The excess accumulation of pulmonary edema, as the most immediate consequence of acute endothelial injury, is the principal cause of hypoxemia, respiratory distress, and the need for mechanical ventilatory support during the adult respiratory distress syndrome. To date, the only effective means of limiting the accumulation of pulmonary edema has been to actively reduce, whenever possible, intrapulmonary hydrostatic pressure. However, more specific manipulations of regional perfusion to injured lung units might accomplish the same goal without the inherent risks of compromised cardiovascular function. Using the quantitative imaging technique of positron emission tomography, we have studied the causes for changes in regional perfusion in an animal model of acute lung injury. Biochemical correlations with the PET data have now suggested that the eicosanoids thromboxane and prostacyclin are important mediators of the most acute changes in regional perfusion pattern. Other factors, still incompletely defined, must also be important as the magnitude of change in the regional perfusion pattern is highly variable--both among different experimental animals and over time within the same animal. Therefore, the current research proposal has three specific aims: 1. To determine the pattern of regional perfusion in human acute lung injury, whether the pattern changes with time, and how it compares with data obtained from the animal model, including the effects of cyclooxygenase inhibition. 2. To determine the reason(s) for variability in the magnitude of perfusion redistribution among experimental animals with acute lung injury, by determining morphologic correlates to the changes in regional perfusion, and the relative roles of thromboxane and nitric oxide in modifying the regional perfusion pattern, and 3. To determine the mechanism(s) responsible for 'delayed' (i.e. > 24 hrs) changes in perfusion pattern after the onset of acute lung injury, which-- -based on recently obtained pilot data---are different than more acute causes. These studies represent a logical extension of our plan to develop a complete and integrated, quantitative understanding of the mechanisms responsible for, and the importance of, changes in the control of regional pulmonary perfusion during acute lung injury.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Diagnostic Radiology Study Section (RNM)
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Washington University
Internal Medicine/Medicine
Schools of Medicine
Saint Louis
United States
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