New method for the detection of bacterial translocation using intestinal permeability with polyethylene glycol 4000

BACKGROUND: Currently, there is no method of accurately diagnosing bacterial translocation (BT) in humans. BT may be related to changes in intestinal permeability. In this study, we examined the correlation between intestinal permeability using polyethylene glycol (PEG) 4000 and BT. MATERIALS AND METHODS: Under general anesthesia, laparotomy was done in rats, and PEG4000 was administered to the small intestine. We prepared models of invasive stimulation in which lipopolysaccharide (LPS) was intravenously administered, and a hemorrhagic shock model in which blood pressure was decreased to 30 mm Hg. Blood PEG4000 levels were measured. We also measured blood PEG levels in a model in which oxygen was administered to treat hemorrhagic shock. In all models, the presence or absence of BT development was evaluated. RESULTS: In groups given LPS, mean blood PEG levels were significant higher than in the group treated with saline solution. In the hemorrhagic shock group, the mean PEG level was increased but was slightly inhibited by oxygen administration. In the LPS and hemorrhagic shock groups, the incidene of BT was significantly greater than in the control group. In the hemorrhagic shock group, the incidence of BT was 0% after oxygen administration. There was a correlation between the incidence of BT and changes in the intestinal permeability of PEG4000 (R(2) = 0.824). CONCLUSIONS: LPS stimulation enhanced intestinal permeability in a dose-dependent manner. An increase in intestinal permeability was correlated with the incidence of BT. Blood PEG4000 levels correlated positively with the grade of invasion and the incidence of BT.     

Evidence for Early Bacteremia/Endotoxemia and Inflammatory Responses after Trauma - Hemorrhage and Complement Activation in a Nonhuman Primate Model

There is criticism that the major line of evidence regarding posttraumatic inflammatory response and bacterial translocation has mainly come from experiments in rodents. The aim of this study was therefore to investigate the very early bacteremia/endotoxemia and inflammatory response in nonhuman primates. Six baboons were subjected to hemorrhagic shock (40 mm Hg mean arterial pressure) preceded by infusion of zymosan-activated plasma (to simulate trauma-associated complement activation) followed by reinfusion for 1 h. Measurements of complement and granulocyte (PMN) activation, cytokines of the inflammatory network, soluble cytokine receptors, and bacteria/endotoxin translocation (BT) were performed. There were significantly increased levels of PMN elastase, interleukin-6, and soluble tumor necrosis factors (TNF) receptors, but not of TNF. BT was evident from positive blood cultures, and from trendwise increased endotoxin plasma levels. Early liver damage was shown from elevated glutathione S-transferase (GST) plasma levels. Complement activation and hemorrhagic shock lead to an early inflammatory response together with bacteremia/endotoxemia as evidence of translocation from the gut already during the shock period in subhuman primates.     

Influences of Intestinal Ligation on Bacterial Translocation and Inflammatory Response in Rats with Hemorrhagic Shock: Implications for Damage Control Surgery

Damage Control Surgery (DCS) treatment of rapid intestinal ligation to control the bowel spillage in severe abdominal trauma induces acute intestinal loop obstruction. The purpose of this study was to investigate the effects of intestinal ligation on bacterial translocation (BT) and inflammatory reaction under the condition of acute hemorrhagic shock and its probable pathophysiology. Escherichia coli TG1 labeled with green fluorescent protein was used to track BT by gavage to rats. Group Shock rats were subjected to hemorrhagic shock for 30 minutes. Group Shock+Ligation (Shock+L) rats were subjected to hemorrhagic shock and following intestinal ligation. We found that hemorrhagic shock alone or in combination with intestinal ligation caused not only morphological damage to ileal mucosa, but also induced BT and promoted release of TNF-α, IL-6, and IL-10 in serum and lymph. Ileal mucosa injuries and BT were significantly aggravated and cytokine levels in serum and lymph were significantly elevated in group Shock+L compared with group Shock. The positive proportions of bacterial culture and cytokine levels were significantly elevated in lymph compared with these in blood in both groups. By fluorescence microscope and XbaI restriction digestion analysis, we elucidated that the bacteria isolated from extraintestinal organs were the same bacteria we gavaged to the rats. We first confirmed that DCS treatment of rapid intestinal ligation under the condition of acute hemorrhagic shock leads to aggravated intestinal mucosa barrier injury and BT and elevated inflammatory response. The intestinal BT and immunoinflammatory factors may act through or mainly through lymph route.     

δ1受体在出血性休克大鼠心肌损伤中的作用

目的 评价δ1受体在出血性休克大鼠心肌损伤中的作用.方法 成年雄性SD大鼠24只,体重250～300 g,随机分为4组(n=6):出血性休克组(HS组)、δ1受体特异性激动剂(TAN-67)组(T组),δ1受体特异性阻断剂(BNTX)组(B组)和δ1受体特异性阻断剂+激动剂组(BT组).经股动脉放血,10 min内使平均动脉压降至40 mm Hg,维持此水平,休克期60 min,复苏期120 min.HS组于复苏前即刻经左颈静脉输注生理盐水0.5 ml;T组于复苏前即刻静脉注射TAN-67 10 mg/kg;B组于复苏前即刻静脉注射BNTX 3 mg/kg;BT组于复苏前即刻静脉注射BNTX 3 mg/kg,10 min后静脉注射TAN-67 10 mg/kg.记录心率、平均动脉压、左室压、左室收缩压最大上升速率和左室收缩压最大下降速率.给药后120 min时,处死大鼠观察心肌超微结构,并测定心肌线粒体通透性转换孔(mPTP)的开放数量.结果 与HS组比较,T组平均动脉压和心功能指标升高,心肌mPTP开放减少,B组mPIP开放增多(P<0.05),B组和BT组平均动脉压和心功能指标差异无统计学意义(P>0.05).T组心肌超微结构损伤较其余3组减轻.结论 大鼠出血性休克致心肌损伤时,机体可在一定程度上激活δ1受体,抑制心肌mPTP开放,该作用可能为机体内源性保护机制之一.     

The role of antibiotic prophylaxis with sodium ceftriaxone to prevent bacterial translocation associated with hypovolemic shock: an experimental study in rats.

One of the measures adopted to reduce or prevent intestinal bacterial translocation (BT) in patients who are in hemorrhagic shock consists of prophylactic antibiotics. This study attempted to assess the effectiveness of administering systemic antibiotic to suppress BT in rats submitted to hemorrhagic shock. Sixty-eight male Wistar rats were divided into two experiments. In experiment 1 (n = 28), the animals were randomly divided into three groups: group I (n = 7), sham operation; group II (n = 11), constituted by animals that were submitted to hemorrhagic shock by removing 40% of the volemia, and were resuscitated after 40 min of sustained shock, replacing the previously removed blood; and group III (n = 10), animals that, besides hemorrhagic shock and volemic replacement, received 50 mg/kg of sodium ceftriaxone intravenous 1 min after blood readministration. Mesenteric lymph nodes (MLN) for culture tests and segments of the small bowel were removed for histopathological studies 1 day after the operation in the three groups. In experiment 2, the same procedures were performed, except the laparotomy for removing MLN and segments of jejunal and ileal bowel, but the animals were followed during 7 days, in order to evaluate the mortality rate. In the control group (group I), the bacteriological assessment of the MLN was negative in all cases. Only 40% of the animals treated with antibiotics after hypovolemic shock (group III) presented positive bacteriological exams of the MLN, and this rate was 90% in the group of animals that did not receive this substance (group II) (p < .05). Escherichia coli was the bacteria identified most frequently in culture tests (92.8%). The villosities atrophy and inflammatory infiltrate of the lamina propria were the most common histological changes in the bowel, although the intensity was similar in groups II and III (p > .05), but more intense that in group I (p < .05). The mortality rates in groups I, II, and III 7 days after hypovolemic shock were 0%, 20%, and 20%, respectively. Prophylactic antibiotics significantly reduced the presence of bacteria in the MLN in situations of hypovolemic shock, in rats. This was probably related to a lower BT. However, this aspect did not modify the mortality rate of the animals. Also, the possibility that BT may not have a significant influence in this outcome should be considered.     

Heart rate variability during massive hemorrhage and progressive hemorrhagic shock in dogs

PURPOSE: To investigate the sequential changes in heart rate (HR), autonomic nervous activity presented by the spectral analysis of heart rate variability (HRV), hemodynamics and metabolism during massive hemorrhage and progressive hemorrhagic shock in dogs. METHODS: Twelve dogs were subjected to acute massive hemorrhage until mean arterial pressure (MAP) reached 50 mm Hg. Then bleeding was stopped and they were allowed to reach a plateau phase. They were divided, post hoc, into bradycardic or tachycardic groups according to their HR response to the acute massive hemorrhage. After reaching a plateau phase, the dogs were further bled to keep their MAP around 50 mmHg (progressive hemorrhagic shock). Their heart rate power spectra were quantified into low-frequency (LF) (0.04-0.15 Hz) and high-frequency (HF) (0.15-0.4 Hz) components. RESULTS: In the bradycardic group, both LF and HF increased after massive hemorrhage, but during progressive hemorrhagic shock these components decreased while HR increased. In the tachycardic group, LF increased after massive hemorrhage, but during progressive hemorrhagic shock LF decreased with continuous suppression of HF CONCLUSION: Massive hemorrhage caused two types of HR response: bradycardia and tachycardia. The HRV profile showed differential autonomic characteristics, and could be a valuable tool in assessing various degrees of hemorrhagic shock.     

The gut as source of sepsis after hemorrhagic shock

In a model of severe hemorrhagic shock in rats, blood culture findings became positive within 2 to 4 hours of shock. The organisms cultured were primarily gram-negative. To test the hypothesis that the gut was the source of the bacteria, E. coli labeled with carbon-14 oleic acid were fed to rats undergoing hemorrhagic shock. Their plasma was then assayed for carbon-14 activity. Seven of the 14 shocked animals demonstrated increased plasma carbon-14 activity during or after shock. The mortality rate was 100 percent 80 hours postshock, and all animals had E. coli on subsequent blood culture. The seven rats without increased plasma carbon-14 activity had a survival rate of 83 percent postshock. Sham-shocked animals did not exhibit plasma carbon-14 levels greater than the background levels. These data suggest that bacterial translocation occurs during hemorrhagic shock and that the gut is the source of the bacteremia seen during hemorrhagic shock.     

Hemorrhagic shock-induced bacterial translocation is reduced by xanthine oxidase inhibition or inactivation

Experiments were performed to determine whether bacterial translocation (BT) after hemorrhagic shock is due to a reperfusion injury mediated by xanthine oxidase-derived oxidants. Rats were subjected to 30 minutes of shock (30 mm Hg) followed by reinfusion of shed blood. Twenty-four hours after hemorrhage and reinfusion, the mesenteric lymph node, liver, and spleen were harvested from each animal for bacterial culture, and the ileum and cecum were examined histologically. Sham-shocked (control) rats were instrumented, but blood was not withdrawn. The incidence of BT was higher in the shocked rats (61%) than in the sham-shocked animals (7%) (p less than 0.01). Allopurinol (50 mg/kg, administered orally), a competitive inhibitor of xanthine oxidase, reduced the incidence of shock-induced BT to 14% (p = 0.02). Similarly, rats fed a tungsten-supplemented molybdenum-free diet, which inactivates xanthine oxidase, reduced shock-induced BT to 10% (p = 0.02). The histologic damage cause by hemorrhagic shock was prevented by blocking xanthine oxidase activity. Thus hemorrhagic shock-induced bacterial translocation from the gut appears to be mediated by oxidants generated by activation of the xanthine oxidase system.     

Cyclic AMP response to epinephrine and shock.

Hormonal regulation is fundamental to homeostasis, and the response in tissues is mediated by adenosine 3':5' equals cyclic phosphate (cyclic AMP). Since circulating levels of catecholamines are elevated during hemorrhagic shock, experiments were carried out to study the effects of epinephrine and of shock on cyclic AMP levels of plasma and of the intestine, a particularly vulnerable organ in canine hemorrhagic shock. Epinephrine was given to normotensive dogs as a constant infusion (group 1) or as a single pulse (group 2). Sequential blood samples showed a marked increase in circulating cyclic AMP, especially in portal and hepatic venous blood. Little change was noted in the tissues. Hemorrhagic shock (group 3) induced a marked increase in plasma cyclic AMP, with a depletion of mucosal cyclic AMP and adenosine triphosphate (ATP). Pretreatment before shock with alpha-blockade (group 4) abolished the decrease in mucosal cyclic AMP and ATP, and reduced the increase in plasma cyclic AMP.     

失血性休克促进细胞移位的发生

目的 探讨失血性休克在细菌移位中的作用。方法 本组１００例患者分４组,对照组（Ｉ组）３４例;闭合性腹部钝伤致失血性休克组（Ⅱ组）２３例;闭合性腹部钝伤无失血性休克组（Ⅲ组）１５例;腹部内出血致失血性休克组（Ⅳ组）２８例;取患者手术前后的外周血、腹膜脏层拭子样品、术中门静脉血、回肠系膜淋巴结、肝活检组织进行需氧与厌氧培养。结果 细菌移位的发生率第Ｉ组为６％（２／３４）,第Ⅱ组６５％（１５／２３）。第     

Moderate hypothermia prevents brain stem oxidative stress injury after hemorrhagic shock

BACKGROUND: The purpose of this study was to investigate the effects of temperature on oxidative stress in brain stem tissue induced by hemorrhagic shock. We researched the hemorrhagic oxidative stress at various core temperatures using reduced glutathione (GSH) levels and thiobarbituric acid-reactive substances (TBARS) as markers of lipid peroxidation in brain stem homogenate. METHODS: Forty rats were divided into four groups, of which one constituted the nonbleeding normothermia control group. In all of the three study groups, 40% of estimated blood volume was removed while they were being held at normothermia, mild hypothermia (32 degrees C), or moderate hypothermia (28 degrees C). Parameters including mean arterial pressure, rectal temperature, and heart and breathing rates were monitored and recorded during the procedures. After an hour at shock state, tissue samples were removed by craniectomy. RESULTS: The tissue levels of TBARS increased significantly in normothermic and mild hypothermic hemorrhagic shock groups (10.74 nmol/g and 8.26 nmol/g) as compared with the control group (3.50 nmol/g) (p < 0.001). However, the tissue TBARS level in the moderate hypothermia group was only minimally increased (4.53 nmol/g). GSH showed a slight decrease in normothermic and mild hypothermic bleeding rats, and were unchanged in the moderate hypothermic rats. CONCLUSION: Moderate systemic hypothermia (28 degrees C) appears to protect brain stem tissue from oxidative stress during severe hemorrhagic shock in rats, as indicated by insignificant change in tissue TBARS and GSH concentrations. These results suggest antioxidant protective effects of moderate systemic hypothermia in metabolically active brain stem tissue during hemorrhagic shock. Similar effects in humans remain to be studied.     

高渗氯化钠高氧液对失血性休克家兔血乳酸和动脉血气的影响

目的:观察高渗氯化钠高氧液对失血性休克家兔动脉血气和血乳酸值的影响，评价其对失血性休克的早期救治效果。方法:制备高渗氯化钠溶液(HS)、生理盐水高氧液（NSO）和高渗氯化钠高氧液(HSO)。30只雄性家兔制备失血性休克模型［于10min内使平均动脉压（MAP）降至40mmHg（1mmHg＝0.133kPa），维持60min］，随机分为NSO，HS，HSO组3个治疗组。分别按6mL/kg剂量5min内静脉输入NSO,HS和HSO。记录休克前后及给药后心率（HR）、呼吸（RR）、MAP及尿滴（UD），测定休克前、休克60min，给药后30，60，120min时血乳酸（BL）和动脉血气值。最后观察尸肺，测定肺系数。结果:HS和HSO组均显著地改善MAP，HR和UD，降低BL，改善代谢性酸中毒,肺系数明显低于NSO组。HSO与NSO及HS比较，能更显著地降低血BL，提高动脉血氧饱和度（SaO2）和动脉血氧分压（PaO2）。结论:HSO较HS和NSO能更显著地降低血BL,提高SaO2和PaO2，对失血性休克的早期救治具有较高的使用价值。     

Effect of sodium D-3-hydroxybutyrate on amino acidemia in hemorrhagic hypotension.

The effect of sodium D-3-hydroxybutyrate (3-OHB) on the amino acidemia caused by hemorrhagic stress was studied. Rats were infused 3-OHB (3-OHB group, n = 11) at a rate of 30 mumol/min.kg or the same volume of saline (control group, n = 11) for 1 h prior to hemorrhage. Mean arterial pressure was maintained at 40 mm Hg using reserved bottle for 30 min. While ketosis was suppressed in control group, plasma ketone body concentration increased from 2,062.9 +/- 223.7 to 3,151.4 +/- 794.8 mumol/l in the 3-OHB group during hemorrhage. Although significant difference in plasma concentrations of amino acids were not shown between two groups at the onset of shock, it was shown after 30 min of shock in alanine, proline, and threonine. Particularly severity of hyperalaninemia was clear. In the control group plasma alanine concentration increased as shock proceeded (p less than 0.01), and no significant change was shown in the 3-OHB group. These results indicate that pretreatment with 3-OHB suppress the hyperalaninemia seen in hemorrhagic hypotension. Ketone body administration may inhibit the protein catabolism in stressed states, such as hemorrhagic hypotension.     

Hemorrhagic shock in the rat: comparison of carotid and femoral cannulation

BACKGROUND: The reservoir model of rat hemorrhagic shock is widely used. In this model, either the carotid or femoral artery can be cannulated to withdraw blood and measure pressure. In animals undergoing hemorrhage using the carotid approach, we observed seizure activity during the post-shock period, suggesting some degree of brain damage. The hypothesis of the present study is that survival in a model of severe hemorrhagic shock would be higher with femoral cannulation than with carotid cannulation. MATERIALS AND METHODS: All animals (n = 90) were anesthetized with isoflurane using an anesthesia vaporizer while breathing spontaneously. In group 1, the left carotid artery and jugular vein were cannulated; in group 2, the left femoral artery and vein were cannulated. Following a period of hemorrhagic shock (20 to 30 mmHg for 30, 60, or 50-90 min), resuscitation was performed through the venous cannula by giving L-lactated Ringer's (21 mL/kg) and returning the shed blood. RESULTS: In the carotid cannulation group, nearly 50% of the animals had seizures after resuscitation, and most of those animals died following the seizures. The 24-h survival rate in the femoral artery cannulation group was significantly higher than in the carotid artery cannulation group. Femoral cannulated animals had no seizures following reperfusion. CONCLUSIONS: Femoral artery cannulation was associated with considerably better survival than carotid artery cannulation in this rodent model of hemorrhagic shock. The occurrence of seizures in animals undergoing carotid cannulation suggests brain damage from inadequate cerebral perfusion or subsequent reperfusion damage.     

高氧复方氯化钠溶液用于大鼠烧伤后休克的观察

目的观察并探讨高氧复方氯化钠溶液对烧伤休克的防治作用. 方法 (1)将Wistar大鼠分为6组,A组正常对照组;B组制作30%TBSAⅢ度烧伤模型,伤后1 h补充复方氯化钠溶液;C组致伤后6 h补充复方氯化钠溶液;D组伤后1 h补充高氧复方氯化钠溶液;E组伤后6 h补充高氧复方氯化钠溶液;F组致伤后不治疗.动态观察各组大鼠内毒素(LPS)、白细胞介素6(IL-6)、二胺氧化酶(DAO)活性、D-乳酸、丙二醛(MDA)的变化.(2)选择烧伤面积为50%～69%TBSA、伤后3 h内入院的患者,随机分为治疗组补充高氧复方氯化钠溶液;对照组补充复方氯化钠溶液.观察患者休克期变化、经皮氧分压、血红蛋白、血细胞比容及有无并发症等. 结果大鼠伤后各组监测指标水平均较A组显著升高,呈逐步上升趋势,F组更加明显,其顺序为F组>C组>B组>E组>D组(P＜0.05).烧伤患者治疗组较对照组休克期度过平稳,补液量减少,氧分压明显升高,并发症少,但血氧饱和度差异无显著性意义. 结论早期应用高氧复方氯化钠溶液,对防治烧伤休克有较好的疗效.     

失血性休克患者血浆肾上腺髓质素与血管阻力变化的关系

目的：观察失血性休克患者血浆肾上腺髓质素（ARM）与血管阻力变化，探讨ARM在失血性休克病理生理过程中的作用。方法：应用放射免疫检测30例休克患血浆ARM浓度，无创胸导生物电阻抗方法测定平均动脉压（MAP）、全身血管阻力指数（SVRI）和心脏指数（CI）。结果：休克组治疗前血浆ARM浓度明显高于正常对照组（P＜0．01）。结论：ARM与血管阻力变化相关，并参与了失血性休克的病理生理过程。     

Plasma fibronectin metabolism during hemorrhagic shock and starvation

In this report we characterize the response of the plasma protein fibronectin to hemorrhagic shock and starvation, conditions associated with decreased function of mononuclear phagocyte system (MPS). Rats were starved for 3 days, then half of the animals were subjected to fixed-volume hemorrhagic shock by removing an estimated 35% of their blood volumes for 20 min. After volume replacement, animals were injected iv with [14C]valine. At time points up to 10 hr after hemorrhage, plasma fibronectin concentrations and fibronectin synthesis were quantitated. In additional rats treated identically, fibronectin clearance was assessed by measuring the disappearance of 125I-fibronectin from the plasma. When compared to control animals, either starvation or hemorrhagic shock produced similar perturbations in plasma fibronectin metabolism; fibronectin concentrations were reduced from 241.3 +/- 34.6 micrograms/ml (mean +/- SEM) (controls) to 123 +/- 32.6 micrograms/ml (starvation) or 150.0 +/- 13.0 micrograms/ml (hemorrhage). Plasma [14C]fibronectin specific radioactivities, indicative of fibronectin synthesis, were also significantly reduced. Hemorrhagic shock in rats that previously had been starved did not depress fibronectin concentrations or synthesis to a greater extent than starvation alone. The rates of 125I-fibronectin clearance were increased in starvation and hemorrhagic shock (t1/2 = 233.0 +/- 13.0 min, controls; 174.6 +/- 10.7 min, starvation; 167.4 +/- 13.6 min, hemorrhage). In contrast to changes observed in fibronectin metabolism, total plasma protein concentrations were not significantly altered in any experimental groups. Furthermore, total plasma protein synthesis increased in rats subjected to either starvation or hemorrhagic shock, but decreased in starved rats that were subsequently shocked.(ABSTRACT TRUNCATED AT 250 WORDS)     

The influence of hemorrhagic shock on etomidate: a pharmacokinetic and pharmacodynamic analysis

We studied the influence of hemorrhagic shock on the pharmacology of etomidate in swine. Sixteen swine were randomly assigned to control and shock groups. The shock group was bled to a mean arterial blood pressure of 50 mm Hg and held there until 30 mL/kg blood was removed. Etomidate 300 micro g x kg(-1) x min(-1) was infused for 10 min to both groups. Fifteen arterial samples were collected until 180 min after the infusion began to determine drug concentration. Pharmacokinetic variables for each group were estimated by using a three-compartment model. The bispectral index scale was used as a measure of drug effect. The pharmacodynamics were characterized by using a sigmoid inhibitory maximal effect model. The raw data revealed a 25% increase in the plasma etomidate concentration at the end of the 10-min infusion which resolved after termination of the infusion in the shock group. The pharmacokinetic analysis revealed subtle changes in the variable estimates between groups. The etomidate infusion produced a similar Bispectral Index Scale change in both groups. These results demonstrated that, unlike the influence of hemorrhagic shock on other sedative hypnotics and opioids, moderate hemorrhagic shock produced minimal changes in the pharmacokinetics and no change in the pharmacodynamics of etomidate. IMPLICATIONS: Hemorrhagic shock produced minimal changes in the pharmacokinetics and no change in the pharmacodynamics of etomidate in swine. These results suggest that, unlike other sedative hypnotics and opioids, minimal adjustment in the dose of etomidate is required to achieve the same drug effect during hemorrhagic shock.     

Surface cooling, which fails to reduce the core temperature rapidly, hastens death during severe hemorrhagic shock in pigs

OBJECTIVE: To examine whether surface cooling (SC) would rapidly decrease the core temperatures and prolong the survival time during volume-controlled lethal hemorrhagic shock in pigs. METHOD: Twelve pigs were randomly assigned to the SC group (group 1, n = 6) or the no cooling control group (group 2, n = 6), after blood withdrawal of 30 mL/kg over 15 minutes, and maintained under spontaneous breathing by light anesthesia with 1.0% halothane. SC was performed by applying ethanol to the skin, blowing with an electric fan, and placing ice packs. Pigs were observed without fluid resuscitation until their death (apnea and no pulse). RESULTS: SC did not lower the rectal temperature (Tr) to 35 degrees C at any time point until death, except one pig; in that animal, Tr was decreased to 34 degrees C after 135 minutes from the start of SC. The survival time was 108 +/- 43 minutes in group 1 and 175 +/- 55 minutes in group 2 (p < 0.05, life table analysis). CONCLUSION: In lightly anesthetized pigs during hemorrhagic shock, SC without resuscitation did not rapidly reduce the core temperature and rather hastened death for reasons that remain to be explored.     

Extracellular-intracellular lactate gradients in skeletal muscle during hemorrhagic shock in the rat

Previous studies performed in our laboratory with a constant-pressure model of hemorrhagic shock in the anesthetized rat have failed to find any significant effect of shock on the glycogen or high-energy phosphate content of the soleus muscle that would be consistent with inadequate oxygen supply. The present study examined the extracellular-intracellular lactate concentration gradients under conditions identical to those of our previous studies to determine whether skeletal muscle lactate accumulation might occur under these conditions. Twenty-seven pentobarbital-anesthetized rats were bled to a mean arterial blood pressure of 40 mm Hg during a 10-minute period and maintained at that level by withdrawal or reinfusion of shed blood. Arterial blood samples were taken and soleus muscles rapidly frozen during four defined phases of hemorrhagic shock: the early compensatory (phase I), maximal compensatory (phase II), early decompensatory (phase III), and late decompensatory (phase IV) phases. The results showed that although the plasma lactate and intracellular lactate concentrations change in parallel during all phases of shock, the extracellular--intracellular concentration gradient for lactate was always positive, ranging from 0.64 +/- 0.61 mmol/L in phase I to 6.41 +/- 0.93 mmol/L in phase III. These findings, together with the previous failure to find significant high-energy phosphate or glycogen changes in the soleus muscle, suggest that this skeletal muscle is not metabolizing anaerobically and does not contribute to the observed lactic acidemia in this model of hemorrhagic shock.