EFFECTS OF INHIBITION OF PROSTAGLANDIN SYNTHESIS ON FLOW AND COMPOSITION OF FETAL URINE, LUNG LIQUID, AND SWALLOWED FLUID IN SHEEP

OBJECTIVE: Our aim was to determine the effects of blocking prostaglan din synthesis, by infusion of indomethacin into the fetal circulation, on factors regulating amniotic fluid volume and on plasma composition in the mother and fetus. STUDY DESIGN: Indomethacin was administered to fetal sheep during 8 hours at 124.0 +/- 1.2 days of gestation (n = 7) and at 134.7 +/- 0.8 days of gestation (n = 7) (term similar to 147 days). Vehicle infusions were performed at 128.8 +/- 1.4 days of gest ation (n = 5). RESULTS: Fetal urine production was significantly reduc ed and both fetal urine osmolality and plasma arginine vasopressin con centrations were significantly elevated in response to indomethacin in fusions at both gestational ages. Fetal blood and urine lactate concen trations were elevated in response to indomethacin. Later in gestation , fetal lung liquid flow was significantly changed from a net efflux t o a net influx. There was no significant effect of indomethacin on the volume of fluid swallowed by the fetus. CONCLUSION: inhibition of fet al prostaglandin synthesis profoundly reduces the production of the tw o major fetal fluids contributing to amniotic fluid, namely urine and lung liquid. These findings may explain why indomethacin reduces amnio tic fluid volume.