Structural and functional characterization of a lymphatic system using computational and experimental approaches

The lymphatic system returns interstitial fluid back to the blood circulation. They have a network of vessels with numerous lymphangions, the segment of lymphatic vessel between two unidirectional valves. The valves aid in transporting lymph against a pressure gradient, in addition to the lymphangion pump which exhibit cyclical variations in diameter. Like blood vessels, baseline lymphatic tone is regulated with changes in transmural pressure; however, the transient response of lymphatic diastolic diameter following changes in transmural pressure has not been studied. The lymphangion pump is often described using cardiac analogies. However, since an active system empties into another active system in a lymphatic vessel, the analogy cannot characterize the principles governing optimal lymphatic vessel function. Furthermore, to optimize lymph flow there is also a need to characterize the lymphatic network structure. To characterize the transient diameter response of lymphatic segment, we used post-nodal bovine mesenteric lymphangions in an isobaric preparation and measured the diameter response to a step change in pressure. An immediate active reduction in enddiastolic diameter with each incremental increase in pressure was observed. To identify the principles governing optimal lymphatic vessel function, we applied the result obtained from optimizing the interaction of the heart-arterial system to measured lymphangion pressure-volume relationships. We assumed that the slope of end systolic pressure-volume relationship (Emax) is equal to the slope of end-diastolic relationship (Emin) above a cutoff pressure and Emax>Emin below the cutoff pressure. Unlike the heart, we found that stroke work is not optimized when Emax = Emin. However, there is a region where lymph flow is insensitive to changes in transmural pressure. To characterize the lymphatic network structure, we used an approximation of time-varying elastance model. We found there is an optimal length for the lymphangion when it produces maximal flow. To develop a fractal network model, we determined the ratio of radius and ratio of length of lymphangion at a confluence. Using conservation of mass and certain simplifying assumptions, we showed that the ratio of radius, as well as ratio of length of upstream lymphangion, to the downstream lymphangion at confluences is 1.26.