Effect of inhibiting prostaglandin synthesis in pregnant sheep with 4-aminoantipyrine under normothermic and hyperthermic conditions.

Infusion of the prostaglandin synthetase inhibitor 4-aminoantipyrine at a rate of 20 mg/min via the fetal tarsal vein during normothermic conditions (ambient temperatures = 24 degrees C) significantly decreased the concentrations of prostaglandins E2 and F2 alpha in maternal and fetal arterial plasma and in uterine and umbilical vein plasma. The infusion was associated with a small but significant rise in fetal temperature and a fall in fetal arterial pH. Respiratory alkalosis developed in fetuses during hyperthermia by raising the ambient temperature to 43 degrees C for 8 hours. In contrast, infusion of 4-aminoantipyrine during hyperthermia produced fetal metabolic acidosis as indicated by a fall in fetal pH and an increase in PaCO2, even though the ewe remained hypocapnic. Four of the 10 fetuses died during or shortly after the 4-aminoantipyrine infusion during hyperthermia. These results indicate that uteroplacental prostaglandin synthesis is essential to allow the fetus to adapt to an increase in body temperature and suggests that prostaglandin synthetase inhibitors should be used with caution during pregnancy.