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Updated: Aug 18, 2026
A Swine Model of Neonatal Asphyxia
Published on: October 11, 2011
Mitigation of pulmonary oxygen toxicity in premature lambs with intravenous antioxidants
F J Walther1, I M Kuipers, Z Pavlova
1Department of Pediatrics, University of Southern California School of Medicine, Los Angeles.
Insights
Long-acting antioxidants, polyethylene glycol (PEG)-conjugated superoxide dismutase (SOD) and catalase, reduced lung injury in premature lambs. These antioxidants mitigated inflammation and cellular damage, even at low doses.
Area of Science:
- Neonatal Medicine
- Biochemistry
- Pulmonary Biology
Background:
- Bronchopulmonary dysplasia (BPD) is a common complication in premature infants, potentially linked to oxidative stress.
- Antioxidants, such as superoxide dismutase (SOD) and catalase, combat free radical damage.
- Long-acting formulations, like polyethylene glycol (PEG)-conjugated enzymes, offer sustained therapeutic effects.
Purpose of the Study:
- To investigate the efficacy of PEG-conjugated SOD and catalase in preventing lung injury in a premature lamb model.
- To determine if these antioxidants can mitigate the inflammatory and cellular damage associated with premature birth and mechanical ventilation.
Main Methods:
- Premature lambs were delivered via cesarean section and ventilated.
- One lamb per twin pair received intravenous PEG-SOD and PEG-catalase at varying doses; the other served as a control.
- Pulmonary function, blood gases, and lung tissue morphometrics were analyzed post-treatment.
Main Results:
- PEG antioxidant administration significantly reduced neutrophil and macrophage infiltration in the lungs.
- Damage to arterioles, bronchiolar mucosa, and type II pneumocytes was decreased.
- These protective effects were dose-dependent and observed even at the lowest administered doses.
Conclusions:
- PEG-conjugated SOD and catalase are effective in reducing lung injury in premature lambs.
- These antioxidants mitigate key pathological features of BPD, including inflammation and cellular damage.
- The findings support the potential therapeutic role of long-acting antioxidants in preventing BPD.
Abstract:
Deficiencies of antioxidants and increased free radical generation may explain the high incidence of bronchopulmonary dysplasia in premature infants. Long-acting antioxidants such as polyethylene glycol (PEG) conjugated superoxide dismutase (SOD), and catalase might modify this process. We delivered 32 premature lambs, 16 pairs of twins, by cesarean section at 125-141 days of gestation (term 146 days) and stabilized them on ventilators in normocapnic hyperoxia for a period of 8 h. One lamb of each twin pair received an intravenous dose of 7,500-50,000 IU/kg of PEG-SOD and of 37,500-1,000,000 IU/kg of PEG-catalase at birth. Their siblings acted as controls. Mean airway pressure, arterial pressure, and heart rate were recorded continuously. Arterial blood gases and pH were obtained every 30 min. After sacrifice, standardized lung biopsies were prepared for quantitative morphometrics and electron microscopy. Administration of PEG antioxidants at birth reduced the influx of neutrophils and macrophages into the lung and damage to arterioles, bronchiolar mucosa, and type II pneumocytes without major changes in alveolar surface area or pulmonary function. These effects were dose-related and detectable even at the lowest doses of PEG antioxidants administered.
