Department of Energy Resources Engineering, Stanford University, Stanford, California.
Department of Bioengineering, University of California, San Diego, California.
J Appl Physiol (1985). 2021 Dec 1;131(6):1815-1823. doi: 10.1152/japplphysiol.00524.2021. Epub 2021 Oct 14.
Although some of the cardiovascular responses to changes in hematocrit (Hct) are not fully quantified experimentally, available information is sufficient to build a mathematical model of the consequences of treating anemia by introducing RBCs into the circulation via blood transfusion. We present such a model, which describes how the treatment of normovolemic anemia with blood transfusion impacts oxygen (O) delivery (DO, the product of blood O content and arterial blood flow) by the microcirculation. Our analysis accounts for the differential response of the endothelium to the wall shear stress (WSS) stimulus, changes in nitric oxide (NO) production due to modification of blood viscosity caused by alterations of both hematocrit (Hct) and cell free layer thickness, as well as for their combined effects on microvascular blood flow and DO. Our model shows that transfusions of 1- and 2-unit of blood have a minimal effect on DO if the microcirculation is unresponsive to the WSS stimulus for NO production that causes vasodilatation increasing blood flow and DO. Conversely, in a fully WSS responsive organism, blood transfusion significantly enhances blood flow and DO, because increased viscosity stimulates endothelial NO production causing vasodilatation. This finding suggests that evaluation of a patients' pretransfusion endothelial WSS responsiveness should be beneficial in determining the optimal transfusion requirements for treating patients with anemia. Transfusion of 1 or 2 units of blood accounts for about 3/4 of the world blood consumption of 119 million units per year, whereas a current world demand deficit is on the order of 100 million units. Therefore, factors supporting the practice of transfusing 1 unit instead of 2 are of interest, given their potential to expand the number of interventions without increasing blood availability. Our mathematical model provides a physiological support for this practice.
虽然一些关于血细胞比容 (Hct) 变化的心血管反应尚未完全通过实验定量，但现有的信息足以构建一个通过输血将 RBC 引入循环系统来治疗贫血的数学模型。我们提出了这样一个模型，描述了通过输血治疗等容性贫血如何影响微循环中的氧输送 (DO，即血液中 O 含量和动脉血流量的乘积)。我们的分析考虑了内皮对壁切应力 (WSS) 刺激的差异反应、由于 Hct 和无细胞层厚度的变化引起的血液粘度变化导致的一氧化氮 (NO) 产生的变化，以及它们对微血管血流和 DO 的联合影响。我们的模型表明，如果微循环对 WSS 刺激无反应，导致血管扩张增加血流量和 DO 的 NO 产生，那么输血 1 或 2 个单位对 DO 的影响最小。相反，在完全 WSS 反应的生物体中，输血会显著增强血流和 DO，因为增加的粘度会刺激内皮细胞产生 NO 导致血管扩张。这一发现表明，评估患者输血前内皮 WSS 反应性有助于确定治疗贫血患者的最佳输血需求。输血 1 或 2 个单位占全球每年 1.19 亿单位血液消耗的约 3/4，而目前全球需求缺口约为 1 亿单位。因此，支持输注 1 单位而不是 2 单位的因素很有趣，因为它们有可能在不增加血液供应的情况下扩大干预措施的数量。我们的数学模型为这种做法提供了生理支持。
