The purpose of the proposed studies is to examine the mechanism(s) of pulmonary edema formation and the resulting insufficency after pulmonary microembolization, such as that occurring after trauma and shock. Studies will be made in sheep in which lung lymph, pulmonary hemodynamics and gas exchange will be monitored. Lung vascular permeability will be assessed. Studies will examine the roles of fibrin entrapment in the lung after secondary thrombosis as well as of sequestration of formed elements (granulocytes and platelets) in mediating the injury. Hence, these studies will enable an assessment of the role of blood components that are currently believed to mediate lung microvascular injury after microenbolization. Other studies will examine the roles of vasoactive and permeability-increasing humoral factors in mediating the increase in extravascular lung water content and impairment in gas exchange. Since low pulmonary blood flow is common to pulmonary insufficiency resulting from several causes (e.g., pulmonary microembolism), we will also examine the role of pulmonary hypoperfusion in mediating lung microvascular injury. The data obtained from these studies will enhance our understanding of the mechanisms of lung microvascular injury after microembolization, and hence, may provide a better scientific basis for the therapy of post-traumatic pulmonary insufficiency. In particular, these studies will be of potential benefit in understanding how blood components mediate lung microvascular injury in the intact animal, so that sound therapeutic regimens which prevent or reverse microvascular injury may evolve.
