Mitigation of meconium-induced lung injury by surfactant and inhaled nitric oxide is associated with suppression of nuclear transcription factor kappa B.

Objective: To investigate whether the mechanism of a combined surfactant and inhaled nitric oxide (iNO) in improvement of oxygenation and mitigation of lung injury is associated with suppression of nuclear transcription factor kappa B (NF-kappaB) in the lung tissue of ventilated rabbits with meconium aspiration. Methods: Adult rabbits (weight 2.0-3.5 kg, n = 33) were anesthetized, intratracheally received human meconium, and were subjected to pressure support ventilation for 30-60 min to induce hypoxemic respiratory failure and lung injury. They were then treated for 6 h in groups: control animals; rabbits receiving iNO; animals receiving surfactant (100 mg/kg), and rabbits receiving both iNO and surfactant. iNO was delivered continuously by mass flow controller in sequence at 1, 10, 20, and 40 ppm each for 60 min at 30-min intervals. Results: Improvement in oxygenation and lung mechanics was found in the animals receiving both iNO and surfactant, associated with a marked response to iNO at 10 and 20 ppm (p < 0.05), a significantly higher ratio of disaturated phosphatidylcholine to total proteins, a lower surface tension of phospholipids from bronchoalveolar lavage fluid, a lower wet-to-dry lung weight ratio and lower lung injury scores, and better alveolar aeration. The iNO- and surfactant-treated groups had only transient or moderate-to-intermediate improvement in the associated parameters. The expression of NF-kappa B in lung tissue was enhanced in the control group, attenuated in the groups treated with either iNO or surfactant, and significantly suppressed in the group receiving both iNO and surfactant. Conclusion: Improvements of lung mechanics and gas exchange and mitigation of lung injury by the combined surfactant and iNO are related to suppression of NF-kappa B expression in lung tissue of ventilated rabbits with hypoxemic respiratory failure. Copyright (C) 2005 S. Karger AG, Basel.