A continuous hemorrhage model of fatal hemorrhagic shock in swine

We studied the effect of bleed rate on survival time and hemodynamics in a continuous hemorrhage model of fatal hemorrhagic shock in lightly anesthetized swine. Fasted immature swine (12-16 kg) were sedated with intramuscular (i.m.) ketamine, endotracheally intubated, anesthetized with halothane (0.75%), nitrous oxide, and oxygen, and then prepared for experimentation by placement of a pulmonary artery thermodilution catheter, femoral arterial and venous catheters, and by splenectomy. After instrumentation, halothane was discontinued and sedation was maintained with nitrous oxide and intravenous lorazepam. Thirty minutes later, the animals were bled continuously at 1.0 ml/kg per min (n = 8, Group I) or 1.25 ml/kg per min (n = 8, Group II) by a roller pump connected to the femoral arterial catheter. Hemodynamic parameters were recorded every 15 min until death occurred. Mean survival time was 50.2 +/- 3.0 min in Group I and 39.8 +/- 3.2 min in Group II (P less than 0.001). There was a stepwise decrease in blood pressure and cardiac index consistent with progressive hemorrhagic shock. This model results in reproducible survival times with small standard deviations. Although the animals are lightly anesthetized and the experiments are performed acutely, the hemodynamic responses and survival times observed are similar to those reported in previous studies of chronically instrumented, unanesthetized swine. This model may be more practical than unanesthetized, chronically instrumented swine models for evaluating the effects of various interventions on survival time and hemodynamics in acute hemorrhagic shock.     

HBOC-201 improves survival in a swine model of hemorrhagic shock and liver injury

BACKGROUND: Blunt abdominal trauma that leads to hemorrhagic shock and cardiac arrest is almost always fatal in the prehospital setting. The current study investigated whether a hemoglobin-based oxygen carrier (HBOC-201) could maintain organ viability during an exsanguinating liver injury and allow for prolonged survival. This hypothesis was tested in a large animal model that simulated blunt abdominal trauma with major organ injury. METHODS: Swine underwent a liver crush, laceration and 50 ml/kg initial blood loss. The liver bled at 3 ml/kg per min during the resuscitation phase. No fluid (NF=6), hetastarch (HES=8), or HBOC-201 (HBOC=8) was given during the resuscitation phase. Swine alive 60 min after the initial injury underwent liver repair and 96 h observation. RESULTS: All HBOC swine survived 60 min versus none of the NF or HES swine (P<0.05). All HBOC swine survived 24 h and 7/8 survived 96 h with good functional recovery. CONCLUSIONS: HBOC resuscitation during liver bleeding in a swine model of hemorrhagic shock and liver injury allowed for 96 h survival. No fluid or HES in the same model was fatal.     

环境低温对非麻醉猪失血性休克血流动力学及氧代谢的影响

目的 探讨环境低温对非麻醉猪失血性休克血流动力学及氧代谢的影响.方法 沈阳军区总医院动物中心提供的巴马香猪16头随机(随机数字法)分为:室温休克组和低温休克组,每组8头.按30 mL/kg放血建立失血性休克模型,记录建模前及建模后4h内不同时点的核心体温、心率、平均动脉压、中心静脉压、心输出量、混合静脉血氧饱和度及血气等变化,并计算氧摄取率、氧供指数和氧耗指数.采用SPSS11.0软件包行计量资料的成组t检验.结果 模型建立后室温组动物的核心体温略有下降,环境低温使核心体温下降更加明显.低温组动物的病死率较室温组明显增加(P＜0.05).休克导致氧供和氧耗明显下降.室温组和低温组的血流动力学指标、氧供和氧耗的差异无统计学意义,但两者在pH值、乳酸和氧提取率上差异具有统计学意义(P＜0.05).结论 环境低温加重了失血性休克后的氧代谢紊乱,使预后进一步恶化.     

Effect of different resuscitation strategies on neutrophil activation in a swine model of hemorrhagic shock

Activated neutrophils play a pivotal role in resuscitation injury. The strategies used for resuscitation (types of fluids and methods of administration) can affect the degree of neutrophil activation. The aim of this study was to test the commonly available resuscitation fluids in a large animal model of hemorrhagic shock to determine the strategy associated with the least degree of neutrophil activation. Methods: Female swine (n=63, weight 45-60 kg) were anesthetized using isoflurane and catheters were placed for hemodynamic monitoring. After 120 min, they were subjected to a volume controlled hemorrhage (28 ml/kg) over 15 min, kept in shock for 60 min, and then resuscitated. The resuscitation groups were as follows: (1) anesthesia only (n=5); (2) hemorrhage, sham resuscitation (n=5); (3) LR-fast rate 3x blood loss (n=6); (4) LR slow rate-3x blood loss (n=6); (5) LR low volume-1x blood loss (n=6); (6) Dextran 40-1x blood loss (n=6); (7) 6% hetastarch-1x blood loss (n=6); (8) 5% albumin-1x blood loss (n=6); (9) 25% albumin-1/5x blood loss (n=6); (10) whole blood resuscitation-1x blood loss (n=6); (11) 7.5% hypertonic saline (HTS)-0.3x blood loss (n=5). Resuscitation fluids were infused over 1 h in all groups except group 4 (LR slow rate, which was over 3 h). Animals were observed for 180 min following the resuscitation period. Neutrophil oxidative burst activity was determined in whole blood using flow cytometery. Results: Animals resuscitated with dextran and hetastarch showed significantly (P<0.05) higher neutrophil burst activity. Resuscitation with LR also caused neutrophil activation (P<0.05), and the highest degree of activation was seen when a large volume of LR was given at a fast rate (group 8). However, all LR infusion protocols were associated with significant neutrophil activation compared with anesthesia (group 1) or sham resuscitation (group 2). No significant activation was seen in the animals resuscitated with albumin or fresh whole blood. Conclusion: Artificial colloids and LR (independent of rate or volume of infusion) caused significant neutrophil activation, which was not seen with albumin and whole blood resuscitation. These findings suggest that the type of resuscitation fluid and method of infusion can influence neutrophil function.     

不同时间输注红细胞悬液对大鼠失血性休克复苏的影响

目的探讨红细胞悬液延迟输注30 min对大鼠失血性休克复苏的影响。方法 24只Wistar大鼠随机分为假手术(SHAM)、RBC 1和RBC 2组(n=8),RBC 1和RBC 2组制备重度失血性休克大鼠模型,先后采用晶胶复合液和红细胞悬液复苏,RBC 2组红细胞悬液延迟输注30 min;监测生理、血气等指标。结果与RBC1组相比,RBC 2组平均动脉压(MAP)和体温恢复延迟,RBC 1组复苏结束后2组MAP分别为(116.99±11.06)和(73.72±14.34)mm Hg(P0.01);RBC 1组复苏结束后30 min,2组MAP分别为(103.07±9.59)和(120.61±10.73)mmHg(P0.01)。RBC 1组复苏结束后120 min RBC 1组体温(37.28±0.80)℃明显低于RBC 2组(38.83±0.58)℃(P0.01)。与SHAM组相比,RBC 1和RBC 2组休克后pH、PCO2、BE和ctHb明显降低,PO2明显升高;复苏后PCO23 h,RBC 1和RBC 2组碱剩余(BE)值明显低于SHAM组。结论在失血性休克液体复苏的基础上,红细胞悬液延迟输注30 min对失血性休克大鼠模型的生理、血气等指标无明显影响。提示紧急救治中输血准备工作耗时可能不影响失血性休克的复苏效果。     

Effects of bovine polymerized hemoglobin on coagulation in controlled hemorrhagic shock in swine

HBOC-201, a bovine polymerized hemoglobin, has been proposed as a novel oxygen-carrying resuscitative fluid for patients with hemorrhagic shock (HS). Herein, we evaluated the hemostatic effects of HBOC-201 in an animal model of HS. A 40% blood loss-controlled hemorrhage and soft tissue injury were performed in 24 invasively monitored Yucatan mini-pigs. Pigs were resuscitated with HBOC-201 (HBOC) or hydroxyethyl starch (HEX), or were not resuscitated (NON) based on cardiac parameters during a 4-h prehospital phase. Afterward, animals received simulated hospital care for 3 days with blood or saline transfusions. Hemostasis measurements included in vivo bleeding time (BT), thromboelastography (TEG), in vitro bleeding time (platelet function; PFA-CT), prothrombin time (PT), and partial thromboplastin time (PTT). Serum lactate was measured and lung sections were evaluated for microthrombi by electron microscopy. During the prehospital phase, BT remained unchanged in the HBOC group. TEG reaction time increased in HBOC pigs during the late prehospital phase and was greater than in NON or HEX pigs at 24 h (P = 0.03). TEG maximum amplitude was similar for the two fluid-resuscitated groups. PFA-CT increased in both resuscitated groups but less with HBOC (P = 0.02) in the prehospital phase; this effect was reversed by 24 h (P = 0.02). In the hospital phase, PT decreased (P < 0.02), whereas PTT increased above baseline (P < 0.01). Lactic acidosis in HBOC and HEX groups was similar. Aspartate aminotransferase was relatively elevated in the HBOC group at 24 h. Electron microscopy showed no evidence of platelet/fibrin clots or microthrombi in any of the animals. Twenty-four-hour group differences mainly reflected the fact that all HEX animals (8/8) received blood transfusions compared with only one HBOC animal (1/8). In swine with HS, HBOC resuscitation induced less thrombopathy than HEX during the prehospital phase. Mild delayed effects on platelet and clot formation during the hospital phase are transient and likely related to fewer blood transfusions. In swine with HS, HBOC resuscitation induced less thrombopathy than HEX during the prehospital phase but more thrombopathy in the hospital phase. The delayed effects on platelet and clot formation during the hospital phase are transient and may be related to the need for fewer blood transfusions.     

Complement activation during hemorrhagic shock and resuscitation in swine

Activation of the complement (C) cascade is known to play a key role in the adverse immune consequences of hemorrhagic trauma with subsequent shock and resuscitation. However, it is not clear whether hypovolemia per se, without trauma and resuscitation, can also lead to C activation. To address this question, we studied the presence, kinetics, and cause of C activation in a porcine model of hemorrhagic shock and resuscitation in the absence of trauma. Pigs were bled to and kept at 35 mmHg for 90 min, followed by hypotensive resuscitation with different fluids and, finally, with shed blood. The animals developed severe lactic acidosis between 30 and 90 min, which was accompanied by a trend for initial rise and subsequent 40% drop of CH50/mL, indicating massive C activation even before resuscitation, i.e., before reperfusion damage could have occurred. Resuscitation with plasma expanders caused 20% additional C consumption, whereas whole blood raised CH50/mL. Plasma C5a decreased initially and then significantly increased at 60 and 180 min, whereas thromboxane B2 showed a 3-fold increase at 30 and 60 min. Plasma LPS was also increased above baseline at 90 and 180 min. In in vitro studies with pig blood, spontaneous C5a formation, as well as zymosan-induced C consumption, was significantly enhanced under the conditions of lactic acidosis. Our data suggest that lactic acidosis, endotoxemia, and possibly other ischemia-related tissue alterations act in a vicious cycle in inducing C activation and, hence, aggravation of shock. The biphasic course of CH50/mL and C5a changes may reflect yet unrecognized physiological responses to hemorrhage-related C activation.     

猪创伤失血性休克模型凝血功能的变化

目的 创伤引起的凝血功能障碍是死亡的重要原因.本研究主要观察猪创伤失血性休克后凝血功能的变化.方法 12只家猪随机(随机数字法)分为对照组(CG,n=6)和实验组(EG,n=6).实验组先受到胸部钝性伤,然后放全血的35％左右,维持平均动脉压(MAP)在(40±3) mmHg(1 mmHg=0.133 kPa)2 h,随后进行复苏.对照组没有创伤、失血及复苏.分别在实验开始时(H0)、创伤失血后15 min (H1)、1 h(H2)、2 h(H3)以及复苏后15 min (R1)、2h (R2)、6 h(R3)、24h (R4)采血,进行血气分析、血常规(Plt)、凝血试验(PT、APTT、Fib)和血栓弹力图(TEG)检测.结果 实验组动物Plt持续下降,复苏后各时间点与对照组差异均有统计学意义(P ＜0.05);Fib创伤放血后15 min开始显著下降直至复苏后2h,期间各时间点均低于对照组(P＜0.05),复苏后24 h显著高于对照组(P＜0.05);PT在创伤放血后15 min显著缩短(P=0.001),之后逐渐延长,复苏后6h开始缩短,放血后2h至复苏后6h期间各时间点与对照组比较,差异有统计学意义(P＜0.05);APTT在创伤放血后15 min显著缩短(P=0.024),后显著延长直至复苏后6h,各时间点差异有统计学意义(P＜0.05).实验组TEG的R值在创伤放血后15 min显著缩短(P＜0.05),复苏后24h较对照组显著延长(P =0.022);K值在创伤放血后15 min显著缩短(P=0.001);MA值在创伤放血后2h显著低于对照组(』P=0.004).结论 创伤失血性休克早期存在一过性高凝状态,表现为PT、APTT、R值和K值的缩短,随后转变为低凝状态,表现为PT、APTT的延长和Fib、MA值的下降.复苏期仍处于低凝状态,早期表现为PT、APTT的延长和Plt、Fib的下降,晚期表现为R值的延长和Plt的下降.     

地塞米松对创伤休克大鼠肝脏热休克蛋白70表达的影响

目的 探讨地塞米松对创伤休克肝组织中热休克蛋白70(HSP70)的表达变化以及对肝脏结构和功能的影响.方法 雄性健康Wistar大鼠72只,采用双侧股骨骨折伴失血性休克创伤模型,随机分成止常对照组12只,创伤休克组30只,创伤休克地塞米松组30只,地塞米松采用腹腔注射给药.动态观察伤后0.5、2、4、6、8 h大鼠肝组织HSP70、肝脏病理、肝功能、TNF-α、IL-6等变化.HSP70采用免疫印迹法测定其蛋白含量,并进行计算机图像分析.结果 HSP70伤后2h较正常对照相比差异有统计学意义,伤后6 h达到高峰,伤后8 h仍持续在较高水平.TNF-α、IL-6伤后逐渐升高,并于伤后6 h达到高峰,和正常组相比,差异有统计学意义.光镜下伤后4 h肝窦内淤血明显,有大量炎性细胞浸润;血清ALT、TB伤后4 h开始增高,8 h达到峰值.腹腔注射地塞米松后,HSP70在伤后各个时相点的表达均较创伤休克组明显增强,峰值仍然在伤后6 h.TNF-α、IL-6伤后各个时相点均迅速回落.肝脏大体淤血、肿胀明显减轻;光镜下伤后4 h肝细胞变性明显好转,肝窦内见淤血减轻,仅见少许淋巴细胞及中性粒细胞浸润;血清ALT、TB明显下降.结论 地塞米松可增强HSP70在创伤失血性休克后肝组织中的表达,可减轻创伤失血性休克后肝脏的继发性损害,表明地塞米松对创伤休克后肝脏的保护作用与HSP70密切相关.     

Effects of increased oxygen breathing in a volume controlled hemorrhagic shock outcome model in rats

It is believed that victims of traumatic hemorrhagic shock (HS) benefit from breathing 100% O(2). Supplying bottled O(2) for military and civilian first aid is difficult and expensive. We tested the hypothesis that increased FiO(2) both during severe volume-controlled HS and after resuscitation in rats would: (1) increase blood pressure; (2) mitigate visceral dysoxia and thereby prevent post-shock multiple organ failure; and (3) increase survival time and rate. Thirty rats, under light anesthesia with halothane (0. 5% throughout), with spontaneous breathing of air, underwent blood withdrawal of 3 ml/100 g over 15 min. After HS phase I of 60 min, resuscitation phase II of 180 min with normotensive intravenous fluid resuscitation (shed blood plus lactated Ringer's solution), was followed by an observation phase III to 72 h and necropsy. Rats were randomly divided into three groups of ten rats each: group 1 with FiO(2) 0.21 (air) throughout; group 2 with FiO(2) 0.5; and group 3 with FiO(2) 1.0, from HS 15 min to the end of phase II. Visceral dysoxia was monitored during phases I and II in terms of liver and gut surface PCO(2) increase. The main outcome variables were survival time and rate. PaO(2) values at the end of HS averaged 88 mmHg with FiO(2) 0.21; 217 with FiO(2) 0.5; and 348 with FiO(2) 1. 0 (P<0.001). During HS phase I, FiO(2) 0.5 increased mean arterial pressure (MAP) (NS) and kept arterial lactate lower (P<0.05), compared with FiO(2) 0.21 or 1.0. During phase II, FiO(2) 0.5 and 1. 0 increased MAP compared with FiO(2) 0.21 (P<0.01). Heart rate was transiently slower during phases I and II in oxygen groups 2 and 3, compared with air group 1 (P<0.05). During HS, FiO(2) 0.5 and 1.0 mitigated visceral dysoxia (tissue PCO(2) rise) transiently, compared with FiO(2) 0.21 (P<0.05). Survival time (by life table analysis) was longer after FiO(2) 0.5 than after FiO(2) 0.21 (P<0. 05) or 1.0 (NS), without a significant difference between FiO(2) 0. 21 and 1.0. Survival rate to 72 h was achieved by two of ten rats in FiO(2) 0.21 group 1, by four of ten rats in FiO(2) 0.5 group 2 (NS); and by four of ten rats of FiO(2) 1.0 group 3 (NS). In late deaths macroscopic necroses of the small intestine were less frequent in FiO(2) 0.5 group 2. We conclude that in rats, in the absence of hypoxemia, increasing FiO(2) from 0.21 to 0.5 or 1.0 does not increase the chance to achieve long-term survival. Breathing FiO(2) 0.5, however, might increase survival time in untreated HS, as it can mitigate hypotension, lactacidemia and visceral dysoxia.     

Single hemorrhage: a clinically relevant canine model of hemorrhagic shock

Clinically encountered hemorrhagic shock is usually caused by a single, rapid hemorrhage secondary to trauma. Experimental models of shock, however, have utilized anesthetic agents and hemorrhage protocols which may compromise the clinical relevance of their findings. This report characterizes the response of conscious, splenectomized dogs to a single hemorrhage of varying rates and volumes, uncomplicated by the presence of anesthetic agents. The duration of a 40 ml kg-1 hemorrhage affected the magnitude of blood pressure recovery, but did not alter the decompensating drop in blood pressure. The shortest hemorrhage duration was chosen for further study, as the blood pressure profile for this hemorrhage duration demonstrated most clearly the recovery, plateau, and decompensation phases. Increasing the hemorrhage volume to 43 ml kg-1 caused a reproducible decrease in the magnitude of the blood pressure recovery, the time to decompensation, and the time to death. Splenectomized dogs, then, demonstrate a reproducible response to a fixed-volume hemorrhage, making chronically instrumented conscious dogs a good animal model with which to study the progression of hypovolemic shock.     

Immunologic alterations in a murine model of hemorrhagic shock.

OBJECTIVE: To study multiple immune parameters in mice subjected to severe hemorrhage without fluid resuscitation. STUDY DESIGN: Controlled animal study. Anesthetized, female mice were hemorrhaged by tail bleeding. Immune parameters (spleen T-cell proliferation and activation, intracellular calcium flux, cytokine production, peritoneal neutrophil respiratory burst, and survival after intra-abdominal septic challenge) were measured at 24, 48, and 72 hrs after hemorrhage. MEASUREMENTS AND MAIN RESULTS: T-cell proliferation was decreased in animals after two 20% blood volume hemorrhages, 30 mins apart; single 30%, 40%, and 50% blood volume hemorrhages did not depress proliferation. "Helper/inducer" T cells from twice-hemorrhaged mice showed decreased expression of activation antigens (interleukin-2 receptor, Ia) after mitogen stimulation. In contrast, "suppressor/cytotoxic" T cells displayed increased activation, shown by augmented expression of interleukin-2 receptor and Ia antigens. Leukocyte production of prostaglandin E2, a mediator frequently implicated in immune down-regulation, was unaffected by hemorrhage. Secretion of tumor necrosis factor-alpha (TNF-alpha) in culture was increased when cells were harvested 48 hrs after injury. Intracellular calcium flux in stimulated lymphocytes was decreased 24 hrs after hemorrhage, suggesting deranged intracellular signal transduction. Respiratory burst activity of peritoneal neutrophils was unchanged following hemorrhage. When animals were subjected to septic challenge, the survival rate was markedly decreased after two hemorrhages (when sepsis was induced 24 hrs after hemorrhage). By 72 hrs posthemorrhage, most of the immunologic alterations, including resistance to septic challenge, had resolved. CONCLUSIONS: This uninstrumented hemorrhagic shock model allows quantification of multiple immune derangements. Immune suppression was identified after two smaller (20% blood volume) hemorrhages, but not after a single, larger hemorrhage. Immune derangements are maximal at 24 hrs posthemorrhage, and resolve in the subsequent 48 hrs.     

麻醉对猪失血性休克模型血流动力学及氧动力学的影响

目的 探讨麻醉对猪失血性休克血流动力学及氧动力学的影响.方法 巴马香猪16头随机分为:麻醉休克组和清醒休克组,每组8头.按30 mL/kg放血建立失血性休克模型,记录建模前及建模后4 h内不同时点的核心体温、心率(HR)、平均动脉压(MAP)、肺动脉压(PAP)、肺动脉楔压(PAWP)、中心静脉压(CVP)、心输出量(CO)、血红蛋白(Hb)、混合静脉血氧饱和度(SvO2)及血气分析变化,并计算氧摄取率(O2ER)、氧供指数(DO2I)和氧耗指数(VO2I).结果 模型建立后清醒组动物核心体温略有下降,但麻醉组动物核心体温下降更加明显.两组的HR、MAP、PaO2、PaCO2及pH值未表现出明显差异,但清醒组乳酸水平明显高于麻醉组.尽管模型建立后两组的DO2I和VO2I都出现了相同幅度的下降,但清醒组的DO2I、VO2I和O2ER在模型建立前后都显著高于麻醉组.结论 麻醉可以减轻失血性休克后的氧代谢紊乱,麻醉引起的诱导性低温可能是造成这种现象的原因.     

Volume replacement with Ringer-lactate is detrimental in severe hemorrhagic shock but protective in moderate hemorrhagic shock: studies in a rat model

Introduction

To date, there are insufficient data demonstrating the benefits of preclinically administered Ringer-lactate (RL) for the treatment of hemorrhagic shock following trauma. Recent animal experiments have shown that lactate tends to have toxic effects in severe hemorrhagic shock. This study aimed to compare the effects of RL administered in a rat model of severe hemorrhagic shock (mean arterial blood pressure (MAP): 25 to 30 mmHg) and moderate hemorrhagic shock (MAP: 40 to 45 mmHg).

Methods

Four experimental groups of eight male Wistar rats each (moderate shock with Ringer-saline (RS), moderate shock with RL, severe shock with RS, severe shock with RL) were established. After achieving the specified depth of shock, animals were maintained under the shock conditions for 60 minutes. Subsequently, reperfusion with RS or RL was performed for 30 minutes, and the animals were observed for an additional 150 minutes.

Results

All animals with moderate shock that received RL survived the entire study period, while six animals with moderate shock that received RS died before the end of the experiment. Furthermore, animals with moderate shock that received RL exhibited considerable improvements in their acid-base parameters and reduced organ damage.In contrast, in animals with severe shock, only two of the animals receiving RS survived but all of the animals receiving RL died early, before the end of the study period. Moreover, the severe shock animals that were treated with RL exhibited considerably worsened acid-base and metabolic parameters.

Conclusions

The preclinical use of RL for volume replacement has different effects depending on the severity of hemorrhagic shock. RL exhibits detrimental effects in cases of severe shock, whereas it has pronounced protective effects in cases of moderate shock.     

Bovine polymerized hemoglobin versus Hextend resuscitation in a swine model of severe controlled hemorrhagic shock with delay to definitive care

To compare the efficacy of low-volume resuscitation with bovine polymerized hemoglobin (HBOC-201) versus hetastarch (HEX) in an intermediate severity combat-relevant hemorrhagic shock swine model with a simulated delay to hospital care. Twenty-four anesthetized pigs were hemorrhaged 55% estimated blood volume in conjunction with a 5-min rectus abdominus crush. At 20 min, pigs were resuscitated with 10 mL/kg of HBOC-201 or HEX or nothing (NON); resuscitated pigs received additional infusions (5 mL/kg) at 30, 60, 120, or 180 min if hypotension or tachycardia persisted. Pigs were monitored for a 4-h "prehospital" period. At 4-h, hospital arrival was simulated: surgical sites were repaired, blood, or saline provided, and pigs were recovered from anesthesia. Pigs were monitored for 72 h and then killed for histological evaluation. One hundred percent (8/8) of HBOC-201-, 75% (6/8) of HEX-, and 25% (2/8) of NON-resuscitated pigs survived to 72 h (P = 0.007 overall, HBOC vs. HEX P > 0.05). Mean arterial pressure and mean pulmonary arterial pressure were highest in the HBOC-201 group (P < 0.001), and HR was lowest (P < 0.001). HBOC-201- and HEX-resuscitated pigs had comparable cardiac index and prehospital fluid requirements. HBOC-201 pigs had higher transcutaneous tissue oxygen tension, P < 0.001) and lower urine output (P < 0.001). At simulated hospital arrival, no HBOC-201 pigs required additional fluids or blood transfusion. In contrast, 100% of HEX pigs required blood transfusions (P < 0.01). In this swine model of controlled hemorrhage with low-volume resuscitation and delayed definitive care, HBOC-201 pigs had improved hemodynamics, transcutaneous tissue oxygen tension, and transfusion avoidance compared with HEX.     

Effects of arterial oxygen content on oxidative stress during resuscitation in a rat hemorrhagic shock model

Objective

To examine whether reactive oxygen species (ROS) production is affected by arterial oxygen content (CaO₂) in attempted resuscitation to restore blood pressure from hemorrhagic shock (HS) or not.

Methods

Under light anesthesia and spontaneous beating, 16 rats underwent HS for 80 min, during which 3.0 mL/100 g of blood was withdrawn, followed by resuscitation attempt for 70 min. At 80 min, rats were randomized into a high-CaO₂ group (Group 1, transfusion under fractional inspired oxygen (F_IO₂) of 1.0, n = 8) or a low-CaO₂ group (Group 2, fluid administration under F_IO₂ of 0.21, n = 8). In each group, either blood or lactate Ringer's (LR) solution was infused to maintain mean arterial pressure ≥75 mmHg under each F_IO₂ concentration. CaO₂, O₂ utilization coefficient (UC) and plasma %CoQ9 were compared between groups.

Results

Mean infused volume for attempted resuscitation was 7.6 ± 1.0 mL of blood in Group 1, and 31.4 ± 5.5 mL of LR solution in Group 2. At the end of resuscitation, CaO₂ was 18.5 ± 1.2 vol% in Group 1, almost double the 9.1 ± 0.8 vol% in Group 2 (P < 0.01). O₂ UC and %CoQ9 in all rats increased from baselines of 0.25 ± 0.12 and 7.6 ± 1.8% to 0.44 ± 0.13 and 9.7 ± 1.8% after resuscitation, respectively (P < 0.05 vs. baseline for each), but did not differ significantly between the groups.

Conclusion

In a rat HS model, attempted resuscitation to restore blood pressure increased O₂ UC as well as %CoQ9. However, the magnitude of %CoQ9 increase that represents ROS production is not affected by CaO₂ during resuscitation from HS.     

Intravenous fluid therapy in the prehospital management of hemorrhagic shock: improved outcome with hypertonic saline/6% Dextran 70 in a swine model

The small quantities of 7.5% hypertonic saline (HTS) in 6% Dextran 70 (DEX 70; Travenol Laboratories, Deerfield, IL) required to produce marked improvement in tissue perfusion may make it an ideal solution for the prehospital management of hypotensive trauma patients. This study shows that the initial treatment of porcine hemorrhagic shock with 7.5% HTS/6% DEX 70 results in significantly improved hemodynamics and higher survival rates than those seen in animals treated with normal saline. These results are very encouraging and dictate the need for evaluation in human trials.     

输液温度对失血性休克模型兔肝功能的影响

目的观察输注不同温度溶液后对失血性休克复苏模型兔肝功能的影响,探讨液体复苏时不同温度溶液对减轻肝脏损害的作用。方法选择健康新西兰雄兔30只,随机分为4组进行手术插管及制作休克模型,在休克模型稳定30min后按相同速度相同液量分别给予低温(10.7±1.6)℃、常温(20.6±1.3)℃及温热(39.5±1.3)℃平衡液和自体血;在休克前、休克及液体复苏1h、2h和4h监测丙氨酸氨基转移酶、门冬氨酸氨基转移酶、血清总蛋白和白蛋白水平。结果失血性休克可以导致肝功能损害,休克时各实验组丙氨酸氨基转移酶及门冬氨酸氨基转移酶均升高,复苏过程中温热组和低温组均低于常温组,以低温组效果更明显。休克后各实验组总蛋白和白蛋白均下降,但各组间的差异无统计学意义。结论失血性休克能引起肝功能异常,丙氨酸氨基转移酶及门冬氨酸氨基转移酶升高;液体复苏时低温溶液和温热溶液有助于改善肝功能,低温溶液效果最佳。     

Effects of sodium bicarbonate in canine hemorrhagic shock

We studied the use of sodium bicarbonate administration in a canine model of hemorrhagic shock to determine its effect on hemodynamics, arterial and venous blood gases, respiratory gases, and blood lactate levels. Thirteen dogs were anesthetized, paralyzed, mechanically ventilated, and hemodynamically monitored. Hypotension was induced and maintained at a mean arterial pressure of 40 to 45 mm Hg using controlled hemorrhage and reinfusion. After 2.5 h of shock, the dogs were randomized into two groups: one group (n = 6) received NaCl infusion; the other (n = 7) received sodium bicarbonate (1 mEq/kg followed by a continuous infusion of 2.5 mEq/kg.h for 2.5 h). CO2 production was increased in the alkali group, but there was no statistically significant difference between groups in any measured hemodynamic, blood gas, or respiratory gas variable. These included heart rate, BP, cardiac output, arterial and venous pH, CO2 production, and bicarbonate levels. Blood lactate levels, however, in the bicarbonate treated animals were significantly (p less than .01) higher than in the group treated with NaCl alone (10.1 +/- 3.2 vs. 5.1 +/- 1.2 mEq/L). These results are similar to the effects of bicarbonate found in other models of lactic acidosis, and suggest that bicarbonate therapy may have limited usefulness in the treatment of lactic acidosis.     

Effects of coenzyme Q10 in hemorrhagic shock

We studied the effects of coenzyme Q10 (CoQ10) on pulmonary function and chemical mediators in a canine model of hemorrhagic shock. One group received 10 mg/kg of CoQ10 before hemorrhage. During the study, percent change from baseline of peak airway pressure, total lung compliance of the lung and chest wall, and blood lactate levels appeared to be significantly smaller in dogs pretreated with CoQ10 than in controls. Furthermore, CoQ10 was found to maintain blood histamine levels and to attenuate the increase in leukotriene C4. The mechanism of the beneficial effects of CoQ10 in hemorrhagic shock is presently unknown, but our data suggest that it may be useful in the treatment of hemorrhagic shock.