Pulmonary edema and pleural effusions often compromise lung function in critically ill patients. These patients often have elevated pulmonary vascular pressures and elevated vena caval (central venous) pressures. It is well documented that elevated pulmonary vascular pressures cause edema and they may cause pleural effusions. Recent preliminary data indicate that 1) increased superior vena caval pressure may slow lymph flow from the lungs and pleural space and thus cause pleural effusions, 2) increased pulmonary vascular pressure and superior vena caval pressure have synergistic effects in producing edema and effusions and 3) the effects of increased pressures may be apparent only after several days of elevated pressures. This last point is important because many critically ill patients experience several days of increased pressures whereas most experiments to investigate edema and effusions have lasted only a few hrs. This proposal is to investigate the development of pulmonary edema and pleural effusions in unanesthetized sheep in which the left atrial pressure and/or superior vena caval pressure are elevated for up to 7 days. The left atrial pressure will be elevated with a balloon and the superior vena caval pressure will be elevated with a cuff around the vena cava. The amount of edema will be determined from the post mortem lung blood free wet and dry weights and the pleural effusion volume will be measured by aspirating the fluid from the pleural space. Experiments will also be performed to test the hypothesis that elevated vena caval pressure causes pleural effusions by slowing the flow of lymph from intrathoracic lymph nodes, and thus causing the lymph to leak from the nodes into the chest. Dye will be caused to flow into the large caudal mediastinal node of sheep and the node, the tissue surrounding the node and the pleural fluid will be examined for the presence of the dye. Additionally, the protein concentration of lymph flowing through nodes in the thorax will be compared to the protein concentration of pleural fluid. These studies valuable information about the roles of pulmonary vascular pressure and vena caval pressure in the development of pulmonary edema and pleural effusions.
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