US EPA

2265421 

Journal Article 

Abstract 

Inhaled nitric oxide (iNO) prevents hypoxic pulmonary vasoconstriction in lambs with persistent pulmonary hypertension of the newborn (PPHN) 

Lakshminrusimha, S; Mathew, B; Wynn, KA; Nair, J; Ryan, RM; Russell, JA; Swartz, DD 

2010 

Yes 

American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 

181 

A3894 

English 

10.1164/ajrccm-conference.2010.181.1_MeetingAbstracts.A3894 

WOS:000208771003243 

is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans

RATIONALE: Persistent pulmonary hypertension of the newborn (PPHN) is a clinical condition characterized by high pulmonary vascular resistance (PVR) and hypoxemia and is associated with high morbidity and mortality. Ventilation with high concentrations of oxygen is the mainstay of therapy in PPHN. Some infants with PPHN are managed with supraphysiological PaO2 levels to prevent episodes of hypoxic pulmonary vasoconstriction. The optimal FiO2 during management of PPHN is not clear. We recently reported that in lambs with PPHN, increasing FiO2 above 0.5 does not result in additional decrease in PVR. However, decreasing FiO2 to 0.21 or 0.1 results in marked elevation in PVR (Pediatr Res. 2009 Nov;66(5):539-44). Inhaled nitric oxide (iNO) is an approved therapy for PPHN. The effect of iNO on the relationship between PVR and FiO2 in the newborn is not known.

METHODS: PPHN was induced by antenatal ligation of the ductus arteriosus in fetal sheep 8 days prior to delivery. Newborn lambs were delivered by C-section and instrumented to measure pulmonary arterial and left atrial pressures and pulmonary blood flow. PVR was calculated [PVR=(PAP-LAP)/Qp] and corrected for body weight. At 2 hours of age, 12 PPHN lambs were randomly and sequentially ventilated with varying concentrations of oxygen (FiO2 0.1, 0.21, 0.5 and 1.0) for 10-20 min each randomly and sequentially. Five PPHN lambs underwent similar sequential ventilation while receiving 20 ppm iNO. Arterial blood gases were analyzed at each FiO level.

RESULTS: There was no increase in PVR in PPHN lambs on iNO despite hypoxic ventilation with 10% oxygen (see figure and table). In lambs with PPHN ventilated without iNO, PVR increased significantly with decreasing FiO2 from 0.5 to 0.21 and from 0.21 to 0.1. PVR did not change with a decrease in FiO2 from 1 to 0.5 in PPHN lambs ventilated with oxygen alone. Inhaled NO significantly improved PaO2 at FiO2 ranging from 0.21 to 1.0. In lambs receiving iNO, profound hypoxemia following ventilation with 0.1 FiO2 did not result in significant increase in PVR. There was no change in PVR at any level of FiO2 between 0.1 and 1 in PPHN lambs ventilated with iNO.

CONCLUSIONS: Hypoxemia results in an acute increase in PVR in lambs with PPHN ventilated with oxygen alone as reported previously. Ventilation with iNO prevents acute increases in PVR following brief periods of hypoxemia and maintains low and stable PVR. We speculate that hyperoxic ventilation to achieve supraphysiological PaO2 levels may not be necessary in infants with PPHN receiving iNO therapy.

*Figures in pdf 

American Thoracic Society 2010 International Conference 

New Orleans, LA 

May 14-19, 2010