INTRAUTERINE GROWTH RESTRICTION AT HIGH ALTITUDES

父母资助“慢性缺氧，子宫动脉血管调节和生长”研究怀孕和慢性缺氧影响子宫动脉（UA）血管调节和生长的机制。 其三个目标，前两个是针对实验动物，使用离体灌注子宫动脉和UA细胞培养系统，以确定妊娠和慢性缺氧对血管调节，生长和凋亡的影响。 第三个目标是对居住在科罗拉多海拔1600米和3100米的妇女进行研究，以确定循环血管调节因子和生长因子、UA血流的系列变化与宫内生长受限（IUGR）和先兆子痫的临床结局之间的关系。 FIRCA将RO 1的研究扩展到玻利维亚，这是一个独特的环境（海拔高达4800米），独特的人口（多代高海拔血统的人和低海拔血统的终身居民或最近的移民），并涉及更广泛地使用新的超声和多普勒技术。 我们假设，与居住在相似海拔的低海拔欧洲血统的妇女相比，高海拔安第斯血统的妇女免受海拔相关的宫内生长受限（IUGR）和先兆子痫的影响，这是子宫胎盘O2输送增加的结果。 我们的具体目标是比较安第斯山脉与欧洲血统的妇女生活在高海拔地区，以证明1）IUGR和先兆子痫是否在安第斯山脉比欧洲妇女更不常见，以及2）动脉氧合增加，3）子宫胎盘血流量增加，4）相对于内皮素-1水平的硝基血管扩张剂。 将利用海拔420 - 4800米的医疗记录进行研究，以实现目标1。 生理学和超声波研究将被用来调查其余的目标在40个安第斯和40个欧洲妇女居民的拉巴斯，玻利维亚在海拔3600米的样本。 这些目标得到了已发表研究的支持，我们关于西藏高海拔居民出生体重和子宫胎盘血流指数的初步研究结果，以及南美洲已发表的报告。 这些研究的意义在于推进我们对慢性缺氧改变子宫胎盘血管对妊娠反应的机制的认识，这反过来将有助于确定诊断和治疗IUGR和先兆子痫的改进方法。

The parent grant "Chronic hypoxia, uterine artery vasoregulation and growth" investigates the mechanisms by which pregnancy and chronic hypoxia influence uterine artery (UA) vasoregulation and growth. Of its three aims, the first two are addressed to experimental animals, using isolated perfused uterine arteries and UA cell culture systems, to determine the effects of pregnancy and chronic hypoxia on vasoregulation, growth, and apoptosis. The third aim involves studies in women residing at 1600 m and 3100 m in Colorado to identify the relationship between serial changes in circulating vasoregulatory and growth factors, UA blood flow, and the clinical outcomes of intrauterine growth restriction (IUGR) and preeclampsia. This FIRCA expands and extends the research of the RO1 to Bolivia, a unique environment (altitudes as high as 4800 m), unique populations (persons of multi-generational high-altitude ancestry and lifelong residents or recent migrants of low-altitude ancestry), and involves more extensive use of novel ultrasound and Doppler technologies. We hypothesize that women of high-altitude, Andean ancestry are protected from altitude-associated intrauterine growth restriction (IUGR) and preeclampsia compared to women of low-altitude, European ancestry residing at similar elevations, as the result of increased uteroplacental O2 delivery. Our specific aims are to compare women of Andean vs. European ancestry living at high altitude to document 1) whether IUGR and preeclampsia are less common in the Andean than European women in conjunction with increased 2) arterial oxygenation, 3) uteroplacental blood flow and, 4) nitrovasodilator relative to endothelin-1 levels. Studies will be conducted using medical records from altitudes ranging from 420 - 4800 m to address aim number 1. Physiological and ultrasound studies will be used to investigate the remaining aims in samples of 40 Andean and 40 European women residents of La Paz, Bolivia at an elevation of 3600 m. These aims are supported by published studies, our preliminary findings concerning birth weight and indices of uteroplacental blood flow in Tibetan high-altitude residents, and by published reports in South Americans. The significance of these studies resides in advancing our knowledge about the mechanisms by which chronic hypoxia alters the uteroplacental vascular response to pregnancy which, in turn, will aid in the identification of improved methods for diagnosis and treatment of IUGR and preeclampsia.