| Phosgene belongs to blackdamp,which may cause toxic pneumonia,diffusive and transudatory pulmonary edema, ARDS and death even. The air becomes thinner in plateau. Hypobaric hypoxia is the main and beginning harmful environmental factor to inhigh altitude. Hypoxia is not only harmful to people but also aggravate toxic symptom. Acute exposure in both high altitude and phosgene will cause acute hybobaric hypoxia and acute phosgene poisoning.At present,it has been reported widely about hybobaric hypoxia but phosgene poisoning in high altitude has not been reported before . Recently, Hyperoxia solution (HOS) is used as an effective way to treat anoxia diseases. This study investigated the effects of HOS on phosgene poisoning and hypobaric hypoxia -induced acute lung injury.Part 1 Experimental studies on damage effects and investigate mechanism on acute rabbit lung injury induced by phosgene poisoning and hypobaric hypoxia AIM: To investigate the damage effects and investigate mechanism on acute rabbit lung injury induced by phosgene poisoning and hypobaric hypoxia.METHODS: 40 New Zealand white rabbits (weight 2.0～2.5kg) were randomly divided into 4 groups(n=10):Control group(group C,with fresh and normal pressure ); Hypobaric hypoxia group(group H,with fresh air for 5 min and exposure to a simulated altitude of 3000 m for 2 hours ); Phosgene poisoning group(group P,exposure to phosgene for 5 min only);Phosgene poisoning and hypobaric hypoxia group(group HP, exposure to phosgene for 5 min and a simulated altitude of 3000 m for 2 hours). Breathing frequency was recorded and blood samples were taken at different time points(T1,T2,T3,T4,T5) for the determination of PaO2, plasma malordialdehyde (MDA) contents , superoxide dismutase(SOD) activity and tumor necrosis factor-α( TNF-2α) contents, interleukin-6(IL-6) . Survival time of each rabbit and death rate was recorded in all groups .RESULTS: (1) The survival time shorten and death rate increased significantly in group HP in comparison with group H(P<0.05 or P<0.01 ).(2) In group P and HP,breathing rate increased, PaO2 and oxygenation index decreased significatly than in group H and C. At T3,T4,T5 time point, plasma MDA contents, TNF2αand IL-6 contents increased and SOD activity decreased distinctly in group P and HP comparied with group H and C(P<0.05 or P<0.01).(3)In group HP,breathing rate and MDA cotents increased, PaO2 and SOD activity decreased significatly(P<0.05或P<0.01)at T3,T4,T5 in comparison with group P. TNF-2αand IL-6 contents raised obviously at T4,T5 in group HP than group H(P<0.05).CONCLUSION:Phosgene poisoning and hypobaric hypoxia result in more serious injury in lung than only phosgene poisoning or hypobaric hypoxia. Part 2 Experimental studies on Protective effects and investigate mechanism of hyperoxia solution infusion on acute rabbit lung injury induced by phosgene poisoning and hypobaric hypoxia.AIM: To investigate the protective effect and mechanism of HOS on rabbit with acute lung injury induced by phosgene and hypobaric hypoxia.METHODS : 40 New Zealand white rabbits (weight 2.0～2.5kg) were randomly divided into 4 groups(n=10):Group HP : with exposure to phosgene for 3 min and a simulated altitude of 3000 m for 2 hours;Group HPB :After exposed to phosgene for 3min ,this group was exposed to a simulated altitude of 3000 m for 2 hours with an infusion of balanced salt solution(BS,20mL·kg-1) in 1h ;Group HPO: After exposed to phosgene for 3min ,this group was exposed to a simulated altitude of 3000 m for 2 hours with continued mask oxygen inhalation (0.3 L·min-1) in 1h; Group HPH: After exposed to phosgene for 3min ,this group was exposed to a simulated altitude of 3000 m for 2 hours with an infusion of HOS (20mL·kg-1) in 1h . Breathing frequency was recorded and blood samples were taken at different time points(T1,T2,T3,T4,T5) for the determination of PaO2, plasma malordialdehyde (MDA) contents , superoxide dismutase(SOD) activity and tumor necrosis factor-α( TNF-2α) contents, interleukin-6(IL-6) . After 6 hours, the chests were opened and lungs removed. The wet left lungs were weight for L·B-1, then after lavaging bronchoalveolar with 0.9% salt solution for plasma MDA contents,GSH-Px activity and protein level in bronchoalveolar lavage fluid(BALF), they were placed in an oven at 70 deg C and dried to a constant weight to measure LW. Small piece of left lung was homogenized and analyzed tissue Glutathione (GSH/GSSG) contents. The remaining parts of left lung were collected to observe pathologic changes.RESULTS: Breathing rate and LW ,L·B-1 was significantly lower and PaO2 was higher in HPH and HPO than in HP and HPB. At T3,T4,T5 time point, plasma MDA contents, TNF2αand IL-6 contents decreased and SOD activity increased distinctly in group HPH and HPO in comparison with group HP and HPB(P<0.05 or P<0.01). In group HPH, MDA contents decreased , PaO2 and SOD activity increased significantly than in group HPO. MDA contents and protein levels in BALF depressed and GSH-Px activity increased distinctly in group HPH and HPO than in group HPB and HP (P<0.01 or P<0.05). ONCLUSION:(1) More serious injury in lung induced by phosgene and hypobaric hypoxia than simple phosgene poisoning or hypobaric hypoxia.(2) Treatment with HOS shown a protective effect on rabbits with acute lung injury induced by phosgene exposure and hypobaric hypoxia.
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