PMID- 17526556
OWN - NLM
STAT- MEDLINE
DCOM- 20071026
LR  - 20220408
IS  - 0958-0670 (Print)
IS  - 0958-0670 (Linking)
VI  - 92
IP  - 5
DP  - 2007 Sep
TI  - Chronic ethanol increases fetal cerebral blood flow specific to the 
      ethanol-sensitive cerebellum under normoxaemic, hypercapnic and acidaemic 
      conditions: ovine model.
PG  - 933-43
AB  - Cerebral hypoxia has been proposed as a mechanism by which prenatal ethanol 
      exposure causes fetal alcohol spectrum disorder (FASD) in children, but no study 
      had tested this hypothesis using a chronic exposure model that mimicks a common 
      human exposure pattern. Pregnant sheep were exposed to ethanol, 0.75 or 1.75 g 
      kg(-1) (to create blood ethanol concentrations of 85 and 185 mg dl(-1), 
      respectively), or saline 3 days per week in succession (a 'binge drinking' model) 
      from gestational day (GD) 109 until GD 132. Fetuses were instrumented on GD 
      119-120 and studied on GD 132. The 1.75 g kg(-1) dose resulted in a significant 
      increase in fetal biventricular output (measured by radiolabelled microsphere 
      technique) and heart rate, and a reduction of mean arterial pressure and total 
      peripheral resistance at 1 h, the end of ethanol infusion. The arterial partial 
      pressure of CO(2) was increased, arterial pH was decreased and arterial partial 
      pressure of O(2) did not change. Fetal whole-brain blood flow increased by 37% 
      compared with the control group at 1 h, resulting in increased cerebral oxygen 
      delivery. The elevation in brain blood flow was region specific, occurring 
      preferentially in the ethanol-sensitive cerebellum, increasing by 44% compared 
      with the control group at 1 h. There were no changes in the lower dose group. 
      Assessment of regional differences in the teratogenic effects of ethanol by 
      stereological cell-counting technique showed a reduced number of cerebellar 
      Purkinje cells in response to the 1.75 g kg(-1) dose compared with the control 
      brains. However, no such differences in neuronal numbers were observed in the 
      hippocampus or the olfactory bulb. We conclude that repeated exposure to moderate 
      doses of ethanol during the third trimester alters fetal cerebral vascular 
      function and increases blood flow in brain regions that are vulnerable to ethanol 
      in the presence of acidaemia and hypercapnia, and in the absence of hypoxia.
FAU - Parnell, Scott E
AU  - Parnell SE
AD  - Bowles Center for Alcohol Studies and Department of Cell and Developmental 
      Biology, The University of North Carolina, Chapel Hill, NC, USA.
FAU - Ramadoss, Jayanth
AU  - Ramadoss J
FAU - Delp, Michael D
AU  - Delp MD
FAU - Ramsey, Michael W
AU  - Ramsey MW
FAU - Chen, Wei-Jung A
AU  - Chen WJ
FAU - West, James R
AU  - West JR
FAU - Cudd, Timothy A
AU  - Cudd TA
LA  - eng
GR  - AA014451/AA/NIAAA NIH HHS/United States
GR  - AA05523/AA/NIAAA NIH HHS/United States
GR  - AA10090/AA/NIAAA NIH HHS/United States
GR  - AA10940/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070525
PL  - England
TA  - Exp Physiol
JT  - Experimental physiology
JID - 9002940
RN  - 0 (Central Nervous System Depressants)
RN  - 142M471B3J (Carbon Dioxide)
RN  - 3K9958V90M (Ethanol)
RN  - S88TT14065 (Oxygen)
SB  - IM
CIN - Exp Physiol. 2007 Sep;92(5):821. PMID: 17827257
MH  - Acidosis, Respiratory/chemically induced/*physiopathology
MH  - Animals
MH  - Blood Pressure
MH  - Carbon Dioxide/blood
MH  - Central Nervous System Depressants/blood/pharmacology
MH  - Cerebellum/blood supply/embryology
MH  - Cerebrovascular Circulation/*drug effects
MH  - Chronic Disease
MH  - Disease Models, Animal
MH  - Ethanol/blood/pharmacology
MH  - Female
MH  - Fetal Alcohol Spectrum Disorders/*physiopathology
MH  - Heart Rate
MH  - Hypercapnia/chemically induced/*physiopathology
MH  - Hypoxia/*physiopathology
MH  - Oxygen/blood
MH  - Pregnancy
MH  - Sheep
EDAT- 2007/05/29 09:00
MHDA- 2007/10/30 09:00
CRDT- 2007/05/29 09:00
PHST- 2007/05/29 09:00 [pubmed]
PHST- 2007/10/30 09:00 [medline]
PHST- 2007/05/29 09:00 [entrez]
AID - expphysiol.2007.038091 [pii]
AID - 10.1113/expphysiol.2007.038091 [doi]
PST - ppublish
SO  - Exp Physiol. 2007 Sep;92(5):933-43. doi: 10.1113/expphysiol.2007.038091. Epub 
      2007 May 25.