INTRAUTERINE GROWTH RESTRICTION AT HIGH ALTITUDES

家长基金“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。它的三个目标中，前两个是针对实验动物，使用隔离的灌流子宫动脉和UA细胞培养系统，以确定怀孕和慢性低氧对血管调节、生长和细胞凋亡的影响。第三个目标涉及对居住在科罗拉多州1600米和3100米的妇女进行的研究，以确定循环血管调节和生长因子、UA血流的一系列变化与胎儿生长受限(IUGR)和先兆子痫的临床结局之间的关系。该机构将RO1的研究扩展到玻利维亚，玻利维亚拥有独特的环境(海拔高达4800米)、独特的人群(多代高海拔血统的人和终生居民或最近移民的低海拔血统)，并涉及更广泛地使用新的超声波和多普勒技术。我们假设，与居住在类似海拔的低海拔欧洲血统的女性相比，高海拔安第斯血统的女性免受海拔相关性宫内生长受限(IUGR)和先兆子痫的保护，这是由于子宫胎盘氧气供应增加的结果。我们的具体目标是比较居住在高海拔地区的安第斯血统和欧洲血统的妇女1)IUGR和先兆子痫在安第斯地区是否比欧洲妇女少见，2)动脉氧合增加，3)子宫胎盘血流量增加，4)硝酸血管扩张剂相对于内皮素-1水平。研究将使用海拔420-4800米的医疗记录进行，以解决目标1。生理和超声研究将被用于调查玻利维亚拉巴斯海拔3600米的40名安第斯山脉居民和40名欧洲女性居民的剩余目标。这些目标得到了已发表的研究、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发现以及南美洲已发表的报告的支持。这些研究的意义在于促进我们对慢性缺氧改变妊娠子宫胎盘血管反应的机制的了解，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.