The objectives of this project are to continue to develop and test theories of blood-tissue-lymph fluid and macromolecule transport, and to apply these to measurements of lung transvascular exchange. We shall examine critically the assumptions of our current theory and evaluate its utility in the interpretation of complex injuries to the lung vasculature and the actions of therapies aimed at preventing or reversing those injuries. We shall extend the theory so that it can be used to analyze protein flux data which has been collected using a minimally invasive external detection system, intended to simulate potential clinical applications of the method, and validate the method by direct comparison with lymph data. Various methods of normalizing transport coefficients computed from externally detected transvascular protein flux will be compared with normalization by dry lung weight. We propose to examine the importance of solute and membrane electrical charge on the transcapillary movement of fluid and solutes. We will seek specific additions and enhancements to our current methods of protein analysis so that we can increase the number of different proteins analyzed, and improve the precision of each measurement. In addition we will measure interstitial volume, protein excluded volume, and the fraction of lung lymph which passes through the cannulated lymphatic, enabling us to study how these factors affect the dynamics of fluid and macromolecular exchange.
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