Mitigation of Meconium-Induced Lung Injury by Surfactant and Inhaled Nitric Oxide Is Associated with Suppression of Nuclear Transcription Factor Kappa B

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Abstract
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. 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. 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-kappaB 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. Improvements of lung mechanics and gas exchange and mitigation of lung injury by the combined surfactant and iNO are related to suppression of NF-kappaB expression in lung tissue of ventilated rabbits with hypoxemic respiratory failure.