Received April 6, 2007
Revised May 4, 2007
Accepted after revision May 15, 2007
Placental-Perinatal [275]
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Chronic Ethanol Increases Fetal Cerebral Blood Flow Specific to the Ethanol Sensitive Cerebellum Under Normoxemic, Hypercapnic and Acidemic Conditions: Ovine Model
Scott E. Parnell 1,
Jayanth Ramadoss 2,
Michael D. Delp 3,
Michael W. Ramsey 4,
Wei-Jung A. Chen 5,
James R. West 6,
Timothy A. Cudd 2*
1 University of North Carolina
2 Texas A&M University
3 West Virginia University School of Medicine
4 East Tennessee State University
5 Texas A&M Health Science Center
6 Texas A&M University Health Science Center
* To whom correspondence should be addressed. E-mail: tcudd{at}cvm.tamu.edu.
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Abstract |
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Cerebral hypoxia has been proposed as a mechanism by which prenatal ethanol exposure causes Fetal Alcohol Spectrum Disorder (FASD) in children though no study had tested this hypothesis using a chronic exposure paradigm that models a common human exposure pattern. Pregnant sheep were exposed to ethanol, 0.75 g/kg or 1.75 g/kg (to create blood ethanol concentrations of 85 and 185 mg/dl respectively) or saline 3 days per week in succession (a binge drinking paradigm) 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 dose resulted in a significant increase in fetal biventricular output (measured by radiolabelled microsphere technique), heart rate and reduction of mean arterial pressure and total peripheral resistance at one hour, the end of ethanol infusion. PaCO2 was increased, pHa was decreased while PaO2 did not change. Fetal whole brain blood flow increased by 37% compared with the control group at 1 hour, 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 hour. 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 1.75 g/kg dose compared with the controls. 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 acidemia and hypercapnea, and in the absence of hypoxia.
Key Words:
Alcohol, Fetal, Neuroanatomy
