The objective of this research are: 1) to obtain as complete a description as possible of the distributions of mean intravascular pressure, volume, and compliance from pulmonary artery to pulmonary vein with reference to alveolar and extraalveolar vessels, to vessel diameters and to vessels involved in gas exchange; 2) to determine some of the effects of passive mechanical factors and vasomotion on these distributions; and 3) to attempt to better understand the information content of the hemodynamic data (pressures, flows and volumes) obtained from measurements made outside the lungs and to maximize their utility for providing quantitative descriptions of the pulmonary microvascular structure and function under normal and pathophysiologic conditions. To fulfill these objectives, we will carry out experiments on isolated and in situ perfused dog lung lobes and on isolated perfused cat lungs. We will use indicator dilution (*low viscosity bolus, either dilution and 125I-serum albumin and 3HOH dilution), micropuncture, and vascular occlusion methods in experiments designed to determine the steady state arterial to venous distribution of vascular resistance compliance and volume according to vessel size and function. We will determine the influence of changing lung volume, vascular pressure and vasomotor tone (with particular attention to hypoxic vasoconstriction) on these distributions. To improve our understanding of the information content of the occlusion data we will carry out experiments designed to reveal the impact of the parallel heterogeneity among flow paths and the viscoelastic behavior of the vessels on interpretation of the data. We will also obtain a range of arterial occlusion responses in conjunction with the other hemodynamic measurements so that correlations between methods may help to reveal how the arterial occlusion data can contribute to the evaluation of pulmonary microvascular hemodynamics. Mathematical models will be used in conjunction with the experimental data to assist in the achievement of these aims. To improve our understanding of the information content of the low viscosity bolus data, we will examine the influence of realistic deviations from the low viscosity bolus model assumptions using a morphometric model of the cat lung in which various relevant parameters can be adjusted to determine their effects on the calculated distributions.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Method to Extend Research in Time (MERIT) Award (R37)
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Medical College of Wisconsin
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