Effects of betamethasone administration to the fetal sheep in late gestation on fetal cerebral blood flow

Autor: Marcus Roedel, Peter W. Nathanielsz, Matthias Schwab, Bernd Walter, Harald Schubert, Thomas Müller, M. Akhtar Anwar, Lynn F. Buchwalder
Rok vydání: 2000
Předmět:
Zdroj: The Journal of Physiology. 528:619-632
ISSN: 1469-7793
0022-3751
Popis: A recent National Institutes of Health consensus conference recommended antenatal glucocorticoid administration to women at risk of preterm delivery to accelerate fetal lung maturation and to avoid bronchopulmonary dysplasia and decrease the incidence of intraventricular haemorrhage (Crowley et al. 1990; Ballard & Ballard, 1995; Elimian et al. 1999). However, little is known about the cerebrovascular side effects of exposure to glucocorticoids during fetal development. Adrenalectomy accompanied by decreased glucocorticoid production results in increased hippocampal and cortical blood flow in adult rats (Endo et al. 1994). Betamethasone has direct vasoconstrictor effects on peripheral femoral resistance vessels in late gestation fetal sheep (Derks et al. 1997; Anwar et al. 1999). In artifically ventilated premature newborns, cerebral blood flow (CBF) was estimated indirectly after dexamethasone treatment by measuring blood flow velocities in carotid or large cerebral arteries using ultrasound Doppler flowmetry. Ohlsson et al. (1994) found a decrease or no change in the blood flow velocity of the middle cerebral artery and Cabanas et al. (1997) an increase in the end-diastolic blood flow velocity in the internal carotid and the anterior cerebral arteries accompanied by an increase in arterial blood pressure following dexamethasone administration to newborn human infants. As the resistance index was lowered they suggested that the effect of glucocorticoids was to produce an increase in CBF. The only study we have been able to find that evaluates the effects of glucocorticoids in the human fetus did not show any change in the blood flow velocity waveforms and the pulsatility index in the large fetal arteries, including the large cerebral arteries, after dexamethasone treatment (Cohlen et al. 1996). There are several limitations to these studies. First, Doppler flowmetry cannot be used to determine global CBF or regional CBF directly. Second, the velocity results were variable. Finally, studies in artifically ventilated premature babies do not reveal the rules by which the fetus lives. We therefore aimed to evaluate the effects of antenatal glucocorticoid treatment on regional CBF under controlled conditions in a well-established animal model. We hypothesised that glucocorticoid administration to the fetal sheep will decrease regional CBF. We infused betamethasone directly into the fetal jugular vein at a rate which produces fetal plasma betamethasone concentrations similar to those measured in human umbilical cord plasma at Caesarean section within 24 h of maternal glucocorticoid treatment (Derks et al. 1997). Betamethasone was administered directly to the fetus to avoid potential influences due to differences in transplacental passage of glucocorticoids between the ovine and primate placentae. Since blood vessels of the fetal sheep brain are responsive to an increase in arterial PCo2 (Pa,CO2) as early as 60 days of gestational age (dGA) (Habgood et al. 1991) and near-term fetal sheep respond to hypercapnia in a way that is qualitatively similar to that in the adult, though the response is less pronounced (Purves & James, 1969; Rosenberg et al. 1982; Ashwal et al. 1984), we measured the effects of betamethasone on a hypercapnic challenge to the fetus. Regional CBF was measured in 10 brain regions using coloured microspheres before and 24 and 48 h after onset of treatment and during hypercapnic challenges that were performed before onset and after 48 h of betamethasone exposure.
Databáze: OpenAIRE
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