title: Betamethasone effects on fetal sheep cerebral blood flow are not dependent on maturation of cerebrovascular system and pituitary-adrenal axis.
abstract: Synthetic glucocorticoids are administered to pregnant women in premature labour to accelerate fetal lung maturation at a time when fetal cerebrovascular and endocrine systems are maturing. Exposure to glucocorticoids at 0.8-0.9 of gestation increases peripheral and cerebrovascular resistance (CVR) in fetal sheep. We examined whether the increase of CVR and its adverse effect on cerebral blood flow (CBF) depend on the current level of maturation of the pituitary-adrenal axis and the cerebrovascular system. Using fluorescent microspheres, regional CBF was measured in 11 brain regions before and 24 h and 48 h after the start of 3.3 microg kg(-1) h(-1) betamethasone (n = 8) or vehicle (n = 7) infusions to fetal sheep at 0.73 of gestation. Hypercapnic challenges were performed before and 24 h after the onset of betamethasone exposure to examine betamethasone effects on cerebrovascular reactivity. Betamethasone exposure decreased CBF by approximately 40% in all brain regions after 24 h of infusion (P < 0.05). The decline in CBF was mediated by a CVR increase of 111 +/- 16% in the cerebral cortex and 129 +/- 29% in subcortical regions (P < 0.05). Hypercapnic cerebral vasodilatation and associated increase in CBF were blunted (P < 0.05). Fetal CBF recovered after 48 h of betamethasone administration. There were no differences in glucocorticoid induced CBF and CVR changes compared with our previous findings at 0.87 of gestation. We conclude that the cerebrovascular effects of antenatal glucocorticoids are independent of cerebrovascular maturation and preparturient increase in activity of the fetal pituitary-adrenal axis.
authors.affiliation: Department of Neurology, Friedrich Schiller University, 07740 Jena, Germany. matthias.schwab@med.uni-jena.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Löhle
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
authors.forename: Carola
authors.initials: C
authors.lastname: Wicher
authors.forename: Marcus
authors.initials: M
authors.lastname: Roedel
authors.forename: Harald
authors.initials: H
authors.lastname: Schubert
authors.forename: Otto W
authors.initials: OW
authors.lastname: Witte
authors.forename: Peter W
authors.initials: PW
authors.lastname: Nathanielsz
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
mesh_terms: D000818:Animals; D001623:Betamethasone / Q000494:pharmacology*; D001921:Brain / Q000098:blood supply* / Q000187:drug effects* / Q000196:embryology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D005260:Female; D005333:Fetus / Q000098:blood supply* / Q000187:drug effects* / Q000196:embryology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000196:embryology; D011247:Pregnancy; D012756:Sheep
chemical_list: D001623:Betamethasone
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