Institute of Fluid Dynamics, ETH Zurich, Sonneggstrasse 3, Zurich, Switzerland.
Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, Zurich, Switzerland.
PLoS Comput Biol. 2019 Aug 30;15(8):e1007231. doi: 10.1371/journal.pcbi.1007231. eCollection 2019 Aug.
Capillaries are the prime location for oxygen and nutrient exchange in all tissues. Despite their fundamental role, our knowledge of perfusion and flow regulation in cortical capillary beds is still limited. Here, we use in vivo measurements and blood flow simulations in anatomically accurate microvascular network to investigate the impact of red blood cells (RBCs) on microvascular flow. Based on these in vivo and in silico experiments, we show that the impact of RBCs leads to a bias toward equating the values of the outflow velocities at divergent capillary bifurcations, for which we coin the term "well-balanced bifurcations". Our simulation results further reveal that hematocrit heterogeneity is directly caused by the RBC dynamics, i.e. by their unequal partitioning at bifurcations and their effect on vessel resistance. These results provide the first in vivo evidence of the impact of RBC dynamics on the flow field in the cortical microvasculature. By structural and functional analyses of our blood flow simulations we show that capillary diameter changes locally alter flow and RBC distribution. A dilation of 10% along a vessel length of 100 μm increases the flow on average by 21% in the dilated vessel downstream a well-balanced bifurcation. The number of RBCs rises on average by 27%. Importantly, RBC up-regulation proves to be more effective the more balanced the outflow velocities at the upstream bifurcation are. Taken together, we conclude that diameter changes at capillary level bear potential to locally change the flow field and the RBC distribution. Moreover, our results suggest that the balancing of outflow velocities contributes to the robustness of perfusion. Based on our in silico results, we anticipate that the bi-phasic nature of blood and small-scale regulations are essential for a well-adjusted oxygen and energy substrate supply.
毛细血管是所有组织中氧气和营养物质交换的主要场所。尽管它们具有重要的作用，但我们对皮质毛细血管床的灌注和流量调节的了解仍然有限。在这里，我们使用体内测量和血流模拟在解剖学上准确的微血管网络中，研究红细胞（RBC）对微血管流动的影响。基于这些体内和计算实验，我们表明 RBC 的影响导致在发散毛细血管分叉处的流出速度值相等的趋势，为此我们创造了“平衡分叉”一词。我们的模拟结果进一步表明，血细胞比容异质性直接由 RBC 动力学引起，即它们在分叉处的不均匀分配及其对血管阻力的影响。这些结果提供了 RBC 动力学对皮质微血管血流场影响的第一个体内证据。通过对我们的血流模拟的结构和功能分析，我们表明毛细血管直径的变化会局部改变流动和 RBC 的分布。在一个 100μm 长的血管中，直径增加 10%会使平衡分叉下游的扩张血管的平均流量增加 21%。RBC 的数量平均增加 27%。重要的是，上游分叉处的流出速度越平衡，RBC 的上调就越有效。总之，我们得出结论，毛细血管水平的直径变化有可能局部改变血流场和 RBC 的分布。此外，我们的结果表明，流出速度的平衡有助于灌注的稳健性。基于我们的计算结果，我们预计血液的双相性质和小规模调节对于适当的氧气和能量底物供应是必不可少的。
