Effects of inhibition of prostaglandin synthesis on flow and composition of fetal urine, lung liquid, and swallowed fluid in sheep

Abstract

Objective: Our aim was to determine the effects of blocking prostaglandin 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 ± E 1.2 days of gestation (n = 7) and at 134.7 ± 0.8 days of gestation (n = 7) (term ∼ 147 days). Vehicle infusions were performed at 128.8 ± 1.4 days of gestation (n = 5). Results: Fetal urine production was significantly reduced and both fetal urine osmolality and plasma arginine vasopressin concentrations were significantly elevated in response to indomethacin infusions at both gestational ages. Fetal blood and urine lactate concentrations were elevated in response to indomethacin. Later in gestation, fetal lung liquid flow was significantly changed from a net efflux to a net influx. There was no significant effect of indomethacin on the volume of fluid swallowed by the fetus. Conclusion: Inhibition of fetal prostaglandin synthesis profoundly reduces the production of the two major fetal fluids contributing to amniotic fluid, namely, urine and lung liquid. These findings may explain why indomethacin reduces amniotic fluid volume. Objective: Our aim was to determine the effects of blocking prostaglandin 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 ± E 1.2 days of gestation (n = 7) and at 134.7 ± 0.8 days of gestation (n = 7) (term ∼ 147 days). Vehicle infusions were performed at 128.8 ± 1.4 days of gestation (n = 5). Results: Fetal urine production was significantly reduced and both fetal urine osmolality and plasma arginine vasopressin concentrations were significantly elevated in response to indomethacin infusions at both gestational ages. Fetal blood and urine lactate concentrations were elevated in response to indomethacin. Later in gestation, fetal lung liquid flow was significantly changed from a net efflux to a net influx. There was no significant effect of indomethacin on the volume of fluid swallowed by the fetus. Conclusion: Inhibition of fetal prostaglandin synthesis profoundly reduces the production of the two major fetal fluids contributing to amniotic fluid, namely, urine and lung liquid. These findings may explain why indomethacin reduces amniotic fluid volume.