Effects of indomethacin on fetal renal function, renal and umbilicoplacental blood flow and lung liquid production.

The effects of indomethacin (10 mg/kg i.v. to the ewe and 12 mg/kg i.v. to the fetus) were examined in 8 chronically catheterized fetal sheep (117-138 days gestation). These doses suppressed fetal 6-keto-prostaglandin F1 alpha and thromboxane B2 levels. Fetal arterial PO2 increased (P < 0.01); PCO2 (P < 0.001) and pH fell (P < 0.001) and arterial pressure did not change. Placental blood flow increased in 4 of the 5 fetuses in which blood flows were measured. Lung liquid flow rate fell (P < 0.001). Fetal renal blood flow did not change but its distribution did, i.e. flow to the inner part of the renal cortex decreased (P < 0.05). Urine flow rates did not change but there was a natriuresis (P < 0.02), kaliuresis (P < 0.02) and chloriuresis (P < 0.02). Urinary osmolality rose (P < 0.001) and free water clearance fell (P = 0.004). It is concluded that when indomethacin is administered to both ewe and fetus, the resulting fall in prostaglandin I2 and thromboxane A2 levels causes marked changes in fetal blood gas status, renal function and lung liquid production. These effects are more profound than those seen when indomethacin is given only to the fetus. They do not however, explain the reason why clinical use of indomethacin is associated with a reversible oligohydramnios.