Philip L Ballard1, Roberta L Keller1, Dennis M Black2, David J Durand3, Jeffrey D Merrill3, Eric C Eichenwald4, William E Truog5, Mark C Mammel6, Robin Steinhorn7, Rita M Ryan8, Sherry E Courtney9, Hart Horneman1, Roberta A Ballard1. 1. Department of Pediatrics, University of California, San Francisco, California. 2. Department of Epidemiology and Biostatistics, University of California, San Francisco, California. 3. Division of Neonatology, Children's Hospital and Research Center Oakland, Oakland, California. 4. Department of Pediatrics, University of Texas Medical School, Houston, Texas. 5. Department of Pediatrics, Children's Mercy Hospitals and Clinics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri. 6. Department of Pediatrics, Children's Hospital and Clinics of Minnesota, St. Paul, Minnesota. 7. Department of Pediatrics, University of California Davis Children's Hospital, Sacramento, California. 8. Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina. 9. Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Abstract
OBJECTIVE:Inhaled nitric oxide (iNO) has been tested to prevent bronchopulmonary dysplasia (BPD) in premature infants, however, the role of cyclic guanosine monophosphate (cGMP) is not known. We hypothesized that levels of NO metabolites (NOx) and cGMP in urine, as a noninvasive source for biospecimen collection, would reflect the dose of iNO and relate to pulmonary outcome. STUDY DESIGN: Studies were performed on 125 infants who required mechanical ventilation at 7 to 14 days and received 24 days of iNO at 20-2 ppm. A control group of 19 infants did not receive iNO. RESULTS: In NO-treated infants there was a dose-dependent increase of both NOx and cGMP per creatinine (maximal 3.1- and 2-fold, respectively, at 10-20 ppm iNO) compared with off iNO. NOx and cGMP concentrations at both 2 ppm and off iNO were inversely related to severity of lung disease during the 1st month, and the NOx levels were lower in infants who died or developed BPD at term. NOx was higher in Caucasian compared with other infants at all iNO doses. CONCLUSION: Urinary NOx and cGMP are biomarkers of endogenous NO production and lung uptake of iNO, and some levels reflect the severity of lung disease. These results support a role of the NO-cGMP pathway in lung development. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
RCT Entities:
OBJECTIVE: Inhaled nitric oxide (iNO) has been tested to prevent bronchopulmonary dysplasia (BPD) in premature infants, however, the role of cyclic guanosine monophosphate (cGMP) is not known. We hypothesized that levels of NO metabolites (NOx) and cGMP in urine, as a noninvasive source for biospecimen collection, would reflect the dose of iNO and relate to pulmonary outcome. STUDY DESIGN: Studies were performed on 125 infants who required mechanical ventilation at 7 to 14 days and received 24 days of iNO at 20-2 ppm. A control group of 19 infants did not receive iNO. RESULTS: In NO-treated infants there was a dose-dependent increase of both NOx and cGMP per creatinine (maximal 3.1- and 2-fold, respectively, at 10-20 ppm iNO) compared with off iNO. NOx and cGMP concentrations at both 2 ppm and off iNO were inversely related to severity of lung disease during the 1st month, and the NOx levels were lower in infants who died or developed BPD at term. NOx was higher in Caucasian compared with other infants at all iNO doses. CONCLUSION: Urinary NOx and cGMP are biomarkers of endogenous NO production and lung uptake of iNO, and some levels reflect the severity of lung disease. These results support a role of the NO-cGMP pathway in lung development. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
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