Newborn cerebrovascular responses after first trimester moderate maternal ethanol exposure in sheep.
Fetal alcohol syndrome is one of the leading causes of mental retardation in the United States, but the pathogenesis of the associated brain damage is unknown. We tested the hypothesis that neonatal cerebrovascular responses to CO2 and/or hypoxia may be altered by moderate chronic maternal ethanol exposure early in gestation. We studied 26 newborn lambs (1-4 d old). Their mothers had received daily i.v. infusions of either ethanol (1 g/kg; ethanol concentration = 167 +/- 3 mg/dL; mean +/- SEM) or a similar volume of saline for 3 wk during the first trimester. In nine lambs, we studied cerebral responses to CO2 (saline, n = 4; ethanol, n = 5) and in 17 lambs, cerebral responses to hypoxia (saline, n = 7; ethanol, n = 10). Cerebrovascular responses to CO2 were not different between the groups. However, the cerebral vasodilatory response to hypoxemia was significantly attenuated in the ethanol lambs, such that cerebral O2 delivery was not maintained. During severe hypoxia (arterial PO2 = 30 mm Hg), cerebral blood flow increased 106 +/- 23% (mean +/- SEM) above baseline in the saline-treated group, but increased only 32 +/- 15% above baseline in the ethanol-treated group (p < 0.02). Similarly, cerebrovascular resistance in the saline group decreased 52 +/- 6% from baseline, but decreased only 16 +/- 11% in the ethanol group (p < 0.02). We conclude that moderate maternal ethanol infusion early in pregnancy attenuates neonatal hypoxic, but not CO2, cerebrovascular responsivity.
Gleason
C A
CA
Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-3200, USA.
Iida
H
H
Hotchkiss
K J
KJ
Northington
F J
FJ
Traystman
R J
RJ
D000437:Alcoholism / Q000150:complications / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D002245:Carbon Dioxide; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000209:etiology / Q000503:physiopathology; D005865:Gestational Age; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000209:etiology; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology; D012756:Sheep; D014664:Vasodilation / Q000187:drug effects
D002245:Carbon Dioxide; D000431:Ethanol