TRANSFUSION TRIGGER EXTENSION BY PLASMA EXPANDERS

描述（根据应用程序改编）：胶体或晶体溶液 用于将血容量恢复至7 g Hb/dL的输血触发。 它们的使用超过这一阈值会降低携氧能力，从而限制 组织供氧和存活本提案审查了以下假设： 除输血外，血浆扩张剂（PE）缺乏临床获益 触发是由于微血管功能障碍，而不是由于氧气减少 承载能力特别是血液性质的改变，包括 粘度和开启压力，超出输液触发原因：1） 小动脉血管收缩和血流量减少; 2）功能降低 毛细血管密度（FCD）;和3）降低组织氧合。一项拟议 这些变化背后的机制是输血触发血液 和血浆粘度的降低超过了 心血管系统，导致毛细血管压力降低，毛细血管 阻塞和FCD降低。此外， 具有常规PE的血液太低而不能通过 小动脉壁剪切应力，导致血管张力降低， 线粒体O2消耗拟议的研究将使用葡聚糖和淀粉 在仓鼠皮肤研究中使用不同粘度的溶液作为PE 折叠微循环模型目的是部分恢复粘度 在极度血液稀释的情况下， （血液稀释超过输血触发。）并检查所述 通过直接体内测量血液中微量PO 2和微量NO假设， 组织，毛细血管压力，血流速度，功能性毛细血管密度 和小动脉反应性。特别是FCD之间的相关性， 组织存活的决定因素和NO调节将被探索。

DESCRIPTION (Adapted from the application): Colloidal or crystalloid solutions are used to restore blood volume up to the transfusion trigger of 7g Hb/dL. Their use beyond this threshold reduces oxygen carrying capacity, which limits tissue oxygen delivery and survival. This proposal examines the hypothesis that the lack of clinical benefit for plasma expanders (PEs) beyond the transfusion trigger is due to a microvascular malfunction, not due to a reduced oxygen carrying capacity. In particular, alteration of blood properties, including viscosity and oncotic pressure, beyond the transfusion trigger causes: 1) arteriolar vasoconstriction and decreased blood flow; 2) reduced functional capillary density (FCD); and, 3) lowered tissue oxygenation. A proposed mechanism underlying these changes is that below the transfusion trigger blood and plasma viscosity are reduced beyond the compensatory capacity of the cardiovascular system, which causes capillary pressure to decrease, capillaries to become obstructed, and a lowering of FCD. Furthermore, the viscosity of blood with conventional PEs is too low to generate endothelial NO through arteriolar wall shear stress, resulting in reduced vascular tone and increased mitochondrial O2 consumption. The proposed studies will use dextran and starch solutions with different viscosities as PEs in hamster studies using the skin fold microcirculatory model. The aim will be to partially restore the viscosity of the circulating blood to near normal values in extreme hemodilution (hemodilution beyond the transfusion trigger.) and examine the stated hypothesis by direct in vivo measurement of micro-p02 and micro-NO in blood and tissue, capillary pressure, blood flow velocity, functional capillary density and arteriolar reactivity. In particular the correlation between FCD, a key determinant of tissue survival, and NO regulation will be explored.