title: Ketamine Attenuates the ACTH Response to Hypoxia in Late-Gestation Ovine Fetus.
abstract: BACKGROUND
  Ketamine, a noncompetitive N-Methyl-D-aspartate (NMDA) receptor antagonist, is a commonly used dissociative anesthetic in neonatology. We have proposed that ketamine reduces fetal stress responsiveness to stimuli that involve reduced oxygen supply to the fetal brain. Previously, we have shown that ketamine inhibits plasma ACTH levels in late-gestation fetal sheep subjected to brachiocephalic artery occlusion (BCO), an ischemic hypoxia model that might activate some of the same direct and reflex responses as hypoxia.
  
  
  OBJECTIVE
  We performed the current study to test the hypothesis that ketamine pretreatment will reduce fetal ACTH responses to hypoxic hypoxia (HH).
  
  
  METHODS
  Fetal sheep were chronically catheterized at least 5 days prior to study. Ketamine (3 mg/kg) was administered intravenously to the fetus 10 min prior to normoxia or a period of hypoxia induced by administration of nitrogen gas to the maternal trachea for 30 min.
  
  
  RESULTS
  Hypoxia significantly increased both fetal ACTH and cortisol levels in both the control and ketamine groups (p < 0.0005, interaction effect of time·stimulus in two-way ANOVA), and the ACTH response was blunted by ketamine (p < 0.005).
  
  
  CONCLUSIONS
  Ketamine reduced fetal ACTH responses to HH, possibly due to antagonism of the NMDA receptors in the fetal brain. Interestingly, in contrast to the responses to BCO, ACTH responses to HH were only partially inhibited, suggesting that multiple neurotransmitter pathways mediate the ACTH response to HH.
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gainesville, Fla., USA.
authors.forename: Eileen I
authors.initials: EI
authors.lastname: Chang
authors.forename: Charles E
authors.initials: CE
authors.lastname: Wood
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000778:Anesthetics, Dissociative / Q000008:administration & dosage*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D006854:Hydrocortisone / Q000097:blood*; D000860:Hypoxia / Q000139:chemically induced*; D007649:Ketamine / Q000008:administration & dosage*; D034561:Sheep, Domestic
chemical_list: D000778:Anesthetics, Dissociative; D007649:Ketamine; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone