Continuous Inhalation of Nitric Oxide From Birth Preserves the Pulmonary Vasoconstrictor Response to Hypoxia in Chronically Ventilated Preterm Lambs• 1614

Abstract

Chronic lung injury from prolonged mechanical ventilation of preterm lambs inhibits the normal postnatal decrease in pulmonary vascular resistance (PVR) and blunts the vasoconstrictor response to hypoxia (Bland et al, Pediatr Res 39:327A, 1996). These abnormalities of lung vascular tone and reactivity may contribute to impaired respiratory gas exchange that often exists in infants with chronic lung disease (CLD). We previously reported that nitric oxide (NO) inhalation for 1 h reduced PVR in preterm lambs with evolving CLD. To see if continuous NO inhalation from birth might inhibit the pulmonary vascular dysfunction that occurs in this model of CLD, we studied 4 preterm lambs (124± 3 d gestation; term = 147 d) that were mechanically ventilated for 3-4 wks at a respirator rate of 20 breaths/min, tidal volume 10-15 ml/kg, with 5-15 ppm NO and sufficient O2 to keep the PaO2 ≅ 50-90 mmHg. All lambs received surfactant at birth and had surgery for ductus arteriosus ligation and catheter placement to allow weekly assessment of PVR from measurements of pulmonary arterial and left atrial pressures and pulmonary blood flow before and during steady-state hypoxia. Results of these studies were compared with those of similar studies done with 10 lambs of the same gestation that were mechanically ventilated the same way but without NO. After 3 wks of mechanical ventilation, baseline PVR was not significantly different in the 4 lambs that received NO compared with the 10 lambs that did not receive NO (PVR = 44.8 ± 5.4 vs 53.9 ± 21.2 mmHg/(L/sec)/kg, respectively). However, in response to hypoxia (baseline FiO2.28±.09, PaO2 73 ± 3; hypoxia FiO2.17 ±.03, PaO2 35 ± 1), PVR consistently increased from 48.3 ± 2.3 to 74.0 ± 20.0 mmHg/(L/sec)/kg at the end of wk 3 in lambs that received NO from birth, whereas PVR did not increase significantly at the end of wk 3 in chronically ventilated lambs that did not receive NO. When inhaled NO was discontinued for 2-4 h after 3 wks of mechanical ventilation in the 4 NO-treated lambs, PVR increased on average from 50.5 ± 11.7 to 64.5± 18.7 mmHg/(L/sec)/kg. Subsequent hypoxia (FiO2.17 ±.03, PaO2 35 ± 4 mmHg), without inhaled NO, further increased PVR to 87.8 ± 27.2 mmHg/(L/sec)/kg. Thus, continuous nitric oxide inhalation from birth may help to preserve the normal pulmonary vasoconstrictor response to hypoxia and thereby facilitate ventilation-perfusion matching and respiratory gas exchange in chronically ventilated preterm lambs.