DOPAMINE AND VOLUME EXPANSION--FETAL CEREBRAL RESPONSES

维持最佳全身血压在以下方面非常重要 新生儿早产儿的护理。这样的婴儿经常会收到 容量扩张剂和/或静脉变力药物(最常见的是多巴胺) 出生后使他们的血压升高。他们可能会对这些做出回应 血压突然升高的疗法，它们可能会 低氧，增加了他们脑损伤的风险。人们对此知之甚少 发育中的大脑对多巴胺或 血压和/或血容量急剧增加，没有研究 已经综合评估了大脑对这些干扰的反应 低氧血症。这项提案的主要目标是确定 常氧和低氧发育中胎儿的脑部反应 静脉注射多巴胺和快速扩容，以提供 新生儿治疗的一个更好的理论基础是保持 降血压和预防脑损伤。不麻醉的，长期的- 将使用插管的胎羊。这其中有四个目标 建议书： 目的#1.确定发育中的胎儿对 多巴胺，有无低氧血症。我们将检验这一假设 多巴胺引起未成熟胎儿脑血管收缩并损害 低氧血症时的氧气输送。 目的#2.确定发育中的胎儿对急性脑损伤的大脑反应 容量负荷；我们将检验血液急剧增加的假设 未成熟胎儿的体积会降低大脑灌注压。 目标#3.评估血脑屏障的完整性，并 确定区域脑水含量的变化发生在 血压和血容量急剧增加。 目的#4.使用多巴胺能和肾上腺素能阻滞剂，我们将测试 外源性多巴胺引起脑血管收缩的假说 未成熟但不成熟的胎儿，因为多巴胺能不完全 受体的发育，因此，不受抑制的肾上腺素能作用。 这些研究的结果将提供重要的新信息。 关于未成熟者的脑血管和代谢反应 脑到多巴胺和容量输注，并有可能提供更好的 早产儿新生儿治疗干预的理论基础。

Maintenance of optimal systemic blood pressure is of major importance in the care of newborn preterm infants. Such infants frequently receive volume expanders and/or intravenous inotropic drugs (most often dopamine) after birth to increase their blood pressure. They may respond to these therapies with abrupt increases in blood pressure and they may be hypoxic, increasing their risk of brain injury. Little is known about the cerebrovascular responses of the developing brain to dopamine or to acute increases in blood pressure and/or blood volume, and no studies have evaluated the cerebral responses to these perturbations combined with hypoxemia. The primary goal of this proposal is to determine the cerebral responses of normoxic and hypoxic developing fetuses to intravenous dopamine and to rapid volume expansion in order to provide a better rationale for neonatal therapeutics directed at maintaining blood pressure and preventing brain damage. Unanesthetized, chronically- catheterized fetal sheep will be used. There are four aims in this proposal: Aim #1. To determine the cerebral responses of developing fetuses to dopamine, with and without hypoxemia. We will test the hypothesis that dopamine causes cerebral vasoconstriction in immature fetuses and impairs oxygen delivery during hypoxemia. Aim #2. To determine cerebral responses of developing fetuses to an acute volume load; we will test the hypothesis that an acute increase in blood volume in immature fetuses decreases cerebral perfusion pressure. Aim #3. To assess the integrity of the blood-brain barrier and to determine changes in regional brain water content which occur during acute increases in blood pressure and blood volume. Aim #4. Using dopaminergic and-adrenergic blockers, we will test the hypothesis that exogenous dopamine causes cerebral vasoconstriction in immature but not mature, fetuses because of incomplete dopaminergic receptor development and thus, uninhibited delta-adrenergic effects. The results of these studies will provide important new information concerning the cerebrovascular and metabolic responses of the immature brain to dopamine and volume infusions and potentially offer a better rationale for neonatal therapeutic interventions in preterm infants.