TRANSFUSION TRIGGER EXTENSION BY PLASMA EXPANDERS

描述(改编自应用)：胶体或晶体溶液 用于恢复高达7g Hb/dL的输血触发量。 超过这一阈值的使用会降低携带氧气的能力，从而限制 组织氧气输送和存活。这项提议检验了这样一种假设 血浆扩张器(PES)在输血后缺乏临床益处 触发是由于微血管故障，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 超过输液触发因素的粘度和肿胀压力：1) 小动脉血管收缩和血流减少；2)功能减退 毛细血管密度(FCD)；3)降低组织氧合。一项建议 这些变化背后的机制是，在输血下面触发血液 和血浆粘度的降低超出了 导致毛细血管压力下降的心血管系统 变得受阻，并降低FCD。此外，它的粘度 传统PES的血液太低，不能通过产生内皮NO 小动脉壁切应力，导致血管张力降低而升高 线粒体耗氧量。拟议的研究将使用葡聚糖和淀粉。 不同粘度的溶液在仓鼠皮肤研究中的应用 折叠微循环模型。其目的将是部分恢复粘度 在极端血液稀释中循环血液恢复到接近正常值 (超出输血触发的血液稀释。)并检查所述的 直接体内测定血和血中微量P02和微量NO的假说 组织、毛细血管压、血流速度、功能性毛细血管密度 和微动脉反应性。特别是FCD、密钥之间的关联 组织存活的决定因素，将不会探索任何调节。

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.