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.
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