Published ahead of print on June 9, 2005, doi:10.1164/rccm.200501-146OC Am. J. Respir. Crit. Care Med., Volume 172, Number 6, September 2005, 745-749 A more recent version of this article appeared on September 15, 2005
Submitted on January 29, 2005 Superoxide Dismutase Improves Gas Exchange and Pulmonary Hemodynamics in Premature LambsJohn P Kinsella1*,1 Department of Pediatrics; Section of Neonatology, Pediatric Heart-Lung Center, The Children's Hospital and the University of Colorado School of Medicine, Denver, CO, USA, 2 Department of Pediatrics; Section of Pulmonary and Critical Care Medicine, Pediatric Heart-Lung Center, The Children's Hospital and the University of Colorado School of Medicine, Denver, CO, USA, 3 Department of Pediatrics and CardioPulmonary Research Institute, Winthrop University Hospital, State University of New York at Stony Brook, Mineola, NY, USA * To whom correspondence should be addressed. 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 in premature animals with RDS are unknown. Objective: We studied the effects of intratracheal recombinant human SOD treatment (rhSOD) on gas exchange, lung compliance (CL), and pulmonary hemodynamics in 46 premature lambs with RDS. Methods: After c-section delivery, lambs were assigned to treatment with SOD (2.5 - 10 mg/kg) with or without inhaled NO (5 ppm), and mechanically ventilated for 4 hours. 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 mmHg at 4 hours). In comparison with controls, early treatment with SOD at 5 and 10 mg/kg improved PaO2 at 4 hours (167±44 and 269±33 mmHg, 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 mmHg vs. 25±8 mmHg, controls; P<0.01), but the response to iNO was not augmented by combined therapy (SOD+iNO). After 4 hours of ventilation FiO2=1.00, rhSOD treatment lowered PVR compared to controls. Conclusions: Early intratracheal rhSOD treatment improves oxygenation in premature lambs with RDS and prevents the development of pulmonary hypertension. Key words: mechanical ventilation, surfactant, bronchopulmonary dysplasia, chronic lung disease, pulmonary hypertension
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