A lumped parameter model of mechanically mediated acute and long-term adaptations of contractility and geometry in lymphatics for characterization of lymphedema

Abstract

A primary purpose of the lymphatic system is to transport fluid from peripheral tissues to the central venous system in order to maintain tissue fluid balance. Failure to perform this task results in lymphedema marked by swelling of the affected limb as well as geometric remodeling and reduced contractility of the affected lymphatic vessels. The mechanical environment has been implicated in the regulation of lymphatic contractility, but it is unknown how changes in the mechanical environment are related to loss of contractile function and remodeling of the tissue. The purpose of this paper is to introduce a new theoretical framework for acute and long-term adaptations of lymphatic vessels to changes in mechanical loading. This theoretical framework combines a simplified version of a published lumped parameter model for lymphangion function and lymph transport, a published microstructurally-motivated constitutive model for the active and passive mechanical behavior of isolated rat thoracic ducts, and novel models for acute mechanically-mediated vasoreactive adaptations and long-term volumetric growth to simulate changes in muscle contractility and geometry of a single isolated rat thoracic duct in response to a sustained elevation in afterload. The illustrative examples highlight the potential role of the mechanical environment in the acute maintenance of contractility and long-term geometric remodeling, presumably aimed at meeting fluid flow demands while also maintaining mechanical homeostasis. Results demonstrate that contractility may adapt in response to shear stress to meet fluid flow demands and show that pressure-induced long-term geometric remodeling may attenuate these adaptations and reduce fluid flow. This modeling framework and illustrative simulations help suggest relevant experiments that are necessary to accurately quantify and predict the acute and long term adaptations of lymphangions to altered mechanical loading.

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