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

3 Citations (Scopus)

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

Cyclic GMP
Premature Infants
Nitric Oxide
Lung
Bronchopulmonary Dysplasia
Lung Diseases
Artificial Respiration
Creatinine
Biomarkers
Urine
Control Groups

Keywords

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

ASJC Scopus subject areas

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

Cite this

Inhaled nitric oxide increases urinary nitric oxide metabolites and cyclic guanosine monophosphate in premature infants : Relationship to pulmonary outcome. / Ballard, Philip L.; Keller, Roberta L.; Black, Dennis M.; Durand, David J.; Merrill, Jeffrey D.; Eichenwald, Eric C.; Truog, William E.; Mammel, Mark C.; Steinhorn, Robin H; Ryan, Rita M.; Courtney, Sherry E.; Horneman, Hart; Ballard, Roberta A.

In: American Journal of Perinatology, Vol. 32, No. 3, 2015, p. 225-232.

Research output: Contribution to journalArticle

Ballard, PL, Keller, RL, Black, DM, Durand, DJ, Merrill, JD, Eichenwald, EC, Truog, WE, Mammel, MC, Steinhorn, RH, Ryan, RM, Courtney, SE, Horneman, H & Ballard, RA 2015, 'Inhaled nitric oxide increases urinary nitric oxide metabolites and cyclic guanosine monophosphate in premature infants: Relationship to pulmonary outcome', American Journal of Perinatology, vol. 32, no. 3, pp. 225-232. https://doi.org/10.1055/s-0034-1382255
Ballard, Philip L. ; Keller, Roberta L. ; Black, Dennis M. ; Durand, David J. ; Merrill, Jeffrey D. ; Eichenwald, Eric C. ; Truog, William E. ; Mammel, Mark C. ; Steinhorn, Robin H ; Ryan, Rita M. ; Courtney, Sherry E. ; Horneman, Hart ; Ballard, Roberta A. / Inhaled nitric oxide increases urinary nitric oxide metabolites and cyclic guanosine monophosphate in premature infants : Relationship to pulmonary outcome. In: American Journal of Perinatology. 2015 ; Vol. 32, No. 3. pp. 225-232.
@article{42d19f202db5440ab56f7907170154fc,
title = "Inhaled nitric oxide increases urinary nitric oxide metabolites and cyclic guanosine monophosphate in premature infants: Relationship to pulmonary outcome",
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.",
keywords = "bronchopulmonary dysplasia, cyclic GMP, nitric oxide, premature, urine",
author = "Ballard, {Philip L.} and Keller, {Roberta L.} and Black, {Dennis M.} and Durand, {David J.} and Merrill, {Jeffrey D.} and Eichenwald, {Eric C.} and Truog, {William E.} and Mammel, {Mark C.} and Steinhorn, {Robin H} and Ryan, {Rita M.} and Courtney, {Sherry E.} and Hart Horneman and Ballard, {Roberta A.}",
year = "2015",
doi = "10.1055/s-0034-1382255",
language = "English (US)",
volume = "32",
pages = "225--232",
journal = "American Journal of Perinatology",
issn = "0735-1631",
publisher = "Thieme Medical Publishers",
number = "3",

}

TY - JOUR

T1 - Inhaled nitric oxide increases urinary nitric oxide metabolites and cyclic guanosine monophosphate in premature infants

T2 - Relationship to pulmonary outcome

AU - Ballard, Philip L.

AU - Keller, Roberta L.

AU - Black, Dennis M.

AU - Durand, David J.

AU - Merrill, Jeffrey D.

AU - Eichenwald, Eric C.

AU - Truog, William E.

AU - Mammel, Mark C.

AU - Steinhorn, Robin H

AU - Ryan, Rita M.

AU - Courtney, Sherry E.

AU - Horneman, Hart

AU - Ballard, Roberta A.

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - bronchopulmonary dysplasia

KW - cyclic GMP

KW - nitric oxide

KW - premature

KW - urine

UR - http://www.scopus.com/inward/record.url?scp=84939890086&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84939890086&partnerID=8YFLogxK

U2 - 10.1055/s-0034-1382255

DO - 10.1055/s-0034-1382255

M3 - Article

VL - 32

SP - 225

EP - 232

JO - American Journal of Perinatology

JF - American Journal of Perinatology

SN - 0735-1631

IS - 3

ER -