HYPOPROTEINEMIA AND MODULATION OF VASCULAR FILTRATION

低蛋白血症和血管滤过的调节

• 批准号: 3365321
• 负责人: BRUCE Allan HARMS
• 金额: $ 17.31万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-24 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3365321
• 关键词: blood; dextrans; endotoxins; fluorescent dye /probe; high performance liquid chromatography; hypoproteinemia; indicator dilution test; lung; lymph; lymph nodes; molecular weight; osmotic pressure; pulmonary edema; sheep; solutions; starch; vascular endothelium permeability

Plasma volume expanders are often required in the management of critical care patients, who are frequently hypoproteinemic, or who have sepsis- induced increases in microvascular permeability. Volume expanders frequently employed include dextran-70, pentafraction, and hetastarch. However, these compounds are composed of a broad range of molecular fractions, and we hypothesize that the smaller fractions, less that 150 kilodaltons (kD), can filter into lung and soft tissue lymph. If this is true it means that the oncotic effectiveness of these solutions is compromised, because in addition to raising the oncotic pressure of the plasma, they would also raise the oncotic pressure of the lymph. This would facilitate vascular filtration and enhance development of lung systemic edema. We propose to test our hypothesis in unanesthetized sheep by measuring oncotic pressures contributed by each of the three volume expanders named above, and by using high performance liquid chromatography (HPLC) to measure their molecular weight distributions in plasma and lymph. Few previous studies have addressed the possibility of volume expander filtration, and to our knowledge, no previous studies have compared starch oncotic pressures nor starch molecular weight profiles between plasma and lymph. Results of such a study are important because they would identify a molecular weight that would result in minimum macromolecular filtration, which could lead to development of an improved volume expander that would exert maximum oncotic effectiveness. Dextran-70, pentafraction and hetastarch have average molecular weights, respectively, of 70, 200, and 450 kD, but the distributions around these averages are quite broad. For example, 80% of dextran-70 ranges from 20 to 200 kD, 80% of pentafraction ranges from 40 to 1,250 kD, and 80% of hetastarch ranges from 25 to 3,000 kD. Our hypothesis implies that dextran-70 should readily enter lymph and enhance filtration because the majority of its molecules are smaller that 150 kD; a recent report confirms this. The smaller pentafraction and hetastarch fractions should also filter, and so should albumin, which has a molecular weight of 66 kD. (The largest fractions in hetastarch are also undesirable and are thought to be associated with coagulopathies.) Sheep, prepared for long-term collection of lung and soft tissue lymph, will be infused with dextran-70, pentafraction, or hetastarch. Autogenous plasma will also be infused for comparison. Plasma and lymph samples will be collected, and starch oncotic pressures and molecular weight distributions will be measured. The solutions will be infused in normal and hypoproteinemic conditions, and in conditions in which vascular permeability is increased.

在关键的管理中，通常需要等离子体量扩展器 经常是低蛋白或患有败血症的患者 诱导的微血管通透性增加。 音量扩展器 经常使用的包括Dextran-70，PentaFraction和Hetastarch。 但是，这些化合物由一定范围的分子组成 分数，我们假设较小的部分，少于150 千达尔顿（KD）可以过滤成肺和软组织淋巴。 如果这个 是真的，这意味着这些解决方案的肿瘤有效性是 受到妥协，因为除了升高 等离子体，它们还会增加淋巴的肿瘤压力。 这 将促进血管过滤并增强肺的发育 系统性水肿。 我们建议在未经麻醉的情况下检验我们的假设 绵羊通过测量三个造成的肿瘤压力 上面命名的音量扩展器，并使用高性能液体 色谱（HPLC），以测量其分子量分布 血浆和淋巴。 以前很少有研究解决了可能性 数量扩展器过滤，据我们所知，以前没有研究 比较了淀粉肿瘤压力和淀粉分子量 血浆和淋巴之间的特征。 这样的研究的结果是 重要的是因为他们会识别出一个分子量 导致最小的大分子过滤，这可能导致 开发改进的数量扩展器，将发挥最大的发挥作用 肿瘤有效性。 Dextran-70，PentaFraction和Hetastarch具有 平均分子量分别为70、200和450 kD，但 这些平均值的分布非常广泛。 例如，80％ Dextran-70范围为20至200 kD，五范围的80％范围从 40至1,250 KD，Hetastarch的80％范围为25至3,000 kD。 我们的 假设意味着Dextran-70应该容易进入淋巴和 增强过滤，因为大多数分子较小 那150 kd;最近的一份报告证实了这一点。 较小的五角形 hetastarch的分数也应该过滤，白蛋白也应该过滤， 分子量为66 kd。 （最大的分数 Hetastarch也是不可取的，被认为与 凝血病。）绵羊，准备长期收集肺和 软组织淋巴，将注入右旋烷-70，五翼或 Hetastarch。 自体等离子体也将被注入以进行比较。 将收集血浆和淋巴样品，淀粉肿瘤压力 将测量和分子量分布。 解决方案将 在正常和降压毒素条件下注入，并在条件下 其中血管通透性增加。