BLOOD VOLUME AND VENOUS RETURN IN THERMAL STRAIN

描述（改编自申请人的摘要）：本研究的总体目标 更新建议是揭示血浆容量的机制 扩张.他们开发了两种模型来研究这些机制。人类 模型，包括32分钟的剧烈运动，产生10%的血浆 在24小时内增加体积和白蛋白。他们的动物模型， 血浆置换，产生完全恢复的体积和白蛋白内 24小时人类和动物模型在某些方面彼此不同。 这两个方面，但这两个是足够相似，使他们能够产生和 在人类身上测试假设，然后进行更具侵入性的实验， 老鼠的机制使用人体模型，他们将测试以下内容 白蛋白合成率、淋巴蛋白 血浆容量扩张过程中的转运和肾钠处理： i）盐水负荷后的钠和水保留增强24小时 在剧烈运动之后。ii）在强烈刺激后增加钠潴留 运动发生在近端小管和远端小管内。（三）强化 剧烈运动后的钠和水潴留是由 肾血流动力学iv）血浆白蛋白含量的升高， 剧烈运动后的前两个小时是由增加的淋巴细胞介导的， 流动，从而通过淋巴流出压力的变化来调节。v）白蛋白 高强度运动后的合成率受姿势依赖性调节 循环应激激素的变化。利用动物模型，他们将测试 以下假设：i）慢性炎症后肝白蛋白mRNA增加 血浆置换是由肝细胞核表达增加介导的， 转录因子1。ii）白蛋白含量增加的主要机制 血浆置换术后，淋巴管将白蛋白输送至血管 空间这些研究描述了白蛋白增加的潜在机制 人体运动后钠合成和肾钠重吸收增加 和血浆置换在体内动物模型中将提供对 体积恢复的潜在机制。这样的知识将导致 开发方法以扩大受感染个体的数量更多 有效地不输血。使用人类和动物模型 能够检验相关的和机械的假设。

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.