Department of Biomedical Engineering, Tulane University, New Orleans, LA 70118, United States.
Microvasc Res. 2012 Sep;84(2):123-32. doi: 10.1016/j.mvr.2012.06.006. Epub 2012 Jun 23.
Previous computational studies have suggested that the capillary blood flow oscillations frequently observed in vivo can originate spontaneously from the non-linear rheological properties of blood, without any regulatory input. Testing this hypothesis definitively in experiments involving real microvasculature has been difficult because in vivo the blood flow in capillaries is always actively controlled by the host. The objective of this study was to test the hypothesis experimentally and to investigate the relative contribution of different blood cells to the capillary blood flow dynamics under static boundary conditions and in complete isolation from the active regulatory mechanisms mediated by the blood vessels in vivo. To accomplish this objective, we passed whole blood and re-constituted blood samples (purified red blood cells suspended in buffer or in autologous plasma) through an artificial microvascular network (AMVN) comprising completely inert, microfabricated vessels with the architecture inspired by the real microvasculature. We found that the flow of blood in capillaries of the AMVN indeed oscillates with characteristic frequencies in the range of 0-0.6 Hz, which is in a very good agreement with previous computational studies and in vivo observations. We also found that the traffic of leukocytes through the network (typically neglected in computational modeling) plays an important role in generating the oscillations. This study represents the key piece of experimental evidence in support of the hypothesis that spontaneous, self-sustained oscillations of capillary blood flow can be generated solely by the non-linear rheological properties of blood flowing through microvascular networks, and provides an insight into the mechanism of this fundamentally important microcirculatory phenomenon.
先前的计算研究表明，体内频繁观察到的毛细血管血流振荡可能自发源自血液的非线性流变特性，而无需任何调节输入。在涉及真实微血管的实验中，明确验证这一假设一直具有挑战性，因为在体内，毛细血管中的血流始终受到宿主的主动控制。本研究的目的是通过静态边界条件下的实验来检验这一假设，并研究不同血细胞对毛细血管血流动力学的相对贡献，实验是在与体内由血管介导的主动调节机制完全隔离的情况下进行的。为了实现这一目标，我们使全血和重组血液样本（悬浮在缓冲液或自体血浆中的纯化红细胞）流经由完全惰性的、受微制造启发的血管组成的人工微血管网络（AMVN），其结构与真实微血管相似。我们发现，AMVN 中毛细血管内的血流确实以 0-0.6Hz 的特征频率振荡，这与先前的计算研究和体内观察结果非常吻合。我们还发现，白细胞在网络中的流动（在计算建模中通常被忽略）在产生振荡方面起着重要作用。这项研究代表了支持假设的关键实验证据，即毛细血管血流的自发、自维持振荡可以仅由流经微血管网络的血液的非线性流变特性产生，并深入了解这种基本重要的微循环现象的机制。
