Replacing the Transfusion of 1-2 Units of Blood with Plasma Expanders that Increase Oxygen Delivery Capacity: Evidence from Experimental Studies.
Replacing the Transfusion of 1-2 Units of Blood with Plasma Expanders that Increase Oxygen Delivery Capacity: Evidence from Experimental Studies.
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DOI：
10.3390/jfb5040232
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发表时间：
2014-10-27
影响因子：
4.8
通讯作者：
Intaglietta M
中科院分区：
文献类型：
--
作者：
Tsai AG;Salazar Vázquez BY;Cabrales P;Kistler EB;Tartakovsky DM;Subramaniam S;Acharya SA;Intaglietta M
世界上至少有三分之一的血液供应用于为每次干预输注1-2单位的浓缩红细胞，并且大多数血液替代品的临床试验都是在这种携氧能力（OCC）恢复水平下进行的。然而，对于分子血红蛋白（Hb）产品，由于其挥之不去的血管活性，所实现的氧合增加是微不足道的或根本没有。这为使用具有高氧亲和力和将氧靶向递送至缺氧区域的基于Hb的分子的“氧治疗剂”的开发提供了动力。然而，这些氧载体如何抵消或减轻由于阻塞、血管收缩和灌注不足而引起的贫血的功能效应仍不清楚。实际上，它们作为低剂量/低体积治疗性Hb（随后在循环池中进一步稀释）施用，因此诱导极小的OCC变化。高粘血浆扩张剂通过增加氧输送能力（ODC）提供了氧治疗的替代方案;在贫血中，它们诱导超灌注并增加组织灌注（流量）多达50%。聚乙二醇结合白蛋白（PEG-Alb）通过增强稀释血液的剪切稀化行为来实现这一点，这增加了微血管内皮剪切应力，导致血管舒张和降低外周血管阻力，从而促进心脏功能。超灌注的诱导利用了ODC是OCC和血流的产物的事实，因此可以通过增加其中之一或两者来维持。动物研究表明，这种方法可以节省相当大一部分的血液供应。它具有增强毒性代谢物的组织清除的额外益处。
At least a third of the blood supply in the world is used to transfuse 1–2 units of packed red blood cells for each intervention and most clinical trials of blood substitutes have been carried out at this level of oxygen carrying capacity (OCC) restoration. However, the increase of oxygenation achieved is marginal or none at all for molecular hemoglobin (Hb) products, due to their lingering vasoactivity. This has provided the impetus for the development of “oxygen therapeutics” using Hb-based molecules that have high oxygen affinity and target delivery of oxygen to anoxic areas. However it is still unclear how these oxygen carriers counteract or mitigate the functional effects of anemia due to obstruction, vasoconstriction and under-perfusion. Indeed, they are administered as a low dosage/low volume therapeutic Hb (subsequently further diluted in the circulatory pool) and hence induce extremely small OCC changes. Hyperviscous plasma expanders provide an alternative to oxygen therapeutics by increasing the oxygen delivery capacity (ODC); in anemia they induce supra-perfusion and increase tissue perfusion (flow) by as much as 50%. Polyethylene glycol conjugate albumin (PEG-Alb) accomplishes this by enhancing the shear thinning behavior of diluted blood, which increases microvascular endothelial shear stress, causes vasodilation and lowering peripheral vascular resistance thus facilitating cardiac function. Induction of supra-perfusion takes advantage of the fact that ODC is the product of OCC and blood flow and hence can be maintained by increasing either or both. Animal studies suggest that this approach may save a considerable fraction of the blood supply. It has an additional benefit of enhancing tissue clearance of toxic metabolites.