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Prevention of oxygen toxicity with superoxide dismutase and catalase in premature lambs
Insights
Exogenous polyethylene glycol conjugated superoxide dismutase (PEG-SOD) and catalase (PEG-CAT) may protect premature infants from chronic lung disease caused by mechanical ventilation. This study showed reduced lung damage in lambs treated with PEG-SOD/PEG-CAT.
Area of Science:
- Neonatology
- Pulmonology
- Biochemistry
Background:
- Mechanical ventilation with high oxygen and pressures causes chronic lung disease in 20-30% of premature infants with respiratory distress syndrome.
- Oxygen toxicity is a significant concern in the management of premature newborns.
- Antioxidant enzymes play a crucial role in mitigating oxidative stress.
Purpose of the Study:
- To investigate the potential of exogenous polyethylene glycol conjugated superoxide dismutase (PEG-SOD) and catalase (PEG-CAT) in preventing oxygen-induced lung injury in premature lambs.
- To assess the efficacy of PEG-SOD and PEG-CAT in mitigating lung damage associated with mechanical ventilation in a model of respiratory distress syndrome.
Main Methods:
- Premature lambs were delivered via cesarean section and received surfactant treatment.
- Lambs were mechanically ventilated with 100% oxygen.
- One group received intravenous PEG-SOD and PEG-CAT, while the control group did not.
- Lung damage was evaluated microscopically after 8 hours or respiratory failure.
Main Results:
- Arterial blood gases, pH, and mean airway pressures were similar between treated and control groups.
- Mean PaO2 remained above 140 mmHg in the first 4 hours for the treated group.
- Microscopic examination revealed less bronchiolar epithelial damage and lung hemorrhages in lambs treated with PEG-SOD/PEG-CAT.
- High levels of SOD and CAT were maintained in the treated lambs throughout the study.
Conclusions:
- Exogenous PEG-SOD and PEG-CAT administration demonstrated a protective effect against oxygen-induced lung injury in premature lambs.
- These antioxidant enzymes show promise in reducing lung damage in premature infants undergoing mechanical ventilation for respiratory distress syndrome.
- Further research is warranted to explore the clinical application of PEG-SOD and PEG-CAT in neonatal respiratory care.
Abstract:
The use of high oxygen concentrations and high mean airway pressures during mechanical ventilation of premature newborn infants with respiratory distress syndrome leads in 20%-30% of the survivors to chronic lung disease. This study explores if exogenous polyethylene glycol conjugated superoxide dismutase (PEG-SOD) and catalase (PEG-CAT) mitigate oxygen toxicity in premature lambs with respiratory distress syndrome. Six pairs of premature lambs were delivered by cesarean section and treated by tracheal instillation of 60 mg natural sheep surfactant/kg/body weight. After birth, all lambs were ventilated with 100% oxygen, and one of each pair received a single intravenous injection of 1 million U/kg PEG-CAT and 50,000 U/kg PEG-SOD. At 8 h of age or after respiratory failure was established, the lambs were killed and the lungs were removed intact. Lung damage was assessed by microscopy. The arterial blood gases, pH, and mean airway pressures of the lambs treated with PEG-SOD/PEG-CAT did not differ from those of the controls. Mean PaO2 was greater than 140 mmHg during the first 4 h of the experiments. In the lambs treated with PEG-SOD/PEG-CAT, SOD and CAT levels were very high during the study period and less bronchiolar epithelial damage and lung hemorrhages were found at microscopy.