MATERNAL BRAIN BLOOD FLOW IN NORMAL PREGNANCY AND PREECLAMPSIS

妊娠与生理性血管舒张有关。我们已经定义，使用多普勒超声在脑动脉，一些生理变化的速度和阻力在正常怀孕期间。子痫前期是一种普遍存在的内皮疾病，可引起血管痉挛和动脉阻力增加。血管反应性增加早于临床综合征（高血压/蛋白尿）数周或数月。在此基础上，人们研究了许多测试来预测子痫前期的能力，但目前还没有一项测试在临床上有用。我们已经确定了子痫前期和血压正常的孕妇在脑/眶多普勒参数上的明显差异。此外，我们开发了3种多普勒分析模型，可用于通过脑动脉阻力指数和估计的脑灌注压可靠地区分足月正常血压和先兆子痫妇女。这些模型可以适用于其他血管床，包括肾脏、子宫胎盘和外周动脉循环。我们的目的是证明同时多普勒脑动脉研究可以(i)在临床前和亚临床阶段识别子痫前期，以及（ii）将确定的早产子痫前期患者分为对保守的临时治疗无效的患者。我们将在脑、动脉床使用标准多普勒方法来确定衍生阻力、血流速度和灌注指数。此外，血管反应性的动态测试使用持续握力和hypercapn将区分应力分布。计划进行两项纵向研究：A：一项针对320名低风险初孕妇女的门诊研究，从16周或更短的时间开始每月评估一次，直到足月/分娩，然后在产后6、12和24周；B：对30例早产先兆子痫患者进行临时治疗的内部方案，最初每天评估一次，每隔一天评估一次，直到分娩。早期发现异常动脉功能可以在临床症状出现之前识别子痫前期。在确定的子痫前期，血管痉挛恶化的证据将提供关于疾病的过程和正在采用的治疗的有效性的信息。

Pregnancy is associated with physiologic vasodilation. We have defined, using Doppler ultrasound in cerebral arteries, some of the physiologic changes in blood velocity and resistance during normal pregnancy. Preeclampsia, an ubiquitous endothelial disease, causes vasospasm and an increase in arterial resistance. Increased vascular reactivity predates the clinical syndrome (hypertension/proteinuria) by weeks or months. Based on this, a number of tests have been studied for their ability to predict preeclampsia, but currently none that are clinically useful. We have identified distinct differences in cerebral/orbital Doppler parameters between preeclamptic and normotensive pregnant women. Furthermore, we have developed 3 Doppler analytical models which can be used to reliably differentiate between term normotensive and preeclamptic women using cerebral arterial resistance indices and estimated cerebral perfusion pressure. These models can be adapted to other vascular beds including the renal, uteroplacental and peripheral arterial circulations. Our objectives in this proposal are to show that simultaneous Doppler studies of cerebral arteries can (i) identify preeclampsia in its preclinical and subclinical phases, and (ii) group patients with established preterm preeclampsia into those who will fail to respond to conservative temporizing management. We will use standard Doppler methods in the cerebral, arterial beds to determine derived resistance, flow-velocity, and perfusion indices. In addition dynamic tests of vascular reactivity using sustained handgrip and hypercapn will differentiate stress profiles. Two longitudinal protocols are planned: A: an outpatient study of 320 low-risk, primigravid women, evaluated monthly from 16 weeks or less until term/delivery, and then at 6, 12 and 24 weeks postpartum; B: an in-house protocol of 30 preterm preeclamptics undergoing temporizing management, evaluated on a daily basis initially, and once stable every other day, until delivery. Early detection of abnormal arterial function may allow identification of preeclampsia before emergence of clinical signs. In established preeclampsia, evidence of worsening vasospasm will provide information on the course of the disease and the effectiveness of the therapy being employed.