Multiscale modeling of the lymphatic system relates lymphangion properties to edema formation and resolution

Abstract

The central challenge of lymphatic research is to relate what is known about contractile lymphangions to the formation and resolution of edema. Because lymphatic system function emerges from the complex interaction of lymphangions that act both like blood vessels and cardiac ventricles, we have developed two complementary modeling approaches. First, we developed a lymphangion model that merges classical hemodynamics with the time‐varying elastance model of ventricles. By theoretically connecting lymphangions, we discovered that lymphangion structure optimizes stroke work, and lymphatic networks optimize lymph flow. Second, we developed an organ‐level compartment model that incorporates microvascular water and protein flux, interstitial storage capacity, and lymphatic drainage. This approach revealed that interstitial volume is a simple function of microvascular permeability, interstitial compliance, and the effective lymphatic resistance, RL. Merging these two modeling approaches provides a critical link between local lymphangion properties and global lymphatic function characterized by RL. Multiscale modeling thus provides a strategy to translate basic lymphatic biology to clinical edema research.