Inhaled Nitric Oxide Intervention On Experimental Meconium Aspiration Pneumonia And Acute Lung Injury

Meconium aspiration pneumonia is one of the most common respiratory problems during neonatal period. And it can cause many complications including persistent pulmonary hypertension with high mortality. Recently, inhaled nitric oxide (iNO) has been successfully used to treat persistent pulmonary hypertension of the newborn caused by meconium aspiration. While few have been focused on whether to early use inhaled nitric oxide and on effects of iNO dosage and fraction of inspired oxygen in the treatment of meconium aspiration pneumonia.Meconium aspiration can lead to pneumonia and acute lung injury. Complicated respiratory failure and persistent pulmonary hypertension are often treated by conventional respiratory support. In 1997, Kinsella reported that inhaled 5ppm nitric oxide could attenuate neutrophils accumulation in the lung of newborn lamb with hyaline membrane disease, which implied inhaled NO might have a potential of anti-inflammatory activity. But the underline mechanism is still poorly understood. Until present, few have been reported on whether and how iNO affected lung neutrophils sequestration and lung injury caused by meconium aspiration. We hypothesized that inhaled nitric oxide does have anti-inflammatory effects on meconium aspiration pneumonia and acute lung injury by inhibition of neutrophil accumulation, which does have significant impacts on lung pathology and repairing progress.In our present studies, we established a rabbit model of meconium aspiration pneumonia2003and treated it with different dose of iNO under room air or 100%O2 for 12 hours. Oxygenation and lung injury were evaluated. Concentration of IL-8 , expression of CDllb on neutrophils in the HALF and expressions of lung collagen I and III mRNA were detected to investigate the possible mechanism of iNO intervention on lung injury and to clarify the clinical implications of iNO in treating neonates with meconium aspiration pneumonia and acute lung injury.Part 1 Effects of Inhaled Nitric Oxide on Oxygenation in ExperimentalMeconium Aspiration Pneumonia Objectives:To evaluate the effects of different dose of iNO (6ppm, lOppm or 20ppm) under 21 %O2 or 100%O2 on Oxygenation in experimental meconium aspiration pneumonia. Methods:The adult rabbit model of mconium aspiration pneumonia was established by infusing 3ml/kg of 20% newborn meconium suspension through endotracheal tube. Sixty adult rabbits were anesthetized and randomized to 10 groups (six in each group): two were control groups under 21% or 100%O2 (meconium was substituted by equal volume of saline). Two were model groups under 21% or 100%O2. And six were inhaled by nitric oxide gas for 12 hours at a dose of 6ppm, lOppm or 20ppm under 21% or 100%O2 after meconium aspiration. Mean systemic arterial pressure, methemoglobin (MetHb), pH, PaCO2 and PaO2 were monitored. PaO2/FiO2 was calculated at each time point (baseline, 0,1,2,3,4 and 12hour) during the experiment. Results:No significant difference was found on mean systemic arterial pressure between groups at each time point. NO2 concentration in the ventilatory circuit was less than 2ppm. And MetHb of each group at different time point was below 2%. pH values of the two model groups were consistently below 7.25 at 3, 4 and 12 hour. However, in the other groups, pH values were within 7.29-7'Al at each time point. There was no significant difference in PaO2/FiO2 at baseline between groups (P>0.05 respectively). PaO2/FiO2 at 0 hour time point2003was <220mmHg in all except the control groups and it was significantly decreased compared with the baseline (P2 at 0 hour time point had no statistical difference between the model and iNO groups under the same oxygen concentration (P>0.05). PaO2/FiO₂ in the lOppm iNO group under 21%O₂ was significantly lower than that under 100%O₂ at 3, 4 and 12 hour time point (P<0.05 respectively). And PaO2/FiO2 of 20ppm iNO group under 21%O2 was significantly lo...