The lymphatic system consists of a network of vessels which return interstitial fluid and protein to the blood circulation. Lymphatic vessels can be divided into smaller units called lymphangions, which contain valves and cyclically contract. Under normal conditions, lymphangions can pump lymph up a n axial pressure gradient, much like the heart pumps blood. Also, like the heart, lymphangions a r e sensitive to both preload and afterload. T o describe contraction of the heart independent of preload and afterload, investigators developed the concept of time-varying elastance, which relates chamber pressure and volume in the time domain. To evaluate the applicability of this concept to lymphangions, we analyzed preliminary pressure-volume data from bovine mesenteric lymphangions in vitro. W e found that there were significant limitations to the applicability of the time-varying elastance concept-there is a high degree of variability in contraction strength and frequency, the end-diastolic pressure-volume relationship is highly nonlinear, and the values of maximum and minimum elastance are sensitive to pressure. Nonetheless, normalized elastance curves show a remarkable degree of consistency. Just as the lymphangion is the fundamental building block of the lymphatic system, this simple description of a Iymphangion can form a fundamental building block of a large-scale lymphatic system model.
Lymphatic vessels transport excess interstitial fluid from the low-pressure tissues to the higher pressure veins. The basic structural unit of lymphatic vessels is the lymphangion, a segment of the vessel separated by two unidirectional valves. Lymphangions cyclically contract like ventricles and can actively pump lymph. Lymphangions, as conduit vessels, also can act as arteries, and resist lymph flow. Functional parameters such as pressures, flow, and efficiency are determined by structural parameters like length, radius, and wall thickness. Since these structural parameters are unalterable experimentally, we developed a computational model to study the effect of a particular structural parameter, lymphangion length, to a particular functional variable, lymph flow. The model predicts that flow is a bimodal function of length, exhibiting an optimal length in the same order of magnitude as that observed experimentally. In essence, when the length to radius ratio is small, lymphangions act more like ventricles, where longer lengths yield greater chamber volume and thus lymph pumped. When the length to radius ratio is large, lymphangions act more like arteries, where longer lengths yield greater resistances to flow. This approach provides the means to explore how lymphatic vessel structure is optimized in a variety of conditions.
The 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 of adjacent lymphangions alters both preload and afterload of each lymphangion and thus mean lymph flow. To explore the effect of timing of contraction on lymph flow, we developed a computational model of a lymphatic vessel with lymphangions described by 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 edema, we found that flow was optimized when the lymphangions in the vessel were pumping with a very little time delay between their cycles. However the flow was reduced when the time delay between the contractions was reduced to zero. This preliminary work provides evidence for a critical role for coordination of lymphatic contraction.
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