Oxygen (O2), in high concentrations, is recognized as a cause of the adult respiratory distress syndrome, a common clinical problem with high mortality. Less commonly appreciated is the possible toxic potential to an already damaged lung of low concentrations of O2, even of the 21% O2 in room air. Oxygen is a known cellular toxin producing its effect through active intermediates against which mammalian cells have mounted biochemical defenses. These include superoxide dysmutase (SOD), glutathione reductase, several peroxidase systems, ascorbate, tocopherol, NADPH and various sulfhydryl compounds. The resistance of these systems to injury is unknown. The failure of cellular protection against toxic O2 products might allow the induction of O2 toxicity at low O2 concentrations (those in room air or below). We propose to study the influence of 21% O2 exposure upon a previously injured lung in awake, spontaneously breathing rats over a 7-day experimental period. Rats will be injured by intraperitoneal injection of butylated hydroxytoluene (400 mg/kg) or by intravenous injection (.06 cc/kg) of oleic acid and then maintained, continuously, in environmental chambers with FO2 equaling 0.10, 0.21, or 0.30. Microscopic results will be analyzed by nonparametric analysis of variance methods. Wet weight/dry weight ratios will be analyzed by analysis of variance. The hypothesis that room air oxygen (FO2 equaling .21) is toxic to an injured lung will be tested.
NIH ExPorter
NIH ExPorter