Lymphangion coordination minimally affects mean flow in lymphatic vessels

Abstract

The lymphatic system returns interstitial fluid to the central venous circulation, in part, by the cyclical contraction of a series of "lymphangion pumps" in a lymphatic vessel. The dynamics of individual lymphangions have been well characterized in vitro; their frequencies and strengths of contraction are sensitive to both preload and afterload. However, lymphangion interaction within a lymphatic vessel has been poorly characterized because it is difficult to experimentally alter properties of individual lymphangions and because the afterload of one lymphangion is coupled to the preload of another. To determine the effects of lymphangion interaction on lymph flow, we adapted an existing mathematical model of a lymphangion (characterizing lymphangion contractility, lymph viscosity, and inertia) to create a new lymphatic vessel model consisting of several lymphangions in series. The lymphatic vessel model was validated with focused experiments on bovine mesenteric lymphatic vessels in vitro. The model was then used to predict changes in lymph flow with different time delays between onset of contraction of adjacent lymphangions (coordinated case) and with different relative lymphangion contraction frequencies (noncoordinated case). Coordination of contraction had little impact on mean flow. Furthermore, orthograde and retrograde propagations of contractile waves had similar effects on flow. Model results explain why neither retrograde propagation of contractile waves nor the lack of electrical continuity between lymphangions adversely impacts flow. Because lymphangion coordination minimally affects mean flow in lymphatic vessels, lymphangions have flexibility to independently adapt to local conditions.

Human thoracic duct in vitro: diameter-tension properties, spontaneous and evoked contractile activity

“…After washout from NE-KPSS to PSS, the vessels were allowed to rest for a minimum of 3 min before stretching to a new internal circumference. For data analysis, the diameter value for each duct where peak active tension was observed was ascribed as L 0 and the corresponding values expressed in relationship to it (L/L 0) (42). Second and third polynomial and exponential regression fit were applied for the total, active, and passive tension curves for each ring segment.…”

“…To maintain pumping and prevent overdistension, the LSMCs must be able to adapt their ability to propel fluid over a wide range of pressures and vessel diameters. In analogy with the heart, increased preload in animal lymphatic vessels has been observed to increase stroke volume and developed pressure (4,20,28,42).The active force produced by smooth muscle cells is directly related to how much they are stretched: this information is provided by the length-tension relationship for the specific cells of interest. Although the passive and active mechanical properties of LSMCs from animal collecting lymphatics have been reported (9, 45), there are no corresponding biomechanical data from human vessels.…”

“…To maintain pumping and prevent overdistension, the LSMCs must be able to adapt their ability to propel fluid over a wide range of pressures and vessel diameters. In analogy with the heart, increased preload in animal lymphatic vessels has been observed to increase stroke volume and developed pressure (4,20,28,42).…”

First-order approximation for the pressure-flow relationship of spontaneously contracting lymphangions

“…This analogy has proved to be particularly appropriate, since lymphangions respond to increased preload by increasing developed pressure and stroke work (both of which correspond in a way that is analogous to the FrankStarling effect) (2,23,27,34). However, unlike the heart, lymphatic vessels consist of many of these pumps in series, and the afterload of one lymphangion is coupled to the preload of the next (16).…”

“…The recurring analogies to both blood vessels and cardiac ventricles were recently leveraged to develop a physics-based mathematical model of a lymphangion (27,34). With the extension of the transmission line equation description of arteries (26,35), the resulting lymphangion model included the effects of lymph inertia and viscosity.…”