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  1. null (Ed.)
    Using numerical simulations, we probe the fluid flow in an axisymmetric peristaltic vessel fitted with elastic bi-leaflet valves. In this biomimetic system that mimics the flow generated in lymphatic vessels, we investigate the effects of the valve and vessel properties on pumping performance of the valved peristaltic vessel. The results indicate that valves significantly increase pumping by reducing backflow. The presence of valves, however, increases the viscous resistance, therefore requiring greater work compared to valveless vessels. The benefit of the valves is the most significant when the fluid is pumped against an adverse pressure gradient and for low vessel contraction wave speeds. We identify the optimum vessel and valve parameters leading to the maximum pumping efficiency. We show that the optimum valve elasticity maximizes the pumping flow rate by allowing the valve to block the backflow more effectively while maintaining low resistance during the forward flow. We also examine the pumping in vessels where the vessel contraction amplitude is a function of the adverse pressure gradient, as found in lymphatic vessels. We find that, in this case, the flow is limited by the work generated by the contracting vessel, suggesting that the pumping in lymphatic vessels is constrained by the performance of the lymphatic muscle. Given the regional heterogeneity of valve morphology observed throughout the lymphatic vasculature, these results provide insight into how these variations might facilitate efficient lymphatic transport in the vessel's local physiologic context. 
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  2. Abstract

    Lymphedema, a disfiguring condition characterized by an asymmetrical swelling of the limbs, is suspected to be caused by dysfunctions in the lymphatic system. A possible source of lymphatic dysfunction is the reduced mechanosensitivity of lymphangions, the spontaneously contracting units of the lymphatic system. In this study, the entrainment of lymphangions to an oscillatory wall shear stress (OWSS) is characterized in rat thoracic ducts in relation to their shear sensitivity. The critical shear stress above which the thoracic ducts show a substantial inhibition of contraction was found to be significantly negatively correlated to the diameter of the lymphangion. The entrainment of the lymphangion to an applied OWSS was found to be significantly dependent on the difference between the applied frequency and the intrinsic frequency of contraction of the lymphangion. The strength of the entrainment was also positively correlated to the applied shear stress when the applied shear was less than the critical shear stress of the vessel. The ejection fraction and fractional pump flow were also affected by the difference between the frequency of the applied OWSS and the vessel's intrinsic contraction frequency. The results suggest an adaptation of the lymphangion contractility to the existing oscillatory shear stress as a function of its intrinsic contractility and shear sensitivity. These adaptations might be crucial to ensure synchronized contraction of lymphangions through mechanosensitive means and might help explain the lymphatic dysfunctions that result from impaired mechanosensitivity.

     
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  3. Key points

    We present the firstin vivoevidence that lymphatic contraction can entrain with an external oscillatory mechanical stimulus.

    Lymphatic injury can alter collecting lymphatic contractility, but not much is known about how its mechanosensitivity to external pressure is affected, which is crucial given the current pressure application methods for treating lymphoedema.

    We show that oscillatory pressure waves (OPW), akin to intermittent pneumatic compression (IPC) therapy, optimally entrain lymphatic contractility and modulate function depending on the frequency and propagation speed of the OPW.

    We show that the OPW‐induced entrainment and contractile function in the intact collecting lymphatics are enhanced 28 days after a contralateral lymphatic ligation surgery.

    The results show that IPC efficacy can be improved through proper selection of OPW parameters, and that collecting lymphatics adapt their function and mechanosensitivity after a contralateral injury, switching their behaviour to a pump‐like configuration that may be more suited to the altered microenvironment.

    Abstract

    Intermittent pneumatic compression (IPC) is commonly used to control the swelling due to lymphoedema, possibly modulating the collecting lymphatic function. Lymphoedema causes lymphatic contractile dysfunction, but the consequent alterations in the mechanosensitivity of lymphatics to IPC is not known. In the present work, the spatiotemporally varying oscillatory pressure waves (OPW) generated during IPC were simulated to study the modulation of lymphatic function by OPW under physiological and pathological conditions. OPW with three temporal frequencies and three propagation speeds were applied to rat tail collecting lymphatics. The entrainment of the lymphatics to OPW was significantly higher at a frequency of 0.05 Hz compared with 0.1 Hz and 0.2 Hz (P = 0.0054 andP = 0.014, respectively), but did not depend on the OPW propagation speed. Lymphatic function was significantly higher at a frequency of 0.05 Hz and propagation speed of 2.55 mm/s (P = 0.015). Exogenous nitric oxide was not found to alter OPW‐induced entrainment. A contralateral lymphatic ligation surgery was performed to simulate partial lymphatic injury in rat tails. The intact vessels showed a significant increase in entrainment to OPW, 28 days after ligation (compared with sham) (P = 0.016), with a similar increase in lymphatic transport function (P = 0.0029). The results suggest an enhanced mechanosensitivity of the lymphatics, along with a transition to a pump‐like behaviour, in response to a lymphatic injury. These results enhance our fundamental understanding of how lymphatic mechanosensitivity assists the coordination of lymphatic contractility and how this might be leveraged in IPC therapy.

     
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