Effects And Mechanism Of Vaporized Perfluorocarbon Therapy On Seawater Respiratory Distress Syndrome In Animal Models

[OBJECTIVE]To investigate the effects of vaporized perfluorocarbon therapy on seawater respiratory distress syndrome in animal models and to approach the mechanism of the therapy.[METHODS]40 Famale Newsealand rabbits were randomly divided into five groups:(1)CMV group: received conventional ventilation, Vt=8ml/kg, PEEP=0cmH₂O, PFC=0ml/kg.h; (2)PEEP group: received CMV and 8cmH₂O positive end expiratory pressure (PEEP ) ventilation, Vt=8ml/kg , PEEP=8cmH₂O, PFC=0mI/kg.h; (3)PFC group: received CMV and 7ml/kg.h PFC vaporized inhalation, Vt=8ml/kg, PEEP=0cmH₂O, PFC=7ml/kg.h; (4)PFC+ PEEP group: received CMV, PEEP and PFC vaporized inhalation, Vt=8ml/kg, PEEP=8cmH₂O , PFC=8ml/kg.h; (5)control group: without ventilation after making models, each group having 8 rabbits. The animals in former four groups received different treatment for 2 hours followed by conventional ventilation 4 hours. Then each animal was killed and underwent left lung lavage to analyse the change of interface tension , and right lung in same area were cut into small slides which partly were fixed in 10% buffered formalin and 2% glutaraldehyde to make morphometry evaluation, partly were storaged in liquid nitrogen to calculate molecular biology indexes. Other 3 rabbits were directly killed to make light microacopy studies.Part 1 To investigate the effects of vaporized perfluorocarbon on respiratory mechanics, hemodynamics mechanics and arterial blood gas indexes during and after different treatments. in addition, to observe the structural changes of lung after treatments.Part 2 In order to approach the mechanism of vaporized perfluorocarbon therapy, we evaluated surfactant biology function by interface tension of bronchial alveolar lavage fluids(BALF) measurement with captive bubble surfactometer, analysed the changes of surfactant composition , including the changes of phosphatides, that of SP-B in protein level and those of SP-B, SP-C mRNA expression in lung among different groups.[RESUILS]1 After lung injury, the data of respiratory mechanics and oxygenation index were significantly getting worsen. After receiving vaporized PFC, PEEP and PFC+PEEP ventilation, these indexes statistically improved compared with CMV in which there was no influence to the indexes. In addition, PFC and PEEP had synergistic effect on oxygenation improvement during treatment. After treatment, the improvement of oxygenation in PFC group could even persist long time, but the oxygenation indexes in PFC+PEEP group decreased to equal with those in PFC group in one hour. All animals in C group died in fifteen minites without ventilation.2 During treatment, PFC vapor had no influence in hemodynamics indexes. Compared C groups, lung injury and laminated body vacuolization decreased in PFC, PEEP, PFC+PEEP groups; in contrast , those got worsen in CMV group. 3 Among the five groups, the levels of interface tension in BALF in CMV and C groups were more increased than those in other three groups. After ten cycles, the minimum interface tension in PFC and PFC+PEEP groups decreased and were statistically lower than CMV and C two groups. There was no statistical difference in interface tension between PEEP group with CMV group, although the minimum interface tension in PEEP group decreased.4 PFC inhalation could influence the levels of differtent phosphatide composition , increasing phosphatidylcholine(PC) content and proportion, but not changing phosphatidylethanolamine (PE) level.5 In this study , we found that the mRNA expressions of SP-B and SP-C in PFC, PEEP and PFC+PEEP groups were significantly higher than those in other two groups, especially in PFC+PEEP group. which indicated vaporized PFC enhanced the mRNA expressions of SP-B and SP-C in lung. Western blot and IPHC results showed that vaporized PFC and PFC+PEEP treatment increased SP-B level in alveolar type II cell.6 Though analyzing the corrrlation coefficient of intersurface tension levels with the data of PE, PC, SP-B, SP-B mRNA, SP-CmRNA, we found that: the concentrations of SP-B mRNA, and SP-CmRNA had positive correlation with levels of intersurface tension.[CONCLUSION]1 Vaporized PFC , PEEP and vaporized PFC + PEEP ventilation could improve oxygenation indexes and lung compliane in SW-RDS animals, especially PFC + PEEP treatment during treatment. But after treatment, oxygenation indexes in group rapidly decreased and had no difference with those in PFC group in one hour.2 Vaporized PFC and PFC+PEEP ventilation enhanced the symehesis of lung surfactant , changing phosphatide composition, increasing SP-B, SP-C mRNA expression and SP-B level in lung, decrease inface tension and attenuate lung injury so as to regulate prognosis of seawater acute respiratory distress syndrome in animal models .