The goal of this project is to determine the role of lung cyt P-450 in mediating lung injury in the newborn premature infant at risk for BPD.
Aim 1 is to determine if the cyt P-450 inhibitor cimetidine will reduce early lung injury, as reflected by pulmonary gas exchange, in human premature infants at risk for BPD.
Aim 2 is to determine the degree of lipid peroxidation in study patients by measuring F2-isoprostane levels in tracheobronchial aspirates and in urine.
Aim 3 is to identify P-450 mediated arachidonic acid (AA) metabolites in tracheobronchial aspirates obtained from patients enrolled in the study and to correlate the levels of specific metabolites with the assigned treatment and gas exchange index.
Aim 4 is to identify inflammatory markers in tracheobronchial aspirates and urine obtained from study patients in order to determine whether the anticipated reduction in O2 free radical generation and P-450 AA metabolite production in patients receiving cimetidine is also accompanied by a reduced inflammatory response.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL056697-03
Application #
2796817
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1996-09-30
Project End
2001-09-29
Budget Start
1998-09-30
Budget End
1999-09-29
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Pediatrics
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Cotton, Robert B; Hazinski, Tom A; Morrow, Jason D et al. (2006) Cimetidine does not prevent lung injury in newborn premature infants. Pediatr Res 59:795-800
Cotton, Robert B; Sundell, Hakan W; Zeldin, Darryl C et al. (2006) Inhaled nitric oxide attenuates hyperoxic lung injury in lambs. Pediatr Res 59:142-6
Xu, K; Arora, V K; Chaudhary, A K et al. (1999) Quantitative analysis of cimetidine in human plasma using LC/APCI/SRM/MS. Biomed Chromatogr 13:455-61