BLOOD VOLUME AND VENOUS RETURN IN THERMAL STRAIN

热应变下的血容量和静脉回流

• 批准号: 6194640
• 负责人: GARY W MACK
• 金额: $ 36.94万
• 依托单位: JOHN B. PIERCE LABORATORY, INC.
• 依托单位国家: 美国
• 财政年份: 1977
• 资助国家: 美国
• 起止时间: 1977-12-01 至 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6194640
• 关键词: baroreflex; blood chemistry; blood flow measurement; blood volume; body temperature; body water dehydration; clinical research; electrolyte balance; exercise; hemodynamics; hormone regulation /control mechanism; human subject; hypovolemia; laboratory rat; plasmapheresis; plethysmography; protein biosynthesis; protein transport; renal tubular transport; saluresis; serum albumin; sodium ion; stress; transcription factor

DESCRIPTION (Adapted from the applicant's abstract): The overall aim of this renewal proposal is to uncover the mechanisms that underlie plasma volume expansion. They have developed two models to study these mechanisms. The human model, involving 32 min of intense exercise, produces a 10 percent plasma volume and albumin expansion within 24 hours. Their animal model, involving plasmapheresis, produces a complete recovery of both volume and albumin within 24 hours. The human and animal models differ from each other in certain respects but the two are sufficiently analogous to permit them to generate and test hypotheses in humans and then perform more invasive experiments to uncover mechanisms in rats. Using the human model they will test the following hypotheses related to the role of albumin synthetic rate, lymphatic protein transport and renal sodium handling in the process of plasma volume expansion: i) Sodium and water retention following saline loading is enhanced 24 hours following intense exercise. ii) Increased sodium retention following intense exercise occurs within both the proximal and distal tubules. iii) Enhanced sodium and water retention following intense exercise is mediated by changes in renal hemodynamics. iv) The elevation in plasma albumin content within the first two hours following intense exercise is mediated by increased lymphatic flow and thus modulated by changes in lymphatic outflow pressure. v) Albumin synthetic rate following intense exercise is modulated by posture dependent changes in circulating stress hormones. Using the animal model, they will test the following hypothesis: i) Increased hepatic albumin mRNA following chronic plasmapheresis is mediated by increased expression of hepatic nuclear transcription factor 1. ii) The primary mechanism for increased albumin content following plasmapheresis is lymphatic delivery of albumin to the vascular space. These studies characterizing the mechanisms underlying increased albumin synthesis and increased renal sodium reabsorption following exercise in humans and plasmapheresis in in vivo animal models will provide insight into the mechanisms underlying volume restoration. Such knowledge will lead to the development of methods to volume-expand compromised individuals more effectively without transfusion. Employment of both human and animal models enables the testing of hypotheses that are both relevant and mechanistic.

描述(改编自申请人的摘要)：本报告的总体目标 更新的提议是揭示血浆体积背后的机制 扩张。他们开发了两个模型来研究这些机制。人类 在32分钟的高强度运动中，人体产生10%的血浆 24小时内血容量和白蛋白膨胀。他们的动物模型，包括 血浆置换，产生完全恢复的体积和白蛋白在 24小时。人类和动物的模型在某些方面是不同的 方面，但两者具有足够的相似性以允许它们生成和 在人类身上测试假设，然后进行更具侵入性的实验来发现 大鼠体内的作用机制。使用人体模型，他们将测试以下内容 与白蛋白合成率、淋巴蛋白作用相关的假说 血浆容量扩张过程中的转运和肾钠转运： I)盐水加载后24小时内钠和水的保留率得到提高 在剧烈运动之后。二)高强度运动后钠滞留量增加 运动发生在近端小管和远端小管内。三)增强版 大强度运动后的钠和水滞留是由 肾脏血流动力学。IV)血浆白蛋白含量的升高 高强度运动后的头两个小时是由淋巴增加所调节的 淋巴流出压力的变化调节了淋巴流出压力。V)白蛋白 高强度运动后的合成率受姿势依赖的调节 循环应激激素的变化。使用动物模型，他们将测试 以下假设：i)慢性阻塞性肺疾病后肝组织白蛋白基因表达增加 血浆置换是通过增加肝细胞核的表达来实现的 转录因子1.ii)白蛋白含量增加的主要机制 血浆置换后白蛋白的淋巴输送到血管 太空。这些研究描述了白蛋白升高的机制 人体运动后肾脏钠的合成和重吸收增加 在活体动物模型中进行血浆置换将为深入了解 卷恢复的基本机制。这样的知识将导致 开发方法以扩大更多受影响的个体 有效地不需要输血。同时使用人类和动物模型 允许对既相关又机械的假设进行测试。