Cerebral and peripheral circulatory responses to intracranial hypertension in fetal sheep.

Harris, Andrew P.; Koehler, Raymond C.; Gleason, Christine A.; Jones, Mathew; Traystman, Richard J.

doi:10.1161/01.res.64.5.991

Cited by 49 publications

(33 citation statements)

References 35 publications

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“…Ampicillin (500 mg) was administered into the amniotic fluid via the amniotic fluid catheter and the estimated volume of lost amniotic fluid was replaced with warmed saline. Fetuses were studied 24 -48 h after surgery (12). Maternal analgesia was maintained with buprenorphine (0.005 mg/kg i.m.…”

Section: Methodsmentioning

confidence: 99%

Cerebrovascular Effects of Rapid Volume Expansion in Preterm Fetal Sheep

Mayock

Gleason

2004

Pediatr Res

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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...

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Section: Methodsmentioning

confidence: 99%

Cerebrovascular Effects of Rapid Volume Expansion in Preterm Fetal Sheep

Mayock

Gleason

2004

Pediatr Res

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“…Chronic instrumentation also allows a wide range of practical and clinically pertinent cerebral insults to be administered. These include global cephalic ischemia [65], systemic hypotension or hypoxemia [66][67][68], single or repeated cord occlusion [69][70][71], increased intracranial pressure [72], and administration of infectious agents or exogenous inflammatory mediators [73][74][75]. These insults can be graded in intensity and duration to mimic the human situation.…”

Section: Advantages and Disadvantages Of The Fetal Sheep To Model Wmimentioning

confidence: 99%

The Instrumented Fetal Sheep as a Model of Cerebral White Matter Injury in the Premature Infant

et al. 2012

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Despite advances in neonatal intensive care, survivors of premature birth remain highly susceptible to unique patterns of developmental brain injury that manifest as cerebral palsy and cognitive-learning disabilities. The developing brain is particularly susceptible to cerebral white matter injury related to hypoxia-ischemia. Cerebral white matter development in fetal sheep shares many anatomical and physiological similarities with humans. Thus, the fetal sheep has provided unique experimental access to the complex pathophysiological processes that contribute to injury to the human brain during successive periods in development. Recent refinements have resulted in models that replicate major features of acute and chronic human cerebral injury and have provided access to complex clinically relevant studies of cerebral blood flow and neuroimaging that are not feasible in smaller laboratory animals. Here, we focus on emerging insights and methodologies from studies in fetal sheep that have begun to define cellular and vascular factors that contribute to white matter injury. Recent advances include spatially defined measurements of cerebral blood flow in utero, the definition of cellular maturational factors that define the topography of injury and the application of high-field magnetic resonance imaging to define novel neuroimaging signatures for specific types of chronic white matter injury. Despite the higher costs and technical challenges of instrumented preterm fetal sheep models, they provide powerful access to clinically relevant studies that provide a more integrated analysis of the spectrum of insults that appear to contribute to cerebral injury in human preterm infants.

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“…Antibiotics were administered intra-amniotically, and lost amniotic fluid was replaced with warmed normal saline via the amniotic catheter. Unanesthetized fetuses were studied 48 h after surgery, at which time endogenous plasma catecholamine and vasopressin levels have normalized (11).…”

Section: Surgical Preparationmentioning

confidence: 99%

Cerebrovascular effects of intravenous dopamine infusions in fetal sheep

Gleason

Robinson

Harris

et al. 2002

Journal of Applied Physiology

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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)....

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Cerebral and peripheral circulatory responses to intracranial hypertension in fetal sheep.

Abstract: Fetal head compression during normal labor can increase intracranial pressure (ICP).

Cited by 49 publications

References 35 publications

Cerebrovascular Effects of Rapid Volume Expansion in Preterm Fetal Sheep

Cerebrovascular Effects of Rapid Volume Expansion in Preterm Fetal Sheep

The Instrumented Fetal Sheep as a Model of Cerebral White Matter Injury in the Premature Infant

Cerebrovascular effects of intravenous dopamine infusions in fetal sheep

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