichia coli [055:B5], n = 5) or saline (n = 5). Between 0.5 hours before endotoxin and 168 hours after its administration, we measured maternal and fetal arterial pressures and heart rates; fetal and maternal blood samples were collected for measurement of blood gases, electrolytes, glucose and lactate concentrations, white cell counts (total and differential), and plasma cortisol.


RESULTS
Fetal arterial carbon dioxide tension and lactate concentration were significantly elevated 6 and 12 hours after endotoxin but returned to pre-endotoxin levels by 24 hours. Fetal plasma cortisol concentrations were significantly elevated at 4 hours and peaked 24 hours after endotoxin, returning to control levels by 2 days. Fetal white cell counts initially decreased (4 hours) and then increased (after 24 hours), becoming significantly elevated 6 days after treatment. Other fetal variables, and all measured maternal variables, were unaffected.


CONCLUSIONS
Our data suggest that fetal sheep respond to intra-amniotic endotoxin with transient, mild physiologic alterations that follow a time course similar to inflammatory responses reported previously. The elevation in fetal cortisol is insufficient to be the cause of preterm lung maturation shown previously with this treatment.
Nitsos
Ilias
I
Department of Obstetrics and Gynaecology, University of Western Australia, Crawley 6009, WA, Australia. initsos@cyllene.uwa.edu.au
Moss
Timothy J M
TJ
Cock
Megan L
ML
Harding
Richard
R
Newnham
John P
JP
D000650:Amnion; D000818:Animals; D001794:Blood Pressure; D002245:Carbon Dioxide / Q000097:blood; D005314:Embryonic and Fetal Development; D004731:Endotoxins / Q000008:administration & dosage*; D004926:Escherichia coli; D005260:Female; D005333:Fetus / Q000502:physiology*; D006340:Heart Rate, Fetal; D006854:Hydrocortisone / Q000097:blood; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D019344:Lactic Acid / Q000097:blood; D007958:Leukocyte Count; D009504:Neutrophils; D010100:Oxygen / Q000097:blood; D011247:Pregnancy; D012756:Sheep
D004731:Endotoxins; D002245:Carbon Dioxide; D019344:Lactic Acid; D010100:Oxygen; D006854:Hydrocortisone