Kornuta Jeffrey A, Nepiyushchikh Zhanna, Gasheva Olga Y, Mukherjee Anish, Zawieja David C, Dixon J Brandon
Parker H. Petite Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia;
Department of Medical Physiology, Texas A&M Health Science Center College of Medicine, Temple, Texas.
Am J Physiol Regul Integr Comp Physiol. 2015 Nov 1;309(9):R1122-34. doi: 10.1152/ajpregu.00342.2014. Epub 2015 Sep 2.
Given the known mechanosensitivity of the lymphatic vasculature, we sought to investigate the effects of dynamic wall shear stress (WSS) on collecting lymphatic vessels while controlling for transmural pressure. Using a previously developed ex vivo lymphatic perfusion system (ELPS) capable of independently controlling both transaxial pressure gradient and average transmural pressure on an isolated lymphatic vessel, we imposed a multitude of flow conditions on rat thoracic ducts, while controlling for transmural pressure and measuring diameter changes. By gradually increasing the imposed flow through a vessel, we determined the WSS at which the vessel first shows sign of contraction inhibition, defining this point as the shear stress sensitivity of the vessel. The shear stress threshold that triggered a contractile response was significantly greater at a transmural pressure of 5 cmH2O (0.97 dyne/cm(2)) than at 3 cmH2O (0.64 dyne/cm(2)). While contraction frequency was reduced when a steady WSS was applied, this inhibition was reversed when the applied WSS oscillated, even though the mean wall shear stresses between the conditions were not significantly different. When the applied oscillatory WSS was large enough, flow itself synchronized the lymphatic contractions to the exact frequency of the applied waveform. Both transmural pressure and the rate of change of WSS have significant impacts on the contractile response of lymphatic vessels to flow. Specifically, time-varying shear stress can alter the inhibition of phasic contraction frequency and even coordinate contractions, providing evidence that dynamic shear could play an important role in the contractile function of collecting lymphatic vessels.
鉴于已知淋巴管系统具有机械敏感性，我们试图研究动态壁面剪应力（WSS）对集合淋巴管的影响，同时控制跨壁压力。我们使用先前开发的能够独立控制离体淋巴管跨轴压力梯度和平均跨壁压力的体外淋巴灌注系统（ELPS），对大鼠胸导管施加多种流动条件，同时控制跨壁压力并测量直径变化。通过逐渐增加通过血管的施加流量，我们确定了血管首次出现收缩抑制迹象时的WSS，并将这一点定义为血管的剪应力敏感性。在5 cmH2O（0.97达因/cm²）的跨壁压力下引发收缩反应的剪应力阈值明显高于3 cmH2O（0.64达因/cm²）时。当施加稳定的WSS时，收缩频率降低，但当施加的WSS振荡时，这种抑制作用会逆转，尽管两种条件下的平均壁面剪应力没有显著差异。当施加的振荡WSS足够大时，血流本身会使淋巴收缩与施加波形的精确频率同步。跨壁压力和WSS的变化率对淋巴管对血流的收缩反应都有显著影响。具体而言，随时间变化的剪应力可以改变对相性收缩频率的抑制，甚至协调收缩，这表明动态剪应力可能在集合淋巴管的收缩功能中发挥重要作用。
