Abstract
We hypothesized that resuscitation with 100% O2 compared with 21% O2 is detrimental to pulmonary tissue. The pulmonary injury was assessed by matrix metalloproteinase (MMP) activity, oxidative stress, IL-8, and histology 2.5 h after resuscitation from a hypoxic state. In pulmonary tissue extracts, MMP activity was analyzed by broad matrix–degrading capacity (total MMP) and zymography. MMP-2 mRNA expression was evaluated by quantitative real-time PCR. Total endogenous antioxidant capacity was measured by the oxygen radical absorbance capacity (ORAC) assay, and IL-8 was analyzed by ELISA technique. In bronchoalveolar lavage (BAL) fluid, MMPs were analyzed by zymography. In pulmonary tissue, pro- and active MMP-2 levels were increased in piglets that were resuscitated with 100% O2 compared with 21% O2. Pro–MMP-9, total MMP activity, and MMP-2 mRNA levels were significantly increased in resuscitated piglets compared with baseline. Net gelatinolytic activity increased in submucosa and blood vessels after 100% O2 and only in the blood vessels after 21% O2. Compared with baseline, ORAC values were considerably lowered in the resuscitated piglets and significantly reduced in the 100% O2 versus 21% O2 group. In BAL fluid, both pro–MMP-9 and pro–MMP-2 increased 2-fold in the 100% O2 group compared with 21% O2. Moreover, IL-8 concentration increased significantly in piglets that were resuscitated with 100% O2 compared with 21% O2, suggesting a marked proinflammatory response in the pulmonary tissue. Altogether, these data strongly suggest that caution must be taken when applying pure O2 to the newborn infant.
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Abbreviations
- BAL:
-
bronchoalveolar lavage
- MMP:
-
matrix metalloproteinase
- ORAC:
-
oxygen radical absorbance capacity
- Paco2:
-
arterial carbon dioxide tension
- Pao2:
-
arterial O2 tension
- RT-PCR:
-
reverse transcriptase–PCR
- TE:
-
Trolox equivalent
- TIMP:
-
tissue inhibitor of MMPs
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Acknowledgements
We thank G. Dyrhaug, J. Lindstad, H. Nilsen, T. Norèn, S. Pettersen, and E.L. Sagen for excellent technical assistance. We are also grateful for valuable advice from G. Aamodt, PhD, and Prof. T. Egeland in the Section of Biostatistics, Rikshospitalet University Hospital, Norway.
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This work was granted by The Norwegian SIDS Society, University of Oslo, AGA AB Medical Research Fund, The Laerdal Foundation for Acute Medicine, and The Norwegian Society of Anaesthesiology. B.H.M. is a Research Fellow at the Faculty Division Rikshospitalet University Hospital, Norway.
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Munkeby, B., Børke, W., Bjørnland, K. et al. Resuscitation of Hypoxic Piglets with 100% O2 Increases Pulmonary Metalloproteinases and IL-8. Pediatr Res 58, 542–548 (2005). https://doi.org/10.1203/01.PDR.0000179407.46810.2D
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DOI: https://doi.org/10.1203/01.PDR.0000179407.46810.2D
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