A well-recognized complication of thermal injury and shock is acute respiratory failure, which may progress to reversible structural and functional changes of the lung. There is increasing evidence that oxygen metabolites (including oxygen free radicals), whether produced in the alveolar or the vascular compartment of the lung, are incriminated in mechanisms of lung injury. In this proposal we will examine the ability of oxygen metabolites produced within either the alveolar or the vascular compartment to inflict acute and/or progressive lung injury. The oxygen metabolites will be produced by activated leukocytes and by enzyme-substrate combinations. Injury produced within the vascular compartment will be accomplished by intravascular infusion of activated neutrophils, infusion of enzyme-linked beads and by in vivo infusion of chemotactic factors. Injury produced within the alveolar compartment will be accomplished by airway instillation of activated neutrophils, activated alveolar macrophages and enzyme-linked substrate combinations. Resulting lung injury will be measured quantitatively be increased in lung permeability, by changes in tissue content of connective tissue products, and by careful morphological analysis (light and scanning and transmission electron microscopy). These studies should establish the susceptibility of the lung to injury induced by oxygen metabolites and conditions that bring about progressive lung injury.
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