Rat Model Of Shock Research Articles

Protective effect of CDP-choline on hypotension and tissue injury in septic shock model

CDP-choline is an endogen molecule and also a drug that is used in several trauma and ischemic conditions. It has been demonstrated that it improves the hemodynamic parameters in different shock models and prevents tissue damage in rats. The current study tested the effect of CDP-choline on hypotension, inflammation and tissue injury induced by septic shock model in rats. Twenty-four adult, male Spraque-Dawley rats, weighing 250-300 g were used. Septic shock was induced by cecal ligation-incision (CLI). CDP-choline (100 mg/kg) injected intravenously (i.v.) at the 180th minute of the experiment. The animals were observed for 180 minutes after the injection, then blood and tissue samples were obtained for cytokine measurements and histological examinations, respectively. The cecal ligation-incision decreased arterial pressure and increased heart rate. Intravenous injection of CDP-choline reversed hypotension and increased arterial pressure up to control levels within the first 60 minutes without changing the increase in heart rate. The effect lasted for 3 hours. CDP-choline attenuated the increases in TNF-α, IL-1β and IL-6 levels in septic shock. Moreover, the drug exerted protective effects for the injury induced by septic shock in lungs, liver and kidney tissues; whereas this effect was not present on spleen. In conclusion, the present data suggested that intravenous CDP-choline administration can improve the deteriorations in hemodynamic and inflammatory parameters and can prevent the tissue injury in septic shock-induced by CLI in rats

Cytochrome c limits oxidative stress and decreases acidosis in a rat model of hemorrhagic shock and reperfusion injury.

Hemorrhagic shock and reperfusion (HSR) injury leads to a cascade of reactive oxygen species (ROS) production and mitochondrial dysfunction, which results in energy failure, cell death, and multiple organ dysfunction. Cytochrome c (cyt c) is the final electron carrier in the mitochondrial electron transport chain providing the electrochemical force for ATP production. We sought to determine whether exogenous cyt c administration would improve parameters of organ dysfunction and/or mitochondrial stability in a rat model of HSR. Male rats were hemorrhaged to a mean arterial pressure (MAP) of 33 ± 2.0 mm Hg for 1 hour before resuscitation. Saline or cyt c (0.8 mg [HSR-LoCC] or 3.75 mg [HSR-HiCC]) was administered (i.v.) 30 minutes before resuscitation. Rats were euthanized by cardiac puncture 2 hours post-surgery and tissue collected and analyzed for lipid peroxidation, endogenous antioxidant activity (glutathione peroxidase (GPx) and catalase), TNF-α expression, mitochondrial function (complex-I activity), and circulating mitochondrial DNA (mtDNA). Cyt c administration improved lactate clearance, decreased hepatic lipid peroxidation, increased hepatic GPx activity, restored pulmonary TNF-α to sham activity levels, and increased hepatic complex-I activity. Furthermore, addition of exogenous cyt c decreased circulating levels of mtDNA. These studies demonstrate that cyt c reduces markers of physiologic stress, decreases oxidative stress, and lowers levels of circulating mtDNA. The impact of cytochrome c is organ specific. Further studies remain to determine the sum of the effects of cytochrome c on overall outcome.

Effects of Quercetin in a Rat Model of Hemorrhagic Traumatic Shock and Reperfusion.

Background: We hypothesized that treatment with quercetin could result in improved hemodynamics, lung inflammatory parameters and mortality in a rat model of hemorrhagic shock. Methods: Rats were anesthetized (80 mg/kg ketamine plus 8 mg/kg xylazine i.p.). The protocol included laparotomy for 15 min (trauma), hemorrhagic shock (blood withdrawal to reduce the mean arterial pressure to 35 mmHg) for 75 min and resuscitation by re-infusion of all the shed blood plus lactate Ringer for 90 min. Intravenous quercetin (50 mg/kg) or vehicle were administered during resuscitation. Results: There was a trend for increased survival 84.6% (11/13) in the treated group vs. the shock group 68.4% (13/19, p > 0.05 Kaplan–Meier). Quercetin fully prevented the development of lung edema. The activity of aSMase was increased in the shock group compared to the sham group and the quercetin prevented this effect. However, other inflammatory markers such as myeloperoxidase activity, interleukin-6 in plasma or bronchoalveolar fluid were similar in the sham and shock groups. We found no bacterial DNA in plasma in these animals. Conclusions: Quercetin partially prevented the changes in blood pressure and lung injury in shock associated to hemorrhage and reperfusion.

C-type natriuretic peptide prevents kidney injury and attenuates oxidative and inflammatory responses in hemorrhagic shock

Oxidative stress induced by hemorrhagic shock (HS) initiates a systemic inflammatory response, which leads to subsequent kidney injury. This study assessed the efficacy of c-type natriuretic peptide (CNP) in attenuating kidney injury in a rat model of hemorrhagic shock and resuscitation (HS/R). Sodium pentobarbital-anesthetized adult male Wistar rats underwent HS induced by the withdrawal of blood to a mean arterial pressure of 30-35mmHg for 50min. Then, the animals received CNP (25μg/kg) or vehicle (saline) intravenously, followed byresuscitation with 1.5 times the shed blood volume in the form of normal saline. Mean arterial pressure was measured throughout the experiment, and acid-base status, oxidative stress, inflammation, tissue injury and kidney function were evaluated after resuscitation. CNP infusion reduced the malondialdehyde content, lowered the myeloperoxidase activity and decreased the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in the kidney. The histologic injury score and the plasma creatinine concentration were also significantly decreased after CNP treatment compared to the vehicle group. CNP treatment ameliorates oxidative stress, the inflammatory response, and consequently acute kidney injury after HS/R. Thus, CNP may represent a promising strategy to improve resuscitation for the treatment of HS and deserves further investigation.

Effects of cococonut water and simvastatin in the treatment of sepsis and hemorrhagic shock in rats

To evaluate the effects of modified coconut water as fluid of resuscitation combined with simvastatin in hemorrhagic shock and sepsis model in rats. Four groups of Wistar rats with hemorrhagic shock and abdominal sepsis were studied (n=8/group). Rats were bled and maintained at a mean blood pressure 35mmHg for 60min. They were then resuscitated with: 1) saline 0.9%; 2) coconut water+3% NaCl; 3) coconut water+NaCl 3%+simvastatin microemulsion (10 mg/kg i.v.; 4) normal coconut water. At 8h post-resuscitation, blood and lungs were collected for exams. Clinical scores, TNF-α, IL-1β, liver/kidney proof levels, and lung injury were significantly reduced in coconut water+NaCl 3%+simvastatin group treated rats, comparing with the other resuscitation treatments. Resuscitation with coconut water with Nacl 3%+simvastatin had a significant beneficial effect on downregulating cytokines and decreasing lung injury in a rat model of abdominal sepsis and hemorrhagic shock. We also demonstrated that coconut water with Nacl 3%+simvastatin administration clearly made liver and kidney function better and improved clinical score.

4-Aminopyridine, A Blocker of Voltage-Dependent K+ Channels, Restores Blood Pressure and Improves Survival in the Wistar Rat Model of Anaphylactic Shock.

Anaphylactic shock is associated with severe hypotension. Potassium channel blockers, such as 4-aminopyridine, induce vasoconstriction. The objective of this study was to test the ability of 4-aminopyridine to restore blood pressure and increase survival in anaphylactic shock. Experimental study. Physiology laboratory. Adult male Wistar rats. Rats were sensitized with ovalbumin (1 mg SC), and anaphylactic shock was induced by IV injection of ovalbumin (1 mg). Experimental groups included non-allergic rats (NA) (n = 6); allergic rats (Controls) (n = 6); allergic rats treated with 4-aminopyridine (4-aminopyridine) (1 mg/kg) (n = 6); and allergic rats treated with epinephrine (EPI) (10 µg/kg) (n = 6). Treatments were administered 1 minute after induction of anaphylactic shock. Mean arterial blood pressure, heart rate, and survival were measured for 60 minutes. Plasma levels of histamine, leukotriene B4, prostaglandin E2, prostaglandin F2, pH, and HCO3 were measured. Mean arterial blood pressure was normal in the NA group; severe hypotension and high mortality were observed in controls; normalization of mean arterial blood pressure, heart rate, and increased survival were observed in 4-aminopyridine and EPI groups. All allergic 4-aminopyridine-treated rats survived after the induction of anaphylactic shock. Histamine level was higher in controls and the 4-aminopyridine group but reduced in the EPI group. Prostaglandin E2 increased in controls and EPI group and decreased in 4-aminopyridine group; prostaglandin F2 increased in controls but decreased in 4-aminopyridine and EPI groups. Leukotriene B4 decreased in 4-aminopyridine and EPI groups. Metabolic acidosis was prevented in the 4-aminopyridine group. Our data suggest that voltage-dependent K+ channel inhibition with 4-aminopyridine treatment restores blood pressure and increases survival in the Wistar rat model of anaphylactic shock. 4-aminopyridine or related voltage-dependent K channel blockers could be a useful additional therapeutic approach to treatment of refractory anaphylactic shock.

Photoacoustic Imaging for the Detection of Hypoxia in the Rat Femoral Artery and Skeletal Muscle Microcirculation.

Photoacoustic (PA) imaging is an emerging technology that combines structural and functional imaging of tissues using laser and ultrasound energy. We evaluated the ability of PA imaging system to measure real-time systemic and microvascular mean oxygen saturation (mSAO2) in a rat model of hypoxic shock. Male Sprague Dawley rats (n = 6) underwent femoral artery catherization and were subjected to acute hypoxia by lowering the fraction of inspired oxygen (FiO2) from 1.0 to 0.21, and then to 0.08. PA measurements of mSaO2 were taken in the femoral artery near the catheter tip using the Vevo 2100 LAZR at each FiO2 and compared to co-oximetry on blood removed from the femoral catheter. Both co-oximetry and PA imaging measured a similar stepwise decline in femoral artery mSaO2 as FiO2 was lowered. We also measured mSaO2 in the feed arteriole of the rat spinotrapezius muscle and adjacent microvessels (n = 6) using PA imaging. A significant decrease in mSaO2 in both the feed arteriole and adjacent microvessels was recorded as FiO2 was decreased from 1.0 to 0.08. Moreover, we detected a rapid return toward baseline mSaO2 in the feed arteriole and microvessels when FiO2 was increased from 0.08 to 1.0. Thus, PA imaging is noninvasive imaging modality that can accurately measure real-time oxygen saturation in the macro and microcirculation during acute hypoxia. This proof-of-concept study is a first step in establishing PA imaging as an investigational tool in critical illness.

Rapid permissive action of dexamethasone on the regulation of blood pressure in a rat model of septic shock.

Glucocorticoids (GCs) play a vital role in the regulation of blood pressure by their permissive effects in potentiating vasoactive responses to catecholamines through glucocorticoid receptors. GCs achieve this function by controlling vascular smooth muscle tone. Clinically, low to moderate doses of GCs are generally used in the treatment of septic shock in recent years. GCs are now known to have both genomic and non-genomic effects. While genomic effects of GCs were well studied, few non-genomic effects were reported, much less the non-genomic mechanisms. One of the most important characters of their non-genomic effects is short latency. The aim of this study was to determine whether GCs can rapidly regulate blood pressure by their permissive action on norepinephrine (NE). Adrenalectomized rats were subjected to cecal ligation and puncture to induce septic shock. The septic rats displayed a significant decrease in the blood pressure response to NE. Dexamethasone (DEX) rapidly restores this hyporeactivity to NE in adrenalectomized septic rats. Further studies showed that DEX potentiates the NE-induced shrinkage and actin cytoskeleton rearrangement of single cell from mesenteric arteries in a short time. These findings suggest that GCs probably exert their permissive actions on the pressure response to NE through rapid non-genomic mechanisms. In this article, we found that as an adjunctive therapy for septic shock, the use of GCs may involve a rapid permissive action, and non-genomic effects of GCs may be involved in these processes.

Anterior wrist and medial malleolus: the optimal sites for tissue selection in electric death through hand-to-foot circuit pathway.

Specific morphological changes may be absent in some cases of electrocution shocked by the voltage of 220V or lower. In this study, we attempted to demonstrate that the anterior wrist and medial malleolus were the optimal sites with promising and significant changes in electric death through the hand-to-foot circuit pathway. We established an electric shock rat model and observed histopathologic changes in the anterior wrist and medial malleolus. The results showed that the current intensities in the left anterior wrist and right medial malleolus were remarkably higher than those in the other sites, and the nuclei long/short (L/S) axis ratios of the arterial endotheliocyte and the skeletal muscle cell in these two areas were significantly higher than those in other parts of the body. These findings suggested that the anterior wrist and/or medial malleolus soft tissues as the narrowest parts of the limbs could be used as promising and useful sites for the assessment of electrical shock death, especially in forensic pathologic evaluation.

Dose-related effects of dexmedetomidine on immunomodulation and mortality to septic shock in rats

Objective To study the immunomodulation effects of different dosage of dexmedetomidine (Dex) in the septic shock model of rats after cecal ligation and puncture (CLP). Methods After CLP, 48 wistar rats were randomly(random number) allocated in four groups: (1) CLP group; (2) small-dose Dex group[2.5 μg/(kg·h)]; (3) medium-dose Dex group[5.0 μg/(kg·h)]; (4)large-dose Dex group[10.0 μg/(kg·h)]. HLA-DR(human leukocyte antigen-DR) and plasma cytokine(IL-4, IL-6, IL-10 and TNF-α) were measured, meanwhile mean arterial blood pressure(MAP), heart rate(HR) and mortality were also documented at 1, 3, and 5 h after the CLP procedure. Results There were no obvious differences in HLA - DR level, levels of inflammatory mediators, MAP and HR among there Dex treatment groups. Compared with CLP group, HLA-DR level decreased in three Dex treatment groups(P=0.020) and pro-inflammatory mediator (IL-6) increased at 3 h (P= 0.011) then declined at 5 h with decreased HR(P<0.01), and without obvious change in MAP(P=0.124), and all of them led to a significantly decrease in the mortality.The mortalities in CLP group, small dose group, medium dose group and large dose group were 91.7%, 66.7%, 25.0% and 18.0%, respectively. Conclusions Dexmedetomidine used in rats with septic shock rats partially induced immunomodulation initiated within 5 h after CLP evidenced by decreased HR, maintenance of MAP and reduction of mortality rate in dose-dependent fashion. Key words: Dexmedetomidine; Immunomodulation; Septic shock

Cryogenic role of central endogenous hydrogen sulfide in the rat model of endotoxic shock

Thermoregulatory responses to lipopolysaccharide (LPS) are affected by modulators that increase (propyretic) or decrease (cryogenic) body temperature (Tb). We tested the hypothesis that central hydrogen sulfide (H2S) acts as a thermoregulatory modulator and that H2S production in the anteroventral preoptic region of the hypothalamus (AVPO) is increased during hypothermia and decreased during fever induced by bacterial lipopolysaccharide (LPS, 2.5mg/kg i.p.) in rats kept at an ambient temperature of 25°C. Deep Tb was recorded before and after pharmacological inhibition of the enzyme cystathionine β-synthase (CBS – responsible for H2S endogenous production in the brain) combined or not with LPS administration. To further investigate the mechanisms responsible for these thermoregulatory adjustments, we also measured prostaglandin D2 (PGD2) production in the AVPO. LPS caused typical hypothermia followed by fever. Levels of AVPO H2S were significantly increased during hypothermia when compared to both euthermic and febrile rats. Intracerebroventricular (icv) microinjection of aminooxyacetate (AOA, a CBS inhibitor; 100 pmol) neither affected Tb nor basal PGD2 production during euthermia. In LPS-treated rats, AOA caused increased Tb values during hypothermia, along with enhanced PGD2 production. We conclude that the gaseous messenger H2S modulates hypothermia during endotoxic shock, acting as a cryogenic molecule.

Lung protection provided by suberoylanilide hydroxamic acid in a rat model of hemorrhagic shock after entering high altitude for the first time:comparison of resuscitation with different fluids

Objective To compare the lung protection provided by suberoylanilide hydroxamic acid (SAHA) in a rat model of hemorrhagic shock after entering high altitude for the first time during resuscitation with different fluids. Methods Forty-eight male Wistar rats, aged 1.5-2.0 months, weighing 250-300 g, were transported from the breeding area at altitude 2 800 m to the experimental area at altitude 3 780 m. The rats were randomized into 4 groups (n=12 each) using a random number table: sham operation group (group Sham), hemorrhagic shock group (group HS), resuscitation with lactated Ringer′s solution combined with SAHA group (group LR+ SAHA), and resuscitation with hypertonic sodium chloride hydroxyethyl starch 40 solution (HSH40) combined with SAHA group (group HSH+ SAHA). Hemorrhagic shock was induced by removing 45%-55% of blood volume from the left femoral artery at a constant speed within 15 min until mean arterial pressure was reduced to 30-40 mmHg and maintained at this level for 90 min through blood-letting or reinfusion of the shed blood.In group Sham, only cannulation was performed, the rats received no blood-letting or resuscitation, blood samples were collected from the abdominal aorta at 3 h of observation, and then the rats were sacrificed.In group HS, hemorrhagic shock was induced, blood samples were collected from the abdominal aorta immediately after successful establishment of the model, and then the rats were sacrificed.In group LR+ SAHA, after successful establishment of the model, lactated Ringer′s solution (1.5 times the volume of blood loss) was infused over 20 min, and then SAHA 7.5 mg/kg (in 0.25 ml of normal saline) was infused over 5 min for resuscitation.In group HSH+ SAHA, after successful establishment of the model, HSH40 4 ml/kg was infused over 5 min, and then SAHA 7.5 mg/kg (in 0.25 ml of normal saline) was infused over 5 min for resuscitation.In LR+ SAHA and HSH+ SAHA groups, the animals were sacrificed after blood samples were collected from the abdominal aorta at 3 h after resuscitation.Blood samples from the abdominal aorta were obtained for blood gas analysis, the oxygenation index was calculated, and the occurrence of acute lung injury (oxygenation index ≤300 mmHg) was recorded.Lungs were removed for examination of the pathologic changes (with light microscope) and ultrastructure (with transmission electronic microscope) and for determination of wet to dry weight ratio (W/D ratio) and expression of claudin-3 and claudin-4 in lung tissues (by Western blot). The lung injury was scored. Results The incidence of acute lung injury was 70% in group HS, and no acute lung injury was found in Sham, LR+ SAHA and HSH+ SAHA groups.Compared with group Sham, the lung injury score and W/D ratio in lung tissues were significantly increased, and the expression of claudin-3 and claudin-4 in lung tissues was significantly down-regulated in HS, LR+ SAHA and HSH+ SAHA groups (P<0.05). Compared with group HS, the lung injury score and W/D ratio in lung tissues were significantly decreased, the expression of claudin-3 and claudin-4 in lung tissues was significantly up-regulated (P<0.05), and the pathologic changes were significantly attenuated in LR+ SAHA and HSH+ SAHA groups.Compared with group LR+ SAHA, the lung injury score and W/D ratio in lung tissues were significantly decreased, the expression of claudin-3 and claudin-4 in lung tissues was significantly up-regulated (P<0.05), and the pathologic changes were significantly attenuated in group HSH+ SAHA. Conclusion SAHA provides better lung protection when resuscitation is performed with HSH40 than with lactated Ringer′s solution in a rat model of hemorrhagic shock after entering high altitude for the first time. Key words: Hydroxamic acids; Sodium lactate; Saline solution, hypertonic; Hetastarch; Altitude; Shock, hemorrhagic; Respiratory distress syndrome, adult

Nanovesicular liposome-encapsulated hemoglobin (LEH) prevents multi-organ injuries in a rat model of hemorrhagic shock

The goals of resuscitation in hemorrhagic shock are to correct oxygen deficit and to maintain perfusion pressure to the vital organs. We created liposome-encapsulated hemoglobin (LEH) as a nanoparticulate oxygen carrier (216±2nm) containing 7.2g/dl hemoglobin, and examined its ability to prevent the systemic manifestations of hemorrhagic shock (45% blood loss) in a rat model. We collected plasma after 6h of shock and LEH resuscitation, and determined the circulating biomarkers of systemic inflammation and functions of liver, gut, heart, and kidney. As is typical of the shock pathology, a significant increase in the plasma levels of cardiac troponin, liver function enzymes, soluble CD163 (macrophage activation), and creatinine, and the liver/gut myeloperoxidase activity was observed in the hemorrhaged rats. The plasma levels of TNF-α, IL-6, IL-1α, CINC-1, and IL-22 also increased after hemorrhagic shock. LEH administration prevented the hemorrhagic shock-induced accumulation of the markers of injury to the critical organs and pro-inflammatory cytokines. LEH also decreased the plasma levels of stress hormone corticosterone in hemorrhaged rats. Although saline also reduced the circulating corticosterone and a few other tissue injury markers, it was not as effective as LEH in restraining the plasma levels of creatinine, alanine transaminase, CD163, TNF-α, IL-6, and IL-1α. These results indicate that resuscitation with nanoparticulate LEH creates a pro-survival phenotype in hemorrhaged rats, and because of its oxygen-carrying capacity, LEH performs significantly better than saline in hemorrhagic shock.

Plasma First Resuscitation Reduces Lactate Acidosis, Enhances Redox Homeostasis, Amino Acid and Purine Catabolism in a Rat Model of Profound Hemorrhagic Shock

The use of aggressive crystalloid resuscitation to treat hypoxemia, hypovolemia, and nutrient deprivation promoted by massive blood loss may lead to the development of the blood vicious cycle of acidosis, hypothermia, and coagulopathy and, utterly, death. Metabolic acidosis is one of the many metabolic derangements triggered by severe trauma/hemorrhagic shock, also including enhanced proteolysis, lipid mobilization, as well as traumatic diabetes. Appreciation of the metabolic benefit of plasma first resuscitation is an important concept. Plasma resuscitation has been shown to correct hyperfibrinolysis secondary to severe hemorrhage better than normal saline. Here, we hypothesize that plasma first resuscitation corrects metabolic derangements promoted by severe hemorrhage better than resuscitation with normal saline. Ultra-high-performance liquid chromatography-mass spectrometry-based metabolomics analyses were performed to screen plasma metabolic profiles upon shock and resuscitation with either platelet-free plasma or normal saline in a rat model of severe hemorrhage. Of the 251 metabolites that were monitored, 101 were significantly different in plasma versus normal saline resuscitated rats. Plasma resuscitation corrected lactate acidosis by promoting glutamine/amino acid catabolism and purine salvage reactions. Plasma first resuscitation may benefit critically injured trauma patients by relieving the lactate burden and promoting other non-clinically measured metabolic changes. In the light of our results, we propose that plasma resuscitation may promote fueling of mitochondrial metabolism, through the enhancement of glutaminolysis/amino acid catabolism and purine salvage reactions. The treatment of trauma patients in hemorrhagic shock with plasma first resuscitation is likely not only to improve coagulation, but also to promote substrate-specific metabolic corrections.

Fully Balanced Fluids do not Improve Microvascular Oxygenation, Acidosis and Renal Function in a Rat Model of Endotoxemia

The expectation of fluid therapy in patients with septic shock is that it corrects hypovolemia, with the aim of restoring tissue perfusion and oxygenation and organ function. This study investigated whether different types of resuscitation fluids were effective in improving renal microcirculatory oxygenation, acidosis, oxidative stress, and renal function in a rat model of endotoxemic shock. Five groups of rats were used: a sham group, a lipopolysaccharide (LPS) group, and three LPS groups that received 30 mL/kg/h of 0.9% sodium chloride (0.9% NaCl), a new bicarbonate buffered crystalloid solution closely resembling the composition of plasma (FB-Cxt) or a hydroxyethyl starch-ringer acetate solution. Systemic hemodynamic variables, renal blood flow, microvascular oxygenation, oxidative/nitrosative stress, and renal function were measured. LPS-induced shock was only partially resolved by fluid administration. Animals became arterially hypotensive despite adequate central venous pressure. Hydroxyethyl starch-ringer acetate was more effective at improving arterial pressures and renal blood flow than 0.9% NaCl or FB-Cxt. Fluids had marginal effects on pH and HCO3 levels irrespective of the buffer, or on renal μPO2 and dysfunction. Colloids increased the markers of renal oxidative stress (P < 0.001), whereas unbalanced crystalloids increased the markers of nitrosative stress during sepsis (P < 0.01). Endotoxemia-induced acidosis and decreases in renal μPO2 or renal injury were not corrected solely by fluid resuscitation, irrespective of the buffer of the fluid. Our study supported the idea that fluids must be supplemented by other compounds that specifically correct renal inflammation and oxygenation to be effective in resolving septic shock-induced renal failure.

A Study for Changes of Blood Pressure and Heart Rate by Acupressure to Acupoints in Rat Model of Hemorrhagic Shock

Objectives : In order to find a possible non-invasive manipulation tool for maintenance of the cardiovascular functions in hemorrhagic shock, this study was aimed at evaluating effects of acupoints acupressure on the changes in blood pressure and heart rate from an animal model of hemorrhagic shock. Methods : In adult Sprague-Dawley rats, hemorrhagic shock was induced by a withdrawal of arterial blood from the femoral artery with volume of 0.8 ml per 100 g of body weight using peristaltic syringe pump. We applied the acupressure with a pressure oscillator to tail as a control and 2 different acupoints of sobu(HT8), youngchun(KI1) under 3 different conditions : 1) normal arterial blood pressure without bleeding, 2) at the beginning of bleeding, and finally 3) hemorrhagic shock. Results : Under normal arterial blood pressure without hemorrhage, there was a significant increase in systolic and diastolic blood pressures by the acupressure to the tail, HT8 and especially KI1 for 30 sec compared with before acupressure. Under hemorrhagic shock condition, the tail acupressure had minimal changes in cardiovascular parameters. Either the HT8 or KI1 acupressure resulted in a significant increase in arterial pressure but did not heart rate. At the beginning of bleeding, tail acupressure failed to change the reduction of arterial pressure and heart rate. However, there was a significant increase in blood pressure and heart rate following either the HT8 or especially KI1 acupressure. Conclusions : HT8 and KI1 acupressure affected cardiovascular signs but tail acupressure did not in rat model of hemorrhagic shock. These experimental data suggest that a acupressure with a pressure oscillator to HT8 or KI1 can be one of alternative emergency manipulations to ameliorate compromised cardiovascular functions under hemorrhagic shock condition.

Hepatoprotective effects of Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] on alcohol-damaged primary rat hepatocyte culture in vitro

We have prepared a novel nanobiotherapeutic, Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase], which not only transports both oxygen and carbon dioxide but also a therapeutic antioxidant. Our previous study in a severe sustained 90 min hemorrhagic shock rat model shows that it has a hepatoprotective effect. We investigate its hepatoprotective effect further in this present report using an alcohol-damaged primary hepatocyte culture model. Results show that it significantly reduced ethanol-induced AST release, lipid peroxidation, and ROS production in rat primary hepatocytes culture. It also significantly enhanced the viability of ethanol-treated hepatocytes. Thus, the result shows that Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] also has some hepatoprotective effects against alcohol-induced injury in in vitro rat primary hepatocytes cell culture. This collaborate our previous observation of its hepatoprotective effect in a severe sustained 90-min hemorrhagic shock rat model.

The role of the sensor kinase, QseC, an adrenergic receptor of Escherichia coli, in bacterial translocation during hemorrhagic shock.

Hemorrhagic shock results in ileal mucosa damage and intestinal bacterial translocation. Additionally, during hemorrhagic shock, norepinephrine levels increase. Past research has shown that the QseC sensor kinase of Escherichia coli modulates the quorum-sensing response to epinephrine and norepinephrine. Therefore, the aim of our study was to examine whether the absence of the ability of E. coli to sense epinephrine/norepinephrine would attenuate the bacterial translocation to extraintestinal organs in a rat model of hemorrhagic shock. An E. coli MC1000 qseC mutant was constructed, and E. coli MC1000 and MC1000ΔqseC with streptomycin resistance were used to track bacterial translocation after gavage in rats. A rat model of nonlethal hemorrhagic shock was used. The rats were divided into six groups: controls (SS), rats that received a sham shock and MC1000 (M-SS), rats that received a sham shock and MC1000ΔqseC (Δ-SS), rats that received a hemorrhagic shock alone (HS), rats that received a hemorrhagic shock and MC1000 (M-HS), and rats that received a hemorrhagic shock and MC1000ΔqseC (Δ-HS). We found the incidence of bacterial translocation in the M-HS rats was higher than in the Δ-HS rats. The observed effects seem to be largely dependent on the inability to sense epinephrine/norepinephrine and the decreased motility of E. coli MC1000ΔqseC. Therefore, a role for E. coli sensing epinephrine/norepinephrine in the pathophysiology of bacterial translocation following hemorrhagic shock is proposed. The demonstration of such an effect would suggest a new mechanism for the development of shock-induced sepsis.

Effects of resuscitation with polymerized porcine hemoglobin (pPolyHb) on hemodynamic stability and oxygen delivery in a rat model of hemorrhagic shock

The objective of this study was to evaluate the effects of polymerized porcine hemoglobin (pPolyHb) on hemodynamic stability and oxygen delivery in a rat model of hemorrhagic shock. Rats underwent controlled hemorrhage, resulting in the loss of 65% of their blood volume in 90 minutes. The results showed that pPolyHb was superior to hetastarch and saline, and similar to whole blood, in restoring hemodynamic stability and reversing anaerobic metabolism caused by hemorrhage. Furthermore, pPolyHb improved oxygen supply and increased blood oxygen content. These data suggest that pPolyHb can be effective in improving tissue perfusion under conditions of severe hemorrhagic shock.

The effect of necrostatin-1 on high mobility group protein-B1 in liver of rats with hemorrhagic shock

Objective To investigate the effect and mechanism of necrostatin-1(Hec-1) on the level of HMGB-1 protein in liver of rats with hemorrhagic-traumatic shock. Methods A number of 96 male SD rats were divided into sham-operated group, dimethyl sulfoxide(DMSO) group and Nec-1 group (n=32 in each) by randomized number method. Rat model of hemorrhagic-traumatic shock was made by fracture of femoral bone and tibia bone and exsanguination from femoral vein until 30 mmHg and maintained at 30-40 mmHg for 90 min, then the shed blood was transfused back with Ringer's solution. The rats in sham-operated group were only under anesthesia for separating and ligating blood vessels, without exsanguination to induce hemorrhagic shock and without replenishment with blood. Rats in Nec-1 group were given 1 mg/kg Nec-1 through femoral vein 5 min before replenishment with blood and Ringer's solution, while the rats in DMSO group were given equal volume of DMSO solution instead. Eight rats in each group were sacrificed separately at 2 h, 8 h, 16 h and 24 h after replenishment. The serum and liver tissues of rats in each group were collected to detect serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST), and to observe the pathological changes in liver with hematoxylin-eosin(HE) staining. The level of HMGB-1 in serum was detected by using ELISA. The cytoplasm protein and total protein expressions of HMGB-1 were assessed by using western blot analysis. Results Compared with DMSO group, levels of serum ALT at 8 h(P<0.05), 16 h(P<0.01) and 24 h(P<0.01) in Nec-1 group were significantly lower. Level of serum AST in Nec-1 group were lower compared with DMSO group at 8 h(P<0.01), 16 h(P<0.01) and 24 h(P<0.01). Compared with DMSO group, levels of serum HMGB-1 at 8 h(P<0.05), 16 h(P<0.01) and 24 h(P<0.01) in Nec-1 group were significantly lower. Under light microscopy and transmission electron microscope, hepatic lobule destroyed, the blood extravasated, the immunocyte infiltrated and cellular organelle destroyed were found. Compared with DMSO group, the level of HMGB-1 protein in cytoplasm protein in Nec-1 group were significantly decreased at 8 h(P<0.01), 16 h(P<0.01) and 24 h(P<0.01). The level of HMGB-1 protein in total protein in Nec-1 group were significantly decreased 8 h(P<0.05) and 24 h(P<0.05). Conclusions Nec-1 can remarkably protect the liver of rats with hemorrhagic-traumatic shock, decrease the level of HMGB-1, and protect the hepatocyte effectively. Key words: High mobility group protein B1; Trauma; Shock, Hemorrhagic; Necrostatin-1; Necroptosis