EFFECT OF INHALED NITRIC-OXIDE ON INTRAPULMONARY RIGHT-TO-LEFT-SHUNTING IN 2 RABBIT MODELS OF SALINE LAVAGE INDUCED SURFACTANT DEFICIENCY AND MECONIUM INSTILLATION

Marked hypoxia secondary to intrapulmonary right-to-left shunting is a characteristic of respiratory failure in human neonates and can somet imes be complicated by additional extrapulmonary right-to-left shuntin g. To investigate the effect of inhaled nitric oxide (iNO) on intrapul monary shunting, two typical pulmonary diseases of the newborn (respir atory distress syndrome and meconium aspiration) were reproduced in 32 mechanically ventilated rabbits weighing approximately 2 kg each. Aft er 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 sh unt by Fick equation). Repeated airway lavages (LAV) with normal salin e or repeated instillations of a suspension of human meconium (MEC) we re continued until both the a/A-ratio was less than or equal to 0.14 a nd a peak inspiratory pressure greater than or equal to 22 mbar was ne eded to keep the tidal volume constant at 10 ml/kg of body weight. Mea surements of shunt, SRVP, systolic systemic pressure, physiological de ad space, tidal volume and a ventilation index were performed before a nd after completion of lung damage and at 20 and 60 min after administ ering iNO at 80 ppm. Four groups of rabbits were studied (n = 8 in eac h 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: 15.1 +/- 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 dem onstrate that iNO decreases intrapulmonary shunt (as well as SRVP and dead space). We suggest that iNO may be beneficial in human newborns w ith severe respiratory failure even if no extrapulmonary shunting via ductus or foramen ovale is apparent.