MATERNAL BRAIN BLOOD FLOW IN NORMAL PREGNANCY AND PREECLAMPSIS

怀孕与生理血管扩张有关。我们利用脑动脉的多普勒超声，确定了正常妊娠期间血流速度和阻力的一些生理变化。先兆子痫是一种普遍存在的内皮疾病，会导致血管痉挛和动脉阻力增加。血管反应性增强比临床症状(高血压/蛋白尿)早几周或几个月。在此基础上，已经研究了一些测试来预测先兆子痫的能力，但目前还没有一种测试在临床上有用。我们发现子痫前期孕妇和正常血压孕妇的大脑/眼眶多普勒参数有明显差异。此外，我们开发了3个多普勒分析模型，可以使用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、子宫胎盘和外周动脉循环。我们在这项建议中的目标是表明，脑动脉的同步多普勒研究可以(I)确定临床前和亚临床阶段的子痫前期，以及(Ii)将已确诊的早产儿先兆子痫患者归入那些对保守的临时治疗无效的患者。我们将在大脑和动脉床上使用标准的多普勒方法来确定派生阻力、血流速度和血流灌注指数。此外，使用持续握力和Hypercapn对血管反应性的动态测试将区分应力分布。计划有两个纵向方案：A：对320名低风险初孕妇女进行门诊研究，从16周或更短时间到足月/分娩，然后在产后6周、12周和24周进行每月评估；B：由30名接受暂时性治疗的早产儿先兆子痫患者组成的内部方案，最初每天进行评估，每隔一天进行一次稳定评估，直到分娩。及早发现动脉功能异常可以在出现临床症状之前识别出先兆子痫。在确诊的先兆子痫患者中，血管痉挛恶化的证据将提供有关病程和所采用的治疗效果的信息。

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.