Nitric oxide inhalation inhibits pulmonary apoptosis but not inflammatory injury in porcine meconium aspiration

To investigate the possible protective effects of nitric oxide (NO) inhalat ion in newborns with meconium aspiration, 18 10-12-d-old piglets were studi ed for 6 h after an intratracheal bolus (3 ml/kg) of a 65-mg/ml mixture: of human meconium. Twelve of the piglets were treated with continuous NO inha lation at a dose of 1 ppm (n = 6) or 10 ppm (n = 6), started 30 min before the insult. Pulmonary haemodynamics and systemic oxygenation were followed, and lung tissue samples were studied for signs of inflammation, evidence o f ultrastructural injury and apoptotic cell changes. Inhalation of 10 ppm N O, in contrast to 1 ppm NO, significantly delayed the meconium-induced pulm onary pressure rise and the increase in intrapulmonary shunt fraction, and maintained better oxygenation in the piglets. Histologically and biochemica lly, treatment with 1 or 10 ppm NO inhalation did not protect the lungs aga inst meconium-induced inflammatory injury. Further, ultrastructural lung ti ssue analysis revealed a significant amount of alveolar exudate and oedemat ous alveolar epithelium and endothelium after meconium instillation, also i n the lungs treated with NO inhalation. However, the increase in apoptotic epithelial cell deaths, previously shown to be stimulated by intratracheal meconium, was significantly impeded after inhalation of 10 ppm. These resul ts thus show that early continuous NO inhalation controls the rise in pulmo nary artery pressure and improves the efficiency of arterial oxygenation, a nd further prevents the increase in epithelial apoptosis; but does not prot ect against early inflammatory damage caused by meconium aspiration.