Inhaled nitric oxide increases urinary nitric oxide metabolites and cyclic guanosine monophosphate in premature infants: Relationship to pulmonary outcome

Philip L. Ballard, Roberta L. Keller, Dennis M. Black, David J. Durand, Jeffrey D. Merrill, Eric C. Eichenwald, William E. Truog, Mark C. Mammel, Robin H Steinhorn, Rita M. Ryan, Sherry E. Courtney, Hart Horneman, Roberta A. Ballard

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)225-232
Number of pages8
JournalAmerican Journal of Perinatology
Volume32
Issue number3
DOIs
StatePublished - 2015

    Fingerprint

Keywords

  • bronchopulmonary dysplasia
  • cyclic GMP
  • nitric oxide
  • premature
  • urine

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

Cite this

Ballard, P. L., Keller, R. L., Black, D. M., Durand, D. J., Merrill, J. D., Eichenwald, E. C., Truog, W. E., Mammel, M. C., Steinhorn, R. H., Ryan, R. M., Courtney, S. E., Horneman, H., & Ballard, R. A. (2015). Inhaled nitric oxide increases urinary nitric oxide metabolites and cyclic guanosine monophosphate in premature infants: Relationship to pulmonary outcome. American Journal of Perinatology, 32(3), 225-232. https://doi.org/10.1055/s-0034-1382255