Flooding of the alveoli is the most serious complication of pulmonary edema. Gas exchange can only be sustained if fluid is removed in some way from the airspaces of the lungs. In this project, studies will be conducted of fluid and solute reabsorption from isolated rat and rabbit lungs filled with fluid. We have obtained evidence that the pulmonary epithelium rapidly consumes glucose in the airspaces, producing a significant osmotic difference between the airspaces and perfusate which favors fluid reabsorption by the vasculature. We also found that terbutaline accelerates fluid reaborption from the airspaces appear to inhibit reaborption in a manner which suggests that the epithelium activity reabsorbs Na+ from the airspaces. The effects upon fluid and solute transport of replacing glucose in the airways with nonmetabolizable substances will be determined. In addition, Na+ and Cl- will be replaced with alternative ions and the effects of a variety of metabolic and transport inhibitors will be studied. A comparison will be made of the relative efficiency with which fluid is extracted from edematous lungs by glucose and a variety of other solutes and the solute content of the extracted fluids will be determined. Fluid transport in lungs which have been made tolerant to 100% oxygen by prior exposure to 85% oxygen will be compared to fluid transport by normal lungs. Radioaerosol studies of regional pulmonary epithelial permeability will be conducted with 2 indicators simultaneously in normal subjects and patients with a variety of pulmonary disorders. The selectivity of the epithelium to indicators of different molecular weight will be determined to see if a more detailed knowledge of the permeability properties of the epithelium will permit distinction between different forms of lung injury. The double indicator approach will also be used to correct clearance curves for accumulation of radioactivity in the blood and chest wall. This will permit use of later portions of the washout curve of indicators from the lungs.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
7R01HL018606-15
Application #
3335641
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1978-09-01
Project End
1991-04-30
Budget Start
1989-09-25
Budget End
1991-04-30
Support Year
15
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Medical College of Wisconsin
Department
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Effros, R M; Jacobs, E R; Schapira, R M et al. (1999) Increasing airway pressures can promote transvascular edema reabsorption. Chest 116:30S-31S
Lin, W; Jacobs, E; Schapira, R M et al. (1998) Stop-flow studies of distribution of filtration in rat lungs. J Appl Physiol 84:47-52
Effros, R M; Schapira, R; Presberg, K et al. (1998) Stop-flow studies of solute uptake in rat lungs. J Appl Physiol 85:986-92
Effros, R M; Darin, C; Jacobs, E R et al. (1997) Water transport and the distribution of aquaporin-1 in pulmonary air spaces. J Appl Physiol 83:1002-16
Schapira, R M; Ghio, A J; Effros, R M et al. (1995) Hydroxyl radical production and lung injury in the rat following silica or titanium dioxide instillation in vivo. Am J Respir Cell Mol Biol 12:220-6
Effros, R M; Murphy, C; Hacker, A et al. (1994) Reduction and uptake of methylene blue from rat air spaces. J Appl Physiol 77:1460-5
Schapira, R M; Ghio, A J; Effros, R M et al. (1994) Hydroxyl radicals are formed in the rat lung after asbestos instillation in vivo. Am J Respir Cell Mol Biol 10:573-9
Effros, R M; Hacker, A; Jacobs, E et al. (1994) Continuous measurements of changes in pulmonary capillary surface area with 201Tl infusions. J Appl Physiol 77:2093-103
Effros, R M; Jacobs, E; Hacker, A et al. (1993) Reversible inhibition of urea exchange in rat hepatocytes. J Clin Invest 91:2822-8
Feng, N H; Hacker, A; Effros, R M (1992) Solute exchange between the plasma and epithelial lining fluid of rat lungs. J Appl Physiol 72:1081-9

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