title: Recombinant human superoxide dismutase reduces lung injury caused by inhaled nitric oxide and hyperoxia.
abstract: We previously demonstrated that 48 h of 100 ppm inhaled nitric oxide (NO) and 90% O2 causes surfactant dysfunction and pulmonary inflammation in mechanically ventilated newborn piglets. Because peroxynitrite (the product of NO and superoxide) is thought to play a major role in the injury process, recombinant human superoxide dismutase (rhSOD, a scavenger of superoxide) might minimize this insult. Four groups of newborn piglets (1-3 days of age) were ventilated with 100 ppm NO and 90% O2 for 48 h. Piglets received no drug, 5 mg/kg rhSOD intratracheally at time 0, 5 mg/kg rhSOD intratracheally at 0 and 24 h, or 10 mg/kg rhSOD by nebulization at time 0. At 48 h, bronchoalveolar lavage (BAL) was performed, and lung tissue was analyzed for markers of inflammation, oxidative injury, acute lung injury, and surfactant function. There were significant differences between rhSOD-treated piglets and untreated controls with respect to BAL neutrophil chemotactic activity, cell counts, and protein concentration as well as lung tissue malondialdehyde concentrations. Minimum surface tension of BAL surfactant from all groups studied was increased, with no differences found among groups. These data suggest that rhSOD, at the doses used, mitigated the inflammatory changes, oxidative damage, and acute lung injury from exposure to 100 ppm NO and 90% O2 but did not appear to improve surfactant function. This has important clinical implications for infants treated with hyperoxia and NO for neonatal lung disorders.
authors.affiliation: CardioPulmonary Research Institute, Winthrop-University Hospital, State University of New York, Stony Brook School of Medicine, Mineola 11501, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Robbins
authors.forename: S
authors.initials: S
authors.lastname: Horowitz
authors.forename: T A
authors.initials: TA
authors.lastname: Merritt
authors.forename: A
authors.initials: A
authors.lastname: Kheiter
authors.forename: J
authors.initials: J
authors.lastname: Tierney
authors.forename: P
authors.initials: P
authors.lastname: Narula
authors.forename: J M
authors.initials: JM
authors.lastname: Davis
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000831:Animals, Newborn; D006801:Humans; D018496:Hyperoxia / Q000378:metabolism / Q000473:pathology*; D016209:Interleukin-8 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D009569:Nitric Oxide / Q000494:pharmacology*; D011663:Pulmonary Surfactants / Q000378:metabolism; D011994:Recombinant Proteins; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013552:Swine
chemical_list: D016209:Interleukin-8; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D009569:Nitric Oxide; D013482:Superoxide Dismutase