The general objectives of this proposal are: a) to examine several aspects of fluid and solute exchange in normal and acutely-injured lungs; b) to understand the alveolar-airway barrier in terms of alveolar fluid and protein clearance; c) to measure interstitial mechanics in relation to fluid movement and accumulation; d) to quantify the interactions of physical, neural and humoral factors on lung hemodynamics and lung fluid balance; and e) to establish the appropriateness of lung lymph for the experimental study of lung fluid balance. The studies to be conducted in fetal, newborn and adult sheep and also in dogs and rabbits include: 1) study of the pathophysiology of neutrophil-associated acute lung microvascular injury; 2) examination of active metabolic and passive hydrostatic mechanisms of alveolar fluid clearance; 3) determination of the quantitative anatomy, blood supply and physiology of the caudal mediastinal lymph node in sheep; 4) examination of physical and humoral factors involved in lung fluid and solute balance in the fetal and newborn lamb; 5) determination of the time course and site of liquid and protein exchange across the alveolar-airway barrier in the isolated lung; 6) clarification of the role of focal and diffuse central nervous system injury on lung fluid balance; 7) examination of the physical and humoral factors involved in lung fluid balance in normal and injured lungs in unanesthetized adult sheep; and 8) measurement of the mechanics of the lung's interstitium in relation to fluid balance.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL025816-12
Application #
3097903
Study Section
Heart, Lung, and Blood Research Review Committee A (HLBA)
Project Start
1980-06-01
Project End
1993-11-30
Budget Start
1992-01-03
Budget End
1992-11-30
Support Year
12
Fiscal Year
1992
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
Sone, Y; Nicolaysen, A; Staub Sr, N C (1997) Effect of particles on sheep lung hemodynamics parallels depletion and recovery of intravascular macrophages. J Appl Physiol 83:1499-507
Longworth, K E; Albertine, K H; Staub, N C (1996) Ultrastructural quantification of pulmonary intravascular macrophages in newborn and 2-week-old lambs. Anat Rec 246:238-44
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
Hastings, R H; Folkesson, H G; Petersen, V et al. (1995) Cellular uptake of albumin from lungs of anesthetized rabbits. Am J Physiol 269:L453-62
Carlton, D P; Cho, S C; Davis, P et al. (1995) Surfactant treatment at birth reduces lung vascular injury and edema in preterm lambs. Pediatr Res 37:265-70
Weinacker, A; Chen, A; Agrez, M et al. (1994) Role of the integrin alpha v beta 6 in cell attachment to fibronectin. Heterologous expression of intact and secreted forms of the receptor. J Biol Chem 269:6940-8
Folkesson, H G; Kheradmand, F; Matthay, M A (1994) The effect of salt water on alveolar epithelial barrier function. Am J Respir Crit Care Med 150:1555-63
Kheradmand, F; Folkesson, H G; Shum, L et al. (1994) Transforming growth factor-alpha enhances alveolar epithelial cell repair in a new in vitro model. Am J Physiol 267:L728-38

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