Computational simulations of the effects of gravity on lymphatic transport

Abstract

Physical forces, including mechanical stretch, fluid pressure and shear forces alter lymphatic vessel contractions and lymph flow. Gravitational forces can affect these forces, resulting in altered lymphatic transport, but the mechanisms involved have not been studied in detail. Here, we combine a lattice Boltzmann-based fluid dynamics computational model with known lymphatic mechanobiological mechanisms to investigate the movement of fluid through a lymphatic vessel under the effects of gravity that may either oppose or assist flow. Regularly spaced, mechanical bi-leaflet valves in the vessel enforce net positive flow as the vessel walls contract autonomously in response to calcium and nitric oxide (NO) levels regulated by vessel stretch and shear stress levels. We find that large gravitational forces opposing flow can stall the contractions, leading to no net flow, but transient mechanical perturbations can reestablish pumping. In the case of gravity strongly assisting flow, the contractions also cease due to high shear stress and NO production, which dilates the vessel to allow gravity-driven flow. In the intermediate range of oppositional gravity forces, the vessel actively contracts to offset nominal gravity levels or to modestly assist the favorable hydrostatic pressure gradients.

A dual-clock-driven model of lymphatic muscle cell pacemaking to emulate knock-out of Ano1 or IP3R

“…However, many of the data that would be needed for a mechanistically detailed model have simply not yet been measured for the LMC. Whole topics have yet to be contemplated experimentally, such as the possible dependence of LMC pacemaker parameter values on matters affecting the mechanical load that the LMC experiences, including gravity ( Olszewski and Engeset, 1980 ; Gashev et al, 2006 ; Li et al, 2022 ), location relative to the high hydraulic resistance presented by a lymph node ( Browse et al, 1984 ), etc. Our approach in this paper and previously has been to add mechanistic detail as required based on the given experimental data.…”

“…Only the intrinsic contractile activity can be regulated, and so it is essential for the matching of lymph transport to demand as represented by the filling state of the initial lymphatics ( Scallan et al, 2012 ), itself a result of the extent of blood capillary extravasation of fluid. The extent of the required contractile activity is also a function of posture, which may set up adverse hydrostatic pressure gradients ( Zawieja, 2009 ; Li et al, 2022 ). Higher pressure in the contractile collecting lymphatics leads to more frequent contractions; this is pressure-dependent chronotropy ( McHale and Roddie, 1976 ; Benoit et al, 1989 ; Zawieja et al, 1993 ).…”

A Multiresolution Approach with Method-Informed Statistical Analysis for Quantifying Lymphatic Pumping Dynamics

“…In clinical settings, it is common to elevate the lower part of a patient’s body above their head in some surgical procedures, which exposes lower extremity lymphatic vessels to favorable hydrostatic pressure gradients and head-and-neck lymphatics to unfavorable pressure gradients. Experiments simulating the effects of microgravity on lymphatic contractility, along with computational modeling, also suggest that gravity alters lymphatic contractility[50, 51]. In the present study, we utilized NIRF imaging and designed a specialized microscope fixture to investigate the effects of gravity on lymphatic contractility.…”

Computational fluid dynamic modeling of the lymphatic system: a review of existing models and future directions

“…A few studies have presented 2D lymphangion models. Li et al ( 2019 , 2022 ) published models including an initial lymphatic vessel and multiple collecting lymphangions with valves embedded in porous tissue. The model of Li et al ( 2019 ) was similar to the work of Contarino and Toro ( 2018 ), where the contraction and relaxation of collecting vessels were passively affected by fluid pressure, while intracellular Ca 2+ fluxes drove active contractions.…”

“…Furthermore, when there was elevated tissue fluid pressure or reduced lymphatic pressure at the system’s outlet, it led to increased shear stress and higher levels of NO, which inhibits contractions. Later, Li et al ( 2022 ) used their computational platform to explain the effects of gravitational forces on lymphatic drainage. They estimated the changes in lymphatic drainage when the gravitational force assisted or opposed flow.…”