Dose-dependent Study On Prevention Of Fat Embolism Syndrome By Low Molecular Dextran Combined With Methylprednisolone In Rabbits

Part oneEstablishment of an animal model of fat embolism syndrome induced by bone marrow fatObjectiveTo explore the possibility of establishing animal model of fracture complicated with fat embolism syndrome(FES)and its influencing factors.MethodsThirty-two New Zealand rabbits,all proven without pathological defect,were randomly divided into four groups.For the groups of A,B,and C,bone marrow of 0.2,0.4,0.8ml/kg were injected intravenously respectively,while the rabbits of group D were treated only with saline as control.Arterial blood gas analysis and blood routine examination were performed before(0 h)and after(1,2,4,6,8 h)injection,respectively.All the rabbits were sacrificed at 8 hours after injection for light and electron microscopic observation.Results?Compared with control group,manifestations like tachypnea were found in treated rabbits within 0.5 h after injection.During the course,death occurred in three rabbits in group B(P>0.05)and all the rabbits in group C(P<0.01),while rabbits in group A and D all survived.?Compared with control group,the minimum values of arterial oxygen pressure(PaO2)in group A and B were(10.79±1.16)kPa(P>0.05)and(6.78±0.93)kPa(P<0.01),respectively.?In the pathological examination of group B,dark red hepatization was observed in the lung specimens,fatty vacuolization was presented by HE staining and a large number of specific orange lipid droplets was identified by using Oil Red O staining.The infiltration of red blood cells and macrophages in the alveolar cavity was also observed under electron microscope with the reduction and evacuation of lamellar bodies.ConclusionsAnimal model of FES was successfully established only in the group B at two hours after injecting bone marrow fat,with a success rate of 85%.Part twoThe preventive effect of low molecular dextran combined with glucocorticoids on fat embolism syndromeObjectiveTo explore the preventive effect of low molecular dextran combined with methylprednisolone or dexamethasone on FES.Methods30 New Zealand rabbits were randomly divided into four groups treated with low molecular dextran(10ml/kg,group A),methylprednisolone(20mg/kg,group B),dexamethasone(4mg/kg,group C),combined low molecular dextran and methylprednisolone(10ml/kg+15mg/kg,group D),combined low molecular dextran and dexamethasone(10ml/kg+3mg/kg,group E)and control(group F),respectively.Different preventive treatments as above were given one hour before injection.Arterial blood gas analysis,blood routine examination,and plasma free fatty acid(FFA)were performed before(0 h)and after(1,2,4,6,8 h)injection,respectively.All the rabbits were sacrificed at 8 hours after injection and changes of lung tissues were observed under light and electron microscopy.Results?The PaO2 of group A,B,C,D and E,reached the minimum 1 h after injection,shown as(7.24±0.97)kPa,(8.13±0.86)kPa,(9.23±0.97)kPa,(11.04±0.60)kPa,(9.82±0.77)kPa,respectively,while the group F reached the minimum 2 h after injection(6.26±0.59)kPa.?At different time points after injection,the number of hemoglobin and platelet in the treatment group were significantly different from those in the control group(P<0.01),but there was no significant difference between the administration groups(P>0.05).?There was significant difference between the administration group and the control group in FFA at different time points after injection(P<0.05).?Under the same ratio,the number of lipid droplets in combined medication group was significantly lower than that in the control group.Erythrocyte exudation,macrophage infiltration and lamellar body reduction accompanied with evacuation were seen in all groups under electron microscope.ConclusionsAll the administered groups had some preventive effects on FES,while combined treatment of low molecular dextran and methylprednisolone turned out with the best results.Combination therapy can't decrease the mortality rate of FES,but it can reduce the incidence of FES.Part threeDose-dependent study on prevention of fat embolism syndrome by low molecular dextran combined with methylprednisolone in rabbitsObjectiveOn the basis of the second part of the study,to further explore the preventive effect by different doses of methylprednisolone combined with low molecular dextran in early prevention on FES.Methods30 New Zealand rabbits were randomly divided into low dose methylprednisolone group(20mg/kg,group A),high dose methylprednisolone group(80mg/kg,group B),low dose methylprednisolone plus low molecular dextran group(15mg/kg+10ml/kg,group C),high dose methylprednisolone plus low molecular dextran group(60mg/kg+10ml/kg,group D),and control group(group E).Each group received the preventive treatment of corresponding drugs 1 h before injection.Arterial blood gas analysis,blood routine examination,and FFA were performed before(0 h)and after(1,2,4,6,8 h)injection,respectively.All the rabbits were sacrificed at 8 hours after injection and changes of lung tissues were observed under light and electron microscopy.Results?The PaO2 of group A,B,C,and D,reached the minimum 1 h after injection,shown as(8.02±0.66)kPa,(8.93±0.86)kPa,(11.04±0.60)kPa,(11.03±0.52)kPa,respectively,while group E reached the minimum 2 h after injection(6.26±0.59)kPa.The PaO2 of group A,B,C,and D was significantly different compared with group E(P<0.01).There was no significant difference in PaO2 of group C and group D at each time point before or after injection(P>0.05).? At different time points after injection,the number of hemoglobin and platelet in the treatment group were significantly different from those in the control group(P<0.01),but there was no significant difference between the administration groups(P>0.05).?There was significant difference between the administration group and the control group in FFA at different time points after injection(P<0.05).?Under the same ratio,the number of lipid droplets in combined medication group was significantly lower than that in the control group.Erythrocyte exudation,macrophage infiltration and lamellar body reduction accompanied with evacuation were seen in all groups under electron microscope.ConclusionsAll the administered groups had certain preventive effect on FES,and the combined group was better than the single drug group.However,there was no statistical significance between different doses of methylprednisolone combined with low molecular dextran.Considering the side effects of hormone,the effect of low dose methylprednisolone combined with low molecular dextran was the best.