Prophylactic effects of recombinant human superoxide dismutase in neonatal lung injury.
To determine if recombinant human Cu-Zn superoxide dismutase (rhSOD) would prevent acute lung injury caused by hyperoxia and barotrauma, 26 newborn piglets were studied. Ten piglets were hyperventilated (arterial PCO2 15-20 Torr) with 100% O2 for 48 h. A second group received identical 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 ventilated (arterial PCO2 40-45 Torr) for 48 h with 21% O2. Pulmonary function and tracheal aspirates were examined at time 0 and at 24 and 48 h, and bronchoalveolar lavage was performed at 48 h. In piglets treated with hyperoxia and hyperventilation, lung compliance decreased 42%, and tracheal aspirates showed an increase in neutrophil chemotactic activity (32%), total cell counts (135%), elastase activity (93%), and albumin concentration (339%) over 48 h (P < 0.05). All variables were significantly lower in rhSOD-treated piglets and comparable to normoxic control values. Surfactant remained active in all groups. Immunohistochemistry demonstrated that at 48 h significant rhSOD was distributed homogeneously in terminal airways. Adding rhSOD to tracheal aspirates of hyperoxic 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 ameliorated by prophylactic intratracheal administration of rhSOD.
Davis
J M
JM
Department of Pediatrics (Neonatology), Winthrop University Hospital, State University of New York, School of Medicine, Stony Brook, Mineola 11501.
Rosenfeld
W N
WN
Sanders
R J
RJ
Gonenne
A
A
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001469:Barotrauma / Q000209:etiology / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007442:Intubation, Intratracheal; D055370:Lung Injury; D009504:Neutrophils / Q000187:drug effects; D010100:Oxygen / Q000633:toxicity; D010101:Oxygen Consumption / Q000187:drug effects; D011663:Pulmonary Surfactants / Q000494:pharmacology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D012121:Respiration, Artificial / Q000009:adverse effects; D012129:Respiratory Function Tests; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013552:Swine
D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D013482:Superoxide Dismutase; D010100:Oxygen