title: Ketamine inhibits fetal ACTH responses to cerebral hypoperfusion.
abstract: The present study tested the effect of ketamine on the fetal reflex responses of late-gestation sheep to brachiocephalic occlusion (BCO), a stimulus that mimics the reduction in cerebral blood flow that results from severe fetal hypotension. Ketamine, a dissociative anesthetic and known noncompetitive antagonist of N-methyl D-aspartate (NMDA) receptors, has previously been shown to impair chemoreceptor responsiveness. Studies from this laboratory suggest that fetal reflex ACTH responses to hypotension are largely mediated by chemoreceptors; therefore, we hypothesized that ketamine would inhibit the reflex hormonal response to BCO. Chronically catheterized fetal sheep were subjected to acute cerebral hypoperfusion through occlusion of the brachiocephalic artery. Fetal blood pressure and heart rate were continuously recorded, and fetal blood samples drawn during the experiment were analyzed with specific hormone assays. Our results demonstrate that ketamine attenuates hemodynamic responses to cerebral hypoperfusion and is a potent inhibitor of ACTH and proopiomelanocortin (POMC)/pro-ACTH release. These data support the hypothesis that fetal reflex responses hypotension are chemoreceptor mediated. Given the potency with which ketamine inhibits ACTH response to fetal hypotension, we suggest that the use of ketamine or other anesthetic or analgesic drugs that block or otherwise interact with the NMDA-glutamate pathways, in late pregnancy or in preterm newborns be reconsidered.
authors.affiliation: Department of Physiology and Functional Genomics, University of Florida College of Medicine, Gaineseville, Florida, USA. Powers.melanie@epamail.epa.gov
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Powers
authors.forename: Charles E
authors.initials: CE
authors.lastname: Wood
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000037:antagonists & inhibitors* / Q000097:blood; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016122:Brachiocephalic Trunk; D002545:Brain Ischemia / Q000196:embryology* / Q000378:metabolism; D002560:Cerebrovascular Circulation; D005260:Female; D005865:Gestational Age; D006339:Heart Rate / Q000187:drug effects; D006854:Hydrocortisone / Q000097:blood; D007022:Hypotension / Q000097:blood / Q000209:etiology / Q000378:metabolism*; D007649:Ketamine / Q000494:pharmacology*; D011247:Pregnancy; D011311:Pressoreceptors / Q000187:drug effects; D011333:Pro-Opiomelanocortin / Q000037:antagonists & inhibitors / Q000097:blood; D012756:Sheep / Q000196:embryology
chemical_list: D000778:Anesthetics, Dissociative; D011333:Pro-Opiomelanocortin; D007649:Ketamine; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone