Confocal Image-Based Computational Modeling of Nitric Oxide Transport in a Rat Mesenteric Lymphatic Vessel
Confocal Image-Based Computational Modeling of Nitric Oxide Transport in a Rat Mesenteric Lymphatic Vessel
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DOI：
10.1115/1.4023986
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发表时间：
2013-05-01
影响因子：
1.7
通讯作者：
Moore, James E., Jr.
中科院分区：
文献类型：
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作者：
Wilson, John T.;Wang, Wei;Moore, James E., Jr.
淋巴系统在蛋白质和溶质运输以及免疫系统中发挥着重要作用。它的功能对体内平衡和体液平衡至关重要。淋巴可能由固有的(主动)血管泵送或来自外部组织运动的被动压迫而推进。关于前者，一氧化氮(NO)被认为在调节淋巴管收缩和血管扩张方面起着重要作用。淋巴管内皮细胞(LECs)对剪切力很敏感，流量的增加会导致LECs产生更多的NO。此外，实验中在肠系膜淋巴管的窦区观察到高浓度的NO。利用从大鼠肠系膜淋巴管共焦图像获得的生理几何形状，建立了一个计算流动和质量传递模型，以确定淋巴流动状态下NO的传输特性。进行了定常和非定常分析。NO的产生是剪切相关的；也产生了使用恒定产生的基本情况。模拟显示了靠近阀门小叶的流动停滞区域，这表明实验中观察到的高浓度是由于该区域的最小对流所致。LEC对剪切的敏感性被发现改变了容器中NO的浓度，并且当Peclet值大于约61时，对流力被发现深刻地影响了NO的浓度。准稳态分析能够将非稳态情况下的壁面剪应力分解在0.15%以内。然而，对于NO浓度，非稳态和准稳态之间的百分比差异更大(6.7%)。我们已经证明，瓣叶附近的高NO浓度最有可能是由于流动介导的过程，而不是剪切敏感的LECs产生的差异。此外，这个模型支持剪切依赖生产的实验结果，因为去除剪切依赖会导致浓度在生理上是违反直觉的。了解淋巴管系统中的传输机制和流动状态有助于开发治疗淋巴疾病的疗法。
The lymphatic system plays important roles in protein and solute transport as well as in the immune system. Its functionality is vital to proper homeostasis and fluid balance. Lymph may be propelled by intrinsic (active) vessel pumping or passive compression from external tissue movement. With regard to the former, nitric oxide (NO) is known to play an important role modulating lymphatic vessel contraction and vasodilation. Lymphatic endothelial cells (LECs) are sensitive to shear, and increases in flow have been shown to cause enhanced production of NO by LECs. Additionally, high concentrations of NO have been experimentally observed in the sinus region of mesenteric lymphatic vessels. A computational flow and mass transfer model using physiologic geometries obtained from confocal images of a rat mesenteric lymphatic vessel was developed to determine the characteristics of NO transport in the lymphatic flow regime. Both steady and unsteady analyses were performed. Production of NO was shear-dependent; basal cases using constant production were also generated. Simulations revealed areas of flow stagnation adjacent to the valve leaflets, suggesting the high concentrations observed here experimentally are due to minimal convection in this region. LEC sensitivity to shear was found to alter the concentration of NO in the vessel, and the convective forces were found to profoundly affect the concentration of NO at a Peclet value greater than approximately 61. The quasisteady analysis was able to resolve wall shear stress within 0.15% of the unsteady case. However, the percent difference between unsteady and quasisteady conditions was higher for NO concentration (6.7%). We have shown high NO concentrations adjacent to the valve leaflets are most likely due to flow-mediated processes rather than differential production by shear-sensitive LECs. Additionally, this model supports experimental findings of shear-dependent production, since removing shear dependence resulted in concentrations that are physiologically counterintuitive. Understanding the transport mechanisms and flow regimes in the lymphatic vasculature could help in the development of therapeutics to treat lymphatic disorders.