BLOOD VOLUME AND VENOUS RETURN IN THERMAL STRAIN

热应变下的血容量和静脉回流

• 批准号: 2215379
• 负责人: ETHAN R NADEL
• 金额: $ 33.31万
• 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 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2215379
• 关键词: baroreceptors; baroreflex; biological models; blood chemistry; blood flow measurement; blood volume; body temperature; calorimetry; exercise; hemodynamics; hemorrhage; human subject; hypotension; hypovolemia; kidney function; laboratory rat; messenger RNA; model design /development; plethysmography; protein biosynthesis; serum albumin; stable isotope; stress; urinalysis

The overall aim of this renewal proposal is to uncover the mechanisms that underlie plasma volume expansion. We have developed two models to study these mechanisms. Our human model, involving 32 min of intense exercise, produces a 10% plasma volume and albumin expansion within the following 24 h. Our animal model, involving hypotensive hemorrhage in rats, produces a complete recovery of both volume and albumin within 24 h. Although the human and animal models differ from each other in certain respects, the two are sufficiently analogous to permit us to generate and test hypotheses in humans and then perform more invasive experiments to uncover mechanisms in rats. Using the human model, we will test the following hypotheses: i) the fall in central venous and/or mean arterial pressure following intense exercise are the primary signals that initiate events leading to increased plasma albumin content. ii) an initial (1-2 h) elevation in plasma albumin content after intense exercise is of interstitial origin and the subsequent (24 h) elevation in plasma albumin content is due to increased hepatic albumin synthetic rate. iii) acute albumin expansion is not sufficient to expand the plasma volume after 24 h. iv) the transcapillary escape rate of albumin is decreased after intense exercise. Using the animal model, we will test the following hypotheses: i) increased albumin synthesis is initiated within hours following hemorrhage. ii) increased albumin synthesis following hemorrhage is due to increased hepatic albumin mRNA transcription. iii) increased hepatic albumin mRNA transcription following hemorrhage is initiated by neural signals generated by unloading cardiopulmonary and/or arterial baroreceptors. iv) certain of the salt and water retention hormones cause increased hepatic albumin mRNA transcription in an isolated, perfused liver preparation. v) a portion of the increased albumin content following hemorrhage is due to a reduction in the transcapillary escape rate of albumin. Our studies characterizing the mechanisms underlying plasma albumin synthesis during recovery from exercise in humans and hemorrhage in in vitro and 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. Our employment of both human and animal models enables the testing of hypotheses that are both relevant and mechanistic.

这一更新提案的总体目标是揭示 是血浆体积膨胀的基础。我们开发了两个模型来研究 这些机制。我们的人体模型，包括32分钟的剧烈运动， 在以下24小时内产生10%的血浆体积和白蛋白膨胀 H.我们的动物模型，包括大鼠的脑出血，产生了一个 在24小时内完全恢复体积和白蛋白。虽然 人类和动物模型在某些方面彼此不同， 两个足够相似，使我们能够生成和测试 然后进行更具侵入性的实验， 老鼠的机制 使用人类模型，我们将测试以下假设：i）跌倒 剧烈运动后中心静脉压和/或平均动脉压 是引发导致血浆增加的事件的主要信号 白蛋白含量ii）血浆白蛋白的初始（1 - 2小时）升高 剧烈运动后的内容是间质起源， 随后（24小时）血浆白蛋白含量的升高是由于 肝白蛋白合成率。iii）急性白蛋白扩张不是 足以在24小时后扩大血浆体积。（四）经毛细血管 剧烈运动后白蛋白逃逸率降低。 使用动物模型，我们将测试以下假设：i） 白蛋白合成增加在以下几小时内开始 出血ii）出血后白蛋白合成增加是由于 肝白蛋白mRNA转录增加。iii）肝细胞增多 出血后白蛋白mRNA的转录由神经元启动， 由心肺和/或动脉卸载产生的信号 压力感受器iv）某些盐和水保持激素导致 在一个离体的，灌流的， 肝脏制备V）在以下情况下增加的白蛋白含量的一部分： 出血是由于经毛细血管逸出率降低所致 白蛋白。 我们的研究描述了血浆白蛋白的机制 人体运动后恢复期的合成和猪的出血 体外和体内动物模型将提供深入了解的机制， 潜在的体积恢复。这样的知识将导致发展 更有效地扩大受害者的数量 没有输血。我们使用人类和动物模型 能够检验相关的和机械的假设。