Aerosolized manganese SOD decreases hyperoxic pulmonary injury in primates. I. Physiology and biochemistry.
Prolonged hyperoxia causes lung injury and respiratory failure secondary to oxidative tissue damage mediated, in part, by the superoxide anion. We hypothesized that aerosol treatment with recombinant human manganese superoxide dismutase (rhMnSOD) would attenuate hyperoxic lung damage in primates. Adult baboons were anesthetized and ventilated with 100% oxygen for 96 h or until death. Six animals were treated with aerosolized rhMnSOD (3 mg . kg-1 . day-1 in divided doses), and six control animals did not receive enzyme therapy. Physiological variables were recorded every 12 h, and ventilation-perfusion ratio relationships were evaluated by using the multiple inert-gas elimination technique. After the experiments, surfactant composition and lung edema were measured. We found that rhMnSOD significantly decreased pulmonary shunt fraction (P < 0.01) and preserved arterial oxygenation (P < 0.01) during hyperoxia. The rhMnSOD increased lung phospholipids, phosphatidylcholine and disaturated phosphatidylcholine, and decreased lung edema in this model. Testing of higher and lower doses of MnSOD (1 and 10 mg . kg-1 . day-1) in two other groups of baboons produced variable physiological protection, suggesting a "window" of effective dosage. We conclude that aerosolized MnSOD (3 mg . kg-1 . day-1) affords significant preservation of pulmonary gas exchange during hyperoxic lung injury.
Simonson
S G
SG
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
Welty-Wolf
K E
KE
Huang
Y C
YC
Taylor
D E
DE
Kantrow
S P
SP
Carraway
M S
MS
Crapo
J D
JD
Piantadosi
C A
CA
D000336:Aerosols; D000818:Animals; D006439:Hemodynamics; D006801:Humans; D018496:Hyperoxia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008168:Lung / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D010215:Papio; D011654:Pulmonary Edema / Q000209:etiology; D011659:Pulmonary Gas Exchange; D011663:Pulmonary Surfactants / Q000737:chemistry; D011994:Recombinant Proteins; D012119:Respiration; D013482:Superoxide Dismutase / Q000494:pharmacology*; D016019:Survival Analysis; D014692:Ventilation-Perfusion Ratio
D000336:Aerosols; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D013482:Superoxide Dismutase