This application is for continued support of multidisciplinary clinical and basic research projects concerned with pulmonary edema and pleural effusion. The objectives are to obtain new knowledge about the pathophysiology of liquid and solute exchange in the lungs and pleural spaces and to use this knowledge to improve the diagnosis, treatment and prevention of pulmonary edema and pleural effusions. To achieve these objectives, there are six research components, one administrative component and a core laboratory that are integrated by a long-standing organizational plan. The most important specific aims of each project are as follows: 1: to develop and apply physiologic and biochemical tests that will identify from among the large number of patients at risk and who might have sustained acute lung injury, those who are actually destined to acquire clinical manifestations of pulmonary parenchymal damage; 2: To examine the roles played by complement-derived peptides and by polymorphonuclear leukocytes in the pathogenesis of certain forms of acute lung injury in sheep characterized by increased permeability pulmonary edema, especially that caused by infusions of endotoxin; 3: To quantify the turnover of liquid and protein in the pleural space to obtain a more complete understanding of pulmonary liquid and solute exchange; and 4: To quantify the mechanical factors affecting pleural liquid pressure and their relationships to pleural liquid exchange and lung static recoil. The administrative and laboratory cores will support all six of the scientific projects. The work will be carried out by a group of investigators with a long tradition of successful interaction and productivity.
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