Fetal Responses to Intra-Amniotic Endotoxin in Sheep

Abstract

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 intraamoniotic injection of either endotoxin (20 mg, Escherichcia cocli [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, electorlytes, glucose and lactate concentrations, white cell counts (total and differential), and plasma cortisol.

Results: Fetal arterial carbon dioxide tension and lactate concentration were concentration were significantly elevated 6 and 12 hours after endotoxin but returned to pre-endotoxin levels by 24 hours. Fetal plasma cortisol oncentrations 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 case of preterm lung maturation shown previously with this treatment.