PERINATAL DEVELOPMENT OF RENAL FUNCTION AND METABOLISM

围产期肾功能和代谢的发育

基本信息

批准号：
3314610
负责人：
ABRAHAM M RUDOLPH
金额：
$ 21.47万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-09-01 至 1989-03-31
项目状态：
已结题

项目摘要

The objectives of this research proposal are to examine the developmental changes in some aspects of renal function during late gestation and after birth. Renal oxygen consumption and uptake of glucose, lactate and free fatty acids will be related to renal functions such as sodium transport and acid-base regulation. The effects of acute hypoxemia, metabolic acidemia, and infusion of hormones such as vasopressin, angiotensin and catecholamines on these functions will be assessed. The possible role of the kidney in providing energy substrate to the body, by glycogenolysis or gluconeogenesis will be studied in fetal and newborn lambs under conditions of hypoxemia, acidemia or stimulation by epinephrine. We will measure rates of renin secretion in response to hormone infusion, acute hypoxemia, bilateral carotid occlusion, reduction in circulating blood volume or reduction in renal blood flow. These studies will be performed in chronically-instrumented fetal and neonatal lambs. We have perfected a technique by which a small catheter is inserted into the left renal vein in these lambs. This catheter does not modify renal blood flow and it permits repeated sampling substrates and renin can be measured. Renal blood flow can be measured repeatedly by the radionuclide-labelled microsphere method. Knowing this and arteriovenous concentration difference, it is possible by application of the Fick method to estimate uptake or release of many substances by the kidney. A chronically-implanted bladder catheter in the lambs provides for collection of urine to measure urinary excretion rates and concentrations of electrolytes. The importance and uniqueness of this project lies in our ability to make repeated, quantitative measurements of renal function and metabolism in the fetus and neonate in the absence of the effects of anesthesia and acute surgery; it will provide information on changes in the metabolic role of the kidney after birth and the role of the kidney during stress responses. The information will greatly expand our knowledge of the physiology of the kidney during the perinatal period and will provide the basis upon which therapeutic management of the infant can be based.

本研究计划的目的是检查发育妊娠晚期及妊娠后肾功能某些方面的变化出生。肾耗氧量和葡萄糖、乳酸和游离的摄取脂肪酸与肾功能有关，例如钠转运和酸碱调节。急性低氧血症、代谢性酸血症的影响以及输注血管加压素、血管紧张素等激素将评估儿茶酚胺对这些功能的影响。可能的作用肾脏通过糖原分解或将在一定条件下研究胎儿和新生羔羊的糖异生作用低氧血症、酸血症或肾上腺素刺激。我们将测量响应激素输注、急性低氧血症的肾素分泌率，双侧颈动脉闭塞、循环血量减少或肾血流量减少。这些研究将在长期接受仪器检测的胎儿和新生羔羊。我们已经完善了一个将小导管插入左肾静脉的技术这些羔羊。该导管不会改变肾血流量，并且允许重复取样可测定底物和肾素。肾血流量可以通过放射性核素标记的微球重复测量方法。知道了这个和动静脉浓度差，就是可以通过应用 Fick 方法来估计吸收或释放许多物质都通过肾脏。长期植入的膀胱导管羔羊收集尿液以测量尿液排泄电解质的速率和浓度。的重要性和独特性这个项目在于我们能够重复、定量胎儿和新生儿肾功能和代谢的测量没有麻醉和急性手术的影响；它将提供有关出生后肾脏代谢作用变化的信息以及肾脏在应激反应中的作用。该信息将极大地扩展了我们对肾脏生理学的了解围产期并将提供治疗的基础可以根据婴儿的管理情况。