title: Role of prostaglandins in the metabolic responses of the fetus to hypoxia.
abstract: OBJECTIVE
  The effect of inhibiting prostaglandin synthesis on the fetal metabolic response to hypoxemia was examined by infusing indomethacin during periods of reduced maternal uterine blood flow.
  
  
  METHODS
  In seven fetal sheep we administered a 6-hour infusion of either indomethacin (n = 5), indomethacin plus prostaglandin E2, or a vehicle solution (n = 5). The last 4 hours of each infusion period coincided with a period of fetal hypoxemia induced by reduced maternal uterine blood flow.
  
  
  RESULTS
  During reduced maternal uterine blood flow indomethacin infusions caused a significantly greater reduction in pHA (reduced from 7.36 +/- 0.01 to 7.10 +/- 0.02) than both the vehicle (from 7.36 +/- 0.01 to 7.20 +/- 0.03) and indomethacin plus prostaglandin E2 infusions (from 7.36 +/- 0.01 to 7.18 +/- 0.02). Before reduced maternal uterine blood flow was induced, indomethacin significantly elevated fetal plasma glucose and lactate concentrations from 0.6 +/- 0.04 and 2.2 +/- 0.1 to 1.3 +/- 0.2 and 6.7 +/- 0.7 mmol/L, respectively. During reduced maternal uterine blood flow indomethacin caused a significantly greater increase in plasma glucose and lactate concentrations than the vehicle; plasma glucose and lactate concentrations increased to a maximum of 1.8 +/- 0.2 and 22.7 +/- 0.8 mmol/L, respectively, during indomethacin infusions compared with 1.1 +/- 0.1 and 15.7 +/- 1.7 mmol/L, respectively, during vehicle infusions. The addition of prostaglandin E2 to the indomethacin infusion prevented the enhanced increase in glucose and lactate concentrations during reduced maternal uterine blood flow and caused a significant increase in fetal plasma insulin concentrations from 12.6 +/- 0.7 to 60.9 +/- 28.1 microU/ml.
  
  
  CONCLUSIONS
  The inhibition of prostaglandin synthesis during fetal hypoxemia alters the metabolic response of the fetus, leading to a severe metabolic acidosis.
authors.affiliation: Department of Physiology, Monash University, Clayton, Victoria, Australia.
authors.forename: S B
authors.initials: SB
authors.lastname: Hooper
authors.forename: R
authors.initials: R
authors.lastname: Harding
authors.forename: J
authors.initials: J
authors.lastname: Deayton
authors.forename: G D
authors.initials: GD
authors.lastname: Thorburn
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005311:Fetal Hypoxia / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D010100:Oxygen / Q000097:blood; D011247:Pregnancy; D011453:Prostaglandins / Q000502:physiology*; D012756:Sheep / Q000196:embryology; D014599:Uterus / Q000098:blood supply
chemical_list: D001786:Blood Glucose; D007328:Insulin; D007773:Lactates; D011453:Prostaglandins; D002245:Carbon Dioxide; D019344:Lactic Acid; D015232:Dinoprostone; D010100:Oxygen; D007213:Indomethacin