Aerosolized manganese SOD decreases hyperoxic pulmonary injury in primates. II. Morphometric analysis

Welty-Wolf, Karen E., Steven G. Simonson, Yuh-Chin T. Huang,Stephen P. Kantrow, Martha S. Carraway, Ling-Yi Chang, James D. Crapo, and Claude A. Piantadosi. Aerosolizedmanganese SOD decreases hyperoxic pulmonary injury in primates. II.Morphometric analysis. J. Appl.Physiol. 83(2): 559-568, 1997.Hyperoxia damages lung parenchyma via increased cellular production of reactive oxygenspecies that exceeds antioxidant defenses. We hypothesized thataerosolized human recombinant manganese superoxide dismutase (rhMnSOD)would augment extracellular antioxidant defenses and attenuateepithelial injury in the lung during hyperoxia in primates. Twenty-fouradult male baboons were anesthetized and mechanically ventilated with100% oxygen for 96 h. The baboons were divided equally into fourgroups. Oxygen alone and oxygen plus rhMnSOD given at 3 mg · kg¹ · day¹were compared to assess efficacy of the drug. Subsequently, aerosolized rhMnSOD was given at 1 or 10 mg · kg¹ · day¹to study dose effects and toxicity. Quantitative morphometry showedprotection of alveolar epithelium from hyperoxia by 3 mg · kg¹ · day¹rhMnSOD (P < 0.05). In addition,interstitial fibroblast volumes were increased in the treatment group(P = 0.06). This effect appearedgreater at the two higher doses of the rhMnSOD. The aerosolized drugwas localized to the surface of airways and air spaces and macrophagesby immunolabeling studies, suggesting efficacy via physicochemicalproperties that localize it to cell surfaces or by effects on alveolarmacrophage function.