Superoxide dismutase improves gas exchange and pulmonary hemodynamics in premature lambs.
BACKGROUND
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.


RESULTS
Despite an initial rise in Pa(O(2)), Pa(O(2)) in control animals progressively declined over the 4-hour treatment period (Pa(O(2)) = 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 Pa(O(2)) 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 Pa(O(2)). Treatment with iNO increased Pa(O(2)) (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 FI(O(2)) = 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.
Kinsella
John P
JP
Department of Pediatrics, Pediatric Heart-Lung Center, Section of Neonatology, University of Colorado School of Medicine, Denver, Colorado, USA. john.kinsella@uchsc.edu
Parker
Thomas A
TA
Davis
Jonathan M
JM
Abman
Steven H
SH
D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D005865:Gestational Age; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006976:Hypertension, Pulmonary / Q000517:prevention & control; D008170:Lung Compliance / Q000187:drug effects; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012120:Respiration Disorders / Q000503:physiopathology*; D012756:Sheep; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology*; D014132:Trachea; D014655:Vascular Resistance / Q000187:drug effects
D011994:Recombinant Proteins; D009569:Nitric Oxide; D013482:Superoxide Dismutase