The pulmonary interstitium is a duct which serves to drain microvascular filtrate from the lung. Thus its properties are important to the understanding of how normal fluid balance is maintained and of the pathogenesis of pulmonary edema. Several mechanical fores may have an important role in determining pulmonary interstitial fluid pressure. Such forces include 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. This is best accomplished by a combined analytical and experimental approach. We have developed a method of isolating a short length of pulmonary interstitium held fixed between silicon rubber. This method allowed us to study the pressure-flow behavior of the interstitium surrounding larger pulmonary vessels, and to determine the hydraulic resistance and thickness of the interstitial tissue. The principles of continuum solid mechanics were applied to quantify the relationship between boundary forces and interstitial pressure. Darcy's law for a permeable material was used to quantify the fluid properties of the interstitial tissue. Now we propose to study the hydraulic resistance of the interstitium to the bulk flow of protein, dextran and other macromolecules. We wi sh to separate the effects of fluid viscosity from the effects of permeability. We will study the effects of albumin and dextran concentration on interstitial conductivity. Since the glycosaminoglycans, hyaluronic acid and heparan sulphate, are major constituents of interstitium, we will study the effects of hyaluronidase and heparanase on interstitial conductivity. We have recently shown that alveolar liquid pressure is a good measure of perivenular interstitial pressure. We will study the relationship of alveolar liquid pressure and lung volume in nonedematous and kerosene and oil-washed air-filled lungs to determine the relationship between alveolar liquid pressure and alveolar surface tension. Isolated sheet lungs we found that the velocities of surface waves are directly related to longitudinal and shear waves. These wave velocities are functions of the bulk and shear moduli of lung parenchyma and the density of the lung. We will test the relationship between the velocities of surface waves and lung density brought about by changes in vascular volume and interstitial edema. This is a potential method for measuring the sequence of pulmonary edema formation in situ.
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