Effects of dynamic shear and transmural pressure on wall shear stress sensitivity in collecting lymphatic vessels

Effects of dynamic shear and transmural pressure on wall shear stress sensitivity in collecting lymphatic vessels
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DOI:
10.1152/ajpregu.00342.2014
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发表时间:
2015-11-01
影响因子:
2.8
通讯作者:
Dixon, J. Brandon
Dixon, J. Brandon
中科院分区:
医学3区
文献类型:
--
作者:
Kornuta, Jeffrey A.;Nepiyushchikh, Zhanna;Dixon, J. Brandon

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鉴于已知的机械敏感性的淋巴管,我们试图研究动态壁切应力(WSS)的影响,收集淋巴管,同时控制跨壁压。使用先前开发的离体淋巴灌注系统(ELPS)能够独立地控制轴向压力梯度和平均跨壁压力对一个孤立的淋巴管,我们施加了大量的流动条件对大鼠胸导管,同时控制跨壁压力和测量直径的变化。通过逐渐增加通过血管的施加流量,我们确定了血管首次显示收缩抑制迹象的WSS,将该点定义为血管的剪切应力敏感性。触发收缩反应的剪切应力阈值在5 cmH(2)O(0.97 dyne/cm(2))的跨壁压下显著大于3 cmH(2)O(0.64 dyne/cm(2))。虽然收缩频率降低时,一个稳定的WSS被施加,这种抑制被逆转时,所施加的WSS振荡,即使条件之间的平均壁面剪应力没有显着差异。当所施加的振荡WSS足够大时,流动本身使淋巴收缩与所施加的波形的精确频率同步。跨壁压和WSS的变化率对淋巴管对血流的收缩反应有显著影响。具体而言,随时间变化的剪切力可以改变相位收缩频率的抑制,甚至协调收缩,提供证据表明,动态剪切可能在集合淋巴管的收缩功能中发挥重要作用。
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 cmH(2)O (0.97 dyne/cm(2)) than at 3 cmH(2)O (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.