| Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) arecommon, life-threatening causes of acute respiratory failure that arise from a variety oflocal and systemic insults. It's characterized as a part progress of systemic inflammatoryresponse syndrome. High permeability of lung vascular, edema of pulmonary stroma,pulmonary atelectasis and intra-alveolar fibrin deposit has long been recognized as apathological hallmark of ALI/ARDS. Meanwhile, study of ALI/ARDS shows thatthrombin mostly produced in may promote gathering and adhering of neutrophilicleukocytes. Therefore, the balances are brokened between blood clotting andanticoagulation, inflammation in the course of ALI/ARDS. To prevent intra-alveolarfibrin deposit by modulate coagulation system may be a important therapy toALI/ARDS.Objective: To establish rabbit ALI/ARDS model by injectinglipopolysaccharide(LPS). To investigate the potential beneficial effects ofanticoagulation and anti-inflammation of heparin on the early stage of ALI/ARDS.Methods:Thirty-six New Zealand white rabbit divided into three groups (n=12): normalcontrol group (group A), LPS group (group B), heparin group (group C). All animals areanesthetize, intubated through arteria cruralis and femoral vein and administeredintravenously Saline 8ml/kg/h. After intubation, group B is injected by LPS 500ug/kgwithin half an hour. Group C is administered intravenously by heparin 50U/kg/h afterinjecting LPS an hour later within 5h. Blood tests are performed at 4, 8, 12, 24, and 48hours.Results1. The levels of PaO2 were decreased progressively after injection of LPS. At four hours after injection, the levels of PaO2 in Group B, C were lower than those in GroupA(P＜0.05). At 8, 12, 24, and 48 hours after injection, the levels of PaO2 in Group Cwere higher than those in Group B(P＜0.05). There was no significant difference in thelevel of PaO2 between Group C and A at 24 and 48 hours(P＞0.05).2. The levels of TNF-a were increased progressively after injection of LPS. At 4, 8,12, 24, 48 hours after injection, the levels of TNF-a in Group B were higher than thosein Group A(P＜0.05). The levels of TNF-a in both Group B and C have a peak level at 8hours. At 24 and 48 hours Group B were high than those in Group C (P＜0.05). Therewas no significant difference in the level of TNF-a between Group C and A(P＞0.05) at48 hours.3. The activity of ATⅢwas decreased progressively after injection of LPS. At 4hours after injection, the activity of ATⅢin Group B and C were lower than those inGroup A (P＜0.05). After 8 hours the activiry of ATⅢrised gradually. At 48 hours, theactivity of ATⅢwas still lower than those in Group A. The activity of ATⅢin Group Cwere higher than those in Group B at 12, 24, 48 hours. And at 24,48 hours,there was nosignificant difference in the activity of ATⅢbetween Group C and A(P＞0.05).4. The levels of PLT were decreased progressively after injection of LPS. At 8, 12,24, 48 hours after injection, the levels of PLT in Group B were lower than those inGroup A(P＜0.05). The levels of PLT in Group C were lower than those in Group A at 8hours (P＜0.05). At 24 and 48 hours Group B were high than those in Group C (P＜0.05).There was no significant difference in the level of TNF-a between Group C and A(P＞0.05) at 24 and 48 hours.5. In Group B, there was significant correlation between ATⅢand TNF-a at hour4,8,12,24,48(r=-0.798, r=-0.895, r=-0.854, r=-0.813. P＜0.01).6. D/W of the lung in Group A, B, and C were 0.2869±0.021, 0.2173±0.015,0.2486±0.018, respectively. D/W of the lung in Group B, C were lower than that inGroup A (P＜0.05).D/W of the lung in Group C were higher than that in Group B(P＜0.05). 7. The scores of lung injury in Group A, B, and C were 6, 18.33±3.47, and12.6±2.41, respectively. The scores of lung injury in Group C were lower than that inGroup B(P＜0.05).8. None of animals in Group A die in the course of experiment. Four rabbits inGroup B died before the end of experiment. One rabbit in Group A died before the endof experiment. The mortality of Group B and C has significant difference (P＜0.05).Conclusion:1. The levels of TNF-a in the plasma arise significantly in the early of ALI/ARDS,related to the severity of rabbit's illness. This indicates that over reaction ofinflammatory system play an important role in tissue injuring in the early stage ofALI/ARDS.2. The activity of and the level of PLT significantly decreased, related to theseverity of rabbit's illness. This indicates that the disorder of coagulation system play animportant role in physiological functions in the early stage of ALI/ARDS.3. Through correlation analysis, we found that the levels of TNF-a and the activityof ATⅢhave significant correlation. This indicates that in the early stage of ALI/ARDS,there has been an effect of strengthen interaction between inflammatory system andcoagulation system.4. This study indicates that heparin has an effect of therapy through blockingcoagulation system and anti-inflammatory, which lead to a lower mortality of rabbits.
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