Published ahead of print on June 9, 2005, doi:10.1164/rccm.200501-146OC
© 2005 American Thoracic Society doi: 10.1164/rccm.200501-146OC Superoxide Dismutase Improves Gas Exchange and Pulmonary Hemodynamics in Premature LambsDepartment of Pediatrics, Pediatric Heart-Lung Center, Sections of Neonatology, and Pulmonary and Critical Care Medicine, University of Colorado School of Medicine, Denver, Colorado; and Department of Pediatrics and Cardiopulmonary Research Institute, Winthrop University Hospital, State University of New York at Stony Brook, Mineola, New York Correspondence and requests for reprints should be addressed to John P. Kinsella, M.D., Division of Neonatology, Box B-070, The Children's Hospital, 1056 East 19th Avenue, Denver, CO 80218. E-mail: john.kinsella{at}uchsc.edu Rationale: Oxidant stress may increase the severity of respiratory distress syndrome (RDS) after premature birth by altering vasoreactivity and increasing lung edema, but the acute effects of superoxide dismutase (SOD) treatment on gas exchange, lung compliance (CL), and pulmonary vascular resistance in premature animals with RDS are unknown. Objective: We studied the effects of intratracheal recombinant human SOD treatment (rhSOD) on gas exchange, CL, and pulmonary hemodynamics in 46 premature lambs with RDS. Methods: After C-section delivery, lambs were randomly assigned to treatment with SOD (2.5–10 mg/kg) with or without inhaled nitric oxide (iNO, 5 ppm), and mechanically ventilated for 4 hours. At the end of the study, pressure–volume curves and wet–dry lung weights were measured to assess CL and edema, respectively. Main Results: Despite an initial rise in PaO2, PaO2 in control animals progressively declined over the 4-hour treatment period (PaO2 = 25.0 ± 7.5 mm Hg at 4 hours). In comparison with control animals, early treatment with SOD at 5 and 10 mg/kg improved PaO2 at 4 hours (167 ± 44 and 269 ± 33 mm Hg, respectively; p < 0.05 vs. control), but did not decrease lung edema or improve CL. In contrast, late treatment with SOD did not improve PaO2. Treatment with iNO increased PaO2 (196 ± 22 vs. 25 ± 8 mm Hg, control animals; p < 0.01), but the response to iNO was not augmented by combined therapy (SOD + iNO). After 4 hours of ventilation with FIO2 = 1.00, rhSOD treatment lowered pulmonary vascular resistance compared with control animals. Conclusions: Early intratracheal rhSOD treatment improves oxygenation in premature lambs with RDS and prevents the development of pulmonary hypertension.
Key Words: bronchopulmonary dysplasia • chronic lung disease • mechanical ventilation • pulmonary hypertension • surfactant This article has been cited by other articles:
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
