Preterm human infants are often treated with volume expansion during their initial stabilization. There are limited data regarding the cerebral vascular effects of this therapeutic approach. The effects of blood volume expansion on cerebral vascular reactivity and oxygen metabolism in very immature animals have not been determined. We examined the effects of volume expansion, with and without hypoxia, on cerebral blood flow and metabolism in unanesthetized, chronically catheterized, preterm fetal sheep. Rapid volume expansion with i.v. dextran increased circulating blood volume. Arterial blood pressure did not increase, nor did cerebral blood flow. However, volume expansion resulted in lower arterial Hb concentration and, consequently, oxygen content without a compensatory increase in cerebral blood flow. Cerebral oxygen delivery fell significantly. Induction of severe hypoxia after volume expansion resulted in an increase in cerebral blood flow, as expected, but the increase in flow was not enough to maintain cerebral oxygen delivery. Rapid volume expansion in normovolemic preterm fetal sheep is associated with decreased cerebral oxygen delivery, and this is further compromised when oxygen content is decreased. Very preterm infants are often treated with boluses of normal saline during their initial stabilization (1-3). The clinical indications are usually low blood pressure and/or poor perfusion, often without other signs of, or risk factors for, hypovolemia. There are limited data regarding the cerebral vascular effects of this therapeutic approach. In piglets, volume expansion after hypotension and asphyxia results in increased CBF (4). In adult dogs, CBF decreases when volume expansion is given with closed-chest cardiopulmonary resuscitation (5). Developmental or species differences in systemic responses, including baroreceptor activation and left ventricular responses, may account for these conflicting results (6).Hypoxic cerebral vasodilatation occurs in the late-term fetal (7, 8), neonatal (9), and adult sheep (9). In preterm fetal sheep, this response is blunted, and severe hypoxia results in a limitation in cerebral OD when compared with the near-term fetus (10). Cerebral oxygen consumption is maintained, in part, by an increase in fractional oxygen extraction (10). Volume expansion in the face of hypoxemia could further impair cerebral OD by limiting oxygen carrying capacity, particularly in very preterm fetuses.We hypothesized that acute volume expansion in normovolemic developing animals could result in abnormalities in CBF regulation, possibly associated with changes in cerebral venous pressure. We further hypothesized that these changes in cerebral venous pressure could limit hypoxic cerebral vasodilatation. We chose to study the preterm fetal sheep because Brace et al. (11) had previously demonstrated that i.v. dextran infusion could significantly expand fetal blood volume and that this effect could be maintained for several hours. However, Brace and colleagues did not examine the effects of vo...