Lymphatic Functional Adaptations to Prolonged Changes in Mechanical Stimuli



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Fluid drainage via the lymphatics prevents swelling due to excess fluid in interstitial space. Since interstitial fluid volume can vary dramatically, the function of lymphangions are rather dynamic so that they can contend with the wide ranges of lymph flow and pressure. Sharing with blood vessels an acute sensitivity to mechanical stresses, lymphangions could be expected to be similarly sensitive to prolonged changes in transmural pressure and flow. The purpose of this research was to quantify the adaptation of lymphangions to prolonged alterations in lymph hydrodynamics and to investigate how adaptation of individual lymphangions acts together within a network to affect the regulation of lymph flow.

In project I, bovine postnodal mesenteric lymphatic vessels were partially occluded for three days, which divided the vessel into two segments. Both segments, therefore, were exposed to the same flow but different transmural pressures. In project II, an isometric preparation was employed to study developed wall tension in lymphangions exposed to mesenteric venous hypertension. In project III, an analytical model of a symmetrical lymphatic network was developed to investigate how its pressure-flow relationship emerges from the complex interaction of its pumping lymphangions.

Results from this research indicate that lymphangions become stronger pumps when exposed to prolonged increases in transmural pressure, but exposure to prolonged venous hypertension attenuates lymphangion pumping. The main mechanism for lymphangion adaptation is the alteration of preload-dependent maximal tension developed by lymphatic muscle. Lower cytosolic Ca2+ concentration is likely to be the underlying cause for weaker developed tension. The analytical model suggests that the ratio of lymphangion systolic contractility to diastolic stiffness results in a differential response of lymph flow to changes in inlet and outlet pressures. This differential sensitivity to inlet and outlet pressures allows homeostatic responses to both microvascular and venous hypertension, and provides a framework for interpreting the functional implications of chronic lymphangion adaption.