The objective of this study is to test a new optical method for measuring lung vascular filtration coefficient. The method does not employ radioactive tracers, and once verified, could eventually be used to follow a patient's progress and assess the efficacy of therapy. Intravascular proteins (primarily albumin) are labeled with indocyanine green (ICG). A step change in pulmonary outlet pressure is applied and the rate of change of ICG-protein is measured at the outlet with a densitometer. The transient ICG curve is analyzed to compute filtration coefficient. The theoretical analysis of the collected data is based on the application of conservation of mass in the microcirculation, and on the well established Starling Equation for transvascular filtration. The theory has been tested in two studies performed in vitro on water permeable fibers, and in two isolated dog lung studies. Computed filtration coefficients agree well with measured values in the in vitro studies, and are comparable with computed values based on the well-established weight gain method in isolated dog lungs. Additional in vitro studies are proposed to confirm these preliminary findings and to examine possible limitations on the theory. Densitometer modifications will allow ICG-protein and sulfhemoglobin labeled red cells to be monitored simultaneously, so that hematocrit transients which accompany a pressure step in blood perfused microvessels (Fahraeus effect) may be detected. Once the method has been thoroughly tested in vitro it will be compared with the weight change method in the blood-perfused isolated dog lung, where surface area and permeability changes can be induced. Finally, the optical method will be applied to unanesthetized sheep, and results compared to multiple indicator results and multiple pore model estimates of filtration coefficient. These studies should establish the suitability of the optical method for future applications in humans.
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