Mechanics of interstitial-lymphatic fluid transport: theoretical foundation and experimental validation

Interstitial fluid movement is intrinsically linked to lymphatic drainage. However, their relationship is poorly understood. and associated pathologie s are mostly untreatable. In this work we test the hypothesis that bulk tis sue fluid movement can be evaluated in situ and described by a linear bipha sic theory which integrates the regulatory function of the lymphatics with the mechanical stresses of the tissue. To accomplish this, we develop a nov el experimental and theoretical model using the skin of the mouse tail. We then use the model to demonstrate how interstitial-lymphatic fluid movement depends on a balance between the elasticity, hydraulic conductivity, and l ymphatic conductance as well as to demonstrate how chronic swelling (edema) alters the equipoise between tissue fluid balance parameters. Specifically , tissue fluid equilibrium is perturbed with a continuous interstitial infu sion of saline into the tip of the tail. The resulting gradients in tissue stress are measured in terms of interstitial fluid pressure using a servo-n ull system. These measurements are then fit to the theory to provide in viv o estimates of the tissue hydraulic conductivity, elastic modulus, and over all resistance to lymphatic drainage. Additional experiments are performed on edematous tails to show that although chronic swelling causes an increas e in the hydraulic conductivity, its greatly increased distensibility (due to matrix remodeling) dampens the driving forces for fluid movement and lea ds to fluid stagnation. This model is useful for examining potential treatm ents for edema and lymphatic disorders as well as substances which may alte r tissue fluid balance and/or lymphatic drainage. (C) 1999 Elsevier Science Ltd. All rights reserved.