MECHANISMS OF PERINATAL CEREBRAL BLOOD FLOW REGULATION

这些研究的目标是审查提供和利用 在正常和正常条件下， 病理情况以及开始获得了解 脑损伤的机制。 两项研究旨在回答关于 调节脑循环。 利用放射性标记的 微球法和矢状窦导管采集大脑 胎儿和新生绵羊静脉引流，脑血流量，氧 输送、O2消耗和分级O2提取将 测量或计算。 这些研究中的第一个试图证明 脑循环对PaCO2变化的反应更剧烈 在成年羊相比，胎儿羊是由于差异， 血红蛋白O2亲和力，而不是血管内的内在差异 未成熟和成熟大脑之间的反应。 第二项研究将 检查潜在有害影响的临床相关问题 治疗诱导的低碳酸血症，特别是是否脑氧 在严重的低碳酸血症期间，消耗量福尔斯下降。 三项研究旨在考虑脑损伤的机制， 窒息 核心假设是大部分脑损伤 与窒息相关的症状发生在事件之后而不是事件发生期间。 这些 研究将利用新生羔羊窒息模型。 一个协议将 考虑脑血流和O2代谢的反应， 窒息缺氧和低血压使用放射性标记的微球和 矢状窦导管 无法维持O2输送和O2 消费与这些扰动是潜在的一个重要手段， 窒息性脑损伤 第二项研究将侧重于 类花生酸和自由基的产生在窒息后病因学中的作用 脑血流量和氧代谢异常。 初步数据将 也可以收集关于这些产品在大脑生成中的作用 水肿和线粒体功能障碍。 最后，窒息前的影响 血糖浓度和随后的乳酸积累 窒息对窒息后血流和O2代谢异常的影响 利用葡萄糖钳夹技术进行评价。 这些的重要性 研究表明，葡萄糖浓度、类花生酸和自由基 生产可能会在治疗上改变，因此了解 它们在脑损伤中的作用有助于未来的治疗进展。

The goals of these studies are to examine the delivery and utilization of oxygen in the brain of the developing sheep under both normal and pathologic circumstances as well as begin to gain an understanding of mechanisms of brain injury. Two studies are designed to answer basic physiologic questions about the regulation of the cerebral circulation. Making use of radiolabelled microsphere methodology and a sagittal sinus catheter to sample cerebral venous drainage in fetal and neonatal sheep, cerebral blood flow, O2 delivery, O2 consumption, and fractionational O2 extraction will be measured or calculated. The first of these studies seeks to demonstrate that the steeper response of the cerebral circulation to changes in PaCO2 in the adult sheep compared to the fetal sheep is due to a difference in hemoglobin O2 affinity rather than an intrinsic difference in vascular reactivity between immature and mature brain. The second study will examine the clinically relevant issue of potential harmful effects of therapeutically induced hypocarbia, specifically whether or not cerebral O2 consumption falls during severe hypocarbia. Three studies are designed to consider mechanisms of brain injury after asphyxia. The central hypothesis is that much of the brain injury associated with asphyxia occurs after rather than during the event. These studies will utilize a neonatal lamb asphyxia model. One protocol will consider the response of cerebral blood flow and O2 metabolism after asphyxia to hypoxia and hypotension using radiolabelled microspheres and a sagittal sinus catheter. An inability to maintain O2 delivery and O2 consumption with these perturbations is potentially an important means of post asphyxial brain injury. A second study will focus on the roles of eicosanoid and free radical production in the etiology of post asphyxial cerebral blood flow and O2 metabolism abnormalities. Preliminary data will also be collected on these products role in the generation of cerebral edema, and mitochondria dysfunction. Finally the effect of preasphyxial blood glucose concentration and subsequent lactate accumulation during asphyxia on post asphyxial blood flow and O2 metabolism abnormalities will be evaluated utilizing glucose clamp technology. The importance of these studies is that glucose concentration, eicosanoid and free radical production are potentially altered therapeutically so an understanding of their role in brain injury lends itself to future therapeutic advances.