Probing the effect of morphology on lymphatic valve dynamic function

Abstract

The lymphatic system is vital to the circulatory and immune systems, performing a range of important functions such as transport of interstitial fluid, fatty acid, and immune cells. Lymphatic vessels are composed of contractile walls and lymphatic valves, allowing them to pump lymph against adverse pressure gradients and to prevent backflow. Despite the importance of the lymphatic system, the contribution of mechanical and geometric changes of lymphatic valves and vessels in pathologies of lymphatic dysfunction, such as lymphedema, is not well understood. We develop a fully coupled fluid-solid, three-dimensional computational model to interrogate the various parameters thought to influence valve behavior and the consequences of these changes to overall lymphatic function. A lattice Boltzmann model is used to simulate the lymph, while a lattice spring model is used to model the mechanics of lymphatic valves. Lymphatic valve functions such as enabling lymph flow and preventing backflow under varied lymphatic valve geometries and mechanical properties are investigated to provide an understanding of the function of lymphatic vessels and valves. The simulations indicate that lymphatic valve function is optimized when valves are of low aspect ratio and bending stiffness, so long as these parameters are maintained at high enough values to allow for proper valve closing. This suggests that valve stiffening could have a profound effect on overall lymphatic pumping performance. Furthermore, dynamic valve simulations showed that this model captures the delayed response of lymphatic valves to dynamic flow conditions, which is an essential feature of valve operation. Thus, our model enhances our understanding of how lymphatic pathologies, specifically those exhibiting abnormal valve morphologies such as has been suggested to occur in cases of primary lymphedema, can lead to lymphatic dysfunctions.

A novel mouse tail lymphedema model for observing lymphatic pump failure during lymphedema development

“…Alternatively, the reductions in transport and pumping pressure could have been caused by changes in valve function resulting in an inability to maintain unidirectional flow and decreasing pumping capacity. We have shown that the valve length to vessel diameter ratio is an important determinant of pump efficacy 43 and thus an increase in vessel lumen diameter due to remodeling without a comparable increase in the valve length would reduce pump function. Under modest mechanical loading, the valves of isolated lymphatic vessel chains have been demonstrated to “lock” resulting in an inability to pump flow against an adverse pressure gradient 44 .…”

Fluid pumping of peristaltic vessel fitted with elastic valves

“…Each leaflet is created from an intersecting plane between an axisymmetric vessel and a plane that cuts through the vessel at an angle (Ballard et al. 2018). Thus, the elastic leaflets are initially flat.…”

“…We recently conducted three-dimensional simulations using a fully coupled fluid–structure interaction model to probe the behaviour of compliant lymphatic valves in a fluid flow (Ballard et al. 2018). Valves with different geometries and mechanics were placed in a rigid axisymmetric vessel and flow was induced by applying oscillating or unidirectional pressure gradients.…”

Renal Lymphatics: Anatomy, Physiology, and Clinical Implications

“…Primary lymphatic disorders are varied and the majority of reported cases do not have an identified mechanism. In most disorders, defects in relation to lymphatic valves are the cause of lymphatic dysfunction (Ballard et al, 2018). These patients generally present with bilateral lower limb lymphedema (e.g., Nonne-Milroy lymphedema, lymphedema praecox).…”