Abstract
NONOates are chemical compounds that are stable as solids but generate nitric oxide (NO) in aqueous solutions. When nebulized or instilled intratracheally, NONOates can attenuate pulmonary hypertension in adult animals with lung injury. To assess the effect of a nebulized NONOate, DPTA/NO, on group B Streptococcus (GBS)-induced pulmonary hypertension in newborn piglets, we studied 20 anesthetized and mechanically ventilated piglets (4–10 d). They were randomly assigned to receive nebulized placebo solution or DPTA/NO (100 mg) 15 min after sustained pulmonary hypertension. Pulmonary artery and wedge, systemic, and right atrial pressures; cardiac output; and arterial blood gases were obtained at baseline and every 15 min during 120 min of continuous GBS infusion (6 × 108 CFU/min). Methemoglobin levels were measured at baseline and 60 min. A significant decrease in pulmonary artery pressure, pulmonary vascular resistance (PVR), systemic arterial pressure, and systemic vascular resistance (SVR) was observed after DPTA/NO nebulization (p < 0.001). Whereas the increase in PVR/SVR observed after GBS infusion was sustained for 120 min in the placebo group, this ratio decreased after DPTA/NO nebulization and remained significantly lower throughout the study period (p < 0.01). Cardiac output, arterial blood gases, and methemoglobin values did not differ between groups. These data demonstrate that the pulmonary hypertension induced by GBS infusion is markedly attenuated by DPTA/NO nebulization. The lower PVR/SVR observed in the treated group indicates that the vasodilatory effect of NONOate is more pronounced in the pulmonary than systemic vasculature. Therefore, NONOates may have clinical application in the management of pulmonary hypertension secondary to sepsis in neonates.
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Abbreviations
- ABG:
-
arterial blood gas
- BL:
-
baseline
- CO:
-
cardiac output
- Crs:
-
respiratory compliance
- GBS:
-
group B Streptococcus
- iNO:
-
inhaled nitric oxide
- NO:
-
nitric oxide
- Paw:
-
mean airway pressure
- PL:
-
placebo
- Ppa:
-
pulmonary artery pressure
- Pra:
-
right atrial pressure
- Psa:
-
systemic arterial pressure
- PVR:
-
pulmonary vascular resistance
- Pwp:
-
pulmonary wedge pressure
- RT:
-
respiratory resistance
- SVR:
-
systemic vascular resistance
- VT:
-
tidal volume
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Supported by the University of Miami: Project New Born, Bachelor Children's Research Institute Department of Pediatrics, Division of Neonatology, University of Miami School of Medicine.Presented in part at the Society for Pediatric Research, May 2002, Baltimore, MD.
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Dabrowska, K., Hehre, D., Young, K. et al. Effects of a Nebulized NONOate, DPTA/NO, on Group B Streptococcus–Induced Pulmonary Hypertension in Newborn Piglets. Pediatr Res 57, 378–383 (2005). https://doi.org/10.1203/01.PDR.0000150802.35283.27
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DOI: https://doi.org/10.1203/01.PDR.0000150802.35283.27
