Abstract
The optimal oxygen concentration for newborn resuscitation is still discussed. Oxygen administration during reoxygenation may induce short- and long-term pathologic changes via oxidative stress and has been associated to later childhood cancer. The aim was to study changes in oxidative stress-associated markers in liver and lung tissue of newborn pigs after acute hypoxia followed by reoxygenation for 30 min with 21, 40, or 100% oxygen compared with room air or to ventilation with 100% oxygen without preceding hypoxia. Nine hours after resuscitation, we found a dose-dependent increase in the matrix metalloproteinase gelatinase activity in liver tissue related to percentage oxygen supply by resuscitation (100% versus 21%; p = 0.002) pointing at more extensive tissue damage. Receiving 100% oxygen for 30 min without preceding hypoxia decreased the expression of VEGFR2 and TGFBR3 mRNA in liver tissue, but not in lung tissue. MMP-, VEGF-, and TGFβ-superfamily are vital for the development, growth, and functional integrity of most tissues and our data rise concern about both short- and long-term consequences of even a brief hyperoxic exposure.
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Abbreviations
- FiO2:
-
fraction of inspired oxygen
- MMP:
-
matrix metalloproteinase
- ROS:
-
reactive oxygen species
- TGFBR3:
-
(TGFβR3) transforming growth factor β receptor 3
- VEGFR1:
-
(Flt-1) vascular endothelial growth factor receptor 1
- VEGFR2:
-
(Flk-1 or KDR) vascular endothelial growth factor receptor 2
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Acknowledgements
We thank Cera T. Sebastian, Aurora M. Pamplona, and Roger Ødegård for assistance with the animal preparations; Monica Atnosen-Åsegg, Vibecke M. Olsen, and Iren Helland for technical assistance; and Are Hugo Pripp for biostatistical support.
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Supported by the South-Eastern Norway Regional Health Authority and the Norwegian SIDS and Stillbirth Society.
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Solberg, R., Andresen, J., Pettersen, S. et al. Resuscitation of Hypoxic Newborn Piglets With Supplementary Oxygen Induces Dose-Dependent Increase in Matrix Metalloproteinase-Activity and Down-Regulates Vital Genes. Pediatr Res 67, 250–256 (2010). https://doi.org/10.1203/PDR.0b013e3181cde843
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DOI: https://doi.org/10.1203/PDR.0b013e3181cde843
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