AEROSOLIZED MANGANESE SOD DECREASES HYPEROXIC PULMONARY INJURY IN PRIMATES .1. PHYSIOLOGY AND BIOCHEMISTRY

Prolonged hyperoxia causes lung injury and respiratory failure seconda ry to oxidative tissue damage mediated, in part, by the superoxide ani on. We hypothesized that aerosol treatment with recombinant human mang anese superoxide dismutase (rhMnSOD) would attenuate hyperoxic lung da mage in primates. Adult baboons were anesthetized and ventilated with 100% oxygen for 96 h or until death. Six animals were treated with aer osolized rhMnSOD (3 mg.kg(-1).day(-1) in divided doses), and six contr ol animals did not receive enzyme therapy. Physiological variables wer e recorded every 12 h, and ventilation-perfusion ratio relationships w ere evaluated by using the multiple inert-gas elimination technique. A fter the experiments, surfactant composition and lung edema were measu red. We found that rhMnSOD significantly decreased pulmonary shunt fra ction (P < 0.01) and preserved arterial oxygenation (P < 0.01) during hyperoxia. The rhMnSOD increased lung phospholipids, phosphatidylcholi ne and disaturated phosphatidylcholine, and decreased lung edema in th is 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 physiolog ical protection, suggesting a ''window'' of effective dosage. We concl ude that aerosolized MnSOD (3 mg.kg(-1).day(-1)) affords significant p reservation of pulmonary gas exchange during hyperoxic lung injury.