Browsing by Author "Madabushi Venugopal, Arun"
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Item A computational approach to study the effect of multiple lymphangion coordination on lymph flow(Texas A&M University, 2005-11-01) Madabushi Venugopal, ArunThe lymphatic system acts to return fluid from the interstitial space back into the blood circulation. In normal conditions, lymphangions, the segment of lymphatic vessel in between valves, cyclically contract and can pump lymph from low pressure tissues to the higher-pressure veins of the neck. With edema, however, this pressure gradient can reverse, and the role of contraction is less clear. Like ventricles, lymphangions are sensitive to both preload and afterload. Unlike ventricles, lymphangions are arranged in series, so that the outlet pressure of one lymphangion becomes the inlet pressure of another. Anything that alters the relative timing and frequency of adjacent lymphangions alters both preload and afterload of each lymphangion and thus mean lymph flow. To explore the effect of timing and frequency of contraction on lymph flow, we developed a computational model of a lymphatic vessel with lymphangions described by the classic description of time-varying elastance. When pumping up a pressure gradient, as in normal conditions, or when pumping down a pressure gradient, as in some cases of edema, we found that flow was optimized when the lymphangions in the vessel were pumping with a very short time delay between their cycles, and the flow was reduced when the time delay between the contractions was reduced to zero. However, a difference in frequency between adjacent lymphangions alters instantaneous flow but does not affect mean flow. These results suggest an important role for the timing of the contraction in optimizing lymph flow. However, a difference in frequencies between adjacent lymphangions has little effect on altering lymph flow, suggesting that tight control of lymphangion coordination may not be critical for lymphatic function.Item Structural and functional characterization of a lymphatic system using computational and experimental approaches(2009-05-15) Madabushi Venugopal, ArunThe 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.