Red blood cell lingering modulates hematocrit distribution in the microcirculation
Red blood cell lingering modulates hematocrit distribution in the microcirculation
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DOI：
10.1101/2022.08.16.504126
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发表时间：
2022-08
影响因子：
3.4
通讯作者：
Yazdan Rashidi;G. Simionato;Qi Zhou;Thomas John;Alexander Kihm;Mohammed Bendaoud;T. Krüger;M. Bernabeu;L. Kaestner;M. Laschke;M. Menger;C. Wagner;A. Darras
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作者：
Yazdan Rashidi;G. Simionato;Qi Zhou;Thomas John;Alexander Kihm;Mohammed Bendaoud;T. Krüger;M. Bernabeu;L. Kaestner;M. Laschke;M. Menger;C. Wagner;A. Darras
红细胞在微循环中的分布决定了组织的氧气输送和溶质运输。该过程依赖于RBC在整个微血管网络中的连续分叉处的分配，并且自上个世纪以来已知RBC的分配与血流分数不成比例，因此导致微血管中红细胞比容（即血液中RBC的体积分数）的异质性。通常，在微血管分叉的下游，具有较高血流分数的血管分支接收甚至更高分数的RBC通量。然而，在最近的工作中，已经观察到时间和时间平均偏差从这个相位分离法。在这里，我们量化了红细胞的微观行为徘徊（即红细胞暂时居住在分叉顶点附近的速度降低）如何影响他们的分区，通过结合体内实验和计算机模拟。我们开发了一种方法来量化细胞滞留在高度受限的毛细血管水平的分叉，并证明它与相分离过程的偏差从建立的经验预测普里斯等人。此外，我们揭示了分叉几何形状和细胞膜刚度如何影响红细胞的滞留行为，例如刚性细胞往往滞留比软的。综上所述，红细胞滞留是一种重要的机制，在研究疟疾和镰状细胞病等疾病中异常的红细胞刚性如何阻碍微循环血流或血管网络如何在病理条件下改变（例如血栓形成，动脉瘤）时应考虑。
The distribution of red blood cells (RBCs) in the microcirculation determines the oxygen delivery and solute transport to tissues. This process relies on the partitioning of RBCs at successive bifurcations throughout the microvascular network and it is known since the last century that RBCs partition disproportionately to the fractional blood flow rate, therefore leading to heterogeneity of the hematocrit (i.e. volume fraction of RBCs in blood) in microvessels. Usually, downstream of a microvascular bifurcation, the vessel branch with a higher fraction of blood flow receives an even higher fraction of RBC flux. However, both temporal and time-average deviations from this phaseseparation law have been observed in recent works. Here, we quantify how the microscopic behavior of RBCs lingering (i.e. RBCs temporarily residing near the bifurcation apex with diminished velocity) influences their partitioning, through combined in vivo experiments and in silico simulations. We developed an approach to quantify the cell lingering at highly-confined capillary-level bifurcations and demonstrate that it correlates with deviations of the phase-separation process from established empirical predictions by Pries et al. Furthermore, we shed light on how the bifurcation geometry and cell membrane rigidity can affect the lingering behavior of RBCs, e.g. rigid cells tend to linger less than softer ones. Taken together, RBC lingering is an important mechanism that should be considered when studying how abnormal RBC rigidity in diseases such as malaria and sickle-cell disease could hinder the microcirculatory blood flow or how the vascular networks are altered under pathological conditions (e.g. thrombosis, aneurysm).