The main objective of these proposed investigations is to determine the time course of recovery from interstitial pulmonary edema. The several routes of clearance will be quantified but the main emphasize will on the newly-discovered mediastinal clearance pathway.
Our specific aims are: 1) to determine the rate at which interstitial edema liquid of high or low protein concentration is cleared from the lung, to test the hypothesis that edema liquid of high protein osmotic pressure, by limiting blood reabsorption, will be cleared less quickly than will edema of low protein osmotic pressure; 2) to quantify the routes of interstitial liquid clearance in various forms of interstitial pulmonary edema, to test the hypothesis that the mediastinal pathway is the principal route of interstitial edema clearance; and 3) to quantify the contribution of peribronchovascular interstitial edema to lung lymph flow, to test the hypothesis that there is little clearance via the lymphatic system. The data we obtain will clarify, quantitatively, the role of various pathways of lung interstitial liquid and protein flow. This will give scientists a better understanding of the total pathophysiology of various forms of pulmonary edema and will give physicians a better understanding of what to expect in terms of the natural history of recovery from edema, which will enable them to design new treatments that will enhance clearance. Experiments will be done in three species (sheep, goat, rabbit); each specifically necessary to provide the best solution to a particular problem, as well as to test the general interspecies applicability of the results.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL040891-02
Application #
3358196
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1988-07-01
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Serikov, V B; Jerome, E H (1997) Noninvasive measurements of cardiac output in sheep: an improved thermometry method. Med Eng Phys 19:618-29
Fukue, M; Serikov, V B; Jerome, E H (1996) Bronchial vascular reabsorption of low-protein interstitial edema liquid in perfused sheep lungs. J Appl Physiol 81:810-5
Jerome, E H; Enzan, K; Douguet, D et al. (1996) Chronic interleukin-2 treatment in awake sheep causes minimal or no injury to the lung microvascular barrier. J Appl Physiol 81:1730-8
Fukue, M; Serikov, V B; Jerome, E H (1994) Recovery from increased pressure or increased leakiness edema in perfused sheep lungs. J Appl Physiol 77:184-9
Lei, D; Jerome, E H; Douguet, D et al. (1994) Effects of interleukin-2 on the pulmonary microvasculature in anesthetized sheep. J Appl Physiol 76:909-15
Kambara, K; Longworth, K E; Serikov, V B et al. (1992) Effect of interstitial edema on lung lymph flow in goats in the absence of filtration. J Appl Physiol 72:1142-8