Study On The Protective Effect Of Inhaled Nitric Oxide, Milrinone Alone And Combined Medication In Treatment Of Experimental Rabbits With Early Endotoxin-induced Acute Lung Injury

Objective To observe the effect of inhaled nitric oxide, milrinone alone and combined medication in treatment of rabbits with early acute lung injury(ALI), and the change of the concentration of TNF-α, IL-1βand IL-10 in serum. To investigate whether earlier treatment with combined medication has any synergistic effect to improve blood oxygenation, and whether it could regulate the balance between inflammatory mediators and anti-inflammatory mediators and mitigate ALI. And to discuss the mechanism of combined medication.Methods 30 rabbits were anesthetized with tracheotomy, and then ventilated mechanically. Six animals were selected as normal control (groupⅤ). The other were induced into ALI by endotoxin, and randomly allocated into four groups: groupⅠ, inhaled NO at 20 ppm combined with intravenous milrinone at 5μg·kg-1·min-1 after a bolus 50μg·kg-1 (n=6); groupⅡ, inhaled NO at 20 ppm(n=6); groupⅢ, intravenous milrinone at 5μg·kg-1·min-1 after a bolus 50μg·kg-1 (n=6); groupⅣ,endotoxin control group(n=6). The mean systemic arterial pressure (MAP), mean pulmonary arterial pressure(mPAP) were recorded ,and blood gas analysis is made and Qs/Qt were calculated at the time of baseline , 0, 120, 150 min after modeling. The concentration of TNF-α, IL-1βand IL-10 in serum were determined at the same time. Total cells, PMN(%) and protein contents in bronchoalveolar lavage fluid(BALF) and Wet-to-dry weight ratio(W/D) were determined after treatment. And lung specimens were obtained to observe the histomorphological changes .Results①Compared with groupⅣ, groupsⅠ,Ⅱ,Ⅲare more effective in increasing PaO2 and lowering mPAP and Qs/Qt without inducing significant change of MAP (p<0.05). And TNF-α,IL-1βin serum were significantly decreased, however IL-10 in serum was significantly enhanced (p<0.05). Total cells, PMN(%), and protein contents in the BALF were significantly decreased too(p<0.05). These results suggest that inhaled NO or intravenous milrinone could attenuate endtoxin-induced ALI and pulmonary inflammation.②Compared with groupsⅡ,Ⅲ, the indexes mentioned above were more significantly improved in groupⅠ. A statistically significant interaction between inhaled NO and intravenous milrinone was observed for PaO2, Qs/Qt, PMN(%), TNF-αand IL-1βwith multiple-factor analysis of variance(p<0.05). The pathological results from lungs showed that the lung was infiltrated by only a few inflammatory cells, alveolar were better expansion and alveoli interval was not thickened, and the pulmonary edema was decreased. The degree of lung injury of groupⅠwere lower than other groups .Conclusion①Milrinone could significantly decrease mPAP and Qs/Qt, and increase PaO2. At the same time it could reduce PMN accumulation in lung tissue and inflammatory factors in serum, and increase anti-inflammatory medium in serum. Milrinone have positive effect on preservation of ALI, and the mechanism is believed to be related to inhibitory effect of pulmonary inflammation.②Compared with medication alone, inhaled NO combined with milrinone could significantly improve pulmonary gas exchange and enhance oxygenation. On the other hand, it could significantly reduce inflammatory mediators and increase anti-inflammatory mediators in serum, and has a role of regulation of balance between inflammatory mediators and anti-inflammatory mediators. Synergistic effect through the cGMP - PDE-cAMP way may be important mechanism of combined medication against ALI. Because it could significantly attenuate injury and suppress the development of ALI, inhaled NO combined with milrinone may be a good way treating ALI/ARDS.