Partial Liquid Ventilation Therapy Of Acute Lung Injury And Observation Of Its Anti-inflammatory Effects

OBJECTIVE:Acute lung injury (ALI) / acute respiratory distress syndrome(ARDS) continue to be clinical serious pathological processes with high mortality. It's critical component is the excessive lung inflammatory response induced by an elevated level of cytokines and activated phlogistic cells. Prompt and significant solutions are required. Partial liquid ventilation (PLV) has showed its advantage in the therapy of ALI/ARDS as an effective new pattern of ventilation with liquid respiratory medium of perfluorocarbon (PFC). Most animal models of acute lung injury have demonstrated that PLV improve oxygenation, lung acclimation, survival and anti-inflammatory effect. In our research, we investigate the anti-inflammatory effect of PLV with PFC in the piglets with lung lavage-induced acute lung injury, aim to provide warrant for clinical therapy of acute lung injury. METHODS:16 healthy piglets weighting 22-25 kg were randomly divided into mechanical ventilation (MV) group (n=8) and PLV group (n=8). The animals were tracheotomized and mechanically ventilated with oxygen (FiO2=1.0). The parameters of gas exchange and hemodynamics were measured before lung lavage as Baseline. Acute lung injury (ALI) were induced by lung lavage according to Lachmann. All piglets were surfactant-depleted by lung lavage using 37 ℃, 40 mL/kg of 9 g/L NaCl until PaO2<100 mmHg (FiO2=1.0) for one hour. Conventional mechanical ventilation was administered in MV group. In PLV group the animals received doses of 30 mL/kg perfluorocarbon FC-77 and mechanical ventilation was administered for 4 h. FC-77 was continued dropping via tracheal tube to redeem the evaporation during therapy. The parameters of gas exchange and hemodynamics were measured at moment of ALI establishment and the time points of 1 h, 2 h, 3 h, 4 h after ALI in both groups. At the end of animal experiment, samples of the venous blood, bronchoalveolar lavage fluid and lung tissue were obtained for detecting the contents of MDA SOD TNF-α IFN-γ and infiltration of PMN. The tissue sections were also prepared for the observationof lung injury under the light and electronic microscopes. RESULTS:After PFC instillation, PaO2 and SaO2 in PLV group were significantly higher, AaDO2 and Qs/Qt significantly reduced than those in MV group. Mean pulmonary artery pressure(MPAP) in MV group significantly increased than Baseline; MPAM, PCWP and other hemodynamics had no significant difference compared with MV group.Histopathologic findings showed that lung edema and hemorrhage were observed in MV group under light microscope. The pulmonary surfactant layer was discontinuous, lamellar bodies and plasmosomes in type II alveolar cells became vacuolization. The above impairments were slighter in PLV group. The W/G and PPI, the content of MDA and activity of MPO in PLV group were significantly lower than those in MV group. The content of TNF-a and IFN-y in plasma and lung tissue in PLV group were significantly lower than those in MV group. No significantly difference of NF-kB between the two groups was observed. CONCLUSION:Our data indicate that PLV protect lung from the excessive lung inflammatory response in ALL The mechanisms of protection might be associated with the decrease in PMN congregation, Hpid oxygenation damage and cytokines release.