Xuebijing Injection Treatment Reduces Fluid Requirements In A Severe Burn Canine Model

Objective: High vasopermeability and excessive inflammation following severe burns may result in circulatory plasma volume loss,tissue edema or organ dysfunction,which can affect the prognosis of patients.The aim of this study is to examine whether Xuebijing Injection(XBJ),an extracts of a traditional Chinese medicine used to treat sepsis in clinic,reduces fluid requirements by inhibition of vasopermeability and tissue edema in a canine model after burn injury.Method:1 Animal modelTwenty-four pure bred Beagle dogs(16�20 months,10-12 kg,purchased from the Institute of Animal Sciences,Chinese Academy of Agricultural Sciences,Beijing,China)were used in this experiment.The dogs were housed in the animal quarter of laboratory for a week.Before the surgery,the dogs were fasted for 12 h.The dogs were anesthesia with intramuscular injection of ketamine,and then placed with a thermodilution aorta catheter of PICCO-PLUS monitor in the carotid and another veins catheter in the jugular veins.The aorta catheter was used to detect the hemodynamic variables and the veins catheter was used to infusion resuscitation fluid and harvest blood samples.And then,a urethral catheter was introduced into the urinary meatus and connected to a supple urine bag which can read the volume.The dogs were infused with propofol(1-2 mg/kg)to make sure that the process were performed under general anesthesia,and then subjected to 50% TBSA full-thickness flam burn injury.Pathological examination was used to assure the depth of burn injury.Dogs were infused with propofol(1-2 ml/kg/h)at 0~8 hours to make sure that the dogs were under general anesthesia,and then,the dogs were return to the cages.2 Groups and treatment24 beagle dogs were randomly allocated to following three groups: lactated Ringer's resuscitation(LR)group(n=8),immediate LR containing XBJ(LR/XBJ)group(n=8),and operation control group(n=8).For LR group,dogs were infused with lactated Ringer's(4 ml/kg)alone according to the Parkland formula(4 m L/kg for 1% TBSA,half of the total fluid was received in the first 8 h,and then given half in the next 16 h).For LR/XBJ group,dogs were infused with lactated Ringer's containing XBJ(4ml/kg,Tianjin Chase Sun Pharmaceutical Co.Ltd,Tianjin,China,with the lot number of 1501261)over 30 minutes after burn injury,and followed by lactated Ringer's using an infusion pump according to the Parkland formula.For OC group each dog was infused with lactated Ringer's according to the physiological need.Infusion rate of each groups adjusted per hour to keep urine output of 1-2 ml/kg/h.3 Measurements and methodsHemodynamics variables including cardiac output index(CI),mean arterial pressure(MAP),extravascular lung water index(ELWI),and pulmonary vascular permeability index(PVPI)were measured using PICCO-PLUS monitor at 0,1,2,4,6,8,24 hours;Plasma volume(PV)was determined by injection of indocyanine green;blood sample were drawn from the veins catheter for measurement of hematocrit;Net fluid accumulation was defined as cumulative infused fluid volume minus cumulative urine output;the vasopermeability of organs were determined by fluorescein isothiocyanate(FITC)-dextran;water content rate of organs in percentage of dry/wet ratio;activities of MPO and NE were measurement by commercial kits;the amount of neutrophil infiltration was quantified by HE staining.Results:1 Hemodynamic variable: compared with OC group,MAP and CI were significantly reduced in LR/XBJ group and LR group after burn injury,there were no difference between LR/XBJ and LR group.PVPI and ELWI were increased after burn injury,and both reduced after 2 h;PVPI and ELWI in LR/XBJ group were lower than that in LR group at 1,2 and 4 h compared with LR group(all P<0.05).2 Plasma volume: The PV in both LR and LR/XBJ group were significantly decreased after burn injury(P<0.05),and recovered 2 hours post injury in both resuscitation groups.The level of PV in LR/XBJ group was significantly higher than that in LR group at 4h after burn injury(P<0.05).3 Hematocrit: compared with OC group,the level of hematocrit in LR/XBJ group and LR group were significantly increased after severe burn injury,and recovered to near baseline levels at 24 h.The levels of hematocrit in LR/XBJ group were significantly lower than that in LR group both at 2 and 4 h(all P<0.05).4 Vasopermeability: The contents of FITC-dextran in organs of LR and LR/XBJ group were higher than that of OC group;the vasopermeability of lung and small intestine in LR/XBJ group were lower than that of LR group(all P<0.05).5 Water contents: Compared with OC group,water content of LR/XBJ group and LR group were significantly increased;Water contents of lung and small intestine in LR/XBJ group were significantly higher than that in LR group(all P<0.05).6 Urine output: the amount of urine output was read in urine bag.Dogs were given fluid resuscitation with adjusted infusion rate to keep output of urine above 1-2 ml/kg/h.There was no statistical difference in the change in urine output(P>0.05).7 Accumulation net fluids: The result showed that the net fluid accumulation in LR and LR/XBJ group was different.The net fluid accumulation of LR/XBJ group was significantly reduced compared with LR group at 4 to 24 h after fluid resuscitation.8 The amount of neutrophil infiltration: the amount of neutrophil infiltration in the essential organs of both LR and LR/XBJ group were higher than that of OC group,and the levels of neutrophil infiltration in lung,small intestine and kidney of LR/XBJ group were significantly lower than that of LR group(all P<0.05).9 Neutrophil elastases(NE): the activity of NE in LR/XBJ group and LR group were significantly increased compared with OC group after burn injury.The levels of NE in lung,heart and small intestine in LR/XBJ group were significantly lower than that in LR group(all P<0.05).10 Activities of myeloperoxidase(MPO): the activity of MPO in LR/XBJ group and LR group were significantly increased compared with OC group after burn injury.The levels of NE in lung and intestine at LR/XBJ group were significantly lower than that at LR group(all P<0.05).Conclusion:These results indicate that XBJ injection can inhibit burn-induced high vasopermeability and tissue edema,and reduces fluid requirements in a canine model.The protective effect of XBJ might possibly due to its inhibiting effect on burn-induced neutrophil infiltration and NE expressing.