Lu Xinran, Galarneau Michelle M, Higgins John M, Wood David K
Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA.
Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN, USA.
Microcirculation. 2017 Jul;24(5). doi: 10.1111/micc.12357.
Our goal was to develop a model of the microvasculature that would allow us to quantify changes in the rheology of sickle blood as it traverses the varying vessel sizes and oxygen tensions in the microcirculation. We designed and implemented a microfluidic model of the microcirculation that comprises a branching microvascular network and physiologic oxygen gradients. We used computational modeling to determine the parameters necessary to generate stable, linear gradients in our devices. Sickle blood from six unique patients was perfused through the microvascular network and subjected to varying oxygen gradients while we observed and quantified blood flow. We found that all sickle blood samples fully occluded the microvascular network when deoxygenated, and we observed that sickle blood could cause vaso-occlusions under physiologic oxygen gradients during the microvascular transit time. The number of occlusions observed under five unique oxygen gradients varied among the patient samples, but we generally observed that the number of occlusions decreased with increasing inlet oxygen tension. The model system we have developed is a valuable tool to address fundamental questions about where in the circulation sickle-cell vaso-occlusions are most likely to occur and to test new therapies.
我们的目标是建立一个微血管模型，使我们能够量化镰状细胞血液在微循环中穿过不同血管大小和氧张力时其流变学的变化。我们设计并实现了一个微循环微流控模型，该模型包含一个分支微血管网络和生理氧梯度。我们使用计算模型来确定在我们的装置中产生稳定线性梯度所需的参数。来自六名不同患者的镰状细胞血液被灌注通过微血管网络，并在我们观察和量化血流的同时，使其处于不同的氧梯度下。我们发现，所有镰状细胞血液样本在脱氧时都会完全阻塞微血管网络，并且我们观察到，在微血管通过时间内，镰状细胞血液在生理氧梯度下会导致血管阻塞。在五个不同氧梯度下观察到的阻塞数量在患者样本中有所不同，但我们通常观察到，阻塞数量随着入口氧张力的增加而减少。我们开发的模型系统是一个有价值的工具，可用于解决关于镰状细胞血管阻塞在循环中最可能发生的位置的基本问题，并用于测试新疗法。
