Cerebrovascular effects of intravenous dopamine infusions in fetal sheep

Abstract

man. Cerebrovascular effects of intravenous dopamine infusions in fetal sheep. J Appl Physiol 92: 717-724, 2002; 10.1152/japplphysiol.00600.2001.-Preterm infants are often treated with intravenous dopamine to increase mean arterial blood pressure (MAP). However, there are few data regarding cerebrovascular responses of developing animals to dopamine infusions. We studied eight near-term and eight preterm chronically catheterized unanesthetized fetal sheep. We measured cerebral blood flow and calculated cerebral vascular resistance (CVR) at baseline and during dopamine infusion at 2.5, 7.5, 25, and 75 g ⅐ kg Ϫ1 ⅐ min Ϫ1 . In preterm fetuses, MAP increased only at 75 g ⅐ kg Ϫ1 ⅐ min Ϫ1 (25 Ϯ 5%), whereas in near-term fetuses MAP increased at 25 g ⅐ kg Ϫ1 ⅐ min Ϫ1 (28 Ϯ 4%) and further at 75 g ⅐ kg Ϫ1 ⅐ min Ϫ1 (51 Ϯ 3%). Dopamine infusion was associated with cerebral vasoconstriction in both groups. At 25 g ⅐ kg Ϫ1 ⅐ min Ϫ1 , CVR increased 77 Ϯ 51% in preterm fetuses and 41 Ϯ 11% in near-term fetuses, and at 75 g ⅐ kg Ϫ1 ⅐ min Ϫ1 , CVR increased 80 Ϯ 33% in preterm fetuses and 83 Ϯ 21% in near-term fetuses. We tested these responses to dopamine in 11 additional near-term fetuses under ␣-adrenergic blockade (phenoxybenzamine, n ϭ 5) and under dopaminergic D1-receptor blockade (SCH-23390, n ϭ 6). Phenoxybenzamine completely blocked dopamine's pressor and cerebral vasoconstrictive effects, while D1-receptor blockade had no effect. Therefore, in unanesthetized developing fetuses, dopamine infusion is associated with cerebral vasoconstriction, which is likely an autoregulatory, ␣-adrenergic response to an increase in blood pressure.brain; fetus; vasoconstriction BLOOD PRESSURE IS AN IMPORTANT "vital sign" that is carefully monitored in preterm infants. Hypotension is believed to be an important risk factor for cerebral ischemic injury and intracranial hemorrhage, and so preterm infants often receive volume expanders (even in the absence of hypovolemia) and/or inotropic drugs (most commonly, dopamine) to increase blood pressure (1, 18). However, concern has been raised about whether these management practices could be detrimental (29). Seri et al. (25) recently reported that low-dose dopamine infusion does not affect cerebral blood flow (CBF) velocity in sick, normotensive preterm infants. However, little else is known about the cerebrovascular responses of the developing brain to intravenous dopamine and/or acute increases in blood pressure. In adult animals, intravenous dopamine at moderate doses causes cerebral vasodilation, presumably by stimulation of specific vasodilatory dopaminergic receptors (32). In immature animals, dopamine is a less effective inotropic agent, presumably because of immaturity of cardiac ␤ 1 -adrenergic receptors. Minimal cerebral vasodilatory, or possibly vasoconstrictive, effects might therefore be expected at low or moderate dopamine doses, because development of vascular dopaminergic receptors is also likely to be incomplete, particularly compared with ␣-adrenergic receptors (8,12,30,31)....

Effects of Exogenous Glucose on Brain Ischemia in Ovine Fetuses

“…The sheep fetus has been used extensively for physiologic and pathophysiological studies of the brain (35)(36)(37)(38)(39)(40). Studies have not examined the pathologic consequences of an acute and/or prolonged exposure to hyperglycemia on brain ischemia in a fetal subject.…”

Cesarean under general or epidural anesthesia: Does it differ in terms of regional cerebral oxygenation?

“…11 In hemodynamically stable near-term sheep, dopamine infusion was associated with cerebral vasoconstriction, which is likely to be an autoregulatory, alpha-adrenergic response to the increase in BP. 12 This may be an explanation for the lower rSO 2 in neonates born by vaginal delivery. In our study, rSO 2 values in the neonates born under GA were lower compared to the neonates born under CSEA.…”

Vasodilator tone in the llama fetus: the role of nitric oxide during normoxemia and hypoxemia

“…(41), and adrenomedullin (12). Possible vasoconstrictors include neuropeptide Y (37), endothelin (8), or changes in the adrenergic action that are gestational agedependent (16). Any or all of these could be responsible, together with NO, in maintaining cerebral oxygen and nutrient delivery to the fetal brain during hypoxemia, an effect that could be different in postnatal life due to cerebral endothelial maturation (41).…”