Abstract
Animal studies have shown that induction of cytochrome P450 (CYP) in the lung by oxygen exposure may result in the release of free radical oxidants and arachidonic acid metabolites, which can cause lung injury that is reduced by treatment with cimetidine, a CYP inhibitor. To determine whether cimetidine would reduce lung injury in human infants at risk for chronic lung disease, we conducted a randomized clinical trial in which we administered either cimetidine or a placebo for 10 d beginning <24 h after birth to 84 newborn infants weighing ≤1250 g who were receiving O2 and mechanical ventilation. Cimetidine had no significant effect on severity of respiratory insufficiency assessed at 10 d postnatal age. F2-isoprostane levels (a marker of oxidant injury) in tracheal aspirates were significantly higher in the cimetidine group at 4 d and at 10 d. There were no significant differences between the groups in tracheal aspirate levels of inflammatory markers (leukotriene B4, IL-8, and nucleated cell count) or arachidonic acid metabolites. We conclude that cimetidine does not reduce lung injury in newborn premature infants receiving O2 and mechanical ventilation. It is possible that cimetidine was not an adequate CYP inhibitor in this context.
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Abbreviations
- AA:
-
arachidonic acid
- CLD:
-
chronic lung disease
- CYP:
-
cytochrome P450
- EET:
-
epoxyeicosatrienoic acid
- IVH:
-
intraventricular hemorrhage
- LTB4:
-
leukotriene B4
- PDA:
-
symptomatic patent ductus arteriosus
- PMA:
-
postmenstrual age
- RII:
-
respiratory insufficiency index
- TA:
-
tracheal aspirate
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Acknowledgements
The authors thank Dr. Robert A. Parker and Dr. Beverly G. Mellen for the valuable advice regarding study design and data analysis. We also thank are Dr. William Walsh, Dr. H\akan Sundell, Dr. Daniel Lindstrom, and Dr. Beverly Mellen for their service on the oversight committee.
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Supported by HL56697, GM42056, GM15431, and DK26657 from the National Institutes of Health and by the Intramural Research Program of the National Environmental Health Services Division, National Institutes of Health.
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Cotton, R., Hazinski, T., Morrow, J. et al. Cimetidine Does Not Prevent Lung Injury in Newborn Premature Infants. Pediatr Res 59, 795–800 (2006). https://doi.org/10.1203/01.pdr.0000219397.35473.5f
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DOI: https://doi.org/10.1203/01.pdr.0000219397.35473.5f
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