Effect of inhaled nitric oxide on intrapulmonary right-to-left-shunting in two rabbit models of saline lavage induced surfactant deficiency and meconium instillation

Abstract

Marked hypoxia secondary to intrapulmonary right-to-left shunting is a characteristic of respiratory failure in human neonates and can sometimes be complicated by additional extrapulmonary right-to-left shunting. To investigate the effect of inhaled nitric oxide (iNO) on intrapulmonary shunting, two typical pulmonary diseases of the newborn (respiratory distress syndrome and meconium aspiration) were reproduced in 32 mechanically ventilated rabbits weighing approximately 2 kg each. After tracheotomy, catheters were inserted into a jugular vein, a carotid artery and the right ventricle (to measure systolic right ventricular pressure [SRVP] and mixed venous oxygen content for calculation of shunt by Fick equation). Repeated airway lavages (LAV) with normal saline or repeated instillations of a suspension of human meconium (MEC) were continued until both the a/A-ratio was ≤0.14 and a peak inspiratory pressure ≥22 mbar was needed to keep the tidal volume constant at 10 ml/kg of body weight. Measurements of shunt, SRVP, systolic systemic pressure, physiological dead space, tidal volume and a ventilation index were performed before and after completion of lung damage and at 20 and 60 min after administering iNO at 80 ppm. Four groups of rabbits were studied (n = 8 in each group): LAV control and intervention, Mec control and intervention. 60 min after starting iNO, there was a decrease in shunt (LAV: 67.6% ± [SD] 11.3% vs 56.2 ± 16.4, P = 0.05; MEC: 52.6 ± 6.3 vs 44.3 ± 8.3, P < 0.05), in SRVP (LAV: 29.7 mmHg ± 10.1 mmHg vs 20.0 ± 8.2, P < 0.01; MEC: 25.1 ± 4.4 vs 22.3 ± 5.0, P = 0.46) and in dead space (% of tidal volume, LAV: 32.7% ± 10.5% vs 25.9 ± 10.1, P < 0.01; MEC: 26.1 ± 16.6 vs 18.9 ± 10.1, P = 0.05). These results demonstrate that iNO decreases intrapulmonary shunt (as well as SRVP and dead space). We suggest that iNO may be beneficial in human newborns with severe respiratory failure even if no extrapulmonary shunting via ductus or foramen ovale is apparent.

Conclusion

Our body weight curves are more adequate to evaluate growth of preterm infants than older published reference values because they are based on infants treated according to current nutritional standards.