WATER COMPARTMENTALIZATION IN CHRONIC FETAL ANEMIA

慢性胎儿贫血中的水分隔

• 批准号: 6183572
• 负责人: LOWELL E DAVIS
• 金额: $ 23.58万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-02-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6183572
• 关键词: anemia; angiogenesis; body water; caveolins; congenital cardiovascular disorder; coronary artery; echocardiography; embryo /fetus; embryo /fetus disorder; gene expression; heart circulation; heart function; laboratory mouse; messenger RNA; nitric oxide; pregnancy circulation; sheep; vascular endothelial growth factors; vascular endothelium permeability; water channel

The long-term goal of this project is to understand the mechanisms underlying cardiac function and coronary vascular growth of the fetus. The overall hypothesis we wish to test is that coronary angiogenesis in the anemic fetus results in an increase in vascular permeability and cardiac lymph flow and an increase in coronary conductance that persists into adulthood. Aim (1) To determine if cardiac lymph flow is increased we will measure left ventricular lymph flow in anemic and non-anemic fetal sheep. To test if lymph flow is necessary to maintain ventricular function we will determine if volume loading or obstruction of left ventricular cardiac lymphatic flow results in a decrease in the peak rate of left ventricular pressure increase (dP/dt). We will also measure protein and mRNA levels of aquaporin-1 to determine if there is increased expression of water channels during anemia. Aim (2) To determine if there are differences in the role of nitric oxide in flow induced versus hypoxic (anemia) induced changes in coronary conductance we will measure coronary conductance before and after chronic anemia or chronic adenosine infusion in the presence and absence of the nitric oxide blocker L-NAME. Aim (3) To determine if an increase in coronary conductance that develops in the fetal period persists in the young adult, we will measure coronary conductance in 8 month old sheep made anemic as fetuses as well as in non anemic controls. We will also measure coronary conductance in a murine model of fetal anemia. Aim (4) We will measure coronary conductance before and after injection of recombinant vascular endothelial growth factor in the proximal circumflex coronary artery to determine if coronary conductance can be increased by local injection of a growth factor. These studies will extend the understanding of the long-term effects of coronary vascular growth in the fetus.

该项目的长期目标是了解胎儿心脏功能和冠状动脉血管生长的基础机制。 我们希望检验的总体假设是，贫血胎儿中的冠状血管生成会导致血管通透性和心脏淋巴流量的增加以及冠状动脉电导的增加，而冠状动脉电导一直持续到成年。目的（1）为了确定心脏淋巴流量是否增加，我们将在贫血和非动态胎儿绵羊中测量左心室淋巴流量。 为了测试是否需要淋巴流以维持心室功能，我们将确定左心室心脏淋巴流量的体积负荷或阻塞是否导致左心室压力升高（DP/DT）的峰值降低。 我们还将测量水通道蛋白-1的蛋白质和mRNA水平，以确定贫血期间水通道表达是否增加。 目的（2）为了确定一氧化氮在冠状动脉电导率变化的流量与低氧（贫血）诱导的变化中是否存在差异，我们将在慢性贫血或慢性腺苷输注之前和之后测量冠状电导，并在存在和不存在硝酸氧化物阻滞剂L-氮N-名中。 目的（3）确定在年轻人中，在胎儿时期发展的冠状动脉电导是否持续存在，我们将测量8个月大的绵羊的冠状动脉电导量成为胎儿和非贫血对照。 我们还将在胎儿贫血的鼠模型中测量冠状动脉电导。 目的（4）我们将在注射重组血管内皮生长因子之前和之后测量冠状动脉冠状动脉冠状动脉冠状动脉，以确定是否可以通过局部注射生长因子来增加冠状动脉电导。 这些研究将扩展对胎儿冠状动脉血管生长的长期影响的理解。