Cerebral Responses to Acute Maternal Alcohol Intoxication in Immature Fetal Sheep

Abstract

ABSTRACT. Previous studies in mature fetal sheep have and behavioral problems (3). Several of these neurologic abnorshown that alcohol depresses cerebral blood flow (CBF), malities have been produced in animals exposed to alcohol in cerebral O2 consumption (CMR02), and cerebral glucose utero (4). However, the mechanism(s) by which alcohol produces consumption (CMRglu). This effect earlier in gestation brain damage and the vulnerable developmental period (if any) might contribute to the pathogenesis of fetal alcohol syn-during which damage occurs are unknown. The depressant efdrome. Physiologic studies of immature fetal sheep have fects of alcohol on CBF and CMR02 have been previously demonstrated lower CBF, CMR02, and CMRglu as well reported in several adult animal models as well as in mature fetal as a blunted vasodilatory response to hypoxia compared sheep. Richardson et al. (5) studied the physiologic responses of with mature fetal sheep. The purpose of this study was to term fetal sheep to acute maternal alcohol intoxication and noted determine whether immature fetal responses to alcohol are a significant decrease in both CBF and CMRO1. In addition, blunted compared with near-term fetal responses. We stud-they noted significant fetal hypoglycemia and a decrease in ied seven immature fetal sheep in utero at 92 f 1 d CMRglu. The fetal sheep brain is very mature near term, both gestation (term = 147 d) 2 d after placement of vascular structurally and functionally. Studies of immature fetal sheep catheters. Pure ethanol (1 g/kg) was infused i.v. to the have shown significantly lower CBF, CMR02, and CMRglu mother over 1 h. We measured CBF and myocardial blood compared with mature fetal sheep (6). Furthermore, the cerebral flow by radioactive microspheres and calculated CMROz vasodilatory response to hypoxemia is "blunted," reflecting either and CMRglu using arterial and sagittal sinus O2 and immature regulatory mechanisms or an inability of cerebral glucose concentrations. At a fetal ethanol concentration of vessels to respond to the usual stimuli (7). We theorized that 33 + 8 mmol/L (150 f 37 mg/dL), there were no significant cerebral responses to acute maternal alcohol intoxication may changes in CBF, CMR02, or CMRglu. There was mild be similarly blunted or absent in immature fetal sheep, and we hypoglycemia (glucose concentration = 1.05 f 0.2 versus therefore compared the physiologic responses to acute alcohol Subjects. Before initiating these studies, all surgical and experMild hypoglycemia and lactic acidemia did develop. The imental procedures were approved by the Animal Care and Use reason for the developmental differences in response to Committee at the University of California, San Francisco. Seven alcohol and their relationship to fetal alcohol syndrome mixed-breed fetal sheep were obtained from time-dated pregnanremain to be elucidated. (Pediatr Res 31: 645-648, 1992) cies.Surgiculpreparation. One d before surgery, food was withheld Abbreviations from the ewe, although she was allowed free access to ...

Chronic ethanol increases fetal cerebral blood flow specific to the ethanol‐sensitive cerebellum under normoxaemic, hypercapnic and acidaemic conditions: ovine model

“…However, their study was acute and was conducted on exteriorized fetal sheep under general anaesthesia, conditions that could have affected the responses to ethanol. Gleason & Hotchkiss (1992) reported that a single ethanol (1 g kg −1 ) infusion did not alter CBF in 92 day gestation fetal sheep. However, developmental differences in the fetal vascular response to maternal ethanol consumption would be expected since, for example, nitric oxide synthase expression varies not only regionally but also temporally during development (Northington et al 1997).…”

Injurious effects of acute ethanol exposure during late gestation on developing white matter in fetal sheep

“…Although we did not measure cerebral oxygen delivery, it is unlikely to have been globally reduced as neither fetal MAP nor PaO 2 were reduced by EtOH. Previous studies have reported that EtOH infusions in pregnant sheep either do not alter fetal cerebral blood flow (Gleason and Hotchkiss, 1992), or may cause transient reductions (Richardson et al, 1985). Alcohol is known to be vasoactive (Mathew and Wilson, 1991) and it may induce regional differences in blood flow within the fetal brain (Parnell et al, 2007); clearly further studies on the effects of fetal alcohol exposure on cerebral oxygen delivery are required.…”

Brain High Energy Phosphate Responses to Alcohol Exposure in Neonatal Rats: An In Vivo 31P‐NMR Study

“…We have found that maternal alcohol infusions that create maternal BACs of 246 mg/dl do not reduce fetal PaO 2 or fetal blood pressure (Cudd et al, 1999). However, these findings do not preclude the possibility that even though systemic PaO 2 and circulation pressures were maintained, brain tissue may have been subject to hypoxic conditions perhaps by a selective alteration in cerebral circulation, a hypothesis supported by literature which demonstrates that alcohol can alter cerebral blood flow during the early (Gleason and Hotchkiss, 1992) and late fetal periods (Richardson et al, 1985) and in the adult (Mayhan, 1992).…”