The general objectives of this study are to: (1) examine the pathophysiological basis of pulmonary vascular injury and edema induced by intravascular coagulation; (2) study interactions between the endothelial barrier and fibronectin and the potential role of neutrophils and macrophages in mediating the endothelial- fibronectin interactions; (3) assess the role of blood components and lipids in the development or pulmonary edema after fat embolism; (4) study the role of arachidonic products in mediating and/or modulating pulmonary transvascular fluid and protein exchange; (5) examine the role of platelets in pulmonary edemagensis; (6) assess the role of the glutathione as a scavenging system that protects the lungs against oxidant-induced lung injury. These studies will be made in sheep, rabbits guinea pigs, mice and in vitro preparations including isolated perfused lungs and cultured endothelial cells. The studies will utilized a variety of physiological and biochemical techniques. In particular, the studies will involve: (a) in vivo and vitro examination of the interactions among coagulation end-products, fibrin, and neutrophils on lung vascular injury; (b) use of cultured endothelial cells and intact sheep for study of the potential role of alterations in fibronectin as a mediator and/or modulator of increased vascular permeability; (c) in vivo and in vitro examination of the effects of fat microemboli (soft tissue fat or bone marrow) on lung fluid balance and the mechanisms by which fat microemboli induce lung injury; (d) assessment of the role of arachidonat products in mediating pulmonary edema using in vivo and in vitro methods; (e) in vivo examination of the role of platelets in mediating or modifying microvascular permeability to fluid and proteins; (f) examination of the role of glutathione as an anti- oxidant that may prevent acute lung injury. The ultimate aim of these studies is to provide a better description of the pathophysiology of lung vascular injury and pulmonary edema.
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