The pulmonary interstitium is a pathway which drains microvascular filtrate from the lung. Thus its properties are important to the understanding how normal fluid balance is maintained and of the pathogenesis of pulmonary edema. Several mechanical forces may have an important role in determining pulmonary interstitial fluid pressure. Such forces include the parenchymal stress acting on the outside of blood vessels and bronchi, alveolar surface tension acting on alveolar walls and viscous forces arising from fluid flow within the interstitium. This project will quantify these forces more precisely in an effort to understand the mechanisms underlying pulmonary edema formation. The focus is on three related areas: the direct measurement of interstitial conductivity, the direct measurement of interstitial and alveolar liquid pressures, and the measurement of lung stress waves as a function of edema formation. A method of isolating a short length of pulmonary interstitium held fixed between silicon rubber was developed to study the pressure-flow behavior of the interstitium surrounding large pulmonary vessels and interstitial fluid conductivity. The effects of hydration, protein concentration, fluid viscosity, electric charge, and hyaluronidase on interstitial conductivity were determined. Darcy's law for a permeable material was used to quantify the fluid properties of the interstitial tissue. However, preliminary studies indicated a protein concentration gradient in the interstitium. The goal is to establish the importance of protein sieving in pulmonary interstitium. Accordingly, the effective reflection coefficient and permeability-surface area product of the interstitium to the flow of protein will be measured in interstitial segments. Longitudinal gradients in protein concentration will be measured during interstitial cuff growth in liquid inflated lungs. The effect of edema formation on alveolar liquid pressure will be measured in intact rabbits. These studies will establish the importance of alveolar surface tension on alveolar liquid balance and will test the validity of previous measurements made in isolated lungs. Stress wave studies in isolated lungs and in the intact chest have shown the feasibility of generating and measuring these waves as an indicator of pulmonary edema formation. Methods for the generation and detector of lung stress waves from the chest surface will be developed in intact pig experiments. The long term goal is to develop a noninvasive method for detecting clinical pulmonary edema.
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