This application is a proposal for the investigation of lung microvascular filtration by the direct micropuncture technique. Two general aims govern this proposal: first, to verify that filtration varies longitudinally along the microvascular tree, second, to quantify hydraulic conductance and macromolecular flux across the single lung microvessel. A major new experiment concerns determination of transmicrovascular liquid flux in single lung microvessels. We will modify the split-drop technique to directly characterize filtration and sieving in single 30 Mu arterioles and venules to determine the effects of intravascular protein content, macromolecular charge and mediators on microvascular liquid flux. In other experiments we will develop the intact dog lung preparation for intervascular pressure measurement. In the excised dog lung, we will compare microvascular pressures measured by the micropuncture, the occlusion and the isogravimetric techniques. In addition, we plan to determine the effects of blood flow, and of several mediators on microvascular pressure. With regard to interstitial liquid pressure, we will determine the arterio-venous distribution, and the effects of lung inflation. Using chemical analyses of nanoliter volumes of interstitial fluid directly sampled by micropuncture, we will explore interstitial liquid protein composition to deduce interstitial protein osmotic pressure and the profile of interstitial macromolecular sieving. Using our combined data we will estimate membrane coefficients which quantify microvascular flux of water and macromolecules. The results of this investigation will elucidate fundamental mechanisms in the regional control of lung microvascular permeability and will promote our understanding of the fundamental processes of pulmonary edema.
