Abstract
Background:
Bronchopulmonary dysplasia is an inflammatory lung disease that afflicts preterm infants requiring supplemental oxygen and is associated with impaired pulmonary angiogenesis. We tested the hypothesis that there is a critical threshold of inspired O2 (FiO2) that alters pulmonary angiogenesis.
Methods:
Within 2–6 h of birth, rat pups were exposed to 10%, 21%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100% FiO2 for 2 h. Mixed arterial–venous blood gases, serum and pulmonary levels of vascular endothelial growth factor (VEGF) and soluble VEGF receptor-1, and pulmonary angiogenesis gene profiles were determined.
Results:
PO2 increased with hyperoxia from 35.6 ± 5.0 (range: 31.5–39.8) at 10% O2 to 108.5 ± 25.0 (range: 82.2–134.8) at 100% O2. PO2 at 21% O2 was 42.4 ± 7.3 (range: 36.8–48.1). Lung VEGF levels declined at 40%–100%. The critical PO2 associated with decreased lung VEGF was 66 mm Hg, achieved with a FiO2 of 0.4. PO2 was inversely correlated with VEGF levels in the lungs (R = −0.377; P < 0.008). Antiangiogenesis genes were robustly upregulated at 70%, predominantly in males. Data are reported as mean ± SD.
Conclusions:
A critical threshold of FiO2 affecting angiogenesis exists in immature lungs. Exposure of preterm lungs to >40% inspired O2, even for 2 h, may result in abnormal expression of biomarkers regulating lung angiogenesis.
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Keenaghan, M., Cai, C., Kumar, D. et al. Response of vascular endothelial growth factor and angiogenesis-related genes to stepwise increases in inspired oxygen in neonatal rat lungs. Pediatr Res 73, 630–638 (2013). https://doi.org/10.1038/pr.2013.21
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DOI: https://doi.org/10.1038/pr.2013.21
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