INDOMETHACIN REVERSAL OF ETHANOL-INDUCED SUPPRESSION OF OVINE FETAL BREATHING MOVEMENTS AND RELATIONSHIP TO PROSTAGLANDIN-E2

The effects of indomethacin on the ethanol-induced suppression of fetal breathing movements and fetal arterial plasma and cerebrospinal fluid (CSF) PGE2 concentrations and maternal arterial plasma PGE2 concentration were determined in the near-term fetal lamb. Eight conscious instrumented pregnant ewes (between 130 and 133 days of gestation; term, 147 days) received 1-h maternal intravenous infusion of 1 g ethanol/kg total body weight, and the fetus received 6-h intravenous infusion of indomethacin (1 mg/h per kg fetal body weight) commencing 30 min later. Serial fetal and maternal arterial blood samples (n = 8) and fetal CSF samples (n = 5) were collected at selected times throughout the 12-h study for the determination of PGE2 concentration. Fetal breathing movements were monitored continuously throughout the experimental period. Maternal ethanol infusion resulted in initial suppression (P < 0.05) of fetal breathing movements for 2 h below pretreatment value, followed by a rapid increase in the incidence of fetal breathing movements after the onset of fetal indomethacin treatment. Fetal and maternal plasma PGE2 concentrations and fetal CSF PGE2 concentration were increased (P < 0.05) above the pre-infusion value during the administration of ethanol and 1 h thereafter. Fetal indomethacin treatment suppressed (P < 0.05) to undetectable levels fetal plasma and CSF PGE2 concentrations, which then became similar (P > 0.05) to pretreatment by 12 h. There was a positive correlation between fetal plasma and CSF PGE2 concentrations. There was an inverse correlation between the incidence of fetal breathing movements and fetal CSF PGE2 concentration. The data indicate that PGE2 plays an integral role in the ethanol-induced suppression of fetal breathing movements and the action of indomethacin as an antagonist of this effect of ethanol on the fetus.