| The initial treatment of hemorrhagic shock often requires fluid resuscitation to replace intravascular blood volume lost due to injury. Clinical practices have advocated early and aggressive fluid resuscitation to restore vascular volume, organ perfusion and tissue oxygen delivery. However, mounting evidence from studies in experimental animals and clinical observation in recent ten years have demonstrated that aggressive resuscitation strategies are associated with cardiac and pulmonary complications, coagulation disturbances, immunological dysfunction, which results in increased blood loss and higher mortality.Based on these considerations, the concept of limited volume resuscitation has been proposed as a compromise strategy. Limited volume resuscitation allows the restoration of blood circulation with minimal fluid requirements and a modest increase in blood pressure, thus reducing the risk of additional blood loss due to continued bleeding or rebleeding. This resuscitation regimen has already shown efficacy in clinical trial of traumatic hemorrhagic shock, as indicated by the decrease of the occurrence of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS).With in-depth study in shock, many reaserchers found that the worst complication of shock is SIRS and MODS. Although the pathophysiological mechanisms responsible for SIRS are complex and are not fully understood, extensive basic science research has widely investigated inflammatory signal molecules involved in the initiation of SIRS. The introduction of the term 'systemic inflammatory response syndrome' (SIRS) by the American College of Chest physicians and Society of Critical Care Medicine (ACCP/SCCM) consensus conference recognized the important role of endogenous mediators play in systemic inflammation. SIRS is the systemic inflammatory response to a variety of severe clinical insults. The response is manifested by two or more of the following conditions: temperature＞38℃or＜36℃; heart rate＞90 beats/min; respiratory rate＞20 breaths/rain or PaCO2＜32 tort (＜4.3 kPa); WBC＞12,000 cells/mm3,＜40000 cells/mm3 or＞10% immature (band) forms.SIRS can be also precipitated by non-infective events such as trauma, pancreatitis, and surgery. As a consequence of an overactive SIRS response, the function of various organ systems may be compromised, resulting in MODS. When SIRS results in MODS and organ failure, the mortality becomes high and can be more than 50%. Therefore SIRS is the dreadful complication that far outweights the direct toxicity of the bacterial infection itself in clinical importance. So how to balance between proand anti-inflammatory mediator is the key factor to prevent shock progress to SIRS or MODS.Postpartum hemorrhage is the leading cause of maternal mortality in our country. Due to special features of maternal hemodynamics, such as increased blood volume and hypercoagulable state, whether limited volume resuscitation could be apply to maternal hemorrhagic shock and prevent the development of SIRS remains unknown and provided the impetus for our study.We establish the pregnant rabbit model of hemorrhagic shock to mimic clinical situation, and test the efficacy of limited volume resuscitation on inflammatory mediators, free radicles, metabolites and bacterial translocaton.PART 1 CHANGES OF LIMITED VOLUME RESUSCITATION ON SIRS IN PREGNANT RABBITS WITH UNCONTROLLED HEMORRHAGIC SOCKOBJECTIVEwe focus on thc effect on limitcd volume rcsucitation on VIP/ET/MDA/TNF-a and thc morbidity of SIRS in pregnant rabbit model with uncontrolled hemorrhagic shock.METHODS1, Surgical procedure: Twenty New Zealand pregnant rabbits at 15-25 days' gestational age were fasted overnight, anaesthetized with an intravenous injection of 20% urethane(5ml/kg). Then the animals were placed in a supine position on an operating table and the left neck was prepared, scrubbed, and draped in a sterile manner. The left common carotid artery was cannulated for continuous blood pressure monitoring and blood withdrawal, while the left jugular vein was cannulated for fluid administration. After cannulation, lower abdominal midline incision was made and uterus was exposed. Baseline data were recorded after 15 min stabilization, and animals began hemorrhaged at time point zero(TO). The experiment consisted of three phases, shock phase (0-30min), prehospital phase (30-90min), and hospital phase (90-180min). In the shock phase, rabbits were hemorrhaged by blood withdrawal to mean arterial pressure (MAP) of 40-45mmHg at an average rate of 2ml.kg-1min-1 within 15min (blood was aspirated into a sterile heparinized syringe). After this initial hemorrhage, blood was withdrawn or reinfused as needed to maintain this level for 15min. In the prehospital phase, a medium vessel in a gestational sac was transected, and enclosed with aseptic sponges (for blood loss calculation). Then animals were underwent resuscitation protocol assigned previously. In hospital phase, bleeding was controlled by surgical intervention, therefore blood vessel was ligated, and animals were reinfused with fluid and shed blood to MAP of 80mmHg and maintained that level for 90min.2,Experimental protocol: Twenty pregnant New Zealand rabbits at 15-25 days' gestational age were randomly assigned to four groups (n=5 for each group), Groupâ… (sham shock group) served as normal control, animals were underwent anesthesia, cannulation, abdominal incision, but no hemorrhage nor fluid resuscitation. Groupâ…¡(simple shock group) served as shock control, animals underwent hemorrhagic shock, but no resuscitation. Groupâ…¢(shock plus aggressive fluid resuscitation, group), animals were underwent shock and aggressively resuscitated with intravenous injection of Ringer solution at a rate of 12ml/min to MAP of 80mmHg in prehospital phase. Groupâ…£(shock plus limited volume resuscitation group), animals were underwent shock and limited volume resuscitation with intravenous injection of Ringer solution at a rate of 4ml/min to MAP of 60mmHg. The third phase is hospital phase, Groupâ…¢andâ…£received hemorrhage control by surgical intervention and adequately resuscitated to a MAP of 80 mmHg.3,Hemodynamic measurement: Hemodynamic variables and respiration rate (RR) were monitored throughout the experiement.4,Heparined whole-blood samples were collected at T0, T30, T90, T180 for determination of white blood cell (WBC) count.5,Serum were collected at at T0, T30, T90, T180, T4h, for measurement of VIP/ET/TNF-a,by using commercial enzyme-linked immunosorbent assay (ELISA) kits according to the manufacturer. MDA by using TBA ways.RESULTS1,Hemodynamics changes: Compared with animals in groupâ…¢, animals in groupâ…£have a more stable hemodynamics parameters as indicated by MAP, heart rate(HR), and RR during the resuscitation phases. MAP, HR, RR at T180 in groupâ…¢ versus that in groupâ…£were: 74 mmHg VS 82mmHg, 263bpm/min VS 232 bpm/min, RR: 72bpm/min, 64bpm/min respectively, P＜0.05. It was demonstrated that limited volume resuscitation promote the stablization of hemodynamics parameters. WBC count: WBC count was 4.5-10.5G/L at T0 in all groups and increased markedly to 12.0-20.0G/L in groupâ…¡,â…¢andâ…£after hemorhage. WBC count in groupâ…¢recovered to normal at T90, while flucutated during the hospital phases, and remained higher than normal at T180. In contrast, that in groupâ…£decreased steadily to normal level and maintained it until T180. WBC count in groupâ…¢versus that in groupâ…£at T90, T120 were 15.0 G/L VS 10.2 G/L, 13.54 G/L VS 9.45 G/L respectively, P＜0.05. It was shown that limited volume resuscitation ameliorate the increase of WBC and prevent the occurrence of SIRS.3,The morbidity of SIRS: NO SIRS occurred in groupâ… , which meant no significant influence of surgical procedure. All animals in groupâ…¡,â…¢andâ…£developed SIRS at T30. Without resucitation, animals in groupâ…¡died before T180. In prehospital phase, the incidence of SIRS in groupâ…¢versus that in groupâ…£at T90 was 4 VS 1. While in hospital phase, after hemorrhage control and complete resuscitation, animals in groupâ…¢andâ…£recovered gradually, the occurence of SIRS in groupâ…¢versus that in groupâ…£was 1∶0. Above data were shown that limited volume resuscitation can decrease the occurrence of SIRS in pregnant rabbits model with hemorrhagic shock.4,Liver and renal function: We defined the changes of liver and renal function by 2 fold increase in serum level of alanine aminotransferase (ALT) and creatinine (CR) value. Without resuscitation, all the animals in groupâ…¡suffered changes in liver and renal function and died before T180min. Number of cases with liver and renal function changes in groupâ…¢was 1 at T90 and increased to 3 at T180, while that in groupâ…£were 1 at T180. The occurrence of liver and renal function changes in groupâ…¢versus that in groupâ…£at T4h was 2∶1. RESULTSThe incidence of SIRS induced by limited volume resuscitation was significantly lower than that in aggressive fluid resuscitation, which reduce the severity of SIRS.PART 2 EFFECT OF LIMITED VOLUME RESUSCITATION ON SIRS IN PREGNANT RABBITS WITH UNCONTROLLED HEMORRHAGIC SHOCK CHAPTER 1 EFFECT OF LIMITED VOLUME RESUSCITATION ON INFLAMMATORY MEDIATORS IN PREGNANT RABBITS WITH UNCONTROLLED HEMORRHAGIC SHOCKOBJECTIVEVascular resistance in the mammalian circulation is affected by many endogenous agents that influence vascular smooth muscle, right ventricular myocardium, endothelial function, collagen and elastin deposition and fluid balance. When the balance of these agents is disturbed, e.g. by hypoxia or hemorrhage, vasoconstriction or vasodilation ensues. To study the effect of complex network of regulatory peptides on the development of maternal hemorrhagic shock, two regulatory peptides including vasoactive intestinal peptide(VIP) and endothelin(ET) were investigated in the model of pregnant rabbit with uncontrolled hemorhagic shock.METHODS1,The shock model and experimental protocol employed were the same as part 1 which has been described in detail.2,Serum were collected at at T0, T30, T90, T180, T4h, T8h for measurement of VIP, ET by using commercial enzyme-linked immunosorbent assay (ELISA) kits according to the manufacturer.RESULTS 1,Determination of VIP level: Serum concentration of VIP in all groups was 8.4-20.3 pg/ml at T0 and increased obviously in groupâ…¡,â…¢andâ…£after hemorhage. No statistical difference were detected between groupâ…¡,â…¢andâ…£at T30. Serum VIP in groupâ…¡peaked at 97.5 pg/ml and all the animals died before T180. VIP decreased in both groupâ…¢andâ…£after resuscitation, and recovered to normal at T8h only in groupâ…£, while that in groupâ…¢remained higher than normal. No statistical difference were demonstrated between groupâ…¢andâ…£at T90. VIP in groupâ…¢versus that in groupâ…£at T180, T4h, T8h was 35.4 pg/ml VS 25.5 pg/ml, 30.7 pg/ml VS 15.7 pg/ml, 25.3 pg/ml VS 11.2 pg/ml, P＜0.05. Above data demenstrated that limited volume resuscitation ameliorate the release of VIP after hemorrhagic shock.2,Determination of ET level: Serum concentration of ET in all groups was 50-60 pg/ml at T0 and increased obviously in groupâ…¡,â…¢andâ…£after hemorrhage. No statistical difference were detected between groupâ…¡,â…¢andâ…£at T30. Serum VIP in groupâ…¡peaked at 197.5 pg/ml and all the animals died before T180. VIP decreased in both groupâ…¢andâ…£after resuscitation, and recovered to normal at T8h only in groupâ…£, while that in groupâ…¢remained higher than normal. No statistical difference were demonstrated between groupâ…¢andâ…£at T90. VIP in groupâ…¢versus that in groupâ…£at T180, T4h, T8h was 70.7 pg/ml VS 88.6 pg/ml, 80.8 pg/ml VS 65.3 pg/ml, 70.2 pg/ml VS 58.1 pg/ml respectively, P＜0.05. Above data demenstrated that limited volume resuscitation ameliorate the release of ET after hemorrhagic shock.CONCLUSIONCompared with aggressive fluid resuscitation, limited volume resuscitation can ameliorate the increase level of VIP and ET after hemorrhagic shock, promote the balance between pro- and anti-inflammatory mediator, resulting in decreased occurrence of SIRS.CHAPTER 2 EFFECT OF LIMITED VOLUME RESUSCITATION ON METABOLITES IN PREGNANT RABBITS WITH UNCONTROLLED HEMORRHAGIC SHOCKOBJECTIVEA fine balance between oxygen delivery and consumption is exsist in the normal physiological state, but when this is perturbed, oxygen debt may ensue. The presence of ongoing oxygen debt is rather deleterious, resulting in metabolic acidosis and inflammatory cascade leading to MODS. Serum PH, lactate (LA), base deficit (BD) and bicarbonate have all been extensively studied as clinical markers of metabolic acidosis in shock. So in this study, we focus on the effect on limited volume resucitation on LA, BD and the morbidity of SIRS in pregnant rabbit model with uncontrolled hemorrhagic sock.METHODS1,The shock model and experimental protocol employed were the same as chapter 1 which has been described in detail.2. Blood-gas analysis: Arterial blood samples were collected at T0, T30, T90, T180 T4h, T8h for measurement of LA and BD by blood gas analyzer (ABL 77, Denmark).3. count. Survival time of each animal was recorded.RESULTS1,Determination of LA: The value of LA in groupâ… remained stable throughout the experiment, which meant no significant influence of surgical procedure. After hemorrhage, LA in groupâ…¡,â…¢andâ…£increased to 2 fold at T30. LA in groupâ…¡notably increased to 25.67 mmol/L at T90 and all the animals died before T180. Compared to groupâ…¢, LA in groupâ…£was only mildly elevated. LA in groupâ…¢ versus that in groupâ…£at T90 was 6.78 mmol/L VS 4.35 mmol/L, P＜0.05. In the hospital phase, after hemorrhage control and complete resuscitation, LA in both groupâ…¢andâ…£began to depress, LA in groupâ…¢versus that in groupâ…£at T4h was 4.52 mmol/L VS 2.26 mmol/L, P＜0.01. LA in groupâ…£recovered to normal at T8h, and that in groupâ…¢was slightly higher than normal. It was shown that limited volume resuscitation decrease anaerobic glycolysis, promote LA clearance accordingly.2,Determination of BD: The value of BD in groupâ… remained stable throughout the experiment, which meant no significant influence of surgical procedure. After hemorrhage, BD in groupâ…¡,â…¢andâ…£increased to 2 fold at T30. LA in groupâ…¡notably increased to-16.98 mmol/L at T90 and all the animals died before T180. Compared to groupâ…¢, LA in groupâ…£was only mildly elevated. LA in groupâ…¢versus that in groupâ…£at T90 was-7.62 mmol/L VS -6.25 mmol/L, P＞0.05. In the hospital phase, after hemorrhage control and complete resuscitation, LA in both groupâ…¢andâ…£began to depress, LA in groupâ…¢versus that in groupâ…£at T180 and T4h was -7.23 mmol/L VS -4.25 mmol/L, -6.56 VS -3.78 respectively, P＜0.05 in those two time points. LA in groupâ…£recovered to normal at T8h, and that in groupâ…¢was slightly higher than normal. It was shown that limited volume resuscitation ameliorate the increase in BD and relieve the seveirity of acidosis.3,Survial rate: No animal died within 180 min, the mortality of 72h in aggressive fluid resuscitation group was significantly greater than limited volume resuscitation group.(40% VS 20%, P＜0.01).CONCLUSIONCompared with aggressive fluid resuscitation, limited volume resuscitation optimize tissue oxygenation as indicated by ameliorate the increase of LA and BD, reduce the severity of metabolic acidosis, resulting in highter survival rate. CHAPTER 3 EFFECT OF LIMITED VOLUME RESUSCITATION ON OXYGEN RADICLES IN PREGNANT RABBITS WITH HEMORRHAGIC SHOCKOBJECTIVEAn imbalance between oxidants and antioxidants in favour of the oxidants, potentially leading to damage, is term 'oxidative stress'. Oxidants are formed as normal product of aerobic metabolism but can be produced at elevated rates under pathophysiological conditions. Antioxidant defense involves several strategies, both enzymatic and non-enzymatic.A free radicle is any molecule capable of independent existence that contains one or more unpaired electrons. Most free radicals in biology fit within the broder category of reactive oxygen species (ROS). The highly reactive primary products of lipid peroxidation are formed when free radicals attack polyunsaturated fatty acids or cholesterol in membranes or lipoproteins. Uncontrolled lipid peroxidation can result in cellular dysfunction and damage.Data accumulated from both exerimental and clinical investigations have implicated lipid peroxidation such as malendialdehyde involved in the pathogenesis of ischemia-reperfusion injury and hundreds of investigations have examined the potential of various oxygen radical scavengers to modulate radical injury. Superoxide dismutase (SOD) historically has been the most intensely investigated oxyradical scavenger.Lung represents a unique tissue for oxidant stress among most organs because it is directly exposed to higher oxygen tensions. Thus local oxygen partial pressure at the aleolar level is much higher than that in other vital organs such heart, liver, and brain. Another special feature of the lung is its large surface area.So in this study, we test the effect of limited volume resuscitation on MDA, SOD, WBC count, and pulmonary wet/dry ratio in pregnant rabbit with uncontrolled hemorrhagic shock.METHODS1,Experimental protocol: eighteen pregnant New Zealand rabbits at 15-25 days' gestational age were randomly assigned to three groups (n=5 for each group), Groupâ… (sham shock group) served as normal control, animals underwent anesthesia, cannulation and abdominal incision, but no hemorrhage nor fluid resuscitation. Groupâ…¡(shock plus aggressive fluid resuscitation group), animals underwent shock and aggressively resuscitated with intravenous injection of Ringer solution at a rate of 12ml/min to MAP of 80mmHg in prehospital phase. Groupâ…¢(shock plus limited volume resuscitation group), animals underwent shock and limited volume resuscitation with intravenous injection of Ringer solution at a rate of 4ml/min to MAP of 60mmHg. The third phase is hospital phase, Groupâ…¡andâ…¢received hemorrhage control by surgical intervention and adequately resuscitated to a MAP of 80 mmHg.2,Whole-blood samples were collected at T0, T30, T90, T180, T240 for WBC count measurement.3,Whole-blood samples were collected at T0, T90, T180, T4h for MDA, SOD determination.4,AT T4h, animals were underwent euthanasia, Lungs were removed, trimmed, blotted, and weighed to obtain lung wet weight (ww). They were then placed in a 60℃oven for 24h and weighed to obtain lung dry weight (dw). The lung ww/dw ratio was then calculated.RESULTS1,WBC count: WBC count was 4.5-10.5G/L at T0 in all groups and increased markedly to 11.0-19.0G/L in groupâ…¡andâ…¢after hemorrhage. WBC count in group â…¡recovered to normal at T90, while fluctuated during the hospital phase, and remained higher than normal at T180. In contrast, that in groupâ…¢decreased steadily to normal level and maintainted it until T180. WBC count in groupâ…¡versus that in groupâ…¢at T90, T120, were 15.10 G/L VS 10.01 G/L, 13.68 G/L VS 9.25 G/L respectively, P＜0.05. It was demonstrated that limited volume resuscitation ameliorate the increase and sequestration of WBC and reduced WBC mediated ischemia- repeffusion injury.2,MDA determination: Plasma concentration of MDA was 6.0-9.0nmol//L at T0 in all groups and increased in groupâ…¡andâ…¢after hemorrhage. Compared to groupâ…¡, MDA in groupâ…¢was mildly increased. MDA in groupâ…¡versus that in groupâ…¢at T90, T180 and T4h was 12.23nmol/L VS 9.15 nmol/L, 13.55 VS 10.53 nmol/L, 19.25nmol/L VS 15.63 nmol/L respectively, p＜0.05. It was demonstrated that limited volume resuscitation ameliorate the increase of MDA and reduce ischemia-reperfusion injury.3,SOD determination: Plasma concentration of SOD was 180-220 u//ml at T0 in all groups and decreased in groupâ…¡andâ…¢after hemorrhage. Compared to groupâ…¡, MDA in groupâ…¢was mildly decreased. MDA in groupâ…¡versus that in groupâ…¢at T180 and T4h was 146.5 u/ml VS 165.9 u/ml, 117.7 u/ml VS 141.8 u/ml respectively P＜0.05. It was shown that limited volume resuscitation enhance antioxidative ability and reduce lipid peroxidation mediated injury accordingy.4,Determination of lung ww/dw ratio (DW/WW): lung DW/WW ratio in groupâ… ,â…¡andâ…¢at T4h was 0.248±0.025, 0.144±0.017 and 0.183±0.016 respectively. Significant difference was detected between groupâ…¡andâ…¢. It was demonstrated limited volume resuscitation decrease pulmonary vascular hyperpermeability and attenuate lung edema finally.CONCLUSION Compared with aggressive fluid resuscitation, limited volume resuscitation attenuate pulmonary ischemia-reperfusion injury as indicated by the decrease of MDA level, the relatively increase of SOD concentration, and the elevation of lung DW/WW ratio.CHAPTER 4 EFFECT OF LIMITED VOLUME RESUSCITATION ON BACTERIAL TRANSLOCATION IN PREGNANT RABBITS WITH UNCONTROLLED HEMORRHAGIC SHOCKOBJECTIVEAn important function of the intestinal mucosal barrier is to prevent bacteria colonizing the gut from invading systemic organs and tissues. However, under certain conditions, indigenous bacteria cross this barrier and appear in mesenteric lymph nodes (MLNs) and possibly other organs, a process termed bacterial translocation. The hypothesis that the gut can be the reservoir for bacteria causing systemic infections is supported by several lines of evidence. So the role of the gut has been described as the motor in the MODS in critically ill patients. Here, we study the effect of limited resuscitation on bacterial translocation, plasma endotoxin level, tumor necrosis factor alpha(TNF-a) concentration in pregnant rabbits with uncontrolled hemorrhagic shock.METHODS1,The shock model and experimental protocol employed were the same as chapter 3 which has been described in detail.2,Blood samples of 2ml were obtained at T4h or directly after the death of the animal for endotoxin assays. Among them, 1ml blood sample was for endotoxin determination by a chromogenic Limulus Amoebocyte Lysate (LAL) assay; another 1ml blood sample was for qualitative peripheral blood bacterial culture. 3,For histologic exanimnation, MLN and a segment of the liver were collected aspetically for bacterial culture. The colonies were counted and results expressed as the number of colony-forming units (cfu) per gram of the tissue.4,Whole-blood samples were collected at T0, T30, T90, T4h for the determination of serum TNF-a concentration by using commercial enzyme-linked immunosorbent assay (ELISA) kits according to the manufacturer..RESULTS1,Bacterial translocation: The mean of colony-forming units found in the liver and MLN of groupâ…¡versus those in groupâ…¢was 2.48×105CFU/g VS 0.21×105CFU/g and 4.01×105CFU/g VS 0.67×105 CFU/g respectively, P＜0.05 for both. It is demonstrated that compared with aggressive fluid resuscitation, limited volume resuscitation improve gut barrier function and attenuate bacterial translocation. Overall, the bacteria most frequently found in the cultures were Escherichia coli.2,Endotoxin determination: Plasma endotoxin level of groupâ…¡(2.61 EU/ml) was significantly higher than that in groupâ…¢(0.42 EU/ml). Above data were shown that limited volume resuscitation can reduce endotoxemia.3,Peripheral blood culture: Positive peripheral blood culture in groupâ…¡versus that in groupâ…¢was 4 VS 1. It is also demonstrated that limited volume resuscitation attenuate bacterial translocation.4,Determination of TNF-a: After hemorrhage, TNF-a level was equally increased in groupâ…¡andâ…¢, without significant difference between them. Whereas, at T90, TNF-a was significantly higher in groupâ…¡(250 pg/ml) than groupâ…¢(170 pg/ml). In the hospital phase, after hemorrhage control and complete resuscitation, TNF-a in both groupâ…¡andâ…¢began to depress, TNF-a in groupâ…¡versus that in groupâ…¢T4h was 205 pg/ml VS 148 pg/ml, P＜0.01 in those two time points. It was shown that limited volume resuscitation decrease serum TNF-a level, resulting in improved cellular immunity.CONCLUSIONCompared with aggressive fluid resuscitation, limited volume resuscitation prevent the deterioration of gut barrier failure as shown by attenuated bacterial translocation and distant organ damage, reduce endotoxemia and serum TNF-a concentration, subsequently resulting in lower incidence of SIRS.SUMMARY1,In refer to thc diagnostic standard of SIRS set up by ACCP/SCCM, both aggressive fluid resuscitation and limited volume resuscitation can inducc SIRS in a pregnant rabbit model of hemorrhagic shock. While the incidence of SIRS induced by limited volume resuscitation (20%) was significantly lower than that in aggressive fluid resuscitation (80%). After prehospital and hospital rcsuscitation, in aggressive fluid rcsuscitation group at T180, 3 rabbits suffer liver and renal changes, 2 pregnant rabbits die, whereas in limited volume resuscitation group, 1 rabbit suffer liver and renal changes, and 1 pregnant rabbit die.2,Compared with aggressive fluid resuscitation, limited volume resuscitation attenuate the increase of inflammatory mediators (ET, VIP, TNF-a), free radical concentration (MDA, SOD), metabolites (BL, BD) and bacterial translocation (colonies count, endotoxin), which reduce the severity of SIRS.3,We established clinically relevant model which mimic limited volume resuscitation during prehospital phase, Compared with aggressive fluid resuscitation, limited volume resuscitation attenuate the increase of WBC count, the releasc of free radicles and inflammatory mediators, which show that limited volume resuscitation ameliorate the tissue ischcmia-reperfusion injury induced by aggressive fluid resuscitation during the the early phase of shock, decrease the release of inflammatory mediators into the blood and subsequent stimulation and magnification. Addditionally, limited volume resuscitation ameliorate the stress response due to the decrease of continue bleeding.4,This study not only demonstrated that limited volume resuscitation during prehospital phase can not only drcrease continue bleeding, but also alleviate the ischemia-reperfusion injury induced by aggressive fluid resuscitation, which warrant further investigation and generalization.
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