SIGNALING OF APOPTOTIC LUNG INJURY BY LIQUID HYDROPEROXIDES

Background: Acute lung injury is common after shock and sepsis, but th e pathophysiology is unclear. Lipid hydroperoxide products including 4 -hydroxynonenal (HNE) increase significantly during these insults and may induce apoptosis. This study investigates the role of pathophysiol ogic concentrations of HNE on isolated lung biophysical function and a poptosis. Methods: Male Sprague-Dawley rat lungs were isolated and per fused with Krebs-Henseleit buffered solution for 120 minutes, Hydroxyn onenal (50 mu mol/L) or vehicle was added to the perfusate at 60 minut es. Lung elastance and perfusion pressure were determined. Perfusate g lutathione and lactate dehydrogenase were determined at 30-minute inte rvals. Genomic DNA was extracted for electrophoretic determination of apoptotic laddering. Results: There were no differences in any paramet er measured before HNE infusion. Lung edema increased significantly wi th HNE infusion; a trend increase in lung elastance and perfusion pres sure was noted. DNA laddering characteristic of apoptosis was noted in HNE-treated lungs that was absent in control animals. Conclusion: Lip id hydroperoxide products formed during shock or sepsis may be causall y related to lung injury. Low concentrations of a candidate metabolite , HNE, appear to induce significant lung injury and apoptosis, which m ay partially mediate lung injury during shock and sepsis.