The effect of a nebulized NO donor, DPTA/NO, on acute hypoxic pulmonary hypertension in newborn piglets

Karen C. Young, John Ladino, Cristina Navarrete, Katarzyna Dabrowska, Dorothy Hehre, Eduardo Bancalari, Cleide Suguihara

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

NONOates, novel NO donors, are complexes of NO with nucleophiles which spontaneously and nonenzymatically release NO in aqueous solution. This study sought to determine the cardiopulmonary effects of the nebulized NONOate dipropylenetriamine (DPTA)/NO in newborn piglets with acute hypoxia-induced pulmonary hypertension. Twenty sedated and mechanically ventilated piglets (4-10 days old) exposed to hypoxia (FiO2 = 0.14) were randomly assigned to receive nebulized saline as placebo (PL) or DPTA/NO (75 mg) after 30 min of hypoxia. Pulmonary artery (Ppa) and wedge pressures, systemic (Psa) and right atrial pressures, cardiac output (CO) and arterial blood gas were measured at baseline and every 15 min for 2 h. Methemoglobin levels were measured at baseline and 1 h after drug nebulization. Data (means ± SD) were analyzed by repeated-measures analysis of variance. Acute hypoxia resulted in an increase in Ppa and pulmonary vascular resistance (PVR), which was significantly attenuated by DPTA/NO nebulization as compared to the PL group (p > 0.0001). Changes in P sa, CO, systemic vascular resistance (SVR), arterial blood gas and methemoglobin levels were not different between groups. In contrast to the increase in PVR/SVR observed during hypoxia in the PL group, there was a significant decrease in this ratio after NONOate administration (p > 0.0001). These data show that acute hypoxic pulmonary hypertension in newborn piglets is markedly attenuated by NONOate nebulization. This response is predominantly in the pulmonary vasculature as the PVR/SVR was significantly lower in the treated group. We speculate that NONOates may have clinical application in the treatment of persistent pulmonary hypertension of the newborn.

Original languageEnglish (US)
Pages (from-to)195-202
Number of pages8
JournalBiology of the Neonate
Volume85
Issue number3
DOIs
StatePublished - Apr 16 2004

Keywords

  • Acute hypoxia
  • Dipropylenetriamine
  • Nitric oxide
  • Nonoate
  • Persistent pulmonary hypertension of the newborn

ASJC Scopus subject areas

  • Developmental Biology
  • Pediatrics, Perinatology, and Child Health

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