PROPHYLACTIC EFFECTS OF RECOMBINANT HUMAN SUPEROXIDE-DISMUTASE IN NEONATAL LUNG INJURY

To determine if recombinant human Cu-Zn superoxide dismutase (rhSOD) w ould prevent acute lung injury caused by hyperoxia and barotrauma, 26 newborn piglets were studied. Ten piglets were hyperventilated (arteri al PCO2 15-20 Torr) with 100% O2 for 48 h. A second group received ide ntical treatment for 4 h (n = 2) or 48 h (n = 8) but was given 5 mg/kg of rhSOD intratracheally at time 0. Six piglets were normally ventila ted (arterial PCO2 40-45 Torr) for 48 h with 21% O2. Pulmonary functio n and tracheal aspirates were examined at time 0 and at 24 and 48 h, a nd bronchoalveolar lavage was performed at 48 h. In piglets treated wi th hyperoxia and hyperventilation, lung compliance decreased 42%, and tracheal aspirates showed an increase in neutrophil chemotactic activi ty (32%), total cell counts (135%), elastase activity (93%), and album in concentration (339%) over 48 h (P < 0.05). All variables were signi ficantly lower in rhSOD-treated piglets and comparable to normoxic con trol values. Surfactant remained active in all groups. Immunohistochem istry demonstrated that at 48 h significant rhSOD was distributed homo geneously in terminal airways. Adding rhSOD to tracheal aspirates of h yperoxic hyperventilated piglets did not alter neutrophil chemotaxis, suggesting that rhSOD protected the lung by reducing the production of chemotactic mediators. Results indicate that acute lung injury caused by 48 h of hyperoxia and hyperventilation is significantly ameliorate d by prophylactic intratracheal administration of rhSOD.