The effects of valve leaflet mechanics on lymphatic pumping assessed using numerical simulations
The effects of valve leaflet mechanics on lymphatic pumping assessed using numerical simulations
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DOI：
10.1038/s41598-019-46669-9
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发表时间：
2019-07-23
影响因子：
4.6
通讯作者：
Munn, Lance L.
中科院分区：
文献类型：
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作者：
Li, Huabing;Mei, Yumeng;Munn, Lance L.
淋巴系统包含腔内小叶瓣，其作用是使淋巴液回流到心脏。这些瓣膜存在于集合淋巴管中，这些淋巴管通常有淋巴肌细胞，可以自发地泵送液体。最近的研究表明，阀门在静止状态下打开，可能会导致一些回流，并且是一氧化氮（NO）的来源。为了研究这些阀门如何作为机械阀门和血管活性物质的来源来优化吞吐量，我们开发了一个明确包括Ca2+调节收缩、NO生产和阀门结构的数学模型。二维晶格玻尔兹曼模型包括一个初始淋巴管和一个嵌入多孔组织的收集淋巴管。淋巴管节段具有机械活性的血管壁，两侧有可变形的瓣膜。血管壁运动被动地受到流体压力的影响，而主动收缩是由细胞内Ca2+通量驱动的。该模型再现了NO和Ca2+动力学、瓣膜运动和组织中流体的排出。我们发现阀门的结构特性对性能有很大的影响，具有更硬的底座和柔性尖端的阀门可以产生更稳定的循环。与实验观察一致，阀门是NO的主要来源。一旦开始，收缩是自发的和自我维持的，并且系统表现出有趣的非线性动力学。例如，组织中流体压力的增加或系统出口淋巴压力的降低会产生高剪切应力和高水平的NO，从而抑制收缩。另一方面，较高的出口压力与流动相反，增加了腔压和血管半径，从而导致壁的机械拉伸产生强烈的收缩。我们还发现，收缩开始的位置受通过阀门的回流程度的影响。
The lymphatic system contains intraluminal leaflet valves that function to bias lymph flow back towards the heart. These valves are present in the collecting lymphatic vessels, which generally have lymphatic muscle cells and can spontaneously pump fluid. Recent studies have shown that the valves are open at rest, can allow some backflow, and are a source of nitric oxide (NO). To investigate how these valves function as a mechanical valve and source of vasoactive species to optimize throughput, we developed a mathematical model that explicitly includes Ca2+ -modulated contractions, NO production and valve structures. The 2D lattice Boltzmann model includes an initial lymphatic vessel and a collecting lymphangion embedded in a porous tissue. The lymphangion segment has mechanically-active vessel walls and is flanked by deformable valves. Vessel wall motion is passively affected by fluid pressure, while active contractions are driven by intracellular Ca2+ fluxes. The model reproduces NO and Ca2+ dynamics, valve motion and fluid drainage from tissue. We find that valve structural properties have dramatic effects on performance, and that valves with a stiffer base and flexible tips produce more stable cycling. In agreement with experimental observations, the valves are a major source of NO. Once initiated, the contractions are spontaneous and self-sustained, and the system exhibits interesting non-linear dynamics. For example, increased fluid pressure in the tissue or decreased lymph pressure at the outlet of the system produces high shear stress and high levels of NO, which inhibits contractions. On the other hand, a high outlet pressure opposes the flow, increasing the luminal pressure and the radius of the vessel, which results in strong contractions in response to mechanical stretch of the wall. We also find that the location of contraction initiation is affected by the extent of backflow through the valves.