George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 801 Ferst Drive, Atlanta, GA 30313, USA.
Wallace H. Coulter Department of Biomedical Engineering, 313 Ferst Drive, Atanta, GA 30332, USA.
J R Soc Interface. 2020 Sep;17(170):20200598. doi: 10.1098/rsif.2020.0598. Epub 2020 Sep 30.
The lymphatic system transports lymph from the interstitial space back to the great veins via a series of orchestrated contractions of chains of lymphangions. Biomechanical models of lymph transport, validated with or experimental results, have proved useful in revealing novel insight into lymphatic pumping; however, a need remains to characterize the contributions of vasoregulatory compounds in these modelling tools. Nitric oxide (NO) is a key mediator of lymphatic pumping. We quantified the active contractile and passive biaxial biomechanical response of rat tail collecting lymphatics and changes in the contractile response to the exogenous NO administration and integrated these findings into a biomechanical model. The passive mechanical response was characterized with a three-fibre family model. Nonlinear regression and non-parametric bootstrapping were used to identify best-fit material parameters to passive cylindrical biaxial mechanical data, assessing uniqueness and parameter confidence intervals; this model yielded a good fit ( = 0.90). Exogenous delivery of NO via sodium nitroprusside (SNP) elicited a dose-dependent suppression of contractions; the amplitude of contractions decreased by 30% and the contraction frequency decreased by 70%. Contractile function was characterized with a modified Rachev-Hayashi model, introducing a parameter that is related to SNP concentration; the model provided a good fit ( = 0.89) to changes in contractile responses to varying concentrations of SNP. These results demonstrated the significant role of NO in lymphatic pumping and provide a predictive biomechanical model to integrate the combined effect of mechanical loading and NO on lymphatic contractility and mechanical response.
淋巴系统通过一系列淋巴管的协调收缩，将淋巴从细胞间隙运输回大静脉。经过 或 实验验证的淋巴传输生物力学模型，已被证明有助于揭示淋巴泵的新见解；然而，仍然需要描述血管调节化合物在这些建模工具中的作用。一氧化氮（NO）是淋巴泵的关键介质。我们定量测量了大鼠尾收集淋巴管的主动收缩和被动双轴生物力学反应，以及对外源性 NO 给药的收缩反应的变化，并将这些发现整合到生物力学模型中。被动机械反应采用三纤维族模型进行描述。非线性回归和非参数引导用于识别被动圆柱双轴力学数据的最佳拟合材料参数，评估独特性和参数置信区间；该模型具有良好的拟合度（ = 0.90）。通过硝普钠（SNP）经外源途径输送的 NO 引起收缩的剂量依赖性抑制；收缩幅度降低 30%，收缩频率降低 70%。通过修改的 Rachev-Hayashi 模型对收缩功能进行了描述，该模型引入了一个与 SNP 浓度相关的参数；该模型对 SNP 浓度变化时的收缩反应变化提供了良好的拟合（ = 0.89）。这些结果表明 NO 在淋巴泵中具有重要作用，并提供了一个预测性的生物力学模型，以整合机械负荷和 NO 对淋巴管收缩性和机械反应的综合影响。
