Department of Material Science and Technology, Guilin University of Electronic Technology, Guilin, 541004, China.
Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Sci Rep. 2019 Jul 23;9(1):10649. doi: 10.1038/s41598-019-46669-9.
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 Ca -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 Ca fluxes. The model reproduces NO and Ca 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.
淋巴系统包含腔内小叶瓣膜，其功能是使淋巴液偏向心脏回流。这些瓣膜存在于收集淋巴管中，通常具有淋巴管平滑肌细胞，并能自发地泵送液体。最近的研究表明，瓣膜在休息时是开放的，可以允许一些回流，并是一氧化氮（NO）的来源。为了研究这些瓣膜如何作为机械瓣膜和血管活性物质的来源来优化吞吐量，我们开发了一个数学模型，该模型明确包括 Ca 调节收缩、NO 产生和瓣膜结构。二维格子玻尔兹曼模型包括一个初始淋巴管和一个嵌入在多孔组织中的收集淋巴管。淋巴管段具有机械活性的血管壁，并由可变形的瓣膜侧翼包围。血管壁的运动被动地受到流体压力的影响，而主动收缩则由细胞内 Ca 通量驱动。该模型再现了 NO 和 Ca 动力学、瓣膜运动和从组织中排出的液体。我们发现瓣膜的结构特性对性能有巨大影响，并且具有更硬基底和灵活尖端的瓣膜产生更稳定的循环。与实验观察一致，瓣膜是 NO 的主要来源。一旦启动，收缩是自发和自我维持的，系统表现出有趣的非线性动力学。例如，组织中的流体压力增加或系统出口处的淋巴压力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，高出口压力会阻碍流动，增加管腔压力和血管半径，从而导致壁的机械拉伸产生强烈的收缩。我们还发现，收缩起始的位置受瓣膜回流程度的影响。
