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J Appl Physiol 83: 559-568, 1997;
8750-7587/97 $5.00
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Journal of Applied Physiology
Vol. 83, No. 2, pp. 559-568, August 1997
CELLULAR ASPECTS OF LUNG FUNCTION

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

Karen E. Welty-Wolf, Steven G. Simonson, Yuh-Chin T. Huang, Stephen P. Kantrow, Martha S. Carraway, Ling-Yi Chang, James D. Crapo, and Claude A. Piantadosi

Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710

Received 19 August 1996; accepted in final form 31 March 1997.

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. Aerosolized manganese 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 oxygen species that exceeds antioxidant defenses. We hypothesized that aerosolized human recombinant manganese superoxide dismutase (rhMnSOD) would augment extracellular antioxidant defenses and attenuate epithelial injury in the lung during hyperoxia in primates. Twenty-four adult male baboons were anesthetized and mechanically ventilated with 100% oxygen for 96 h. The baboons were divided equally into four groups. Oxygen alone and oxygen plus rhMnSOD given at 3 mg · kg-1 · day-1 were compared to assess efficacy of the drug. Subsequently, aerosolized rhMnSOD was given at 1 or 10 mg · kg-1 · day-1 to study dose effects and toxicity. Quantitative morphometry showed protection of alveolar epithelium from hyperoxia by 3 mg · kg-1 · day-1 rhMnSOD (P < 0.05). In addition, interstitial fibroblast volumes were increased in the treatment group (P = 0.06). This effect appeared greater at the two higher doses of the rhMnSOD. The aerosolized drug was localized to the surface of airways and air spaces and macrophages by immunolabeling studies, suggesting efficacy via physicochemical properties that localize it to cell surfaces or by effects on alveolar macrophage function.

superoxide dismutase; antioxidant enzymes; oxygen; acute lung injury; acute respiratory distress syndrome; lung ultrastructure

0161-7567/97 $5.00 Copyright © 1997 the American Physiological Society




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