SUMMARY

The lymphatic system is crucial for normal physiologic function, performing such basic functions as maintaining tissue fluid balance, trafficking immune cells, draining interstitial proteins, as well as transporting fat from the intestine to the blood. To perform these functions properly, downstream vessels (known as collecting lymphatics) actively pump like the heart to dynamically propel lymph from the interstitial spaces of the body to the blood vasculature. However, despite the fact that lymphatics are so important, there exists very little knowledge regarding the details of this active pumping. Specifically, it is known that external mechanical loading such as fluid shear stress and hoop stress due to transmural pressure affect pumping response; however, anything other than simple, static relationships remain unknown. Because mechanical environment has been implicated in lymphatic diseases such as lymphedema, understanding these dynamic relationships between lymphatic pumping and mechanical loading during normal function are crucial to grasp before these pathologies can be unraveled. For this reason, this proposal describes several tools developed to study lymphatic function in response to the unique mechanical loads these vessels experience both in vitro and ex vivo. Moreover, several nonlinear identification methodologies are described for elucidating the dynamic response of the intrinsic lymphatic pump to mechanical stimuli, specifically fluid shear stress and transmural pressure.