Mice subjected to uncontrollable electric shocks show depression-like behaviors irrespective of their state of helplessness.

PubMed

Kim, Jin Yong; Yang, Soo Hyun; Kwon, Jihyun; Lee, Hyun Woo; Kim, Hyun

2017-03-30

The unpredictable and inescapable electric shock-induced "learned helplessness" paradigm has long been used to produce an animal model of depression to identify the molecules associated with depressive symptoms or to assess the efficacy of pharmacological treatments for depression. After exposure to unpredictable and inescapable shocks (uncontrollable stress), most of mice showed defect in escape behavior in active avoidance test (learned helplessness, LH), while others did not (non-learned helplessness, NLH). Here, we investigated whether mice with LH or NLH exhibited depressive symptoms, including anhedonia, anxiety, and despair. We found that compared with control naïve mice, both uncontrollable shocks-induced LH and NLH mice showed increased anhedonia- and anxiety- but not despair-like behaviors. Notably, mice subjected to uncontrollable shocks showed similar behaviors, irrespective of whether they also showed LH or NLH. Furthermore, since both LH and NLH mice showed only anhedonia- and anxiety- but not despair-like behaviors, this model may be generally inadequate for classic depression-like behavior assessment. In conclusion, uncontrollable electric shock induces depression-like behavior, irrespective of the state of helplessness. Copyright © 2017 Elsevier B.V. All rights reserved.

[Protective effects of micro-encapsulated Bifidobacteria on gut barrier after hemorrhagic shock and resuscitation: experiment with rats].

PubMed

Ruan, Xiang-cai; Wang, Shen-ming; Shi, Han-ping; Li, Xiao-xi; Xia, Feng-geng; Ming, Fei-ping

2009-03-10

To investigate the effects of micro-encapsulated bifidobacteria on gut barrier and bacterial translocation after hemorrhagic shock and resuscitation. Sprague-Dawley rats were divided into 6 groups: PBS+sham shock group fed with PBS for 7 days and then undergoing sham shock, bifidobacteria+sham shock group fed with bifidobacteria (10(9) cfu/d) for 7 days and then undergoing sham shock, micro-encapsulated bifidobacteria+sham shock group, fed with micro-encapsulated bifidobacteria (10(9) cfu/d) for 7 days and then undergoing sham shock, PBS+hemorrhagic shock group fed with PBS for 7 days and then undergoing hemorrhagic shock, bifidobacteria+shock group fed with bifidobacteria for 7 days and then undergoing hemorrhagic shock, and micro-encapsulated bifidobacteria+shock group, fed with micro-encapsulated bifidobacteria for 7 days and then undergoing hemorrhagic shock. Three hours after resuscitation laparotomy was performed, distal cecum was resected to undergo bacteriological analysis of the cecal content, mesenteric lymph nodes (MLNs), a liver lobe, and the middle part of spleen were resected to undergo bacterial culture for bacterial translocation, and the terminal ileum was resected to observe the villous damage. There was no significant difference in the amount of blood loss among the 3 hemorrhagic shock groups. The amounts of aerobes in cecum of the bifidobacteria+shock and micro-encapsulated bifidobacteria+shock groups, especially that of the latter group, were significantly lower than that of the PBS+shock group. The amounts of anaerobes and the amounts of bifidobacteria in cecum of the bifidobacteria+shock group and micro-encapsulated bifidobacteria+shock group, especially those of the latter group, were significantly higher than those of the PBS+shock group. No bacterial translocation to liver was observed in all groups. The magnitudes of total aerobes translocation in spleen of the bifidobacteria+shock and encapsulated bifidobacteria+shock groups were significantly lower than that of the PBS+shock group, however, there were not significant differences in the translocation in the MLN of total aerobes ad bifidobacteria among different groups. The percentage of ileal villous damage of the bifidobacteria+shock and encapsulated bifidobacteria+shock groups were significantly lower than that of the PBS+shock group. Bifidobacteria effectively protects the gut barrier, reduces bacterial translocation from the gut after hemorrhagic shock and resuscitation. And micro-encapsulated Bifidobacteria can enhance those effects further.

Preliminary profiling of blood transcriptome in a rat model of hemorrhagic shock.

PubMed

Braga, D; Barcella, M; D'Avila, F; Lupoli, S; Tagliaferri, F; Santamaria, M H; DeLano, F A; Baselli, G; Schmid-Schönbein, G W; Kistler, E B; Aletti, F; Barlassina, C

2017-08-01

Hemorrhagic shock is a leading cause of morbidity and mortality worldwide. Significant blood loss may lead to decreased blood pressure and inadequate tissue perfusion with resultant organ failure and death, even after replacement of lost blood volume. One reason for this high acuity is that the fundamental mechanisms of shock are poorly understood. Proteomic and metabolomic approaches have been used to investigate the molecular events occurring in hemorrhagic shock but, to our knowledge, a systematic analysis of the transcriptomic profile is missing. Therefore, a pilot analysis using paired-end RNA sequencing was used to identify changes that occur in the blood transcriptome of rats subjected to hemorrhagic shock after blood reinfusion. Hemorrhagic shock was induced using a Wigger's shock model. The transcriptome of whole blood from shocked animals shows modulation of genes related to inflammation and immune response (Tlr13, Il1b, Ccl6, Lgals3), antioxidant functions (Mt2A, Mt1), tissue injury and repair pathways (Gpnmb, Trim72) and lipid mediators (Alox5ap, Ltb4r, Ptger2) compared with control animals. These findings are congruent with results obtained in hemorrhagic shock analysis by other authors using metabolomics and proteomics. The analysis of blood transcriptome may be a valuable tool to understand the biological changes occurring in hemorrhagic shock and a promising approach for the identification of novel biomarkers and therapeutic targets. Impact statement This study provides the first pilot analysis of the changes occurring in transcriptome expression of whole blood in hemorrhagic shock (HS) rats. We showed that the analysis of blood transcriptome is a useful approach to investigate pathways and functional alterations in this disease condition. This pilot study encourages the possible application of transcriptome analysis in the clinical setting, for the molecular profiling of whole blood in HS patients.

Acute Bradykinin Receptor Blockade During Hemorrhagic Shock in Mice Prevents the Worsening Hypotensive Effect of Angiotensin-Converting Enzyme Inhibitor.

PubMed

Charbonneau, Hélène; Buléon, Marie; Minville, Vincent; Faguer, Stanislas; Girolami, Jean-Pierre; Bascands, Jean-Loup; Tack, Ivan; Mayeur, Nicolas

2016-09-01

Angiotensin-converting enzyme inhibitors are associated with deleterious hypotension during anesthesia and shock. Because the pharmacologic effects of angiotensin-converting enzyme inhibitors are partly mediated by increased bradykinin B2 receptor activation, this study aimed to determine the impact of acute B2 receptor blockade during hemorrhagic shock in angiotensin-converting enzyme inhibitor-treated mice. In vivo study. University research unit. C57/Bl6 mice. The hemodynamic effect of B2 receptor blockade using icatibant (B2 receptor antagonist) was studied using a pressure-targeted hemorrhagic shock and a volume-targeted hemorrhagic shock. Animals were anesthetized with ketamine and xylazine (250 mg/kg and 10 mg/kg, respectively), intubated using intratracheal cannula, and ventilated (9 mL/kg, 150 min). Five groups were studied: 1) sham-operated animals, 2) control shocked mice, 3) shocked mice treated with ramipril for 7 days (angiotensin-converting enzyme inhibitors) before hemorrhagic shock, 4) shocked mice treated with angiotensin-converting enzyme inhibitors and a single bolus of icatibant (HOE-140) immediately before anesthesia (angiotensin-converting enzyme inhibitors + icatibant), and 5) shocked mice treated with a single bolus of icatibant. One hour after volume-targeted hemorrhagic shock, blood lactate was measured to evaluate organ failure. During pressure-targeted hemorrhagic shock, the mean blood volume withdrawn was significantly lower in the angiotensin-converting enzyme inhibitor group than in the other groups (p < 0.001). During volume-targeted hemorrhagic shock, icatibant prevented blood pressure lowering in the angiotensin-converting enzyme inhibitor group (p < 0.001). Blood lactate was significantly higher in the angiotensin-converting enzyme inhibitor group than in the other groups, particularly the HOE groups. During hemorrhagic shock, acute B2 receptor blockade significantly attenuates the deleterious hemodynamic effect of angiotensin-converting enzyme inhibitor treatment in mice. This beneficial effect of B2 receptor blockade is rapidly reached and sustained with a single bolus of icatibant. This benefit could be of interest in angiotensin-converting enzyme inhibitor-treated patients during both emergency anesthesia and resuscitation.

Hepatic and pulmonary apoptosis after hemorrhagic shock in swine can be reduced through modifications of conventional Ringer's solution.

PubMed

Ayuste, Eduardo C; Chen, Huazhen; Koustova, Elena; Rhee, Peter; Ahuja, Naresh; Chen, Zhang; Valeri, C Robert; Spaniolas, Konstantinos; Mehrani, Tina; Alam, Hasan B

2006-01-01

Cytotoxic properties of racemic (D-,L-isomers) lactated Ringer's solution detected in vitro and in small animal experiments, have not been confirmed in large animal models. Our hypothesis was that in a clinically relevant large animal model of hemorrhage, resuscitation with racemic lactated Ringer's solution would induce cellular apoptosis, which can be attenuated by elimination of d-lactate. Yorkshire swine (n = 49, weight 40-58 kg) were subjected to uncontrolled (iliac arterial and venous injuries) and controlled hemorrhage, totaling 40% of estimated blood volume. They were randomized (n = 7/group) to control groups, which consisted of (1) no hemorrhage (NH), (2) no resuscitation (NR), or resuscitation groups, which consisted of (3) 0.9% saline (NS), (4) racemic lactated Ringer's (DL-LR), (5) L-isomer lactated Ringer's (L-LR), (6) Ketone Ringer's (KR), (7) 6% hetastarch in 0.9% saline (Hespan). KR was identical to LR except for equimolar substitution of lactate with beta-hydroxybutyrate. Resuscitation was performed in three phases, simulating (1) prehospital, (2) operative, (3) postoperative/recovery periods. Arterial blood gasses, circulating cytokines (TNF-alpha, IL-1, -6, -10), and markers of organ injury were serially measured. Metabolic activity of brain, and liver, was measured with microdialysis. Four hours postinjury, organs were harvested for Western blotting, ELISA, TUNEL assay, and immunohistochemistry. All resuscitation strategies restored blood pressure, but clearance of lactic acidosis was impeded following DL-LR resuscitation. Metabolic activity decreased during shock and improved with resuscitation, without any significant inter-group differences. Levels of cytokines in circulation were similar, but tissue levels of TNF in liver and lung increased six- and threefolds (p < 0.05) in NR group. In liver, all resuscitation strategies significantly decreased TNF levels compared with the NR group, but in the lung resuscitation with lactated Ringer (DL and L isomers) failed to decrease tissue TNF levels. DL-LR resuscitation also increased apoptosis (p < 0.05) in liver and lung, which was not seen after resuscitation with other solutions. In this large animal model of hemorrhagic shock, resuscitation with conventional (racemic) LR solution increased apoptotic cell death in liver and lung. This effect can be prevented by simple elimination of D-lactate from the Ringer's solution.

Enteral tranexamic acid attenuates vasopressor resistance and changes in α1-adrenergic receptor expression in hemorrhagic shock.

PubMed

Santamaria, Marco Henry; Aletti, Federico; Li, Joyce B; Tan, Aaron; Chang, Monica; Leon, Jessica; Schmid-Schönbein, Geert W; Kistler, Erik B

2017-08-01

Irreversible hemorrhagic shock is characterized by hyporesponsiveness to vasopressor and fluid therapy. Little is known, however, about the mechanisms that contribute to this phenomenon. Previous studies have shown that decreased intestinal perfusion in hemorrhagic shock leads to proteolytically mediated increases in gut permeability, with subsequent egress of vasoactive substances systemically. Maintenance of blood pressure is achieved in part by α1 receptor modulation, which may be affected by vasoactive factors; we thus hypothesized that decreases in hemodynamic stability and vasopressor response in shock can be prevented by enteral protease inhibition. Rats were exposed to experimental hemorrhagic shock (35 mm Hg mean arterial blood pressure for 2 hours, followed by reperfusion for 2 hours) and challenged with phenylephrine (2 μg/kg) at discrete intervals to measure vasopressor responsiveness. A second group of animals received enteral injections with the protease inhibitor tranexamic acid (TXA) (127 mM) along the small intestine and cecum 1 hour after induction of hemorrhagic shock. Blood pressure response (duration and amplitude) to phenylephrine after reperfusion was significantly attenuated in animals subjected to hemorrhagic shock compared with baseline and control nonshocked animals and was restored to near baseline by enteral TXA. Arteries from shocked animals also displayed decreased α1 receptor density with restoration to baseline after enteral TXA treatment. In vitro, rat shock plasma decreased α1 receptor density in smooth muscle cells, which was also abrogated by enteral TXA treatment. Results from this study demonstrate that experimental hemorrhagic shock leads to decreased response to the α1-selective agonist phenylephrine and decreased α1 receptor density via circulating shock factors. These changes are mitigated by enteral TXA with correspondingly improved hemodynamics. Proteolytic inhibition in the lumen of the small intestine improves hemodynamics in hemorrhagic shock, possibly by restoring α1 adrenergic functionality necessary to maintain systemic blood pressure and perfusion.

Learned helplessness: effects of response requirement and interval between treatment and testing.

PubMed

Hunziker, M H L; Dos Santos, C V

2007-11-01

Three experiments investigated learned helplessness in rats manipulating response requirements, shock duration, and intervals between treatment and testing. In Experiment 1, rats previously exposed to uncontrollable or no shocks were tested under one of four different contingencies of negative reinforcement: FR 1 or FR 2 escape contingency for running, and FR1 escape contingency for jumping (differing for the maximum shock duration of 10s or 30s). The results showed that the uncontrollable shocks produced a clear operant learning deficit (learned helplessness effect) only when the animals were tested under the jumping FR 1 escape contingency with 10-s max shock duration. Experiment 2 isolated of the effects of uncontrollability from shock exposure per se and showed that the escape deficit observed using the FR 1 escape jumping response (10-s shock duration) was produced by the uncontrollability of shock. Experiment 3 showed that using the FR 1 jumping escape contingency in the test, the learned helplessness effect was observed one, 14 or 28 days after treatment. These results suggest that running may not be an appropriate test for learned helplessness, and that many diverging results found in the literature might be accounted for by the confounding effects of respondent and operant contingencies present when running is required of rats.

Blood autotransfusion outcomes compared with Ringer lactate infusion in dogs with hemorrhagic shock induced by controlled bleeding.

PubMed

Safaei, Mansour; Takami, Hassan Mousavi

2011-10-01

The most common cause of shock in the surgical or trauma patient is hemorrhage. Crystalloid solutions and blood transfusion are the mainstays of treatment of hemorrhagic shock. Considering the disadvantages of allogeneic blood transfusion, such as risk of transmission of infectious diseases, and access and maintenance limitations, treatment of shock with autologous blood seems to be a decent solution. Autologous blood accumulated in body cavities in traumatic bleeding (such hemothorax), and bloodshed in operation field during open heart or vascular surgeries, and similar situations, can be utilized again. In this study, autotransfusion effects compared with crystalloid fluid in the treatment of hemorrhagic shock was investigated. After induction of hemorrhagic shock in dogs by Wiggers type controlled bleeding, treating them in a group with autologous blood and another group with Ringer lactate were performed, and the results of treatment were studied. There was no mortality in both treatment approaches. Immediately after treatment, crystalloid positive effects such as renormalized vital signs and appropriate consciousness were more noticeable than autotransfusion, while twenty-four hours after, the desired effects of autologous blood were more pronounced like decreased metabolic acidosis and improvement of diuresis. Crystalloid during the first hours after treatment of hemorrhagic shock may be better than autologous blood as preferred treatment, while autotransfusion showed its benefits some hours after. This finding can be used to develop better strategies for treatment of hemorrhagic shock.

Preliminary profiling of blood transcriptome in a rat model of hemorrhagic shock

PubMed Central

Braga, D; Barcella, M; D’Avila, F; Lupoli, S; Tagliaferri, F; Santamaria, MH; DeLano, FA; Baselli, G; Schmid-Schönbein, GW; Kistler, EB; Aletti, F

2017-01-01

Hemorrhagic shock is a leading cause of morbidity and mortality worldwide. Significant blood loss may lead to decreased blood pressure and inadequate tissue perfusion with resultant organ failure and death, even after replacement of lost blood volume. One reason for this high acuity is that the fundamental mechanisms of shock are poorly understood. Proteomic and metabolomic approaches have been used to investigate the molecular events occurring in hemorrhagic shock but, to our knowledge, a systematic analysis of the transcriptomic profile is missing. Therefore, a pilot analysis using paired-end RNA sequencing was used to identify changes that occur in the blood transcriptome of rats subjected to hemorrhagic shock after blood reinfusion. Hemorrhagic shock was induced using a Wigger’s shock model. The transcriptome of whole blood from shocked animals shows modulation of genes related to inflammation and immune response (Tlr13, Il1b, Ccl6, Lgals3), antioxidant functions (Mt2A, Mt1), tissue injury and repair pathways (Gpnmb, Trim72) and lipid mediators (Alox5ap, Ltb4r, Ptger2) compared with control animals. These findings are congruent with results obtained in hemorrhagic shock analysis by other authors using metabolomics and proteomics. The analysis of blood transcriptome may be a valuable tool to understand the biological changes occurring in hemorrhagic shock and a promising approach for the identification of novel biomarkers and therapeutic targets. Impact statement This study provides the first pilot analysis of the changes occurring in transcriptome expression of whole blood in hemorrhagic shock (HS) rats. We showed that the analysis of blood transcriptome is a useful approach to investigate pathways and functional alterations in this disease condition. This pilot study encourages the possible application of transcriptome analysis in the clinical setting, for the molecular profiling of whole blood in HS patients. PMID:28661205

Attenuation of Multiple Organ Damage by Continuous Low-Dose Solvent-Free Infusions of Resveratrol after Severe Hemorrhagic Shock in Rats

PubMed Central

Kirsch, Michael; Petrat, Frank

2017-01-01

Therapeutic effects of continuous intravenous infusions of solvent-free low doses of resveratrol on organ injury and systemic consequences resulting from severe hemorrhagic shock in rats were studied. Hemorrhagic shock was induced by withdrawing arterial blood until a mean arterial blood pressure (MAP) of 25–30 mmHg was reached. Following a shock phase of 60 min, rats were resuscitated with the withdrawn blood plus lactated Ringer’s. Resveratrol (20 or 60 μg/kg × h) was continuously infused intravenously starting with the resuscitation phase (30 min) and continued until the end of the experiment (total treatment time 180 min). Animals of the shock control group received 0.9% NaCl solution. After the observation phase (150 min), rats were sacrificed. Resveratrol significantly stabilized the MAP and peripheral oxygen saturation after hemorrhagic shock, decreased the macroscopic injury of the small intestine, significantly attenuated the shock-induced increase in tissue myeloperoxidase activity in the small intestine, liver, kidney and lung, and diminished tissue hemorrhages (particularly in the small intestine and liver) as well as the rate of hemolysis. Already very low doses of resveratrol, continuously infused during resuscitation after severe hemorrhagic shock, can significantly improve impaired systemic parameters and attenuate multiple organ damage in rats. PMID:28817064

Encapsulated Bifidobacteria reduced bacterial translocation in rats following hemorrhagic shock and resuscitation.

PubMed

Ruan, Xiangcai; Shi, Hanping; Xia, Gengfeng; Xiao, Ying; Dong, Jiaxi; Ming, Feiping; Wang, Shenming

2007-10-01

The aim of the present study was to determine the effects of peroral encapsulated Bifidobacteria on intestinal microflora, bacterial translocation (BT), plasma endotoxin, and ileal villi injury in a rat model of hemorrhagic shock. Sprague-Dawley rats were fed daily with three different diet supplements: phosphate buffered saline, Bifidobacteria (10(9) colon-forming units/day), or microencapsulated Bifidobacteria (10(9) colony-forming units/day). After 7 d of treatment, rats were anesthetized for hemorrhagic or sham shock. Then a laparotomy was performed to determine microbiological analysis of cecal content, BT to mesenteric lymph nodes, plasma endotoxin, and terminal ileal villous damage. In the hemorrhagic-shock model, rats pretreated with Bifidobacteria showed decreases in total aerobes in cecum, magnitude of total aerobes to BT, levels of plasma endotoxin, and percentage of ileal villous damage when compared with rats treated with phosphate buffered saline. Encapsulated Bifidobacteria induced greater decreases than intact Bifidobacteria in this model, except for no difference in percentage of ileal villous damage between the two groups. In addition, the incidence of BT was decreased in hemorrhagic rats pretreated with Bifidobacteria compared with control. However, the magnitude of total anaerobes and Bifidobacteria BT were similar among hemorrhagic-shocked rats receiving three different supplements. Bifidobacteria can be useful in preventing BT in hemorrhagic-shocked rats, and encapsulated Bifidobacteria can augment this effect further. Peroral administration of Bifidobacteria may be a favorable strategy to prevent sepsis and multiple organ dysfunction syndrome in hemorrhagic shock.

Blood autotransfusion outcomes compared with Ringer lactate infusion in dogs with hemorrhagic shock induced by controlled bleeding*

PubMed Central

Safaei, Mansour; Takami, Hassan Mousavi

2011-01-01

BACKGROUND: The most common cause of shock in the surgical or trauma patient is hemorrhage. Crystalloid solutions and blood transfusion are the mainstays of treatment of hemorrhagic shock. Considering the disadvantages of allogeneic blood transfusion, such as risk of transmission of infectious diseases, and access and maintenance limitations, treatment of shock with autologous blood seems to be a decent solution. Autologous blood accumulated in body cavities in traumatic bleeding (such hemothorax), and bloodshed in operation field during open heart or vascular surgeries, and similar situations, can be utilized again. In this study, autotransfusion effects compared with crystalloid fluid in the treatment of hemorrhagic shock was investigated. METHODS: After induction of hemorrhagic shock in dogs by Wiggers type controlled bleeding, treating them in a group with autologous blood and another group with Ringer lactate were performed, and the results of treatment were studied. RESULTS: There was no mortality in both treatment approaches. Immediately after treatment, crystalloid positive effects such as renormalized vital signs and appropriate consciousness were more noticeable than autotransfusion, while twenty-four hours after, the desired effects of autologous blood were more pronounced like decreased metabolic acidosis and improvement of diuresis. CONCLUSIONS: Crystalloid during the first hours after treatment of hemorrhagic shock may be better than autologous blood as preferred treatment, while autotransfusion showed its benefits some hours after. This finding can be used to develop better strategies for treatment of hemorrhagic shock. PMID:22973328

The medical antigravity suit for management of surgically uncontrollable bleeding associated with abdominal pregnancy.

PubMed

Sandberg, E C; Pelligra, R

1983-07-01

Three patients with abdominal pregnancy have been treated at Stanford University Hospital in recent years. Common to each was surgically uncontrolled hemorrhage for which circumferential pneumatic compression (supplied by a medical antigravity suit) was used to stop the bleeding. In each patient, the hemostatic effect of treatment was dramatic. In published accounts of the use of the garment in other severely hemorrhaging patients, the effects have been similarly dramatic and equally successful. These observations lead to a compelling consideration in regard to optimum management of patients with abdominal pregnancy. If our experience is confirmed by others, optimum management in abdominal pregnancy hereafter should regularly and routinely include removal of the placenta at the primary operation. This approach would anticipate use of the medical antigravity suit to provide hemostasis if surgically uncontrollable bleeding is encountered. Theoretically, the complications and long-term morbidity associated with retention of the placenta would be eliminated by this means while the previous disadvantage of placental removal, the potential for exsanguinating hemorrhage, would be circumvented.

Clonidine Reduces Norepinephrine and Improves Bone Marrow Function in a Rodent Model of Lung Contusion, Hemorrhagic Shock and Chronic Stress

PubMed Central

Alamo, Ines G.; Kannan, Kolenkode B.; Ramos, Harry; Loftus, Tyler J.; Efron, Philip A.; Mohr, Alicia M.

2016-01-01

Background Propranolol has been shown previously to restore bone marrow function and improve anemia after lung contusion/hemorrhagic shock. We hypothesized that daily clonidine administration would inhibit central sympathetic outflow and restore bone marrow function in our rodent model of lung contusion/hemorrhagic shock with chronic stress. Methods Male Sprague-Dawley rats underwent six days of restraint stress after lung contusion/hemorrhagic shock during which the animals received clonidine (75μg/kg) after the restraint stress. On post-injury day seven, we assessed urine norepinephrine, blood hemoglobin, plasma granulocyte colony stimulating factor (G-CSF), and peripheral blood mobilization of hematopoietic progenitor cells (HPC), as well as bone marrow cellularity and erythroid progenitor cell growth. Results The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress, significantly decreased urine norepinephrine levels, improved bone marrow cellularity, restored erythroid progenitor colony growth, and improved hemoglobin (14.1±0.6 vs. 10.8±0.6 g/dL). The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased HPC mobilization and restored G-CSF levels. Conclusions After lung contusion/hemorrhagic shock with chronic restraint stress, daily administration of clonidine restored bone marrow function and improved anemia. Alleviating chronic stress and decreasing norepinephrine is a key therapeutic target to improve bone marrow function after severe injury. PMID:27742030

Effects of Stomach Inflation on Cardiopulmonary Function and Survival During Hemorrhagic Shock: A Randomized, Controlled, Porcine Study.

PubMed

Braun, Patrick; Putzer, Gabriel; Strapazzon, Giacomo; Wimmer, Angela; Schnell, Hermann; Arnold, Henrik; Neururer, Sabrina; Brugger, Hermann; Wenzel, Volker; Paal, Peter

2016-07-01

Ventilation of an unprotected airway may result in stomach inflation. The purpose of this study was to evaluate the effect of clinically realistic stomach inflation on cardiopulmonary function during hemorrhagic shock in a porcine model. Pigs were randomized to a sham control group (n = 9), hemorrhagic shock (35 mL kg over 15 min [n = 9]), and hemorrhagic shock combined with stomach inflation (35 mL kg over 15 min and 5 L stomach inflation [n = 10]). When compared with the control group, hemorrhagic shock (n = 9) increased heart rate (103 ± 11 vs. 146 ± 37 beats min; P = 0.002) and lactate (1.4 ± 0.5 vs. 4.0 ± 1.9 mmol L; P < 0.001), and decreased mean arterial blood pressure (81.3 ± 12.8 vs. 35.4 ± 8.1 mmHg; P < 0.001) and stroke-volume index (38.1 ± 6.4 vs. 13.6 ± 4.8 mL min m; P < 0.001). Hemorrhagic shock combined with stomach inflation (n = 10) versus hemorrhagic shock only (n = 9) increased intra-abdominal pressure (27.0 ± 9.3 vs. 1.1 ± 1.0 mmHg; P < 0.001), and decreased stroke-volume index (9.9 ± 6.0 vs. 20.8 ± 8.5 mL min m; P = 0.007), and dynamic respiratory system compliance (10.8 ± 4.5 vs. 38.1 ± 6.1 mL cmH2O; P < 0.001). Before versus after stomach evacuation during hemorrhagic shock, intra-abdominal pressure decreased (27.0 ± 9.3 vs. 9.8 ± 5.4 mmHg; P = 0.042). Survival in the sham control and hemorrhagic shock group was 9 of 9, respectively, and 3 of 10 after hemorrhagic shock and stomach inflation (P < 0.001). During hemorrhagic shock stomach inflation caused an abdominal compartment syndrome and thereby impaired cardiopulmonary function and aerobic metabolism, and increased mortality. Subsequent stomach evacuation partly reversed adverse stomach-inflation triggered effects.

Sodium hydrosulfide alleviates lung inflammation and cell apoptosis following resuscitated hemorrhagic shock in rats

PubMed Central

Xu, Dun-quan; Gao, Cao; Niu, Wen; Li, Yan; Wang, Yan-xia; Gao, Chang-jun; Ding, Qian; Yao, Li-nong; Chai, Wei; Li, Zhi-chao

2013-01-01

Aim: To investigate the protective effects of hydrogen sulfide (H2S) against inflammation, oxidative stress and apoptosis in a rat model of resuscitated hemorrhagic shock. Methods: Hemorrhagic shock was induced in adult male SD rats by drawing blood from the femoral artery for 10 min. The mean arterial pressure was maintained at 35–40 mmHg for 1.5 h. After resuscitation the animals were observed for 200 min, and then killed. The lungs were harvested and bronchoalveolar lavage fluid was prepared. The levels of relevant proteins were examined using Western blotting and immunohistochemical analyses. NaHS (28 μmol/kg, ip) was injected before the resuscitation. Results: Resuscitated hemorrhagic shock induced lung inflammatory responses and significantly increased the levels of inflammatory cytokines IL-6, TNF-α, and HMGB1 in bronchoalveolar lavage fluid. Furthermore, resuscitated hemorrhagic shock caused marked oxidative stress in lung tissue as shown by significant increases in the production of reactive oxygen species H2O2 and ·OH, the translocation of Nrf2, an important regulator of antioxidant expression, into nucleus, and the decrease of thioredoxin 1 expression. Moreover, resuscitated hemorrhagic shock markedly increased the expression of death receptor Fas and Fas-ligand and the number apoptotic cells in lung tissue, as well as the expression of pro-apoptotic proteins FADD, active-caspase 3, active-caspase 8, Bax, and decreased the expression of Bcl-2. Injection with NaHS significantly attenuated these pathophysiological abnormalities induced by the resuscitated hemorrhagic shock. Conclusion: NaHS administration protects rat lungs against inflammatory responses induced by resuscitated hemorrhagic shock via suppressing oxidative stress and the Fas/FasL apoptotic signaling pathway. PMID:24122010

Resuscitation of severe uncontrolled hemorrhage: 7.5% sodium chloride/6% dextran 70 vs 0.9% sodium chloride.

PubMed

Stern, S A; Jwayyed, S; Dronen, S C; Wang, X

2000-08-01

Resuscitation studies of hypertonic saline using controlled and uncontrolled hemorrhage models yield conflicting results with regard to efficacy. These disparate results reflect the use of models and resuscitation regimens that are not comparable between studies. This study evaluated the effects of comparable and clinically relevant resuscitation regimens of 7.5% sodium chloride/6% dextran 70 (HSD) and 0.9% sodium chloride (NS) in a near-fatal uncontrolled hemorrhage model. Thirty-six swine (14.2 to 21.4 kg) with 4-mm aortic tears were bled to a pulse pressure of 5 mm Hg (40-45 mL/kg). The animals were resuscitated with either NS or HSD administered in volumes that provided equivalent sodium loads at similar rates. Group II (n = 12) was resuscitated with 80 mL/kg of NS at a rate of 4 mL/kg/min. Group III (n = 12) received 9.6 mL/kg of HSD at a rate of 0.48 mL/kg/min. In both groups, crystalloid resuscitation was followed by shed blood infusion (30 mL/kg) at a rate of 2 mL/kg/min. Group I (controls; n = 12) were not resuscitated. One-hour mortality was significantly greater in group I (92%) as compared with group II (33%) and group III (33%) (Fisher's exact test; p = 0.004). Intraperitoneal hemorrhage was significantly greater in group II (34 +/- 20 mL/kg) and group III (31 +/- 13 mL/ kg) as compared with group I (5 +/- 2 mL/kg) (ANOVA; p < 0.05). There was no significant difference in hemodynamic parameters between groups II and III. In this model of severe uncontrolled hemorrhage, resuscitation with HSD or NS, administered in volumes that provided equivalent sodium loads at similar rates, had similar effects on mortality, hemodynamic parameters, and hemorrhage from the injury site.

Activation of sirtuin 1/3 improves vascular hyporeactivity in severe hemorrhagic shock by alleviation of mitochondrial damage

PubMed Central

Li, Pengyun; Meng, Xianzhong; Bian, Huining; Burns, Nana; Zhao, Ke-seng; Song, Rui

2015-01-01

Vascular hyporeactivity is one of the major causes responsible for refractory hypotension and associated mortality in severe hemorrhagic shock. Mitochondrial permeability transition (mPT) pore opening in arteriolar smooth muscle cells (ASMCs) is involved in the pathogenesis of vascular hyporeactivity. However, the molecular mechanism underlying mitochondrial injury in ASMCs during hemorrhagic shock is not well understood. Here we produced an in vivo model of severe hemorrhagic shock in adult Wistar rats. We found that sirtuin (SIRT)1/3 protein levels and deacetylase activities were decreased in ASMCs following severe shock. Immunofluorescence staining confirmed reduced levels of SIRT1 in the nucleus and SIRT3 in the mitochondria, respectively. Acetylation of cyclophilin D (CyPD), a component of mPT pore, was increased. SIRT1 activators suppressed mPT pore opening and ameliorated mitochondrial injury in ASMCs after severe shock. Furthermore, administration of SIRT1 activators improved vasoreactivity in rats under severe shock. Our data suggest that epigenetic mechanisms, namely histone post-translational modifications, are involved in regulation of mPT by SIRT1/SIRT3- mediated deacetylation of CyPD. SIRT1/3 is a promising therapeutic target for the treatment of severe hemorrhagic shock. PMID:26473372

Clonidine reduces norepinephrine and improves bone marrow function in a rodent model of lung contusion, hemorrhagic shock, and chronic stress.

PubMed

Alamo, Ines G; Kannan, Kolenkode B; Ramos, Harry; Loftus, Tyler J; Efron, Philip A; Mohr, Alicia M

2017-03-01

Propranolol has been shown previously to restore bone marrow function and improve anemia after lung contusion/hemorrhagic shock. We hypothesized that daily clonidine administration would inhibit central sympathetic outflow and restore bone marrow function in our rodent model of lung contusion/hemorrhagic shock with chronic stress. Male Sprague-Dawley rats underwent 6 days of restraint stress after lung contusion/hemorrhagic shock during which the animals received clonidine (75 μg/kg) after the restraint stress. On postinjury day 7, we assessed urine norepinephrine, blood hemoglobin, plasma granulocyte colony stimulating factor, and peripheral blood mobilization of hematopoietic progenitor cells, as well as bone marrow cellularity and erythroid progenitor cell growth. The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased urine norepinephrine levels, improved bone marrow cellularity, restored erythroid progenitor colony growth, and improved hemoglobin (14.1 ± 0.6 vs 10.8 ± 0.6 g/dL). The addition of clonidine to lung contusion/hemorrhagic shock with chronic restraint stress significantly decreased hematopoietic progenitor cells mobilization and restored granulocyte colony stimulating factor levels. After lung contusion/hemorrhagic shock with chronic restraint stress, daily administration of clonidine restored bone marrow function and improved anemia. Alleviating chronic stress and decreasing norepinephrine is a key therapeutic target to improve bone marrow function after severe injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Lack of species-specific difference in pulmonary function when using mouse versus human plasma in a mouse model of hemorrhagic shock.

PubMed

Peng, Zhanglong; Pati, Shibani; Fontaine, Magali J; Hall, Kelly; Herrera, Anthony V; Kozar, Rosemary A

2016-11-01

Clinical studies have demonstrated that the early and empiric use of plasma improves survival after hemorrhagic shock. We have demonstrated in rodent models of hemorrhagic shock that resuscitation with plasma is protective to the lungs compared with lactated Ringer's solution. As our long-term objective is to determine the molecular mechanisms that modulate plasma's protective effects in injured bleeding patients, we have used human plasma in a mouse model of hemorrhagic shock. The goal of the current experiments is to determine if there are significant adverse effects on lung injury when using human versus mouse plasma in an established murine model of hemorrhagic shock and laparotomy. Mice underwent laparotomy and 90 minutes of hemorrhagic shock to a mean arterial pressure (MAP) of 35 ± 5 mm Hg followed by resuscitation at 1× shed blood using either mouse fresh frozen plasma (FFP), human FFP, or human lyophilized plasma. Mean arterial pressure was recorded during shock and for the first 30 minutes of resuscitation. After 3 hours, animals were killed, and lungs collected for analysis. There was a significant increase in early MAP when mouse FFP was used to resuscitate animals compared with human FFP or human lyophilized plasma. However, despite these differences, analysis of the mouse lungs revealed no significant differences in pulmonary histopathology, lung permeability, or lung edema between all three plasma groups. Analysis of neutrophil infiltration in the lungs revealed that mouse FFP decreased neutrophil influx as measured by neutrophil staining; however, myeloperoxidase immunostaining revealed no significant differences in between groups. The study of human plasma in a mouse model of hemorrhagic shock is feasible but does reveal some differences compared with mouse plasma-based resuscitation in physiologic measures such as MAP postresuscitation. Measures of end organ function such as lung injury appear to be comparable in this acute model of hemorrhagic shock and resuscitation.

[Effect of hypertonic saline solution on the viscoelasticities of erythrocyte membrane in rats subjected to hemorrhagic shock].

PubMed

Zhou, X; Hu, D; Liu, L; Wu, Z; Qin, J; Cai, S

2001-12-01

We have studied the effect of hypertonic saline solution on the viscoelasticities of erythrocyte membrane in hemorrhage-shocked rats using micropippette aspiration technique. Wistar rats were randomly divided into three groups of 0.9% NaCl(NS), 7.5% NaCl (HS) and 5% NaCl-3.5% NaAc (HSA), respectively. The animals were bled to reach a mean arterial pressure of 5.3 kPa in 10 minutes and maintained in shock for 90 minutes. 4 ml/kg NS, HS and HSA was given intravenously and respectively in 5 minutes following hemorrhagic shock. The blood was collected to determine the viscoelasticities of erythrocyte membrane at baseline, shock and after treatment. The results showed that the elastic moduli and viscous coefficients of erythrocyte membrane were increased obviously following hemorrhagic shock. HS raised elastic moduli and reduced viscous coefficients significantly compared with NS after treatment. The elastic moduli and viscous coefficients of erythrocyte membrane were decreased remarkably in HSA group than in NS and HS group. These data suggested that HSA could improve the viscoelasticities of erythrocyte membrane significantly in rats subjected to hemorrhagic shock.

The effect of piracetam on brain damage and serum nitric oxide levels in dogs submitted to hemorrhagic shock.

PubMed

Ozkan, Seda; Ikizceli, Ibrahim; Sözüer, Erdoğan Mütevelli; Avşaroğullari, Levent; Oztürk, Figen; Muhtaroğlu, Sebahattin; Akdur, Okhan; Küçük, Can; Durukan, Polat

2008-10-01

To demonstrate the effect of piracetam on changes in brain tissue and serum nitric oxide levels in dogs submitted to hemorrhagic shock. The subjects were randomized into four subgroups each consisting of 10 dogs. Hemorrhagic shock was induced in Group I for 1 hour and no treatment was given to this group. Blood and saline solutions were administered to Group II following 1 hour hemorrhagic shock. Blood and piracetam were given to Group III following 1 hour shock. No shock was induced and no treatment was applied to Group IV. Blood samples were obtained at the onset of the experiment and at 60, 120 and 180 minutes for nitric oxide analysis. For histopathological examination, brain tissue samples were obtained at the end of the experiment. The observed improvement in blood pressure and pulse rates in Group III was more than in Group II. Nitric oxide levels were increased in Group I; however, no correlation between piracetam and nitric oxide levels was determined. It was seen that recovery in brain damage in Group III was greater than in the control group. Piracetam, added to the treatment, may ecrease ischemic damage in hemorrhagic shock.

Inhibition of intraluminal pancreatic enzymes with nafamostat mesilate improves clinical outcomes after hemorrhagic shock in swine.

PubMed

Kim, Hubert D; Malinoski, Darren J; Borazjani, Boris; Patel, Madhukar S; Chen, Joseph; Slone, Johnathan; Nguyen, Xuan-Mai T; Steward, Earl; Schmid-Schonbein, Geert W; Hoyt, David B

2010-05-01

Recent studies suggest that intraluminal pancreatic enzymes play a major role in the initiation of the inflammatory cascade by the gut after hemorrhagic shock. Previous animal models have shown that the inhibition of enteral pancreatic enzymes with a serine protease inhibitor, nafamostat mesilate (NM), decreases leukocyte activation and transfusion requirements after hemorrhagic shock. The objective of this study was to determine whether enteroclysis with NM would improve the clinical outcomes in swine after hemorrhagic shock and intestinal hypoperfusion. Thirty-three male Yucatan minipigs weighing 25 kg to 30 kg underwent a controlled hemorrhage of 25 mL/kg with mesenteric clamp for further gut ischemia. Animals were allocated to three groups: (1) shock only (n = 15), (2) shock + enteroclysis with 100 mL/kg GoLYTELY (GL) as a carrier (n = 11), and (3) shock + enteroclysis with GL + 0.37 mmol/L NM (GL+NM, n = 7). Animals were resuscitated, recovered from anesthesia, observed for 3 days, and graded on a daily 4-point clinical scoring system. A score of 0 indicated a moribund state or early death, and a score of 4 indicated normal behavior. Pigs treated with GL + NM had significantly higher mean postoperative recovery scores (3.8 +/- 0.4, essentially normal behavior with no early deaths) compared with animals within the shock only and shock + GL groups (2.1 +/- 1 with one early death and 2.2 +/- 1.2 with two early deaths, respectively, analysis of variance p < 0.003). The inhibition of intraluminal pancreatic enzymes using enteroclysis with the serine protease inhibitor, NM, after hemorrhagic shock significantly improves the clinical outcome.

A Laparoscopic Swine Model of Noncompressible Torso Hemorrhage

DTIC Science & Technology

2014-01-01

Various porcine models of hemorrhage have been developed for civilian and military trauma research. However, the predominant contemporary models lack...significant predictors of mortality. CONCLUSION: This study describes a model of NCTH that reflects clinically relevant physiology in trauma and...uncontrolled hemorrhage. In addition, it quantitatively assesses the role of the swine contractile spleen in the described model. (J Trauma Acute Care Surg

HIF-1α regulates Cx40-dependent vasodilatation following hemorrhagic shock in rats

PubMed Central

Duan, Chenyang; Chen, Ken; Yang, Guangming; Li, Tao; Liu, Liangming

2017-01-01

HIF-1α plays an essential role in hemorrhagic shock-induced vasoconstriction. However, the underlying mechanisms remain poorly understood. Here, we studied both the role of HIF-1α in regulating vasodilatation, and the involvement of Cx40 in this process. We found that endothelium-dependent vasodilatation exhibited an overall decline after hemorrhagic shock: at the beginning of shock vasodilatation reactivity significantly decreased, followed by a slight increase from 0.5 h to 2 h after shock. After 2 h vasodilatation dropped again. Throughout this process, protein levels of HIF-1α gradually increased. In the late period of shock, vasodilatation reactivity was enhanced by oligomycin, an HIF-1α inhibitor, suggesting that HIF-1α may promote vasoconstriction. Moreover, in the late period of shock Cx40 levels gradually increased and exhibited a negative correlation with endothelium-dependent vasoconstriction reactivity. Furthermore, Cx40 AODN significantly improved vasoconstriction reactivity and could be regulated by either an HIF-1α inhibitor or an agonist. Together, these data suggest that HIF-1α may inhibit endothelium-dependent vasodilatation reactivity following hemorrhagic shock by up-regulating Cx40, especially in the late period of shock. PMID:28386353

Impact of Behavioral Control on the Processing of Nociceptive Stimulation

PubMed Central

Grau, James W.; Huie, J. Russell; Garraway, Sandra M.; Hook, Michelle A.; Crown, Eric D.; Baumbauer, Kyle M.; Lee, Kuan H.; Hoy, Kevin C.; Ferguson, Adam R.

2012-01-01

How nociceptive signals are processed within the spinal cord, and whether these signals lead to behavioral signs of neuropathic pain, depends upon their relation to other events and behavior. Our work shows that these relations can have a lasting effect on spinal plasticity, inducing a form of learning that alters the effect of subsequent nociceptive stimuli. The capacity of lower spinal systems to adapt, in the absence of brain input, is examined in spinally transected rats that receive a nociceptive shock to the tibialis anterior muscle of one hind leg. If shock is delivered whenever the leg is extended (controllable stimulation), it induces an increase in flexion duration that minimizes net shock exposure. This learning is not observed in subjects that receive the same amount of shock independent of leg position (uncontrollable stimulation). These two forms of stimulation have a lasting, and divergent, effect on subsequent learning: controllable stimulation enables learning whereas uncontrollable stimulation disables it (learning deficit). Uncontrollable stimulation also enhances mechanical reactivity. We review evidence that training with controllable stimulation engages a brain-derived neurotrophic factor (BDNF)-dependent process that can both prevent and reverse the consequences of uncontrollable shock. We relate these effects to changes in BDNF protein and TrkB signaling. Controllable stimulation is also shown to counter the effects of peripheral inflammation (from intradermal capsaicin). A model is proposed that assumes nociceptive input is gated at an early sensory stage. This gate is sensitive to current environmental relations (between proprioceptive and nociceptive input), allowing stimulation to be classified as controllable or uncontrollable. We further propose that the status of this gate is affected by past experience and that a history of uncontrollable stimulation will promote the development of neuropathic pain. PMID:22934018

[Whole-blood transfusion for hemorrhagic shock resuscitation: two cases in Djibouti].

PubMed

Cordier, P Y; Eve, O; Dehan, C; Topin, F; Menguy, P; Bertani, A; Massoure, P L; Kaiser, E

2012-01-01

Hemorrhagic shock requires early aggressive treatment, including transfusion of packed red blood cells and hemostatic resuscitation. In austere environments, when component therapy is not available, warm fresh whole-blood transfusion is a convenient treatment. It provides red blood cells, clotting factors, and functional platelets. Therefore it is commonly used in military practice to treat hemorrhagic shock in combat casualties. At Bouffard Hospital Center in Djibouti, the supply of packed red blood cells is limited, and apheresis platelets are unavailable. We used whole blood transfusion in two civilian patients with life-threatening non-traumatic hemorrhages. One had massive bleeding caused by disseminated intravascular coagulation due to septic shock; the second was a 39 year-old pregnant woman with uterine rupture. In both cases, whole blood transfusion (twelve and ten 500 mL bags respectively), combined with etiological treatment, enabled coagulopathy correction, hemorrhage control, and satisfactory recovery.

Polydatin Alleviates Small Intestine Injury during Hemorrhagic Shock as a SIRT1 Activator

PubMed Central

Zeng, Zhenhua; Chen, Zhongqing; Xu, Siqi; Song, Rui; Yang, Hong; Zhao, Ke-seng

2015-01-01

Objective. To evaluate the role of SIRT1 in small intestine damage following severe hemorrhagic shock and to investigate whether polydatin (PD) can activate SIRT1 in shock treatment. Research Design and Methods. The severe hemorrhagic shock model was reproduced in Sprague Dawley rats. Main Outcome Measures. Two hours after drug administration, half of the rats were assessed for survival time evaluation and the remainder were used for small intestinal tissue sample collection. Results. Bleeding and swelling appeared in the small intestine with epithelial apoptosis and gut barrier disturbance during hemorrhagic shock. SIRT1 activity and PGC-1α protein expression of the small intestine were decreased, which led to an increase in acetylated SOD2 and decreases in the expression and activity of SOD2, resulting in severe oxidative stress. The decreased SIRT1 activity and expression were partially restored in the PD administration group, which showed reduced intestine injury and longer survival time. Notably, the effect of PD was abolished after the addition of Ex527, a selective inhibitor of SIRT1. Conclusions. The results collectively suggest a role for the SIRT1-PGC-1α-SOD2 axis in small intestine injury following severe hemorrhagic shock and that PD is an effective SIRT1 activator for the shock treatment. PMID:26301045

[Intensive care treatment of traumatic brain injury in multiple trauma patients : Decision making for complex pathophysiology].

PubMed

Trimmel, H; Herzer, G; Schöchl, H; Voelckel, W G

2017-09-01

Traumatic brain injury (TBI) and hemorrhagic shock due to uncontrolled bleeding are the major causes of death after severe trauma. Mortality rates are threefold higher in patients suffering from multiple injuries and additionally TBI. Factors known to impair outcome after TBI, namely hypotension, hypoxia, hypercapnia, acidosis, coagulopathy and hypothermia are aggravated by the extent and severity of extracerebral injuries. The mainstays of TBI intensive care may be, at least temporarily, contradictory to the trauma care concept for multiple trauma patients. In particular, achieving normotension in uncontrolled bleeding situations, maintenance of normocapnia in traumatic lung injury and thromboembolic prophylaxis are prone to discussion. Due to an ongoing uncertainty about the definition of normotensive blood pressure values, a cerebral perfusion pressure-guided cardiovascular management is of key importance. In contrast, there is no doubt that early goal directed coagulation management improves outcome in patients with TBI and multiple trauma. The timing of subsequent surgical interventions must be based on the development of TBI pathology; therefore, intensive care of multiple trauma patients with TBI requires an ongoing and close cooperation between intensivists and trauma surgeons in order to individualize patient care.

Tactical Damage Control Resuscitation.

PubMed

Fisher, Andrew D; Miles, Ethan A; Cap, Andrew P; Strandenes, Geir; Kane, Shawn F

2015-08-01

Recently the Committee on Tactical Combat Casualty Care changed the guidelines on fluid use in hemorrhagic shock. The current strategy for treating hemorrhagic shock is based on early use of components: Packed Red Blood Cells (PRBCs), Fresh Frozen Plasma (FFP) and platelets in a 1:1:1 ratio. We suggest that lack of components to mimic whole blood functionality favors the use of Fresh Whole Blood in managing hemorrhagic shock on the battlefield. We present a safe and practical approach for its use at the point of injury in the combat environment called Tactical Damage Control Resuscitation. We describe pre-deployment preparation, assessment of hemorrhagic shock, and collection and transfusion of fresh whole blood at the point of injury. By approaching shock with goal-directed therapy, it is possible to extend the period of survivability in combat casualties. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

The Noninvasive Carbon Dioxide Gradient (NICO2G) during Hemorrhagic Shock

DTIC Science & Technology

2014-07-01

as well as a tPCO2- PaCO2 gap more than 16 mmHg were reported to be associated with poor outcomes in patients with septic shock (18). Previously, our...shortcomings, which include the need for frequent calibration with a tank of standardized cali- bration gas (24), relative bulk, need for a heated sensor, and...hemorrhagic, septic , and cardiogenic shock (27). Van der Linden et al. (28) demonstrated a venous-arterial gradient for PCO2 in hemorrhaged dogs. There was

In vivo analysis of intestinal permeability following hemorrhagic shock

PubMed Central

Alsaigh, Tom; Chang, Marisol; Richter, Michael; Mazor, Rafi; Kistler, Erik B

2015-01-01

AIM: To determine the time course of intestinal permeability changes to proteolytically-derived bowel peptides in experimental hemorrhagic shock. METHODS: We injected fluorescently-conjugated casein protein into the small bowel of anesthetized Wistar rats prior to induction of experimental hemorrhagic shock. These molecules, which fluoresce when proteolytically cleaved, were used as markers for the ability of proteolytically cleaved intestinal products to access the central circulation. Blood was serially sampled to quantify the relative change in concentration of proteolytically-cleaved particles in the systemic circulation. To provide spatial resolution of their location, particles in the mesenteric microvasculature were imaged using in vivo intravital fluorescent microscopy. The experiments were then repeated using an alternate measurement technique, fluorescein isothiocyanate (FITC)-labeled dextrans 20, to semi-quantitatively verify the ability of bowel-derived low-molecular weight molecules (< 20 kD) to access the central circulation. RESULTS: Results demonstrate a significant increase in systemic permeability to gut-derived peptides within 20 min after induction of hemorrhage (1.11 ± 0.19 vs 0.86 ± 0.07, P < 0.05) compared to control animals. Reperfusion resulted in a second, sustained increase in systemic permeability to gut-derived peptides in hemorrhaged animals compared to controls (1.2 ± 0.18 vs 0.97 ± 0.1, P < 0.05). Intravital microscopy of the mesentery also showed marked accumulation of fluorescent particles in the microcirculation of hemorrhaged animals compared to controls. These results were replicated using FITC dextrans 20 [10.85 ± 6.52 vs 3.38 ± 1.11 fluorescent intensity units (× 105, P < 0.05, hemorrhagic shock vs controls)], confirming that small bowel ischemia in response to experimental hemorrhagic shock results in marked and early increases in gut membrane permeability. CONCLUSION: Increased small bowel permeability in hemorrhagic shock may allow for systemic absorption of otherwise retained proteolytically-generated peptides, with consequent hemodynamic instability and remote organ failure. PMID:26557479

Embolization of Rectal Arteries: An Alternative Treatment for Hemorrhagic Shock Induced by Traumatic Intrarectal Hemorrhage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pichon, Nicolas, E-mail: nicolas.pichon@unilim.fr, E-mail: nicolas.pichon@chu-limoges.fr; Francois, Bruno; Pichon-Lefievre, Florence

2005-05-15

Rectal injuries caused by foreign bodies or iatrogenic insertions may lead to severe complications whose therapeutic management remains controversial. At times, both the rapid identification and treatment of subsequent active rectal bleeding may be challenging, especially when endoscopy fails to locate and control the arterial hemorrhage. We present the first two successful cases of middle rectal artery embolization in patients presenting with sustained bleeding and hemorrhagic shock.

Heat Shock Protein-70 Inducers and iNOS Inhibitors as Therapeutics to Ameliorate Hemorrhagic Shock

DTIC Science & Technology

2004-09-01

downregulation of iNOS can limit tissue injury caused by ischemia / reperfusion or hemorrhage/resuscitation. In our laboratory, geldanamycin, a member of... ischemia / reperfusion [Charier 1999]. Mice deficient in inducible NO synthase (iNOS) also demonstrate limited hemorrhage/resuscitation-induced injury ...tissues and leukotriene B4 (LTB4) generation increases. In a hemorrhage/resuscitation-induced injury model, iNOS, cyclooxygenase- 2 , and CD14 are all

The effect of permissive hypotension in combined traumatic brain injury and blunt abdominal trauma: an experimental study in swines.

PubMed

Vrettos, T; Poimenidi, E; Athanasopoulos, P; Balasis, S; Karagiorgos, N; Siklis, T; Gatzounis, G; Fligkou, F

2016-01-01

Optimal hemodynamic resuscitation strategy of the trauma patient with uncontrolled hemorrhage and severe head injury in the pre-hospital setting remains a special challenge. Permissive hypotension prior to definite surgical haemostasis promotes coagulation, decreases blood loss and favors survival. However, hypotension is associated with poor outcome in severe head injury. The purpose of this experimental animal study was to assess the impact of permissive hypotension on survival, hemodynamic profile and brain oxygenation parameters before and/or after definite surgical haemostasis. Six-week-old pigs (n=12) underwent general anesthesia and brain injury was produced by the fluid percussion model. Animals were instrumented to measure hemodynamic parameters and cerebral blood flow. All animals (n=12) were subjected to laparotomy and a surgical knot was placed through the abdominal aorta wall. Uncontrolled hemorrhage was simulated by pulling out the intentionally left protruding free ends of the suture (goal MAP=30 mmHg). Animals were randomly divided into two groups; group A (n=6) was subjected to aggressive fluid resuscitation (goal SAP >80 mmHg) and group B (n=6) was left hypotensive (permissive hypotension). Animals who survived one hour of hypotensive shock underwent definite surgical haemostasis and were resuscitated for one hour. We measured survival, hemodynamic and brain oxygenation parameters at different time points before and after surgical haemostasis. All animals from Group A and 50% from Group B died before surgical haemostasis. In surviving animals (Group B, 50%, p=0.033), MAP, CO, rCBF, SjO2 and AVDO2 were restored to pre-procedural levels. Permissive hypotension by delaying fluid resuscitation up to definite surgical haemostasis improves survival, hemodynamics and allows restoration of cerebral oxygenation in severe head injury.

Pelvic fracture in multiple trauma: A 67-case series.

PubMed

Caillot, M; Hammad, E; Le Baron, M; Villes, V; Leone, M; Flecher, X

2016-12-01

Severe pelvic trauma remains associated with elevated mortality, largely due to hemorrhagic shock. The main study objective was to test for correlation between fracture type and mortality. The secondary objective was to assess the efficacy in terms of mortality of multidisciplinary management following a decision-tree in multiple trauma victims admitted to a level 1 trauma center. Between July 2011 and July 2013, 534 severe trauma patients were included in a single-center continuous prospective observational study. All patients with hemorrhagic shock received early treatment by pelvic binder. Patients with active bleeding on full-body CT or persisting hemorrhagic shock underwent arteriography with or without embolization. Pelvic trauma was graded on the Tile classification. The principle end-point was mortality. Median age was 40 years (range, 26-48 years), with a 79% male/female sex ratio. Thirty-two of the 67 patients with pelvic trauma (48%) were in hemorrhagic shock at admission. Median injury severity score (ISS) was 36 (range, 24-43). On the Tile classification, 22 patients (33%) were grade A, 33 (49%) grade B and 12 (18%) grade C. Overall mortality was 19%, and 42% in case of hemorrhagic shock. Mortality was significantly higher with Tile C than A or B (58% vs. 9.1% and 12.1%, respectively; P=0.001). Vertical shear fracture (Tile C) was associated with greater mortality from hemorrhagic shock. IV, case series. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

4-Phenylbutyrate Benefits Traumatic Hemorrhagic Shock in Rats by Attenuating Oxidative Stress, Not by Attenuating Endoplasmic Reticulum Stress.

PubMed

Yang, Guangming; Peng, Xiaoyong; Hu, Yi; Lan, Dan; Wu, Yue; Li, Tao; Liu, Liangming

2016-07-01

Vascular dysfunction such as vascular hyporeactivity following severe trauma and shock is a major cause of death in injured patients. Oxidative stress and endoplasmic reticulum stress play an important role in vascular dysfunction. The objective of the present study was to determine whether or not 4-phenylbutyrate can improve vascular dysfunction and elicit antishock effects by inhibiting oxidative and endoplasmic reticulum stress. Prospective, randomized, controlled laboratory experiment. State key laboratory of trauma, burns, and combined injury. Five hundred and fifty-two Sprague-Dawley rats. Rats were anesthetized, and a model of traumatic hemorrhagic shock was established by left femur fracture and hemorrhage. The effects of 4-phenylbutyrate (5, 20, 50, 100, 200, and 300 mg/kg) on vascular reactivity, animal survival, hemodynamics, and vital organ function in traumatic hemorrhagic shock rats and cultured vascular smooth muscle cells, and the relationship to oxidative stress and endoplasmic reticulum stress was observed. Lower doses of 4-phenylbutyrate significantly improved the vascular function, stabilized the hemodynamics, and increased the tissue blood flow and vital organ function in traumatic hemorrhagic shock rats, and markedly improved the survival outcomes. Among all dosages observed in the present study, 20 mg/kg of 4-phenylbutyrate had the best effect. Further results indicated that 4-phenylbutyrate significantly inhibited the oxidative stress, decreased shock-induced oxidative stress index such as the production of reactive oxygen species, increased the antioxidant enzyme levels such as superoxide dismutase, catalase, and glutathione, and improved the mitochondrial function by inhibiting the opening of the mitochondrial permeability transition pore in rat artery and vascular smooth muscle cells. In contrast, 4-phenylbutyrate did not affect the changes of endoplasmic reticulum stress markers following traumatic hemorrhagic shock. Furthermore, 4-phenylbutyrate increased the nuclear levels of nuclear factor-E2-related factor 2, and decreased the nuclear levels of nuclear factor κB in hypoxic vascular smooth muscle cells. 4-phenylbutyrate has beneficial effects for traumatic hemorrhagic shock including improving animal survival and protecting organ function. These beneficial effects of 4-phenylbutyrate in traumatic hemorrhagic shock result from its vascular function protection via attenuation of the oxidative stress and mitochondrial permeability transition pore opening. Nuclear factor-E2-related factor 2 and nuclear factor-κB may be involved in 4-phenylbutyrate-mediated inhibition of oxidative stress.

Alterations of Mg2+ After Hemorrhagic Shock.

PubMed

Lee, Mun-Young; Yang, Dong Kwon; Kim, Shang-Jin

2017-11-01

Hemorrhagic shock is generally characterized by hemodynamic instability with cellular hypoxia and diminishing cellular function, resulting from an imbalance between systemic oxygen delivery and consumption and redistribution of fluid and electrolytes. Magnesium (Mg) is the fourth most abundant cation overall and second most abundant intracellular cation in the body and an essential cofactor for the energy production and cellular metabolism. Data for blood total Mg (tMg; free-ionized, protein-bound, and anion-bound forms) and free Mg 2+ levels after a traumatic injury are inconsistent and only limited information is available on hemorrhagic effects on free Mg 2+ as the physiologically active form. The aim of this study was to determine changes in blood Mg 2+ and tMg after hemorrhage in rats identifying mechanism and origin of the changes in blood Mg 2+ . Hemorrhagic shock produced significant increases in blood Mg 2+ , plasma tMg, Na + , K + , Cl - , anion gap, partial pressures of oxygen, glucose, and blood urea nitrogen but significant decreases in RBC tMg, blood Ca 2+ , HCO 3 - , pH, partial pressures of carbon dioxide, hematocrit, hemoglobin, total cholesterol, and plasma/RBC ATP. During hemorrhagic shock, K + , anion gap, and BUN showed significant positive correlations with changes in blood Mg 2+ level, while Ca 2+ , pH, and T-CHO correlated to Mg 2+ in a negative manner. In conclusion, hemorrhagic shock induced an increase in both blood-free Mg 2+ and tMg, resulted from Mg 2+ efflux from metabolic damaged cell with acidosis and ATP depletion.

Development and Resuscitation of a Sedated, Mature Male Miniature Swine Severe Hemorrhage Model

DTIC Science & Technology

2011-07-01

control. Results: Hemorrhage resulted in a characteristic hypotension and metabolic acidosis . Survival time for the control swine was 64 minutes...domestic swine4 and was characteristic of a hemorrhage- induced metabolic acidosis , with a decrease in blood HCO3, and BE and an increase in blood...Hammett M, Asher L, et al. Effects of bovine polymerized hemoglobin on coagulation in controlled hemorrhagic shock in swine. Shock. 2005;24:145–152

[Beneficial effect of thyrotropin-releasing hormone in combination with HSD on hemorrhagic shock with pulmonary edema at high altitude in the rat].

PubMed

Hu, De-yao; Liu, Liang-ming; Li, Ping; Liu, Jian-cang; Liu, Hou-dong; He, Yan-mei; Huo, Xiao-ping; Tian, Kun-lun; Shi, Quan-gui; Xiao, Nan; Zhou, Xue-wu

2003-05-01

To study the effects of thyrotropin-releasing hormone (TRH) in combination with hypertonic saline/dextran (7.5% NaCl + 6% Dextran 40, HSD ) on hemorrhagic shock with pulmonary edema in the rats which were recently brought to high altitude. Forty-nine SD rats, transported to Lasa, Tibet, which was 3,760 meters above the sea level, were anesthetized one week later with sodium pentobarbital (30 mg/kg, intraperitoneal). Hemorrhagic shock with pulmonary edema was induced by hemorrhage (50 mm Hg maintained for 1 hour,1 mm Hg=0.133 kPa) plus intravenous injection of oleic acid (50 microl/kg). They were equally divided into seven groups (n=7): normal control, hemorrhagic shock, hemorrhagic shock with pulmonary edema (HSPE), HSPE plus TRH (5 mg/kg), HSPE plus HSD (4 ml/kg), and HEPE plus TRH and HSD in combination. Hemodynamic parameters including mean arterial blood pressure(MAP), left intraventricular systolic pressure (LVSP) and the maximal change rate of intraventricular pressure rise or decline (+/- dp/dt max) were observed at 15, 30, 60 and 120 minutes, blood gases were analyzed at 30 and 120 minutes, and the water content of lung and brain was determined at 120 minutes after drug administration. TRH or HSD used alone or in combination significantly increased MAP, LVSP and +/- dp/dt max (P<0.05 or P<0.01 ), ameliorated acid-base imbalance, and decreased the water content of lung and brain. The effect of the two in combination was superior to either drug used alone. TRH in combination with HSD can be used in the treatment of hemorrhagic shock with pulmonary edema at high altitude.

Is Survival Time After Hemorrhage a Heritable, Quantitative Trait?: An Initial Assessment

DTIC Science & Technology

2008-06-01

The epidemiology of traumatic death. A population-based analysis. Arch Surg 128:571Y575, 1993. 5. Sauaia A, Moore FA, Moore EE, Moser KS, Brennan R...therapeutic goals and early warning of death. Arch Surg 106:630Y636, 1973. 752 SHOCK VOL. 29, NO. 6 KLEMCKE ET AL. Copyright @ 200 by the Shock...Hemorrhagic shock in rats. Measured blood volumes as the basis for the extent of hemorrhage. Arch Surg 99:484Y488, 1969. 19. Nose H, Morita M, Yawata T

Kaolin-based hemostatic dressing improves hemorrhage control from a penetrating inferior vena cava injury in coagulopathic swine.

PubMed

Koko, Kiavash R; McCauley, Brian M; Gaughan, John P; Nolan, Ryan S; Fromer, Marc W; Hagaman, Ashleigh L R; Choron, Rachel L; Brown, Spencer A; Hazelton, Joshua P

2017-07-01

Retrohepatic inferior vena cava (RIVC) injuries are often lethal due to challenges in obtaining hemorrhage control. We hypothesized that packing with a new kaolin-based hemostatic dressing (Control+; Z-Medica, Wallingford, CT) would improve hemorrhage control from a penetrating RIVC injury compared with packing with standard laparotomy sponges alone. Twelve male Yorkshire pigs received a 25% exchange transfusion of blood for refrigerated normal saline to induce a hypothermic coagulopathy. A laparotomy was performed and a standardized 1.5 cm injury to the RIVC was created which was followed by temporary abdominal closure and a period of uncontrolled hemorrhage. When the mean arterial pressure reached 70% of baseline, demonstrating hemorrhagic shock, the abdomen was re-entered, and the injury was treated with perihepatic packing using standard laparotomy sponges (L; n = 6) or a new kaolin-based hemostatic dressing (K; n = 6). Animals were then resuscitated for 6 hours with crystalloid solution. The two groups were compared using the Wilcoxon rank sum test and Fisher exact test. A p value of 0.05 or less was considered statistically significant. There was no difference in the animal's temperature, heart rate, mean arterial pressure, cardiac output, and blood loss at baseline or before packing was performed (all p > 0.05). In the laparotomy sponge group, five of six pigs survived the entire study period, whereas all six pigs treated with kaolin-based D2 hemostatic dressings survived. Importantly, there was significantly less blood loss after packing with the new hemostatic kaolin-based dressing compared with packing with laparotomy sponge (651 ± 180 mL vs. 1073 ± 342 mL; p ≤ 0.05). These results demonstrate that the use of this new hemostatic kaolin-based dressing improved hemorrhage control and significantly decreased blood loss in this penetrating RIVC model. This is basic science research based on a large animal model, level V.

Use of artificial intelligence to identify cardiovascular compromise in a model of hemorrhagic shock.

PubMed

Glass, Todd F; Knapp, Jason; Amburn, Philip; Clay, Bruce A; Kabrisky, Matt; Rogers, Steven K; Garcia, Victor F

2004-02-01

To determine whether a prototype artificial intelligence system can identify volume of hemorrhage in a porcine model of controlled hemorrhagic shock. Prospective in vivo animal model of hemorrhagic shock. Research foundation animal surgical suite; computer laboratories of collaborating industry partner. Nineteen, juvenile, 25- to 35-kg, male and female swine. Anesthetized animals were instrumented for arterial and systemic venous pressure monitoring and blood sampling, and a splenectomy was performed. Following a 1-hr stabilization period, animals were hemorrhaged in aliquots to 10, 20, 30, 35, 40, 45, and 50% of total blood volume with a 10-min recovery between each aliquot. Data were downloaded directly from a commercial monitoring system into a proprietary PC-based software package for analysis. Arterial and venous blood gas values, glucose, and cardiac output were collected at specified intervals. Electrocardiogram, electroencephalogram, mixed venous oxygen saturation, temperature (core and blood), mean arterial pressure, pulmonary artery pressure, central venous pressure, pulse oximetry, and end-tidal CO(2) were continuously monitored and downloaded. Seventeen of 19 animals (89%) died as a direct result of hemorrhage. Stored data streams were analyzed by the prototype artificial intelligence system. For this project, the artificial intelligence system identified and compared three electrocardiographic features (R-R interval, QRS amplitude, and R-S interval) from each of nine unknown samples of the QRS complex. We found that the artificial intelligence system, trained on only three electrocardiographic features, identified hemorrhage volume with an average accuracy of 91% (95% confidence interval, 84-96%). These experiments demonstrate that an artificial intelligence system, based solely on the analysis of QRS amplitude, R-R interval, and R-S interval of an electrocardiogram, is able to accurately identify hemorrhage volume in a porcine model of lethal hemorrhagic shock. We suggest that this technology may represent a noninvasive means of assessing the physiologic state during and immediately following hemorrhage. Point of care application of this technology may improve outcomes with earlier diagnosis and better titration of therapy of shock.

Acute Hemorrhage into Adrenal Pseudocyst Presenting with Shock: Diagnostic Dilemmas — Report of Three Cases and Review of Literature

PubMed Central

Sivasankar, Amarapathy; Jeswanth, Sathyanesan; Johnson, Maria Antony; Ravichandran, Palaniappan; Rajendran, Shanmugasundaram; Kannan, Devy Gounder; Surendran, Rajagopal

2006-01-01

We report three cases of acutely bleeding adrenal pseudocysts presenting as hemorrhagic shock. Pregnancy was associated in two cases. The diagnostic dilemmas are discussed with special reference to their unusual presentations, diagnosis, and treatment. We believe that our cases, complicated by intracystic hemorrhage, may be related to pregnancy. PMID:17619705

Resuscitation and Transfusion Principles for Traumatic Hemorrhagic Shock

DTIC Science & Technology

2009-11-01

hyperfibrinolysis. We also describe the concept of damage control resuscitation (DCR), an early and aggressive prevention and treatment of hemorrhagic shock... prevention and treatment of acidosis, hypothermia, and hypocalcemia, avoidance of hemodilution, and hemostatic resuscitation with transfusion of red...are potentially preventable and 66–80% of these deaths occur from hemorrhage.3,4 Rural civilian data indicate that approximately 10% of traumatic

Hypertonic/Hyperoncotic Resuscitation from Shock: Reduced Volume Requirement and Lower Intracranial Pressure

DTIC Science & Technology

1989-10-01

in Dogs with Hemorrhagic Shock and an Intracranial Mass. Seventh International Symposium on Intracranial Pressure and Brain Injury , Ann Arbor, Michigan...with Hemorrhagic Shock and an Intracranial Mass. Seventh International Symposium on Intracranial Pressure and Brain Injury . Intracranial Pressure VII...and MCI US groups. Discussion: Following this severe insult a iETTiFMT3-a clinical head injury combined wit6i hemorrha Ic shock, a cobntnc/h rcctc

Resveratrol Rescues Kidney Mitochondrial Function Following Hemorrhagic Shock

PubMed Central

Wang, Hao; Guan, Yuxia; Karamercan, Mehmet Akif; Ye, Lan; Bhatti, Tricia; Becker, Lance B.; Baur, Joseph A.; Sims, Carrie A.

2015-01-01

Objective Hemorrhagic shock may contribute to acute kidney injury by profoundly altering renal mitochondrial function. Resveratrol (RSV), a naturally occurring sirtuin-1 (SIRT1) activator, has been shown to promote mitochondrial function and reduce oxidative damage in a variety of aging-related disease states. We hypothesized that RSV treatment during resuscitation would ameliorate kidney mitochondrial dysfunction and decrease oxidative damage following hemorrhagic shock. Method Using a decompensated hemorrhagic shock model, male Long-Evans rats (n=6 per group) were sacrificed prior to hemorrhage (Sham), at severe shock, and following either lactated Ringer’s (LR) Resuscitation or LR+RSV Resuscitation (RSV: 30mg/kg). At each time point, blood samples were assayed for arterial blood gases, lactate, blood urea nitrogen (BUN) and serum creatinine. Mitochondria were also isolated from kidney samples in order to assess individual electron transport complexes (CI, CII, and CIV) using high-resolution respirometry. Total mitochondria reactive oxygen species (ROS) were measured using fluorometry and lipid peroxidation was assessed by measuring 4-hydroxynonenal by Western blot. qPCR was used quantify mRNA from PGC1-α, SIRT1, and proteins known to mitigate oxidative damage and promote mitochondrial biogenesis. Results RSV supplementation during resuscitation restored mitochondrial respiratory capacity, decreased mitochondrial ROS and lipid peroxidation. Compared to standard LR resuscitation, RSV treatment significantly increased SIRT1 and PGC1-α expression and significantly increased both SOD2 and catalase expression. Although RSV was associated with decreased lactate production, pH, BUN and serum creatinine values did not differ between resuscitation strategies. Conclusions Resuscitation with RSV significantly restored renal mitochondrial function and decreased oxidative damage following hemorrhagic shock. PMID:25895148

[Observation of therapeutic effect by combined administration of Salvia miltiorrhiza, ligustrazine and Panax notoginseng on late hemorrhagic shock of rabbits].

PubMed

Wang, Z W; Gao, S Z; Cheng, B C

1997-05-01

To explore the therapeutic mechanism of Salvia miltiorrhize, ligustrazine and Panax notoginseng in treating late hemorrhagic shock in rabbit. Rabbit hemorrhagic shock models (MPA 5.3 kPa) were set up according to Wiggers' method and administrated Salvia miltiorrhiza, ligustrazine, Panax notoginseng. The values of blood RBC superoxide dismutase (SOD) and blood lactate (BL), plasma malondialdehyde (MDA) and magnesium (Mg++) were continuously monitored before shock, 120 minutes after shock, 60 and 120 minutes after hydraulic dilatation. (1) In 120 minutes after shock, the level of SOD decreased and the concentrations of MDA, BL, Mg++ were markedly increased, which indicated that the cell membrane damage caused by oxygen free radicals in rabbit hemorrhagic shock. (2) Salvia miltiorrhiza, Ligustrazine or Panax notoginseng could alleviate lipidperoxidation injury to tissue. Compared with the single drug administration groups, the effects of oxygen free radicals scavangers by combined administration with half dose of 2 drugs were better than the single drug with full dose alone and the side effects such as depression of blood pressure and heart rates would be alleviated. Combined administration of Salvia miltiorrhiza, ligustrazine and Panax notoginseng would half the dosage, the blood pressure depression and heart rate reduction alleviated and better result obtained.

Hypertonic Saline Resuscitation Restores Inflammatory Cytokine Balance in Post-Traumatic Hemorrhagic Shock Patients

DTIC Science & Technology

2004-08-01

immunocompetant cells experience bidirectional communication with hormones and cytokines [35,40]. Thus, despite compelling experimental findings, HSD has not...hypertonic saline with 6% dextran-70 (HSD) has been shown in experimental studies to reduce shock/resuscitation-induced inflammatory reactions and...alterations have been described in clinical and experimental investigations of post-traumatic hemorrhagic shock [13]. The initial immunological

Investigation of Intravenous Hydroxocobalamin Compared to Hextend for Resuscitation in a Swine Model of Uncontrolled Hemorrhagic Shock: A Preliminary Report

DTIC Science & Technology

2017-06-16

Iy Dlrec~ b. Is not ~j’lnll I’cr ~pport. res, ~ es or otollr~phs for pu -.. 2. Pilnt your ~me, r~nk;;. l ~Ge. sllln dll~ tt. ’brm In tt.e ~utho(s block...or e eledronl: slgnal1Jre. :> ..••• 1t21 a COP)’of the S9 [e.O.=e report, QA’ DWIR:E> IAC\\JC sl1JGY,progr ev~1 ~ the r8~arch ~ l ". ed l .1udy. If this...a ~chnl~1 U! l caU:,"!IJ~SCI’l~3I1on,~e the ~pe rn~DtlTllI.llon report. eft< , etc.) In the "P~co Tltee" t: x. 4 ..•••1tll a copy of your b’WIlc1

Rodent models of depression: learned helplessness induced in mice.

PubMed

Anisman, H; Merali, Z

2001-05-01

Uncontrollable stressors induce a variety of behavioral disturbances that are in many ways reminiscent of the symptoms that characterize clinical depression. These deficits are evident across a range of species, including mice. Given the increasing focus on genetic techniques involving mice to identify the mechanisms subserving these behavioral disturbances (e.g., recombinant, knockout, and transgenic strains), it is of particular interest to provide a detailed description of the method to induce behavioral deficits in response to uncontrollable stressors. This unit describes the procedure used to assess the effects of controllable and uncontrollable shock on subsequent shock escape performance in mice using an escape-delay procedure.

Of hemorrhagic shock, spherical cows and Aloe vera

PubMed Central

Gutierrez, Guillermo; Fuller, Stephanie P

2004-01-01

The central question explored in this commentary is whether the beneficial effects of an Aloe vera derived drag-reducing polymer during hemorrhagic shock is due to its O2 radical scavenging properties or to changes in blood rheology. PMID:15566601

Increased metabolic activity in the septum and habenula during stress is linked to subsequent expression of learned helplessness behavior.

PubMed

Mirrione, Martine M; Schulz, Daniela; Lapidus, Kyle A B; Zhang, Samuel; Goodman, Wayne; Henn, Fritz A

2014-01-01

Uncontrollable stress can have a profound effect on an organism's ability to respond effectively to future stressful situations. Behavior subsequent to uncontrollable stress can vary greatly between individuals, falling on a spectrum between healthy resilience and maladaptive learned helplessness. It is unclear whether dysfunctional brain activity during uncontrollable stress is associated with vulnerability to learned helplessness; therefore, we measured metabolic activity during uncontrollable stress that correlated with ensuing inability to escape future stressors. We took advantage of small animal positron emission tomography (PET) and 2-deoxy-2[(18)F]fluoro-D-glucose ((18)FDG) to probe in vivo metabolic activity in wild type Sprague Dawley rats during uncontrollable, inescapable, unpredictable foot-shock stress, and subsequently tested the animals response to controllable, escapable, predictable foot-shock stress. When we correlated metabolic activity during the uncontrollable stress with consequent behavioral outcomes, we found that the degree to which animals failed to escape the foot-shock correlated with increased metabolic activity in the lateral septum and habenula. When used a seed region, metabolic activity in the habenula correlated with activity in the lateral septum, hypothalamus, medial thalamus, mammillary nuclei, ventral tegmental area, central gray, interpeduncular nuclei, periaqueductal gray, dorsal raphe, and rostromedial tegmental nucleus, caudal linear raphe, and subiculum transition area. Furthermore, the lateral septum correlated with metabolic activity in the preoptic area, medial thalamus, habenula, interpeduncular nuclei, periaqueductal gray, dorsal raphe, and caudal linear raphe. Together, our data suggest a group of brain regions involved in sensitivity to uncontrollable stress involving the lateral septum and habenula.

Increased metabolic activity in the septum and habenula during stress is linked to subsequent expression of learned helplessness behavior

PubMed Central

Mirrione, Martine M.; Schulz, Daniela; Lapidus, Kyle A. B.; Zhang, Samuel; Goodman, Wayne; Henn, Fritz A.

2013-01-01

Uncontrollable stress can have a profound effect on an organism's ability to respond effectively to future stressful situations. Behavior subsequent to uncontrollable stress can vary greatly between individuals, falling on a spectrum between healthy resilience and maladaptive learned helplessness. It is unclear whether dysfunctional brain activity during uncontrollable stress is associated with vulnerability to learned helplessness; therefore, we measured metabolic activity during uncontrollable stress that correlated with ensuing inability to escape future stressors. We took advantage of small animal positron emission tomography (PET) and 2-deoxy-2[18F]fluoro-D-glucose (18FDG) to probe in vivo metabolic activity in wild type Sprague Dawley rats during uncontrollable, inescapable, unpredictable foot-shock stress, and subsequently tested the animals response to controllable, escapable, predictable foot-shock stress. When we correlated metabolic activity during the uncontrollable stress with consequent behavioral outcomes, we found that the degree to which animals failed to escape the foot-shock correlated with increased metabolic activity in the lateral septum and habenula. When used a seed region, metabolic activity in the habenula correlated with activity in the lateral septum, hypothalamus, medial thalamus, mammillary nuclei, ventral tegmental area, central gray, interpeduncular nuclei, periaqueductal gray, dorsal raphe, and rostromedial tegmental nucleus, caudal linear raphe, and subiculum transition area. Furthermore, the lateral septum correlated with metabolic activity in the preoptic area, medial thalamus, habenula, interpeduncular nuclei, periaqueductal gray, dorsal raphe, and caudal linear raphe. Together, our data suggest a group of brain regions involved in sensitivity to uncontrollable stress involving the lateral septum and habenula. PMID:24550809

In vivo Evaluation of Venular Glycocalyx during Hemorrhagic Shock in Rats using Intravital Microscopy

DTIC Science & Technology

2013-01-01

Brief Communication In vivo evaluation of venular glycocalyx during hemorrhagic shock in rats using intravital microscopy☆,☆☆ Ivo Torres Filho...pathophysiology and tested the hypothesis that hemorrhage causes glycocalyx degrada- tion in cremaster muscle microvessels. We utilized intravital microscopy...bound (Reitsma et al., 2007; Weinbaum et al., 2007). Intravital microscopy has been an invaluable resource for in vivo measurements of critically

Hepatoprotective Effects of Corilagin Following Hemorrhagic Shock are Through Akt-Dependent Pathway

PubMed Central

Liu, Fu-Chao; Chaudry, Irshad H.; Yu, Huang-Ping

2017-01-01

ABSTRACT Corilagin, a component of Phyllanthus urinaria extract, possesses antioxidant, thrombolytic, antiatherogenic, and hepatoprotective properties, but the mechanism underlying these effects remains unclear. Previous studies showed that the Akt (protein kinase B) signaling pathway exerts anti-inflammatory and organ protective effects. The aim of this study was to investigate the mechanism of action of corilagin and determine whether these effects are mediated through the Akt-dependent pathway in a trauma-hemorrhagic shock-induced liver injury rodent model. Hemorrhagic shock was induced in male Sprague–Dawley rats; mean blood pressure was maintained at 35 mm Hg to 40 mm Hg for 90 min, followed by fluid resuscitation. During resuscitation, three doses of corilagin alone (1 mg/kg, 5 mg/kg, or 10 mg/kg, intravenously) were administered. Furthermore, a single dose of corilagin (5 mg/kg) with and without Wortmannin (1 mg/kg, PI3K inhibitor), Wortmannin alone, or vehicle was administered. Twenty-four hours after resuscitation, plasma alanine aminotransferase and aspartate aminotransferase concentration and hepatic parameters were measured. One-way ANOVA was used for statistical analysis. Hepatic myeloperoxidase activity and the concentrations of plasma alanine aminotransferase and aspartate aminotransferase, interleukin-6, tumor necrosis factor-α, intercellular adhesion molecule-1, and cytokine-induced neutrophil chemoattractant-1 (CINC-1) and CINC-3 increased following hemorrhagic shock. These parameters were significantly attenuated in corilagin-treated rats following hemorrhagic shock. Hepatic phospho-Akt expression was also higher in corilagin-treated rats than in vehicle-treated rats. The elevation of phospho-Akt was abolished by combined treatment with Wortmannin and corilagin. Our results suggest that corilagin exerts its protective effects on hemorrhagic shock-induced liver injury, at least, via the Akt-dependent pathway. PMID:27559697

Platelet closure time in anesthetized Greyhounds with hemorrhagic shock treated with hydroxyethyl starch 130/0.4 or 0.9% sodium chloride infusions.

PubMed

McBride, Duana; Hosgood, Giselle; Raisis, Anthea; Smart, Lisa

2016-07-01

To measure platelet closure time (PCT) in dogs during controlled hemorrhagic shock and after fluid resuscitation with hydroxyethyl starch (HES) 130/0.4 or 0.9% sodium chloride. Experimental interventional study. University veterinary teaching hospital. Eleven healthy Greyhounds. Dogs were anesthetized and had 48 mL/kg of blood removed to induce hemorrhagic shock. Dogs received 20 mL/kg of HES 130/0.4 (n = 6) or 80 mL/kg of 0.9% sodium chloride (NaCl; n = 5) intravenously over 20 minutes. PCT was measured using the Platelet Function Analyzer-100 with collagen and adenosine-diphosphate cartridges at: T0 = 60 minutes after induction of anesthesia prior to hemorrhage, T1 = during hemorrhagic shock, and T2 = 40 minutes after completion of fluid bolus. Packed cell volume and platelet count were concurrently measured. Hemorrhagic shock did not significantly change PCT, with no difference between T0 and T1. Both the HES 130/0.4 and 0.9% NaCl group had a significantly increased mean PCT at T2 of 91.4 seconds (95% CI 69.3-113.4) and 95.5 seconds (95% CI 78.2-112.8), respectively, compared to T1. The magnitude of change was significantly greater for the 0.9% NaCl group than the HES 130/0.4 group. There was no difference in the magnitude of change in PCV and platelet count between the 2 groups. The PCV and platelet count were >25% and >100,000/μL, respectively, in all dogs, except for dogs in the HES 130/0.4 group at T2 where platelet counts were <100,000/μL. Controlled hemorrhagic shock in Greyhounds under anesthesia did not cause a significant change in PCT. Both HES 130/0.4 and 0.9% NaCl administration after induction of shock increased PCT. These results do not support that HES 130/0.4 causes relevant platelet dysfunction beyond hemodilution. © Veterinary Emergency and Critical Care Society 2016.

Effects of Psychosocial Stress on Subsequent Hemorrhagic Shock and Resuscitation in Male Mice.

PubMed

Langgartner, Dominik; Wachter, Ulrich; Hartmann, Clair; Gröger, Michael; Vogt, Josef; Merz, Tamara; McCook, Oscar; Fink, Marina; Kress, Sandra; Georgieff, Michael; Kunze, Julia F; Radermacher, Peter L; Reber, Stefan O; Wepler, Martin

2018-06-08

Hypoxemia and tissue ischemia during hemorrhage as well as formation of oxygen and nitrogen radicals during resuscitation promote hyperinflammation and, consequently, trigger severe multiple-organ-failure (MOF). Individuals diagnosed with stress-related disorders or reporting a life history of psychosocial stress are characterized by chronic low-grade inflammation and a reduced glucocorticoid (GC) signaling. We hypothesized that exposure to chronic psychosocial stress during adulthood prior to hemorrhagic shock increases oxidative/nitrosative stress and therefore the risk of developing MOF in mice. To induce chronic psychosocial stress linked to mild immune activation and reduced GC signaling in male mice, the chronic subordinate colony housing (CSC) paradigm was employed. Single-housed (SHC) mice were used as controls. Subsequently, CSC and SHC mice were exposed to hemorrhagic shock following resuscitation to investigate the effects of prior psychosocial stress load on survival, organ function, metabolism, oxidative/nitrosative stress, and inflammatory readouts. An increased adrenal weight in CSC mice indicates that the stress paradigm reliably worked. However, no effect of prior psychosocial stress on outcome after subsequent hemorrhage and resuscitation could be detected. Chronic psychosocial stress during adulthood is not sufficient to promote hemodynamic complications, organ dysfunction, metabolic disturbances and did not increase the risk of MOF after subsequent hemorrhage and resuscitation. Intravenous norepinephrine to keep target hemodynamics might have led to a certain level of oxidative stress in both groups and, therefore, disguised potential effects of chronic psychosocial stress on organ function after hemorrhagic shock in the present murine trauma model.

Loss of Syndecan-1 Abrogates the Pulmonary Protective Phenotype Induced by Plasma After Hemorrhagic Shock.

PubMed

Wu, Feng; Peng, Zhanglong; Park, Pyong Woo; Kozar, Rosemary A

2017-09-01

Syndecan-1 (Sdc1) is considered a biomarker of injury to the endothelial glycocalyx following hemorrhagic shock, with shedding of Sdc1 deleterious. Resuscitation with fresh frozen plasma (FFP) has been correlated with restitution of pulmonary Sdc1 and reduction of lung injury, but the precise contribution of Sdc1 to FFPs protection in the lung remains unclear. Human lung endothelial cells were used to assess the time and dose-dependent effect of FFP on Sdc1 expression and the effect of Sdc1 silencing on in vitro endothelial cell permeability and actin stress fiber formation. Wild-type and Sdc1 mice were subjected to hemorrhagic shock followed by resuscitation with lactated Ringers (LR) or FFP and compared with shock alone and shams. Lungs were harvested after 3 h for analysis of permeability, histology, and inflammation and for measurement of syndecan- 2 and 4 expression. In vitro, FFP enhanced pulmonary endothelial Sdc1 expression in time- and dose-dependent manners and loss of Sdc1 in pulmonary endothelial cells worsened permeability and stress fiber formation by FFP. Loss of Sdc1 in vivo led to equivalency between LR and FFP in restoring pulmonary injury, inflammation, and permeability after shock. Lastly, Sdc1 mice demonstrated a significant increase in pulmonary syndecan 4 expression after hemorrhagic shock and FFP-based resuscitation. Taken together, our findings support a key role for Sdc1 in modulating pulmonary protection by FFP after hemorrhagic shock. Our results also suggest that other members of the syndecan family may at least be contributing to FFP's effects on the endothelium, an area that warrants further investigation.

Hemorrhagic shock as a sequela of splenic rupture in a patient with infectious mononucleosis: focus on the potential role of salicylates.

PubMed

Bouliaris, Konstantinos; Karangelis, Dimos; Daskalopoulos, Marios; Spanos, Konstantinos; Fanariotis, Michael; Giaglaras, Anargyros

2012-01-01

Despite the fact that the vast majority of splenic ruptures are traumatic, infectious mononucleosis has been incriminated as a major predisposing factor that affects the integrity of the spleen, thus causing atraumatic ruptures and life-threatening hemorrhages. Herein we present a case of a 23-year-old Caucasian male who underwent an emergency laparotomy for acute abdomen and hemorrhagic shock, caused by spontaneous splenic rupture secondary to infectious mononucleosis. The potential role of salicylates in the development of a hemorrhagic complication in a patient with infectious mononucleosis is discussed.

IRREVERSIBLE HEMORRHAGIC SHOCK IN GERMFREE RATS

PubMed Central

Zweifach, B. W.; Gordon, H. A.; Wagner, M.; Reyniers, J. A.

1958-01-01

Evidence has been provided that a state of irreversible hemorrhagic shock can be induced in a bacteria-free environment in rats reared under germfree conditions. The response to bleeding, the duration of the hypotensive episode and the pathological changes were the same in the germfree and in normal stock rats. The findings are interpreted as evidence opposed to the concept that bacteria or bacterial products are implicated, as primary factors, in the pathogenicity of shock. PMID:13513911

Evaluation of hemodynamic effects of xenon in dogs undergoing hemorrhagic shock

PubMed Central

Franceschi, Ruben C.; Malbouisson, Luiz; Yoshinaga, Eduardo; Auler, José Otavio Costa; de Figueiredo (in memoriam), Luiz Francisco Poli; Carmona, Maria José C.

2013-01-01

OBJECTIVES: The anesthetic gas xenon is reported to preserve hemodynamic stability during general anesthesia. However, the effects of the gas during shock are unclear. The objective of this study was to evaluate the effect of Xe on hemodynamic stability and tissue perfusion in a canine model of hemorrhagic shock. METHOD: Twenty-six dogs, mechanically ventilated with a fraction of inspired oxygen of 21% and anesthetized with etomidate and vecuronium, were randomized into Xenon (Xe; n = 13) or Control (C; n = 13) groups. Following hemodynamic monitoring, a pressure-driven shock was induced to reach an arterial pressure of 40 mmHg. Hemodynamic data and blood samples were collected prior to bleeding, immediately after bleeding and 5, 20 and 40 minutes following shock. The Xe group was treated with 79% Xe diluted in ambient air, inhaled for 20 minutes after shock. RESULT: The mean bleeding volume was 44 mL.kg−1 in the C group and 40 mL.kg−1 in the Xe group. Hemorrhage promoted a decrease in both the cardiac index (p<0.001) and mean arterial pressure (p<0.001). These changes were associated with an increase in lactate levels and worsening of oxygen transport variables in both groups (p<0.05). Inhalation of xenon did not cause further worsening of hemodynamics or tissue perfusion markers. CONCLUSIONS: Xenon did not alter hemodynamic stability or tissue perfusion in an experimentally controlled hemorrhagic shock model. However, further studies are necessary to validate this drug in other contexts. PMID:23525321

Changes in lung ultrastructure following heterologous and homologous serum albumin infusion in the treatment of hemorrhagic shock.

PubMed Central

Moss, G S; Das Gupta, T K; Brinkman, R; Sehgal, L; Newsom, B

1979-01-01

The object of this study was to compare the ultrastructure pulmonary effects of the infusion of homologous and heterologous serum albumin solution in the treatment of hemorrhagic shock in baboons. Adult baboons subjected to hemorrhagic shock were resuscitated with either baboon serum albumin, human serum albumin, or Ringer's lactate solution. The lungs were fixed in vivo with potassium pyroantimony, a solution which produces electron dense interstitial precipitation of sodium. The lungs from animals resuscitated with baboon serum albumin showed evidence of interstitial edema, including dispersion of collagen fibers, interstitial smudging and increased interstital sodium concentrations. Similar changes were seen following human serum albumin infusions. Lung tissue from animals treated with Ringer's lactate solution showed minimal changes from normal. These results suggest that interstitial pulmonary edema develops after either homologous or heterologous serum albumin infusion in the treatment of hemorrhagic shock in baboons. Images Figs. 2a and b. Figs. 3a and b. Figs. 4a and b. Figs. 5a and b. Figs. 6a and b. PMID:106780

THE 5-LIPOXYGENASE PATHWAY IS REQUIRED FOR ACUTE LUNG INJURY FOLLOWING HEMORRHAGIC SHOCK

PubMed Central

Eun, John C.; Moore, Ernest E.; Mauchley, David C.; Johnson, Chris A.; Meng, Xianzhong; Banerjee, Anirban; Wohlauer, Max V.; Zarini, Simona; Gijón, Miguel A.; Murphy, Robert C.

2012-01-01

The cellular and biochemical mechanisms leading to acute lung injury and subsequent multiple organ failure are only partially understood. In order to study the potential role of eicosanoids, particularly leukotrienes, as possible mediators of acute lung injury, we used a murine experimental model of acute lung injury induced by hemorrhagic shock after blood removal via cardiac puncture. Neutrophil sequestration as shown by immunofluorescence, and protein leakage into the alveolar space, were measured as markers of injury. We used liquid chromatography coupled to tandem mass spectrometry to unequivocally identify several eicosanoids in the bronchoalveolar lavage fluid of experimental animals. MK886, a specific inhibitor of the 5-lipoxygenase pathway, as well as transgenic mice deficient in 5-lipoxygenase, were used to determine the role of this enzymatic pathway in this model. Leukotriene B4 and leukotriene C4 were consistently elevated in shock-treated mice compared to sham-treated mice. MK886 attenuated neutrophil infiltration and protein extravasation induced by hemorrhagic shock. 5-lipoxygenase-deficient mice showed reduced neutrophil infiltration and protein extravasation after shock treatment, indicating greatly reduced lung injury. These results support the hypothesis that 5-lipoxygenase, most likely through the generation of leukotrienes, plays an important role in the pathogenesis of acute lung injury induced by hemorrhagic shock in mice. This pathway could represent a new target for pharmacological intervention to reduce lung damage following severe primary injury. PMID:22392149

Hemorrhagic Shock as a Sequela of Splenic Rupture in a Patient with Infectious Mononucleosis: Focus on the Potential Role of Salicylates

PubMed Central

Bouliaris, Konstantinos; Karangelis, Dimos; Daskalopoulos, Marios; Spanos, Konstantinos; Fanariotis, Michael; Giaglaras, Anargyros

2012-01-01

Despite the fact that the vast majority of splenic ruptures are traumatic, infectious mononucleosis has been incriminated as a major predisposing factor that affects the integrity of the spleen, thus causing atraumatic ruptures and life-threatening hemorrhages. Herein we present a case of a 23-year-old Caucasian male who underwent an emergency laparotomy for acute abdomen and hemorrhagic shock, caused by spontaneous splenic rupture secondary to infectious mononucleosis. The potential role of salicylates in the development of a hemorrhagic complication in a patient with infectious mononucleosis is discussed. PMID:22431933

Safety of a condom uterine balloon tamponade (ESM-UBT) device for uncontrolled primary postpartum hemorrhage among facilities in Kenya and Sierra Leone.

PubMed

Ramanathan, Aparna; Eckardt, Melody J; Nelson, Brett D; Guha, Moytrayee; Oguttu, Monica; Altawil, Zaid; Burke, Thomas

2018-05-15

Postpartum hemorrhage is the leading cause of maternal mortality in low- and middle-income countries. While evidence on uterine balloon tamponade efficacy for severe hemorrhage is encouraging, little is known about safety of this intervention. The objective of this study was to evaluate the safety of an ultra-low-cost uterine balloon tamponade package (named ESM-UBT) for facility-based management of uncontrolled postpartum hemorrhage (PPH) in Kenya and Sierra Leone. Data were collected on complications/adverse events in all women who had an ESM-UBT device placed among 92 facilities in Sierra Leone and Kenya, between September 2012 and December 2015, as part of a multi-country study. Three expert maternal health investigator physicians analyzed each complication/adverse event and developed consensus on whether there was a potential causal relationship associated with use of the ESM-UBT device. Adverse events/complications specifically investigated included death, hysterectomy, uterine rupture, perineal or cervical injury, serious or minor infection, and latex allergy/anaphylaxis. Of the 201 women treated with an ESM-UBT device in Kenya and Sierra Leone, 189 (94.0%) survived. Six-week or longer follow-up was recorded in 156 of the 189 (82.5%). A causal relationship between use of an ESM-UBT device and one death, three perineal injuries and one case of mild endometritis could not be completely excluded. Three experts found a potential association between these injuries and an ESM-UBT device highly unlikely. The ESM-UBT device appears safe for use in women with uncontrolled PPH. Trial registration was not completed as data was collected as a quality assurance measure for the ESM-UBT kit.

Daily propranolol prevents prolonged mobilization of hematopoietic progenitor cells in a rat model of lung contusion, hemorrhagic shock, and chronic stress.

PubMed

Bible, Letitia E; Pasupuleti, Latha V; Gore, Amy V; Sifri, Ziad C; Kannan, Kolenkode B; Mohr, Alicia M

2015-09-01

Propranolol has been shown previously to decrease the mobilization of hematopoietic progenitor cells (HPCs) after acute injury in rodent models; however, this acute injury model does not reflect the prolonged period of critical illness after severe trauma. Using our novel lung contusion/hemorrhagic shock/chronic restraint stress model, we hypothesize that daily administration of propranolol will decrease prolonged mobilization of HPCs without worsening lung healing. Male Sprague-Dawley rats underwent 6 days of restraint stress after undergoing lung contusion or lung contusion/hemorrhagic shock. Restraint stress consisted of a daily 2-hour period of restraint interrupted every 30 minutes by alarms and repositioning. Each day after the period of restraint stress, the rats received intraperitoneal propranolol (10 mg/kg). On day 7, peripheral blood was analyzed for granulocyte-colony stimulating factor (G-CSF) and stromal cell-derived factor 1 via enzyme-linked immunosorbent assay and for mobilization of HPCs using c-kit and CD71 flow cytometry. The lungs were examined histologically to grade injury. Seven days after lung contusion and lung contusion/hemorrhagic shock, the addition of chronic restraint stress significantly increased the mobilization of HPC, which was associated with persistently increased levels of G-CSF and increased lung injury scores. The addition of propranolol to lung contusion/chronic restraint stress and lung contusion/hemorrhagic shock/chronic restraint stress models greatly decreased HPC mobilization and restored G-CSF levels to that of naïve animals without worsening lung injury scores. The daily administration of propranolol after both lung contusion and lung contusion/hemorrhagic shock subjected to chronic restraint stress decreased the prolonged mobilization of HPC from the bone marrow and decreased plasma G-CSF levels. Despite the decrease in mobilization of HPC, lung healing did not worsen. Alleviating chronic stress with propranolol may be a future therapeutic target to improve healing after severe injury. Copyright © 2015 Elsevier Inc. All rights reserved.

Acute right heart failure after hemorrhagic shock and trauma pneumonectomy-a management approach: A blinded randomized controlled animal trial using inhaled nitric oxide.

PubMed

Lubitz, Andrea L; Sjoholm, Lars O; Goldberg, Amy; Pathak, Abhijit; Santora, Thomas; Sharp, Thomas E; Wallner, Markus; Berretta, Remus M; Poole, Lauren A; Wu, Jichuan; Wolfson, Marla R

2017-02-01

Hemorrhagic shock and pneumonectomy causes an acute increase in pulmonary vascular resistance (PVR). The increase in PVR and right ventricular (RV) afterload leads to acute RV failure, thus reducing left ventricular (LV) preload and output. Inhaled nitric oxide (iNO) lowers PVR by relaxing pulmonary arterial smooth muscle without remarkable systemic vascular effects. We hypothesized that with hemorrhagic shock and pneumonectomy, iNO can be used to decrease PVR and mitigate right heart failure. A hemorrhagic shock and pneumonectomy model was developed using sheep. Sheep received lung protective ventilatory support and were instrumented to serially obtain measurements of hemodynamics, gas exchange, and blood chemistry. Heart function was assessed with echocardiography. After randomization to study gas of iNO 20 ppm (n = 9) or nitrogen as placebo (n = 9), baseline measurements were obtained. Hemorrhagic shock was initiated by exsanguination to a target of 50% of the baseline mean arterial pressure. The resuscitation phase was initiated, consisting of simultaneous left pulmonary hilum ligation, via median sternotomy, infusion of autologous blood and initiation of study gas. Animals were monitored for 4 hours. All animals had an initial increase in PVR. PVR remained elevated with placebo; with iNO, PVR decreased to baseline. Echo showed improved RV function in the iNO group while it remained impaired in the placebo group. After an initial increase in shunt and lactate and decrease in SvO2, all returned toward baseline in the iNO group but remained abnormal in the placebo group. These data indicate that by decreasing PVR, iNO decreased RV afterload, preserved RV and LV function, and tissue oxygenation in this hemorrhagic shock and pneumonectomy model. This suggests that iNO may be a useful clinical adjunct to mitigate right heart failure and improve survival when trauma pneumonectomy is required.

Coagulopathy and traumatic shock: Characterizing hemostatic function during the critical period prior to fluid resuscitation

PubMed Central

White, Nathan J.; Martin, Erika J.; Brophy, Donald F.; Ward, Kevin R.

2009-01-01

Aims Identifying early changes in hemostatic clot function as a result of tissue injury and hypoperfusion may provide important information regarding the mechanisms of traumatic coagulopathy. A combat-relevant swine model was used to investigate the development of coagulopathy during trauma by monitoring hemostatic function during increasing severity of shock. Methods Swine were injured (soft tissue + femur fracture) and hemorrhaged while continuously monitoring Oxygen Debt (OD) by indirect calorimetry at the airway. Hemostatic function was assessed by Thrombelastography (TEG), prothrombin time (PT), partial Thromboplastin time (PTT), and fibrinogen concentration and compared before hemorrhage (D0) and during shock when OD= 40 and 80 ml/kg. An instrumented sham group was used for comparison. Results N=23 swine (n=18 hemorrhage, n=5 sham) weighing 45+/−6 Kg were studied after removing an average of 34+/−14% of blood volume during hemorrhage. Hgb, Hct, platelet counts, PT and PTT did not change with increasing OD (p>0.05). Fibrinogen was reduced significantly by OD=40 ml/kg (mean diff =−59.9 mg/dl, 95% CI diff [−95.1, −24.6]). TEG parameters representing clot initiation (R) and polymerization (K and Alpha Angle) did not change with increasing OD during shock (p>0.053). Clot strength (MA) was reduced in the hemorrhage group by OD=80 ml/kg (mean diff = −4.1 mm, 95% CI diff [−7.4, −0.8]). Conclusion In this swine model of traumatic shock, fibrinogen was significantly reduced and an isolated reduction in clot strength (MA) was found with increasing OD. Fibrinogen consumption and altered platelet function may account for the earliest changes in hemostatic function during traumatic shock. PMID:19854556

Hydrogen gas inhalation inhibits progression to the "irreversible" stage of shock after severe hemorrhage in rats.

PubMed

Matsuoka, Tadashi; Suzuki, Masaru; Sano, Motoaki; Hayashida, Kei; Tamura, Tomoyoshi; Homma, Koichiro; Fukuda, Keiichi; Sasaki, Junichi

2017-09-01

Mortality of hemorrhagic shock primarily depends on whether or not the patients can endure the loss of circulating volume until radical treatment is applied. We investigated whether hydrogen (H2) gas inhalation would influence the tolerance to hemorrhagic shock and improve survival. Hemorrhagic shock was achieved by withdrawing blood until the mean arterial blood pressure reached 30-35 mm Hg. After 60 minutes of shock, the rats were resuscitated with a volume of normal saline equal to four times the volume of shed blood. The rats were assigned to either the H2 gas (1.3% H2, 26% O2, 72.7% N2)-treated group or the control gas (26% O2, 74% N2)-treated group. Inhalation of the specified gas mixture began at the initiation of blood withdrawal and continued for 2 hours after fluid resuscitation. The survival rate at 6 hours after fluid resuscitation was 80% in H2 gas-treated rats and 30% in control gas-treated rats (p < 0.05). The volume of blood that was removed through a catheter to induce shock was significantly larger in the H2 gas-treated rats than in the control rats. Despite losing more blood, the increase in serum potassium levels was suppressed in the H2 gas-treated rats after 60 minutes of shock. Fluid resuscitation completely restored blood pressure in the H2 gas-treated rats, whereas it failed to fully restore the blood pressure in the control gas-treated rats. At 2 hours after fluid resuscitation, blood pressure remained in the normal range and metabolic acidosis was well compensated in the H2 gas-treated rats, whereas we observed decreased blood pressure and uncompensated metabolic acidosis and hyperkalemia in the surviving control gas-treated rats. H2 gas inhalation delays the progression to irreversible shock. Clinically, H2 gas inhalation is expected to stabilize the subject until curative treatment can be performed, thereby increasing the probability of survival after hemorrhagic shock.

NRC/AMRMC Resident Research Associateship Program

DTIC Science & Technology

2013-05-01

Intravital Microscopy was successfully employed for investigating EG sheddÍng in hemorrhagic shock/resuscitation for the very first time; 2) Intravital ...during Hemorrhagic Shock in Rats using Intravital Microscopy. Submitted to Microvascular Research, 2012 (under review). FINAL REPORT Laboratory or...Glycocalyx using Intravital Microscopy. In Preparation. IO) PATENT OR COPYRIGHT APPLICATIONS KESULTING FROM NRC ASSOCIATESHIP KESEARCH Provide titles

NRC/AMRMC Resident Research Associateship Program

DTIC Science & Technology

2013-03-01

l) Intravital Microscopy was successfully employed for investigating EG sheddÍng in hemorrhagic shock/resuscitation for the very first time; 2... Intravital microscopy integrated with systemic hemodynamics evaluations may be essential and more accurate tools to identify changes and study mechanisms...Glycocalyx during Hemorrhagic Shock in Rats using Intravital Microscopy. Submitted to Microvascular Research, 2012 (under review). FINAL REPORT Laboratory

2017 Military Supplement: Dodecafluoropentane Emulsion (Ddfpe) as a Resuscitation Fluid for Treatment of Hemorrhagic Shock and Traumatic Brain Injury: A Review.

PubMed

Graham, Kaitlin; Moon-Massat, Paula F; Unger, Evan C

2017-11-15

Dodecafluoropentane emulsion (DDFPe) is a novel nanotechnology for oxygen delivery with therapeutic potential for hemorrhagic shock and/or traumatic brain injury (TBI). DDFPe demonstrates efficacy at smaller doses than previously tested perfluorocarbon oxygen therapeutics. This smaller dose potentially eliminates toxicities exhibited by previous oxygen therapeutics, while anti-inflammatory properties of DDFPe may alleviate damage from ischemia reperfusion injury. This mini-review summarizes our progress in developing a battle-field ready product to prevent combat death due to hemorrhagic shock and/or TBI. Preclinical studies, for both indications, show promising effects of DDFPe as a resuscitation fluid. DDFPe may become a part of the toolkit for tactical healthcare professionals in battlefield and domestic emergency medicine.

Recombinant activated factor VII: its mechanism of action and role in the control of hemorrhage.

PubMed

Allen, Geoffrey A; Hoffman, Maureane; Roberts, Harold R; Monroe, Dougald M

2002-12-01

Recombinant activated factor VII (rFVIIa) has proven both safe and efficacious in the treatment of bleeding episodes in patients with hemophilia A or B who have developed inhibitors. More recently, a growing number of reports suggests that rFVIIa may also have indications for the treatment of bleeding in patients with other hemostatic disorders, including qualitative and quantitative platelet defects, factor deficiencies other than hemophilia, and in otherwise healthy patients with uncontrollable hemorrhage following surgery or trauma. We have attempted to reconcile the various proposed mechanisms of action of rFVIIa with its apparent efficacy in such diverse clinical settings. A review of the literature was performed to determine those clinical scenarios in which rFVIIa appears to have been effective in controlling associated hemorrhage. Findings from our group and others have demonstrated that rFVIIa is able to directly activate factor X and increase thrombin production on the surface of activated platelets in the absence of factor VIII or IX, as well as to improve thrombin generation in thrombocytopenia, and to yield a fibrin dot more resistant to fibrinolysis in vitro. Through these primary mechanisms, we believe that rFVIIa may be able to compensate for a variety of defects in hemostasis and merits further investigation as a general therapeutic for uncontrollable hemorrhage.

Increased circulating D-lactate levels predict risk of mortality after hemorrhage and surgical trauma in baboons.

PubMed

Sobhian, Babak; Kröpfl, Albert; Hölzenbein, Thomas; Khadem, Anna; Redl, Heinz; Bahrami, Soheyl

2012-05-01

Patients with hemorrhagic shock and/or trauma are at risk of developing colonic ischemia associated with bacterial translocation that may lead to multiple organ failure and death. Intestinal ischemia is difficult to diagnose noninvasively. The present retrospective study was designed to determine whether circulating plasma D-lactate is associated with mortality in a clinically relevant two-hit model in baboons. Hemorrhagic shock was induced in anesthetized baboons (n = 24) by controlled bleeding (mean arterial pressure, 40 mmHg), base excess (maximum -5 mmol/L), and time (maximum 3 h). To mimic clinical setting more closely, all animals underwent a surgical trauma after resuscitation including midshaft osteotomy stabilized with reamed femoral interlocking nailing and were followed for 7 days. Hemorrhagic shock/surgical trauma resulted in 66% mortality by day 7. In nonsurvivor (n = 16) hemorrhagic shock/surgical trauma baboons, circulating D-lactate levels were significantly increased (2-fold) at 24 h compared with survivors (n = 8), whereas the early increase during hemorrhage and resuscitation declined during the early postresuscitation phase with no difference between survivors and nonsurvivors. Moreover, D-lactate levels remained elevated in the nonsurvival group until death, whereas it decreased to baseline in survivors. Prediction of death (receiver operating characteristic test) by D-lactate was accurate with an area under the curve (days 1-3 after trauma) of 0.85 (95% confidence interval, 0.72-0.93). The optimal D-lactate cutoff value of 25.34 μg/mL produced sensitivity of 73% to 99% and specificity of 50% to 83%. Our data suggest that elevation of plasma D-lactate after 24 h predicts an increased risk of mortality after hemorrhage and trauma.

Obstetric hemorrhage and shock management: using the low technology Non-pneumatic Anti-Shock Garment in Nigerian and Egyptian tertiary care facilities.

PubMed

Miller, Suellen; Fathalla, Mohamed M F; Ojengbede, Oladosu A; Camlin, Carol; Mourad-Youssif, Mohammed; Morhason-Bello, Imran O; Galadanci, Hadiza; Nsima, David; Butrick, Elizabeth; Al Hussaini, Tarek; Turan, Janet; Meyer, Carinne; Martin, Hilarie; Mohammed, Aminu I

2010-10-18

Obstetric hemorrhage is the leading cause of maternal mortality globally. The Non-pneumatic Anti-Shock Garment (NASG) is a low-technology, first-aid compression device which, when added to standard hypovolemic shock protocols, may improve outcomes for women with hypovolemic shock secondary to obstetric hemorrhage in tertiary facilities in low-resource settings. This study employed a pre-intervention/intervention design in four facilities in Nigeria and two in Egypt. Primary outcomes were measured mean and median blood loss, severe end-organ failure morbidity (renal failure, pulmonary failure, cardiac failure, or CNS dysfunctions), mortality, and emergency hysterectomy for 1442 women with ≥750 mL blood loss and at least one sign of hemodynamic instability. Comparisons of outcomes by study phase were assessed with rank sum tests, relative risks (RR), number needed to treat for benefit (NNTb), and multiple logistic regression. Women in the NASG phase (n = 835) were in worse condition on study entry, 38.5% with mean arterial pressure <60 mmHg vs. 29.9% in the pre-intervention phase (p = 0.001). Despite this, negative outcomes were significantly reduced in the NASG phase: mean measured blood loss decreased from 444 mL to 240 mL (p < 0.001), maternal mortality decreased from 6.3% to 3.5% (RR 0.56, 95% CI 0.35-0.89), severe morbidities from 3.7% to 0.7% (RR 0.20, 95% CI 0.08-0.50), and emergency hysterectomy from 8.9% to 4.0% (RR 0.44, 0.23-0.86). In multiple logistic regression, there was a 55% reduced odds of mortality during the NASG phase (aOR 0.45, 0.27-0.77). The NNTb to prevent either mortality or severe morbidity was 18 (12-36). Adding the NASG to standard shock and hemorrhage management may significantly improve maternal outcomes from hypovolemic shock secondary to obstetric hemorrhage at tertiary care facilities in low-resource settings.

Pressure threshold for shock wave induced renal hemorrhage.

PubMed

Mayer, R; Schenk, E; Child, S; Norton, S; Cox, C; Hartman, C; Cox, C; Carstensen, E

1990-12-01

Studies were performed with an interest in determining a pressure threshold for extracorporeal shock wave induced renal damage. Histological evidence of intraparenchymal hemorrhage was used as an indicator of tissue trauma. Depilated C3H mice were anesthetized and placed on a special frame to enhance visualization and treatment of the kidneys in situ. A Wolf electrohydraulic generator and 9 French probe designed for endoscopic use were utilized to expose the kidneys to 10 double spherically divergent shock waves. Measurements of the shock waves revealed two positive pressure peaks of similar magnitude for each spark discharge. The kidneys were exposed to different peak pressures by choice of distance from the spark source and were removed immediately after treatment for histologic processing. A dose response was noted with severe corticomedullary damage apparent following 15 to 20 MPa shocks. Hemorrhage was more apparent in the medulla where evidence of damage could be seen following pressures as low as three to five MPa. When a latex membrane was interposed to prevent possible collapse of the initial bubble from the spark source against the skin surface, histological evaluation revealed substantial reduction of severe tissue damage associated with the highest pressures tested, 20 MPa. However, the threshold level for evidence of hemorrhage remained about three to five MPa. Hydrophonic measurements indicated that the membrane allowed transmission of the acoustic shock waves and suggested that collapse of the bubble generated by electrohydraulic probes may have local effects due to a cavitation-like mechanism.

Interferon Response Factors 3 and 7 Protect against Chikungunya Virus Hemorrhagic Fever and Shock

PubMed Central

Rudd, Penny A.; Wilson, Jane; Gardner, Joy; Larcher, Thibaut; Babarit, Candice; Le, Thuy T.; Anraku, Itaru; Kumagai, Yutaro; Loo, Yueh-Ming; Gale, Michael; Akira, Shizuo; Khromykh, Alexander A.

2012-01-01

Chikungunya virus (CHIKV) infections can produce severe disease and mortality. Here we show that CHIKV infection of adult mice deficient in interferon response factors 3 and 7 (IRF3/7−/−) is lethal. Mortality was associated with undetectable levels of alpha/beta interferon (IFN-α/β) in serum, ∼50- and ∼10-fold increases in levels of IFN-γ and tumor necrosis factor (TNF), respectively, increased virus replication, edema, vasculitis, hemorrhage, fever followed by hypothermia, oliguria, thrombocytopenia, and raised hematocrits. These features are consistent with hemorrhagic shock and were also evident in infected IFN-α/β receptor-deficient mice. In situ hybridization suggested CHIKV infection of endothelium, fibroblasts, skeletal muscle, mononuclear cells, chondrocytes, and keratinocytes in IRF3/7−/− mice; all but the latter two stained positive in wild-type mice. Vaccination protected IRF3/7−/− mice, suggesting that defective antibody responses were not responsible for mortality. IPS-1- and TRIF-dependent pathways were primarily responsible for IFN-α/β induction, with IRF7 being upregulated >100-fold in infected wild-type mice. These studies suggest that inadequate IFN-α/β responses following virus infection can be sufficient to induce hemorrhagic fever and shock, a finding with implications for understanding severe CHIKV disease and dengue hemorrhagic fever/dengue shock syndrome. PMID:22761364

Coenzyme Q10: A New Treatment for Hemorrhagic Shock

DTIC Science & Technology

2014-10-29

SUBJECT TERMS hemorrhagic shock, ubiquinol, Coenzyme Q10, patient outcome 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18...o leo& to tboOigllll failure. The < Iota fur AlM •1 ha"’ boon ._...runym.,..,; •• ted in p=en~atlons and publiobed tn Expu""’""" P/u<llology. Tho

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

PubMed

Medeiros, Vanessa de Fátima Lima Paiva; Azevedo, Ítalo Medeiros; Carvalho, Marília Daniela Ferreira; Egito, Eryvaldo Sócrates Tabosa; Medeiros, Aldo Cunha

2016-12-01

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.

Myocardial oxygen delivery after experimental hemorrhagic shock.

PubMed Central

Archie, J P; Mertz, W R

1978-01-01

The two components of myocardial oxygen delivery, coronary blood flow to capillaries and diffusion from capillaries to mitochondria, were studied in six dogs, (1) prior to shock, (2) after three hours of hemorrhage shock at a mean systemic arterial pressure of 40 torr, (3) after reinfusion of shed blood, and (4) during the irreversible late posttransfusion stage. There was a maldistribution of left ventricular coronary flow during late shock consistent with subendocardial ischemia. Cardiac performance was significantly impaired after resuscitation and all dogs became irreversible. Total and regional left ventricular coronary blood flow and myocardial oxygen delivery to capillaries were significantly greater than preshock values in (3) but not different from preshock values in (4). However, the myocardial oxygen diffusion area to distance ratio was significantly lower than preshock values in (3), and slightly lower in (4). These data suggest that myocardial oxygen diffusion may be impaired in the early post transfusion period, (3). Accordingly, the probable etiology of left ventricular dysfunction and possibly irreversibility after resuscitation from hemorrhagic shock is subendocardial ischemia during shock with either post-resuscitation impairment of myocardial oxygen diffusion, or in cellular oxygen utilization, or both. PMID:629622

Spectral analysis of heart rate variability predicts mortality and instability from vascular injury.

PubMed

Koko, Kiavash R; McCauley, Brian D; Gaughan, John P; Fromer, Marc W; Nolan, Ryan S; Hagaman, Ashleigh L; Brown, Spencer A; Hazelton, Joshua P

2018-04-01

Spectral analysis of continuous blood pressure and heart rate variability provides a quantitative assessment of autonomic response to hemorrhage. This may reveal markers of mortality as well as endpoints of resuscitation. Fourteen male Yorkshire pigs, ranging in weight from 33 to 36 kg, were included in the analysis. All pigs underwent laparotomy and then sustained a standardized retrohepatic inferior vena cava injury. Animals were then allowed to progress to class 3 hemorrhagic shock and where then treated with abdominal sponge packing followed by 6 h of crystalloid resuscitation. If the pigs survived the 6 h resuscitation, they were in the survival (S) group, otherwise they were placed in the nonsurvival (NS) group. Fast Fourier transformation calculations were used to convert the components of blood pressure and heart rate variability into corresponding frequency classifications. Autonomic tones are represented as the following: high frequency (HF) = parasympathetic tone, low frequency (LF) = sympathetic, and very low frequency (VLF) = renin-angiotensin aldosterone system. The relative sympathetic to parasympathetic tone was expressed as LF/HF ratio. Baseline hemodynamic parameters were equal for the S (n = 11) and NS groups. LF/HF was lower at baseline for the NS group but was higher after hemorrhage and the resuscitation period indicative of a predominately parasympathetic response during hemorrhagic shock before mortality. HF signal was lower in the NS group during the resuscitation indicating a relatively lower sympathetic tone during hemorrhagic shock, which may have contributed to mortality. Finally, the NS group had a lower VLF signal at baseline (e.g., [S] 16.3 ± 2.5 versus [NS] 4.6 ± 2.9 P < 0.05,) which was predictive of mortality and hemodynamic instability in response to a similar hemorrhagic injury. An increased LF/HF ratio, indicative of parasympathetic predominance following injury and during resuscitation of hemorrhagic shock was a marker of impending death. Spectral analysis of heart rate variability can also identify autonomic lability following hemorrhagic injuries with implications for first responder triage. Furthermore, a decreased VLF signal at baseline indicates an additional marker of hemodynamic instability and marker of mortality following a hemorrhagic injury. These data indicate that continuous quantitative assessment of autonomic response can be a predictor of mortality and potentially guide resuscitation of patients in hemorrhagic shock. Copyright © 2017 Elsevier Inc. All rights reserved.

Wound shock: a history of its study and treatment by military surgeons.

PubMed

Hardaway, Robert M

2004-04-01

The treatment of wounds has received considerable attention from the time of the Trojan War. However, it was not until the American Civil War that shock was described as an entity distinct from the wounds themselves and that efforts were directed at more than just treatment of the wound. The need for fluid resuscitation in the treatment of hemorrhagic shock was first recognized in the Spanish American War, as was the association of sepsis with shock. World War I showed the need for blood in the treatment of "wound shock," a lesson that had to be relearned in World War II through bitter experience. Studies in the Korean War described the concept of disseminated intravascular coagulation and multiple organ failure, and the existence of disseminated intravascular coagulation was confirmed by studies in Vietnam. The treatment of hemorrhagic shock is now very effective, but the treatment of traumatic and septic shock remains unsatisfactory.

Shock in the Nonhuman Primate. Volume 2. Abstracts of the Published Literature, 1974-1977

DTIC Science & Technology

1977-06-01

primates from hemorrhagic and septic shock. Trunkey, D., J. Holcroft, and M. A. Carpenter ... ........... .... 42 Calcium flux during hemorrhagic...virtually absent. In vitro endotoxin-leukocyte interaction reproduced all changes seen in sequestered PMN-leukocytes with the exception of leukocyte...Although there is no pre- sently known clinical state referable to lead-endotoxin interaction and since our experimental conditions were not

The Effect of Infrarenal Aortic Balloon Occlusion on Weaning from Supraceliac Aortic Balloon Occlusion in a Porcine Model (Sus scrofa) of Hemorrhagic Shock

DTIC Science & Technology

2017-06-15

all animals , and continued for six hours. Half of the animals were randomly assigned to Zone-3 REBOA for an additional 45 minutes following Zone-1...concentration or resuscitation requirements.Conclusion: In an animal model of hemorrhagic shock and Zone-1 REBOA, subsequent Zone-3 aortic occlusion did not add

An exogenous hydrogen sulphide donor, NaHS, inhibits the apoptosis signaling pathway to exert cardio-protective effects in a rat hemorrhagic shock model.

PubMed

Xu, Yanjie; Dai, Xiongwei; Zhu, Danxia; Xu, Xiaoli; Gao, Cao; Wu, Changping

2015-01-01

Hydrogen sulfide (H2S) has been reported to be interwined in multiple systems, specifically in the cardiovascular system. However, the mechanisms underlying remain controversial. In the present study, we assessed the cardio-protective effects of H2S in the rat hemorrhagic shock model. Hemorrhagic shock was induced in adult male Sprague-Dawley rats by drawing blood from the femoral artery to maintain the mean arterial pressure at 35-40 mmHg for 1.5 h. The rats were assigned to four groups and the H2S donor, NaHS (28 μmol/kg, i.p.), was injected before the resuscitation in certain groups. After resuscitation the animals were observed and then killed to harvest the hearts. The morphological investigation and ultrastructural analyses were done and apoptotic cells were detected. The levels of relevant proteins were examined using Western blotting and immunohistochemical analyses. Resuscitated hemorrhagic shock induced heart injury and significantly increased the levels of serum myocardial enzymes, creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Furthermore, it caused marked increase of apoptotic cells in heart tissue. Moreover, the expression of death receptor Fas and Fas-ligand, as well as the expression of apoptosis-relevant proteins active-caspase 3 and active-caspase 8 were markedly increased. Administration of NaHS significantly ameliorated hemorrhagic shock caused hemodynamic deterioration, decreased myocardial enzymes elevation, protected myocardial ultrastructure, and inhibited the expression of apoptosis-relevant proteins. It suggested that H2S might exert its cardio-protective roles via both the extrinsic Fas/FasL/caspase-8/caspase-3 pathway and the intrinsic mitochondria-involved pathways.

Hemorrhage and Hemorrhagic Shock in Swine: A Review

DTIC Science & Technology

1989-11-01

17 Temperature Regulation ....................... 18 Blood Gas and Acid- Base Status ....................... 18 Electrolyte...22 Renal Function .................................. 23 Hepatic Function ................................ 24 Central Nervous System Function...MODELS Most porcine hemorrhage models are based on concepts and procedures previously developed in other species, especially the dog. As a consequence

Plasma first resuscitation reduces lactate acidosis, enhances redox homeostasis, amino acid and purine catabolism in a rat model of profound hemorrhagic shock

PubMed Central

D’Alessandro, Angelo; Moore, Hunter B; Moore, Ernest E; Wither, Matthew J.; Nemkov, Travis; Morton, Alexander P; Gonzalez, Eduardo; Chapman, Michael P; Fragoso, Miguel; Slaughter, Anne; Sauaia, Angela; Silliman, Christopher C; Hansen, Kirk C; Banerjee, Anirban

2016-01-01

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 vs 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. PMID:26863033

The Role of Neuropeptide Y (NPY) in Uncontrolled Alcohol Drinking and Relapse Behavior Resulting from Exposure to Stressful Events

DTIC Science & Technology

2011-01-01

effects of stressors on excessive and uncontrolled drinking and relapse-like drinking. We proposed to use foot-shock as the stressor to elicit increase...did significantly increase deprivation-induced relapse-like drinking, and that this effect was more robust in mutant mice lacking the NPY Y1R. Thus...ethanol consumption using a models of excessive uncontrolled drinking, and mutant mice lacking NPY or the Y1R were more sensitive to the effects of

Mesenchymal Stem Cells for the Prevention of Acute Respiratory Distress Syndrome after Pulmonary Contusion and Hemorrhagic Shock

DTIC Science & Technology

2017-10-01

Contusion and Hemorrhagic Shock PRINCIPAL INVESTIGATOR: Martin Schreiber, MD CONTRACTING ORGANIZATION: Oregon Health & Science University Portland, OR...PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Oregon Health & Science University 3181 SW Sam Jackson Park Road, Portland, OR 97239 Blood Systems...extubated the animals was not logistically or physically feasible. To improve the welfare of the animal and consistency in the model, we revised our model

Arterioureteral Fistula: Treatment of a Hemorrhagic Shock with Massive Hematuria by Placing a Balloon Catheter.

PubMed

Merzeau, Nicolas; Riquet, Hervé; Nicolacopoulos, Ioannis; Alame, Abbas; Larré, Stéphane

2017-01-01

Arterioureteral fistulas (AUF) are serious diseases with increasing incidence. This case report relates the management of AUF in a patient with a history of abdominal oncological surgery, pelvic radiotherapy, and a double J stent in place. The fistula was discovered during a hemorrhagic shock with massive hematuria. The bleeding was controlled by a balloon catheter which led to endovascular treatment consisting of a covered stent.

Arterioureteral Fistula: Treatment of a Hemorrhagic Shock with Massive Hematuria by Placing a Balloon Catheter

PubMed Central

Riquet, Hervé; Nicolacopoulos, Ioannis; Alame, Abbas

2017-01-01

Arterioureteral fistulas (AUF) are serious diseases with increasing incidence. This case report relates the management of AUF in a patient with a history of abdominal oncological surgery, pelvic radiotherapy, and a double J stent in place. The fistula was discovered during a hemorrhagic shock with massive hematuria. The bleeding was controlled by a balloon catheter which led to endovascular treatment consisting of a covered stent. PMID:28465857

[Effect of different volumes of fluid resuscitation on hemorrhagic shock with pulmonary edema at high altitude in the unacclimated rat].

PubMed

Liu, Liang-ming; Hu, De-yao; Liu, Jian-cang; Li, Ping; Liu, Hou-dong; Xiao, Nan; Zhou, Xue-wu; Tian, Kun-lun; Huo, Xiao-ping; Shi, Quan-gui; He, Yan-mei; Yin, Zuo-ming

2003-05-01

To study the effects of different volumes of fluid resuscitation on hemorrhagic shock with pulmonary edema at high altitude in the unacclimated rat. One hundred and twenty-six SD rats transported to Lasa, Tibet, 3 760 meters above the sea level, were anesthetized one week later with sodium pentobarbital (30 mg/kg, intraperitoneal). Hemorrhagic shock with pulmonary edema model was induced by hemorrhage (50 mm Hg for 1 hour, 1 mmHg=0.133 kPa) plus intravenous injection of oleic acid (50 microl/kg). Experiments were then conducted in two parts. Sixty-three rats in part I were equally divided into nine groups (n=7): normal control, hemorrhagic shock control, hemorrhagic shock with pulmonary edema (HSPE) without fluid infusion, HSPE plus infusing lactated Ringer's solution (LR) with 0.5-, 1-, 1.5-, 2- or 3- fold volume shed blood, and 1 volume of LR plus mannitol (10 ml/kg). Hemodynamic parameters including mean arterial blood pressure (MAP), left intraventricular systolic pressure (LVSP) and the maximal change rate of intraventricular pressure rise or decline (+/- dp/dt max) were observed at 15, 30, 60 and 120 minutes after infusion, blood gases were measured at 30 and 120 minutes after infusion and the water content of lung and brain was determined at 120 minutes after infusion. In part II, additional 63 rats were used to observe the effect of different volumes of fluid resuscitation on survival time of HSPE rats. 0.5 volume of LR infusion significantly improved MAP, LVSP and +/- dp/dt max, prolonged the survival time of HSPE animals (all P<0.01), while it did not increase the water content of lung and brain and had no marked influence on blood gases. One volume of LR infusion slightly improved hemodynamic parameters, prolonged the survival time and increased the water content of lung. More than 1 volume of LR infusion including 1.5-, 2- and 3- fold volume LR deteriorated the hemodynamic parameters and decreased the survival time of shocked animal, meanwhile they apparently increased the water content of lung. One volume of LR plus mannitol (10 ml/kg) infusion did not improve the hemodynamic parameters and blood gases; also it did not decrease the water content of lung. The tolerance to fluid infusion for the unacclimated animal subjected to hemorrhagic shock with pulmonary edema at high altitude is significantly decreased. 0.5-1 volume of LR infusion appears to be beneficial effect on resuscitation at high altitude, while over 1 volume of LR infusion would aggravate pulmonary edema and exacerbate fluid resuscitation effect.

Emergent Embolization of Arterial Bleeding after Vacuum-Assisted Breast Biopsy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fischman, Aaron M., E-mail: aaron.fischman@mountsinai.org; Epelboym, Yan, E-mail: yan.epelboym@mssm.edu; Siegelbaum, Robert H., E-mail: rhsiegelbaum@gmail.com

2012-02-15

Vacuum-assisted core breast biopsy has become important in evaluating patients with suspicious breast lesions. It has proven to be a relatively safe procedure that in rare cases can result in vascular complications. These are the first reported cases of transcatheter embolization of uncontrolled breast hemorrhage after vacuum-assisted breast biopsy. With increased use of biopsy and larger-gauge devices, breast imaging groups may consider embolotherapy as a safe alternative for treatment of hemorrhage in a select group of patients.

Postconditioning with sevoflurane ameliorates spatial learning and memory deficit via attenuating endoplasmic reticulum stress induced neuron apoptosis in a rat model of hemorrhage shock and resuscitation.

PubMed

Hu, Xianwen; Wang, Jingxian; Zhang, Li; Zhang, Qiquan; Duan, Xiaowen; Zhang, Ye

2018-06-02

Hemorrhage shock could initiate endoplasmic reticulum stress (ERS) and then induce neuronal apoptosis. The aim of this study was to investigate whether sevoflurane postconditioning could attenuate brain injury via suppressing apoptosis induced by ERS. Seventy male rats were randomized into five groups: sham, shock, low concentration (sevo1, 1.2%), middle concentration (sevo2, 2.4%) and high concentration (sevo3, 3.6%) of sevoflurane postconditioning. Hemorrhage shock was induced by removing 40% of the total blood volume during an interval of 30 min. 1h after the completion of bleeding, the animals were reinfused with shed blood during the ensuing 30 min. The spatial learning and memory ability of rats were measured by Morris water maze (MWM) test three days after the operation. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positive cells in the hippocampus CA1 region were assessed after the MWM test. The expression of C/EBP-homologousprotein (CHOP) and glucose-regulated protein 78 (GRP78) in the hippocampus were measured at 24h after reperfusion. We found that sevoflurane postconditioning with the concentrations of 2.4% and 3.6% significantly ameliorated the spatial learning and memory ability, decreased the TUNEL-positive cells, and reduced the GRP78 and CHOP expression compared with the shock group. These results suggested that sevoflurane postconditioning with the concentrations of 2.4% and 3.6% could ameliorate spatial learning and memory deficit after hemorrhage shock and resuscitation injury via suppressing apoptosis induced by ERS. Copyright © 2018. Published by Elsevier B.V.

Lyophilized plasma attenuates vascular permeability, inflammation and lung injury in hemorrhagic shock.

PubMed

Pati, Shibani; Peng, Zhanglong; Wataha, Katherine; Miyazawa, Byron; Potter, Daniel R; Kozar, Rosemary A

2018-01-01

In severe trauma and hemorrhage the early and empiric use of fresh frozen plasma (FFP) is associated with decreased morbidity and mortality. However, utilization of FFP comes with the significant burden of shipping and storage of frozen blood products. Dried or lyophilized plasma (LP) can be stored at room temperature, transported easily, reconstituted rapidly with ready availability in remote and austere environments. We have previously demonstrated that FFP mitigates the endothelial injury that ensues after hemorrhagic shock (HS). In the current study, we sought to determine whether LP has similar properties to FFP in its ability to modulate endothelial dysfunction in vitro and in vivo. Single donor LP was compared to single donor FFP using the following measures of endothelial cell (EC) function in vitro: permeability and transendothelial monolayer resistance; adherens junction preservation; and leukocyte-EC adhesion. In vivo, using a model of murine HS, LP and FFP were compared in measures of HS- induced pulmonary vascular inflammation and edema. Both in vitro and in vivo in all measures of EC function, LP demonstrated similar effects to FFP. Both FFP and LP similarly reduced EC permeability, increased transendothelial resistance, decreased leukocyte-EC binding and persevered adherens junctions. In vivo, LP and FFP both comparably reduced pulmonary injury, inflammation and vascular leak. Both FFP and LP have similar potent protective effects on the vascular endothelium in vitro and in lung function in vivo following hemorrhagic shock. These data support the further development of LP as an effective plasma product for human use after trauma and hemorrhagic shock.

Instrument to detect syncope and the onset of shock

NASA Astrophysics Data System (ADS)

McAdams, Daniel R.; Kolodziejski, Noah J.; Stapels, Christopher J.; Fernandez, Daniel E.; Podolsky, Matthew J.; Farkas, Dana; Christian, James F.; Joyner, Michael J.; Johnson, Christopher P.; Paradis, Norman A.

2016-03-01

Currently the diagnosis of hemorrhagic shock is essentially clinical, relying on the expertise of nurses and doctors. One of the first measurable physiological changes that marks the onset of hemorrhagic shock is a decrease in capillary blood flow. Diffuse correlation spectroscopy (DCS) quantifies this decrease. DCS collects and analyzes multiply scattered, coherent, near infrared light to assess relative blood flow. This work presents a preliminary study using a DCS instrument with human subjects undergoing a lower body negative pressure (LBNP) protocol. This work builds on previous successful DCS instrumentation development and we believe it represents progress toward understanding how DCS can be used in a clinical setting.

Protective role of endogenous carbon monoxide in hepatic microcirculatory dysfunction after hemorrhagic shock in rats.

PubMed Central

Pannen, B H; Köhler, N; Hole, B; Bauer, M; Clemens, M G; Geiger, K K

1998-01-01

Maintenance of hepatic microcirculatory flow after ischemia of the liver is essential to prevent hepatic dysfunction. Thus, we determined the differential role of carbon monoxide (CO) and nitric oxide (NO) in the intrinsic control of sinusoidal perfusion, mitochondrial redox state, and bile production in the isolated perfused rat liver after hemorrhagic shock. Administration of tin protoporphyrin-IX (50 microM), a specific inhibitor of the CO generating enzyme heme oxygenase, caused a decrease in sinusoidal flow that was more pronounced after shock compared with sham shock, as determined by in situ epifluorescence microscopy. This was associated with a shift in hepatocellular redox potential to a more reduced state (increased fluorescence intensity of reduced pyridine nucleotides in hepatocytes, decreased acetoacetate/beta-hydroxybutyrate ratio in the perfusate) and a profound reduction in bile flow. In sharp contrast, the preferential inhibitor of the inducible isoform of NO synthase S-methylisothiourea sulfate (100 microM) did not affect sinusoidal flow, hepatic redox state, or function. This indicates that 1.) endogenously generated CO preserves sinusoidal perfusion after hemorrhagic shock, 2.) protection of the hepatic microcirculation by CO may serve to limit shock-induced liver dysfunction, and 3.) in contrast to CO, inducible NO synthase-derived NO is of only minor importance for the intrinsic control of hepatic perfusion and function under these conditions. PMID:9739056

Different Recovery Profiles of Coagulation Factors, Thrombin Generation, and Coagulation Function After Hemorrhagic Shock in Pigs

DTIC Science & Technology

2012-06-06

Different recovery profiles of coagulation factors, thrombin generation, and coagulation function after hemorrhagic shock in pigs Wenjun Z. Martini ...Defense. Address for reprints: Wenjun Z. Martini , PhD, The US Army Institute of Surgical Research, 3698 Chambers Pass, Ft. Sam Houston, San Antonio, TX...control number 1. REPORT DATE 01 SEP 2015 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Different recovery profiles of

Comparisons of Normal Saline and Lactated Ringer’s Resuscitation on Hemodynamics, Metabolic Responses, and Coagulation in Pigs after Severe Hemorrhagic Shock

DTIC Science & Technology

2013-12-11

vasodilator effects and the risks of metabolic acidosis and hyperkalemia . Keywords: Hemorrhagic shock, Oxygen metabolism, Coagulation, Pre-hospital...www.sjtrem.com/content/21/1/86 of hyperchloremic acidosis from NS resuscitation [37]. Consistent with our current results, clinically significant hyperkalemia ...risks of meta- bolic acidosis and hyperkalemia . Currently, military first responders have NS, LR and Hextend available [20]. How- ever, the results from

Granulocyte colony-stimulating factor (G-CSF) production in hemorrhagic shock requires both the ischemic and resuscitation phase.

PubMed

Hierholzer, C; Kelly, E; Billiar, T R; Tweardy, D J

1997-01-01

Granulocyte colony-stimulating factor (G-CSF) is the cytokine that is critical for polymorphonuclear neutrophilic granulocyte (PMN) production as well as being a potent agonist of PMN activation. We have recently reported that in the lung and the liver of rats resuscitated after hemorrhagic shock (HS) G-CSF mRNA expression is induced. It is not known if both phases of HS, the ischemic and the reperfusion phase, are required for G-CSF mRNA induction. The present study was designed to test the hypothesis that the upregulation of G-CSF mRNA expression is the consequence of HS followed by resuscitation and that ischemia alone is insufficient to induce G-CSF mRNA expression in the affected organs. Male Sprague-Dawley rats were subjected to resuscitated and unresuscitated shock protocols of varying severity. Control animals were subjected to anesthesia and all surgical preparations except for hemorrhage. Lungs and livers were isolated and their RNA extracted. Using semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we demonstrated that G-CSF mRNA was induced in the lung and liver of shock animals above the level observed in control animals. Upregulation of G-CSF mRNA relative to controls occurred only in animals undergoing resuscitated HS and not in ones subjected to unresuscitated HS. These results indicate that G-CSF production specific for the hemorrhage component of shock is dependent on resuscitation. As a consequence, the production of this cytokine may be decreased through modifications in the resuscitation protocols.

Pathogenesis of Crimean-Congo hemorrhagic fever.

PubMed

Akıncı, Esragül; Bodur, Hürrem; Leblebicioglu, Hakan

2013-07-01

Although Crimean-Congo hemorrhagic fever (CCHF) is a widespread tick-borne disease, little is known about its pathogenesis. The interaction of the virus with host cells is most likely responsible for the pathogenesis of CCHF. The main contributors are endothelial cells (ECs) and immune cells. There are 2 theories underlying the CCHF pathogenesis: One is that the virus interacts with the ECs directly and the other that it interacts indirectly via immune cells with subsequent release of soluble mediators. ECs are activated upon infection by the upregulation of soluble molecules and proinflammatory cytokines. Probably, in severe cases, deregulation and excessive release of the cytokines accompanied by endothelial activation have toxic effects, leading to increased vascular permeability, vasodilatation, and subsequently hypotension, multiple organ failure, shock, and death. Studies indicate that CCHF virus (CCHFV) also can impair the innate immune system and cause a delay in adaptive immune response, which is critical for the clearance of CCHFV. The virus has many different ways to block the immune response, leading to uncontrolled viral replication followed by systemic spread of the virus throughout the body. Partial activation of dendritic cells and macrophages, delayed induction of interferons, weak antibody response, apoptosis of lymphocytes, and hemophagocytosis are some of these tactics. However, there are many points waiting for clarification about the pathogenesis of CCHF. Although the high risk of contagiousness limits research, we need more studies to understand the CCHF pathogenesis better. Here we review the main characteristics of the pathogenesis of CCHF.

Temporal profile of inflammatory response to fracture and hemorrhagic shock: Proposal of a novel long-term survival murine multiple trauma model.

PubMed

Kleber, Christian; Becker, Christopher A; Malysch, Tom; Reinhold, Jens M; Tsitsilonis, Serafeim; Duda, Georg N; Schmidt-Bleek, Katharina; Schaser, Klaus D

2015-07-01

Hemorrhagic shock (hS) interacts with the posttraumatic immune response and fracture healing in multiple trauma. Due to the lack of a long-term survival multiple trauma animal models, no standardized analysis of fracture healing referring the impact of multiple trauma on fracture healing was performed. We propose a new long-term survival (21 days) murine multiple trauma model combining hS (microsurgical cannulation of carotid artery, withdrawl of blood and continuously blood pressure measurement), femoral (osteotomy/external fixation) and tibial fracture (3-point bending technique/antegrade nail). The posttraumatic immune response was measured via IL-6, sIL-6R ELISA. The hS was investigated via macrohemodynamics, blood gas analysis, wet-dry lung ration and histologic analysis of the shock organs. We proposed a new murine long-term survival (21 days) multiple trauma model mimicking clinical relevant injury patterns and previously published human posttraumatic immune response. Based on blood gas analysis and histologic analysis of shock organs we characterized and standardized our murine multiple trauma model. Furthermore, we revealed hemorrhagic shock as a causative factor that triggers sIL-6R formation underscoring the fundamental pathophysiologic role of the transsignaling mechanism in multiple trauma. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Lactated ringer's solution and hetastarch but not plasma resuscitation after rat hemorrhagic shock is associated with immediate lung apoptosis by the up-regulation of the Bax protein.

PubMed

Deb, S; Sun, L; Martin, B; Talens, E; Burris, D; Kaufmann, C; Rich, N; Rhee, P

2000-07-01

We previously demonstrated that the type of resuscitation fluid used in hemorrhagic shock affects apoptosis. Unlike crystalloid, whole blood seems to attenuate programmed cell death. The purpose of this study was to determine whether the acellular components of whole blood (plasma, albumin) attenuated apoptosis and to determine whether this process involved the Bax protein pathway. Rats were hemorrhaged 27.5 mL/kg, kept in hypovolemic shock for 75 minutes, then resuscitated over 1 hour (n = 44). Control animals underwent anesthesia only (sham, n = 7). Treatment animals were bled then randomly assigned to the following resuscitation groups: no resuscitation (n = 6), whole blood (n = 6), plasma (n = 6), 5% human albumin (n = 6), 6% hetastarch (n = 7), and lactated Ringer's solution (LR, n = 6). Hetastarch was used to control for any colloid effect. LR was used as positive control. Immediately after resuscitation, the lung was collected and evaluated for apoptosis by using two methods. TUNEL stain was used to determine general DNA damage, and Bax protein was used to specifically determine intrinsic pathway involvement. LR and hetastarch treatment resulted in significantly increased apoptosis in the lung as determined by both TUNEL and Bax expression (p < 0.05). Plasma infusion resulted in significantly less apoptosis than LR and hetastarch resuscitation. Multiple cell types (epithelium, endothelium, smooth muscle, monocytes) underwent apoptosis in the lung as demonstrated by the TUNEL stain, whereas Bax expression was limited to cells residing in the perivascular and peribronchial spaces. Apoptosis after volume resuscitation of hemorrhagic shock can be affected by the type of resuscitation fluid used. Manufactured fluids such as lactated Ringer's solution and 6% hetastarch resuscitation resulted in the highest degree of lung apoptosis. The plasma component of whole blood resulted in the least apoptosis. The process of apoptosis after hemorrhagic shock resuscitation involves the Bax protein.

Large-Volume Crystalloid Fluid Is Associated with Increased Hyaluronan Shedding and Inflammation in a Canine Hemorrhagic Shock Model.

PubMed

Smart, Lisa; Boyd, C J; Claus, M A; Bosio, E; Hosgood, G; Raisis, A

2018-05-04

Shedding of the endothelial glycocalyx precedes leukocyte activation and adherence in acute inflammation. Rapid administration of crystalloid or colloid fluids for treating hemorrhagic shock may cause endothelial glycocalyx shedding, thereby increasing inflammation. This study aimed to compare the effect of different fluid treatments in a canine shock model on glycocalyx biomarker, hyaluronan, and inflammatory biomarkers. Greyhound dogs under general anesthesia subject to hemorrhage for 60 min were given 20 mL kg -1 of either fresh whole blood (FWB), hydroxyethyl starch (HES) 130/0.4, 4% succinylated gelatin (GELO), or 80 mL kg -1 of isotonic crystalloid (CRYST) over 20 min (n = 6 per group). Plasma biomarkers hyaluronan, interleukin (IL) 6, 8, 10, tumor necrosis factor-α, monocyte chemoattractant protein-1, keratinocyte chemokine-like, and atrial natriuretic peptide were measured at baseline, end of hemorrhage (Shock), end of fluid administration (T20), and then 40 (T60), 100 (T120), and 160 (T180) minutes later. Biomarker concentrations were compared between groups using the Kruskal-Wallis test or Fisher's exact test (measurable versus unmeasurable) (significance set at P < 0.05). Hyaluronan concentration peaked early in the CRYST group at T20, compared to HES (P = 0.005) and GELO (P = 0.018), and later in the GELO group at T60, compared to FWB (P < 0.001). The CRYST group had significantly more samples with measurable IL6 at T180 (P = 0.015), compared to GELO, and IL10 at T60, T120, and T180 (all P = 0.015), compared to FWB. There were no significant differences in other biomarker concentrations. In conclusion, rapid large-volume crystalloid administered for hemorrhagic shock was associated with increased hyaluronan and a greater inflammatory response.

Systemic release of cytokines and heat shock proteins in porcine models of polytrauma and hemorrhage

PubMed Central

Baker, Todd A.; Romero, Jacqueline; Bach, Harold H.; Strom, Joel A.; Gamelli, Richard L.; Majetschak, Matthias

2011-01-01

Objective To define systemic release kinetics of a panel of cytokines and heat shock proteins (HSP) in porcine polytrauma/hemorrhage models and to evaluate whether they could be useful as early trauma biomarkers. Design and Setting Prospective study in a research laboratory. Subjects Twenty-one Yorkshire pigs. Measurements and Main Results Pigs underwent polytrauma (femur fractures/lung contusion, P), hemorrhage (mean arterial pressure 25-30mmHg, H), polytrauma plus hemorrhage (P/H) or sham procedure (S). Plasma was obtained at baseline, in 5-15min intervals during a 60min shock period without intervention and in 60-120min intervals during fluid resuscitation for up to 300min. Plasma was assayed for IL-1β, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12/IL-23p40, IL-13, IL-17, IL-18, IFNγ, TGFβ, TNFα, HSP40, HSP70 and HSP90 by ELISA. All animals after S, P and H survived (n=5/group). Three of six animals after P/H died. IL-10 increased during shock after P and this increase was attenuated after H. TNFα increased during the shock period after P, H and also after S. P/H abolished the systemic IL-10 and TNFα release and resulted in 20-30% increased levels of IL-6 during shock. As fluid resuscitation was initiated TNFα and IL-10 levels decreased after P, H and P/H, HSP 70 increased after P, IL-6 levels remained elevated after P/H and also increased after P and S. Conclusions Differential regulation of the systemic cytokine release after polytrauma and/or hemorrhage, in combination with the effects of resuscitation, can explain the variability and inconsistent association of systemic cytokine/HSP levels with clinical variables in trauma patients. Insults of major severity (P/H) partially suppress the systemic inflammatory response. The plasma concentrations of the measured cytokines/HSPs do not reflect injury severity or physiological changes in porcine trauma models and are unlikely to be able to serve as useful trauma biomarkers in patients. PMID:21983369

Point-of-care optical tool to detect early stage of hemorrhage and shock

NASA Astrophysics Data System (ADS)

Gurjar, Rajan S.; Riccardi, Suzannah L.; Johnson, Blair D.; Johnson, Christopher P.; Paradis, Norman A.; Joyner, Michael J.; Wolf, David E.

2014-02-01

There is a critical unmet clinical need for a device that can monitor and predict the onset of shock: hemorrhagic shock or bleeding to death, septic shock or systemic infection, and cardiogenic shock or blood flow and tissue oxygenation impairment due to heart attack. Together these represent 141 M patients per year. We have developed a monitor for shock based on measuring blood flow in peripheral (skin) capillary beds using diffuse correlation spectroscopy, a form of dynamic light scattering, and have demonstrated proof-of-principle both in pigs and humans. Our results show that skin blood flow measurement, either alone or in conjunction with other hemodynamic properties such as heart rate variability, pulse pressure variability, and tissue oxygenation, can meet this unmet need in a small self-contained patch-like device in conjunction with a hand-held processing unit. In this paper we describe and discuss the experimental work and the multivariate statistical analysis performed to demonstrate proof-of-principle of the concept.

Shock-induced neutrophil mediated priming for acute lung injury in mice: divergent effects of TLR-4 and TLR-4/FasL deficiency.

PubMed

Ayala, Alfred; Chung, Chun-Shiang; Lomas, Joanne L; Song, Grace Y; Doughty, Lesley A; Gregory, Stephen H; Cioffi, William G; LeBlanc, Brian W; Reichner, Jonathan; Simms, H Hank; Grutkoski, Patricia S

2002-12-01

Acute lung injury (ALI) leading to respiratory distress is a common sequela of shock/trauma, however, modeling this process in mice with a single shock or septic event is inconsistent. One explanation is that hemorrhage is often just a "priming insult," thus, secondary stimuli may be required to "trigger" ALI. To test this we carried out studies in which we assessed the capacity of hemorrhage alone or hemorrhage followed by septic challenge (CLP) to induce ALI. Lung edema, bronchoalveolar lavage interleukin (IL)-6, alveolar congestion, as well as lung IL-6, macrophage inflammatory protein (MIP)-2, and myeloperoxidase (MPO) activity were all increased in mice subjected to CLP at 24 but not 72 hours following hemorrhage. This was associated with a marked increase in the susceptibility of these mice to septic mortality. Peripheral blood neutrophils derived from 24 hours post-hemorrhage, but not Sham animals, exhibited an ex vivo decrease in apoptotic frequency and an increase in respiratory burst capacity, consistent with in vivo "priming." Subsequently, we observed that adoptive transfer of neutrophils from hemorrhaged but not sham-hemorrhage animals to neutropenic recipients reproduce ALI when subsequently septically challenged, implying that this priming was mediated by neutrophils. We also found marked general increases in lung IL-6, MIP-2, and MPO in mice deficient for toll-like receptor (TLR-4) or the combined lack of TLR-4/FasL. However, the TLR-4 defect markedly attenuated neutrophil influx into the lung while not altering the change in local cytokine/chemokine expression. Alternatively, the combined loss of FasL and TLR-4 did not inhibit the increase in MPO and exacerbated lung IL-6/MIP-2 levels even further.

Effect of gender and sex hormones on immune responses following shock.

PubMed

Angele, M K; Schwacha, M G; Ayala, A; Chaudry, I H

2000-08-01

Several clinical and experimental studies show a gender dimorphism of the immune and organ responsiveness in the susceptibility to and morbidity from shock, trauma, and sepsis. In this respect, cell-mediated immune responses are depressed in males after trauma-hemorrhage, whereas they are unchanged or enhanced in females. Sex hormones contribute to this gender-specific immune response after adverse circulatory conditions. Specifically, studies indicate that androgens are responsible for the immunodepression after trauma-hemorrhage in males. In contrast, female sex steroids seem to exhibit immunoprotective properties after trauma and severe blood loss, because administration of estrogen prevents the androgen-induced immunodepression in castrated male mice. Nonetheless, the precise underlying mechanisms for these immunomodulatory effects of sex steroids after shock remain unknown. Although testosterone depletion, testosterone receptor antagonism, or estrogen treatment has been shown to prevent the depression of immune functions after trauma-hemorrhage, it remains to be established whether differences in the testosterone-estradiol ratio are responsible for the immune dysfunction. Furthermore, sex hormone receptors have been identified on various immune cells, suggesting direct effects. Thus, the immunomodulatory properties of sex hormones after trauma-hemorrhage might represent novel therapeutic strategies for the treatment of immunodepression in trauma patients.

Establishing a learned-helplessness effect paradigm in C57BL/6 mice: behavioural evidence for emotional, motivational and cognitive effects of aversive uncontrollability per se.

PubMed

Pryce, Christopher R; Azzinnari, Damiano; Sigrist, Hannes; Gschwind, Tilo; Lesch, Klaus-Peter; Seifritz, Erich

2012-01-01

Uncontrollability of major life events has been proposed to be central to depression onset and maintenance. The learned helplessness (LH) effect describes a deficit in terminating controllable aversive stimuli in individuals that experienced aversive stimuli as uncontrollable relative to individuals that experienced the same stimuli as controllable. The LH effect translates across species and therefore can provide an objective-valid readout in animal models of depression. Paradigms for a robust LH effect are established and currently applied in rat but there are few reports of prior and current study of the LH effect in mouse. This includes the C57BL/6 mouse, typically the strain of choice for application of molecular-genetic tools in pre-clinical depression research. The aims of this study were to develop a robust paradigm for the LH effect in BL/6 mice, provide evidence for underlying psychological processes, and study the effect of a depression-relevant genotype on the LH effect. The apparatus used for in/escapable electro-shock exposure and escape test was a two-way shuttle arena with continuous automated measurement of locomotion, compartment transfers, e-shock escapes, vertical activity and freezing. Brother-pairs of BL/6 mice were allocated to either escapable e-shocks (ES) or inescapable e-shocks (IS), with escape latencies of the ES brother used as e-shock durations for the IS brother. The standard two-way shuttle paradigm was modified: the central gate was replaced by a raised divider and e-shock escape required transfer to the distal part of the safe compartment. These refinements yielded reduced superstitious, pre-adaptive e-shock transfers in IS mice and thereby increased the LH effect. To obtain a robust LH effect in all brother pairs, pre-screening for minor between-brother ES differences was necessary and did not confound the LH effect. IS mice developed reduced motor responses to e-shock, consistent with a motivational deficit, and absence of a learning curve for escapes at escape test, consistent with a cognitive deficit. When a tone CS was used to predict e-shock, IS mice exhibited increased reactivity to the CS, consistent with hyper-emotionality. There was no ES-IS difference in pain sensitivity. Mice heterozygous knockout for the 5-HTT gene exhibited an increased LH effect relative to wildtype mice. This mouse model will allow for the detailed molecular study of the aetiology, psychology, neurobiology and neuropharmacology of uncontrollability of aversive stimuli, a potential major aetiological factor and state marker in depression. This article is part of a Special Issue entitled 'Anxiety and Depression'. Copyright © 2011 Elsevier Ltd. All rights reserved.

Clinical Study of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for Severe Pelvic Fracture and Intra Abdominal Hemorrhagic Shock using Continuous Vital Signs

DTIC Science & Technology

2016-03-01

AWARD NUMBER: W81XWH-15-1-0025 TITLE: Clinical Study of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for Severe Pelvic...Intra-Abdominal Hemorrhagic Shock 5b. GRANT NUMBER W81XWH-15-1-0025 Clinical Study of Resuscitative Endovascular Balloon Occlusion of the Aorta ...sites. Resuscitative balloon occlusion of the aorta (REBOA) has been clinically demonstrated to stop bleeding below the diaphragm. It has the potential

Arterial Blood Gases, Electrolytes and Metabolic Indices Associated with Hemorrhagic Shock: Inter-and Intrainbred Rat Strain Variation

DTIC Science & Technology

2013-03-07

hyperkalemia can also have adverse effects on car- diovascular and neuromuscular function (42, 58, 66). Hence, at least in some inbred rat strains such as BN...to know to interpret arterial blood gases. Philadelphia: Lippincott Williams and Wilkins, 1999. 42. Mazze RI, Escue HM, Houston JB. Hyperkalemia and...MC, Carmona MJ, Auler Júnior JO. Hyperkalemia accompanies hemorrhagic shock and correlates with mor- tality. Clinics (Sao Paulo) 64: 591–597, 2009. 56

The use of resuscitative endovascular balloon occlusion of the aorta to control hemorrhagic shock during video-assisted retroperitoneal debridement or infected necrotizing pancreatitis.

PubMed

Weltz, Adam S; Harris, Donald G; O'Neill, Natalie A; O'Meara, Lindsay B; Brenner, Megan L; Diaz, Jose J

2015-01-01

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a technique that has been shown to provide central vascular control to support proximal aortic pressure and minimize hemorrhage in a wide variety of clinic settings, however the role of REBOA for emergency general surgery is less defined. This is a report of a 44 year old man who experienced hemorrhagic shock during video-assisted retroperitoneal debridement (VARD) for necrotizing pancreatitis where REBOA was used to prevent ongoing hemorrhage and death. This is the first documented report REBOA being used during pancreatic debridement in the literature and one of the first times it has been used in emergency general surgery. The use of REBOA is an option for those in hemorrhagic shock whom conventional aortic cross-clamping or supra-celiac aortic exposure is either not possible or exceedingly dangerous. REBOA allows for adequate resuscitation and can be used as a bridge to definitive therapy in a range of surgical subspecialties with minimal morbidity and complications. The risks associated with insertion of wires, sheaths, and catheters into the arterial system, as well as the risk of visceral and spinal cord ischemia due to aortic occlusion mandate that the use of this technique be utilized in only appropriate clinical scenarios. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Small-volume fluid resuscitation with hypertonic saline prevents inflammation but not mortality in a rat model of hemorrhagic shock.

PubMed

Bahrami, Soheyl; Zimmermann, Klaus; Szelényi, Zoltán; Hamar, János; Scheiflinger, Friedrich; Redl, Heinz; Junger, Wolfgang G

2006-03-01

Hemorrhage remains a primary cause of death in civilian and military trauma. Permissive hypotensive resuscitation is a possible approach to reduce bleeding in patients until they can be stabilized in an appropriate hospital setting. Small-volume resuscitation with hypertonic saline (HS) is of particular interest because it allows one to modulate the inflammatory response to hemorrhage and trauma. Here, we tested the utility of permissive hypotensive resuscitation with hypertonic fluids in a rat model of hemorrhagic shock. Animals were subjected to massive hemorrhage [mean arterial pressure (MAP) = 30 - 35 mmHg for 2 h until decompensation] and partially resuscitated with a bolus dose of 4 mL/kg of 7.5% NaCl (HS), hypertonic hydroxyl ethyl starch (HHES; hydroxyl ethyl starch + 7.5% NaCl), or normal saline (NS) followed by additional infusion of Ringer solution to maintain MAP at 40 to 45 mmHg for 40 min (hypotensive state). Finally, animals were fully resuscitated with Ringer solution and the heparinized shed blood. Hypotensive resuscitation with NS caused a significant increase in plasma interleukin (IL)-1beta, IL-6, IL-2, interferon gamma (IFNgamma), IL-10, and granulocyte-macrophage colony stimulating factor (GM-CSF). This increase was blocked by treatment with HS. HHES treatment significantly reduced the increase of IL-1beta and IL-2 but not that of the other cytokines studied. Despite the strong effects of HS and HHES on cytokine production, both treatments had little effect on plasma lactate, base excess (BE), white blood cell (WBC) count, myeloperoxidase (MPO) content, and the wet/dry weight ratio of the lungs. Moreover, on day 7 after shock, the survival rate in rats treated with HS was markedly, but not significantly, lower than that of NS-treated animals (47% vs. 63%, respectively). In summary, hypotensive resuscitation with hypertonic fluids reduces the inflammatory response but not lung tissue damage or mortality after severe hemorrhagic shock.

THE AMPK ACTIVATOR AICAR AMELIORATES AGE-DEPENDENT MYOCARDIAL INJURY IN MURINE HEMORRHAGIC SHOCK

PubMed Central

Matsiukevich, Dzmitry; Piraino, Giovanna; Klingbeil, Lindsey R.; Hake, Paul W.; Wolfe, Vivian; O’Connor, Michael; Zingarelli, Basilia

2016-01-01

The development of myocardial dysfunction in patients with hemorrhagic shock is significantly impacted by the patient age. AMP-activated protein kinase (AMPK) is a pivotal orchestrator of energy homeostasis, which coordinates metabolic recovery after cellular stress. We investigated whether AMPK-regulated pathways are age-dependent in hemorrhage-induced myocardial injury and whether AMPK activation by 5-amino-4-imidazole carboxamide riboside (AICAR) affords cardioprotective effects. Anesthetized C57/BL6 young (3–5 months old) and mature male mice (9–12 months old) were subjected to hemorrhagic shock by blood withdrawing followed by resuscitation with shed blood and Lactated Ringer’s solution. Mice were sacrificed at 3 hours after resuscitation, and plasma and hearts were harvested for biochemical assays. Vehicle-treated mature mice exhibited higher myocardial injury and higher levels of plasma biomarkers of cardiovascular injury (endocan and follistatin) when compared with young mice. Cardiac cell mitochondrial structure was also markedly impaired in vehicle-treated mature mice when compared to young mice. At molecular analysis, an increase of the phosphorylated catalytic subunit pAMPKα was associated with nuclear translocation of the peroxisome proliferator-activated receptor γ co-activator-α in young, but not mature mice. No changes in autophagy were observed as evaluated by the conversion of the light-chain (LC)3B-I protein to LC3B-II form. Treatment with AICAR ameliorated myocardial damage in both age groups. However, AICAR therapeutic effects were less effective in mature mice compared to young mice and involved distinct mechanisms of action. Thus, our data demonstrate that during hemorrhagic shock AMPK-dependent metabolic mechanisms are important for mitigating myocardial injury. However, these mechanisms are less competent with age. PMID:27513082

Amelioration of Ischemia/Reperfusion Injury During Resuscitation from Hemorrhage by Induction of Heme Oxygenase-1 (HO-1) in a Conscious Mouse Model of Uncontrolled Hemorrhage

DTIC Science & Technology

2013-10-01

gauze. For bioluminescence imaging, mice were anes1hetized with isoflurane/a1r and injected ,v; th I 00 µ I of lucifcnn (dissolved m phosphate...buffered salme mto the peritoneal cavity. F1\\ e min after luciferin injection , mice "’ere imaged for 1-5 minutes. Photons emitted from specific regions...kidney. spleen, duodenum, jejunum, ileum, stomach, brain. salivary gland, skeletal muscle, and testes) were removed 5 min following injection of

Impact of Glycemic Control on Morbidity and Mortality in Adult Idiopathic Scoliosis Patients Undergoing Spinal Fusion.

PubMed

Shin, John I; Phan, Kevin; Kothari, Parth; Kim, Jun S; Guzman, Javier Z; Cho, Samuel K

2017-08-01

This is a retrospective analysis of administrative database. To elucidate the effect of glycemic control on surgical outcomes of middle-aged and elderly idiopathic scoliosis patients undergoing spinal fusion surgery. Diabetes mellitus (DM) is a condition thought to adversely affect outcomes of spine surgery. However, no study has stratified glycemic control levels and their impact on outcome for idiopathic scoliosis patients receiving a spinal fusion surgery. Previous studies may have reported higher than true rates of complications for controlled diabetic patients, who are the majority of diabetic patients. The Nationwide Inpatient Sample was queried from years 2002 to 2011. We extracted idiopathic scoliosis patients older than 45 years of age that received spinal fusion and analyzed complications and outcomes variables among 3 cohorts: nondiabetic patients, controlled diabetics, and uncontrolled diabetics. Multivariate analyses were used to assess whether glycemic control was a risk factor for adverse postoperative outcomes. Controlled diabetics had significantly increased rates of acute renal failure (ARF), while uncontrolled diabetics had significantly increased rates of acute postoperative hemorrhage. In multivariate analyses controlling for patient factors and comorbidities, controlled DM was found to be an independent predictor of ARF [odds ratio (OR), 1.863; 95% confidence interval (CI), 1.346-2.579; P=0.0002), and uncontrolled DM was found to be a significant risk factor for acute postoperative hemorrhage (OR, 2.182; 95% CI, 1.192-3.997; P=0.0115), ARF (OR, 4.839; 95% CI, 1.748-13.392; P=0.0024), deep vein thrombosis (OR, 5.825; 95% CI, 1.329-25.522, P=0.0194) and in-patient mortality (OR, 8.889; 95% CI, 1.001-78.945; P=0.0499). Controlled DM was found to be a risk factor for ARF in adult idiopathic scoliosis patients undergoing spinal fusion surgery, while uncontrolled DM was shown to be a risk factor for postoperative hemorrhage, ARF, deep vein thrombosis, and mortality. The present study provides valuable data for better informed consent for patients with diabetes considering surgery for idiopathic scoliosis. Level III.

Inhibition of glycogen synthase kinase (GSK)-3-β improves liver microcirculation and hepatocellular function after hemorrhagic shock.

PubMed

Jellestad, Lena; Fink, Tobias; Pradarutti, Sascha; Kubulus, Darius; Wolf, Beate; Bauer, Inge; Thiemermann, Chris; Rensing, Hauke

2014-02-05

Ischemia and reperfusion may cause liver injury and are characterized by hepatic microperfusion failure and a decreased hepatocellular function. Inhibition of glycogen synthase kinase (GSK)-3β, a serine-threonine kinase that has recently emerged as a key regulator in the modulation of the inflammatory response after stress events, may be protective in conditions like sepsis, inflammation and shock. Therefore, aim of the study was to assess the role of GSK-3β in liver microcirculation and hepatocellular function after hemorrhagic shock and resuscitation (H/R). Anesthetized male Sprague-Dawley rats underwent pretreatment with Ringer´s solution, vehicle (DMSO) or TDZD-8 (1 mg/kg), a selective GSK-3β inhibitor, 30 min before induction of hemorrhagic shock (mean arterial pressure 35±5 mmHg for 90 min) and were resuscitated with shed blood and Ringer´s solution (2h). 5h after resuscitation hepatic microcirculation was assessed by intravital microscopy. Propidium iodide (PI) positive cells, liver enzymes and alpha-GST were measured as indicators of hepatic injury. Liver function was estimated by assessment of indocyanine green plasma disappearance rate. H/R led to a significant decrease in sinusoidal diameters and impairment of liver function compared to sham operation. Furthermore, the number of PI positive cells in the liver as well as serum activities of liver enzymes and alpha-GST increased significantly after H/R. Pretreatment with TDZD-8 prevented the changes in liver microcirculation, hepatocellular injury and liver function after H/R. A significant rise in the plasma level of IL-10 was observed. Thus, inhibition of GSK-3β before hemorrhagic shock modulates the inflammatory response and improves hepatic microcirculation and hepatocellular function. Copyright © 2013 Elsevier B.V. All rights reserved.

Early structural changes of the heart after experimental polytrauma and hemorrhagic shock

PubMed Central

Halbgebauer, Rebecca; Eisele, Philipp; Messerer, David A. C.; Weckbach, Sebastian; Schultze, Anke; Braumüller, Sonja; Gebhard, Florian

2017-01-01

Evidence is emerging that systemic inflammation after trauma drives structural and functional impairment of cardiomyocytes and leads to cardiac dysfunction, thus worsening the outcome of polytrauma patients. This study investigates the structural and molecular changes in heart tissue 4 h after multiple injuries with additional hemorrhagic shock using a clinically relevant rodent model of polytrauma. We determined mediators of systemic inflammation (keratinocyte chemoattractant, macrophage chemotactic protein 1), activated complement component C3a and cardiac troponin I in plasma and assessed histological specimen of the mouse heart via standard histomorphology and immunohistochemistry for cellular and subcellular damage and ongoing apoptosis. Further we investigated spatial and quantitative changes of connexin 43 by immunohistochemistry and western blotting. Our results show significantly increased plasma levels of both keratinocyte chemoattractant and cardiac troponin I 4 h after polytrauma and 2 h after induction of hypovolemia. Although we could not detect any morphological changes, immunohistochemical evaluation showed increased level of tissue high-mobility group box 1, which is both a damage-associated molecule and actively released as a danger response signal. Additionally, there was marked lateralization of the cardiac gap-junction protein connexin 43 following combined polytrauma and hemorrhagic shock. These results demonstrate a molecular manifestation of remote injury of cardiac muscle cells in the early phase after polytrauma and hemorrhagic shock with marked disruption of the cardiac gap junction. This disruption of an important component of the electrical conduction system of the heart may lead to arrhythmia and consequently to cardiac dysfunction. PMID:29084268

Supplemental arginine vasopressin during the resuscitation of severe hemorrhagic shock preserves renal mitochondrial function

PubMed Central

Yuxia, Guan; Singh, Khushboo; Reilly, Patrick M.

2017-01-01

Arginine vasopressin (AVP), a hormone secreted by the posterior pituitary, plays a vital role in maintaining vasomotor tone during acute blood loss. We hypothesized that decompensated hemorrhagic shock is associated with decreased AVP stores and supplementation during resuscitation would improve both blood pressure and renal function. Using a decompensated hemorrhagic shock model, male Long-Evans rats were bled to mean arterial blood pressure (MAP) of 40mmHg and maintained until the MAP could not be sustained without fluid. Once 40% of the shed volume was returned in lactated Ringer’s (Severe Shock), animals were resuscitated over 60 minutes with 4x the shed volume in lactated Ringer’s (LR) or the same fluids with AVP (0.5 units/kg+ 0.03 units/kg/min). Animals (n = 6-9/group) were sacrificed before hemorrhage (Sham), at Severe Shock, following resuscitation (60R, 60R with AVP) or 18 hours post-resuscitation (18hr, 18hr with AVP). Blood samples were taken to measure AVP levels and renal function. Pituitaries were harvested and assayed for AVP. Kidney samples were taken to assess mitochondrial function, histology, and oxidative damage. Baseline pituitary AVP stores (30,364 ± 5311 pg/mg) decreased with severe shock and were significantly depressed post-resuscitation (13,910 ± 3016 pg/ml. p<0.05) and at 18hr (15,592 ±1169 pg/ml, p<0.05). Resuscitation with LR+AVP led to higher serum AVP levels at 60R (31±8 vs 79±12; p<0.01) with an improved MAP both at 60R (125±3 vs 77±7mmHg; p<0.01) and 18hr (82±6 vs 69±5mmHg;p<0.05). AVP supplementation preserved complex I respiratory capacity at 60R and both complex I and II function at 18hr (p<0.05). AVP was also associated with decreased reactive oxygen species at 60R (856±67 vs 622±48F RFU) and significantly decreased oxidative damage as measured by mitochondrial lipid peroxidation (0.9±0.1 vs 1.7±0.1 fold change, p<0.01) and nitrosylation (0.9±0.1 vs 1.4±0.2 fold change, p<0.05). With AVP, renal damage was mitigated at 60R and histologic architecture was conserved at 18 hours. In conclusion, pituitary and serum AVP levels decrease during severe hemorrhage and may contribute to the development of decompensated hemorrhagic shock. Supplementing exogenous AVP during resuscitation improves blood pressure, preserves renal mitochondrial function, and mitigates acute kidney injury. PMID:29065123

The effects of BleedArrest on hemorrhage control in a porcine model.

PubMed

Gegel, Brian; Burgert, James; Loughren, Michael; Johnson, Don

2012-01-01

The purpose of this study was to examine the effectiveness of the hemostatic agent BleedArrest compared to control. This was a prospective, experimental design employing an established porcine model of uncontrolled hemorrhage. The minimum number of animals (n=10 per group) was used to obtain a statistically valid result. There were no statistically significant differences between the groups (P>.05) indicating that the groups were equivalent on the following parameters: activating clotting time, the subject weights, core body temperatures, amount of one minute hemorrhage, arterial blood pressures, and the amount and percentage of total blood volume. There were significant differences in the amount of hemorrhage (P=.033) between the BleedArrest (mean=72, SD±72 mL) and control (mean=317.30, SD±112.02 mL). BleedArrest is statistically and clinically superior at controlling hemorrhage compared to the standard pressure dressing control group. In conclusion, BleedArrest is an effective hemostatic agent for use in civilian and military trauma management.

N-Acetylcysteine and Desferoxamine Reduce Pulmonary Oxidative Stress Caused by Hemorrhagic Shock in a Porcine Model.

PubMed

Mani, Alexandra; Staikou, Chryssoula; Karmaniolou, Iosifina; Orfanos, Nikolaos; Mylonas, Anastassios; Nomikos, Tzortzis; Pafiti, Agathi; Papalois, Apostolos; Arkadopoulos, Nikolaos; Smyrniotis, Vassilios; Theodoraki, Kassiani

2017-02-01

To investigate the pulmonary oxidative stress and possible protective effect of N-Acetylcysteine (NAC) and Desferoxamine (DFX)in a porcine model subjected to hemorrhagic shock. Twenty-one pigs were randomly allocated to Group-A (sham, n = 5), Group-B (fluid resuscitation, n = 8) and Group-C (fluid, NAC and DFX resuscitation, n = 8). Groups B and C were subjected to a 40-min shock period induced by liver trauma, followed by a 60-min resuscitation period. During shock, the mean arterial pressure (MAP) was maintained at 30-40 mmHg. Resuscitation consisted of crystalloids (35 mL/kg) and colloids (18 mL/kg) targeting to MAP normalization (baseline values ± 10%). In addition, Group-C received pretreatment with NAC 200 mg/kg plus DFX 2 g as intravenous infusions. Thiobarbituric Acid Reactive Substances (TBARS), protein carbonyls and glutathione peroxidase (GPx) activity were determined in lung tissue homogenates. Also, histological examination of pulmonary tissue specimens was performed. TBARS were higher in Group-B than in Group-A or Group-C: 2.90 ± 0.47, 0.57 ± 0.10, 1.78 ± 0.47 pmol/μg protein, respectively (p < 0.05). Protein carbonyls content was higher in Group-B than in Group-A or Group-C: 3.22 ± 0.68, 0.89 ± 0.30, 1.95 ± 0.54 nmol/mg protein, respectively (p > 0.05). GPx activity did not differ significantly between the three groups (p > 0.05). Lung histology was improved in Group-C versus Group-B, with less alveolar collapse, interstitial edema and inflammation. NAC plus DFX prevented the increase of pulmonary oxidative stress markers and protein damage after resuscitated hemorrhagic shock and had beneficial effect on lung histology. NAC/DFX combination may be used in the multimodal treatment of hemorrhagic shock, since it may significantly prevent free radical injury in the lung.

Immobilization of lysozyme on cotton fabrics; synthesis, characterization, and activity

USDA-ARS?s Scientific Manuscript database

Uncontrolled hemorrhage is the leading cause of death on the battlefield and second leading cause of death in civilian trauma. Recent animal testing using a lethal arterial injury model compared a variety of woven and non woven products with granular products, and found only one product (WoundStat) ...

Improving on Army Field Gauze for Lethal Vascular Injuries: Challenges in Dressing Development

USDA-ARS?s Scientific Manuscript database

Accounting for half of all deaths, uncontrolled hemorrhage remains the leading cause of death on the battlefield. Gaining hemostatic control of lethal vascular injuries sustained in combat using topical agents remains a challenge. Recent animal testing using a lethal arterial injury model compared a...

Thrombelastography is Better Than PT, aPTT, and Activated Clotting Time in Detecting Clinically Relevant Clotting Abnormalities After Hypothermia, Hemorrhagic Shock and Resuscitation in Pigs

DTIC Science & Technology

2008-09-01

hypothermia group using a cold blanket with 4°C circulating water. In the combined group, hemorrhagic shock and LR re- suscitation were induced the same... circulation and a decrease in platelet counts. Fibrinogen levels, in con- trast, were not changed significantly from baseline by hypo- thermia in this...et al. Effect of skin temperature on platelet function in patients undergoing extracorporeal bypass. J Thorac Cardiovasc Surg. 1992;104:108–116. The

Ruptured superior gluteal artery pseudoaneurysm with hemorrhagic shock: Case report.

PubMed

Corbacioglu, Kerem Seref; Aksel, Gokhan; Yildiz, Altan

2016-03-01

Pseudoaneurysm of the superior gluteal artery (SGA) is very rare and the most common causes are blunt or penetrating pelvic traumas. Although pseudoaneurysm can be asymptomatic at the time of initial trauma, it can be symptomatic weeks, months, even years after initial trauma. We present a case of a ruptured superior gluteal artery pseudoaneurysm with hemorrhagic shock twenty days after a bomb injury in the Syria civil war. In addition, we review the anatomy of the SGA, clinical presentation and pitfalls of pseudoaneurysm, and imaging and treatment options.

Pancreatic Digestive Enzyme Blockade in the Intestine Increases Survival After Experimental Shock

PubMed Central

DeLano, Frank A.; Hoyt, David B.; Schmid-Schönbein, Geert W.

2015-01-01

Shock, sepsis, and multiorgan failure are associated with inflammation, morbidity, and high mortality. The underlying pathophysiological mechanism is unknown, but evidence suggests that pancreatic enzymes in the intestinal lumen autodigest the intestine and generate systemic inflammation. Blocking these enzymes in the intestine reduces inflammation and multiorgan dysfunction. We investigated whether enzymatic blockade also reduces mortality after shock. Three rat shock models were used here: hemorrhagic shock, peritonitis shock induced by placement of cecal material into the peritoneum, and endotoxin shock. One hour after initiation of hemorrhagic, peritonitis, or endotoxin shock, animals were administered one of three different pancreatic enzyme inhibitors—6-amidino-2-naphtyl p-guanidinobenzoate di-methanesulfate, tranexamic acid, or aprotinin—into the lumen of the small intestine. In all forms of shock, blockade of digestive proteases with protease inhibitor attenuated entry of digestive enzymes into the wall of the intestine and subsequent autodigestion and morphological damage to the intestine, lung, and heart. Animals treated with protease inhibitors also survived in larger numbers than untreated controls over a period of 12 weeks. Surviving animals recovered completely and returned to normal weight within 14 days after shock. The results suggest that the active and concentrated digestive enzymes in the lumen of the intestine play a central role in shock and multi-organ failure, which can be treated with protease inhibitors that are currently available for use in the clinic. PMID:23345609

Microwave Processing for Sample Preparation to Evaluate Mitochondrial Ultrastructural Damage in Hemorrhagic Shock

NASA Astrophysics Data System (ADS)

Josephsen, Gary D.; Josephsen, Kelly A.; Beilman, Greg J.; Taylor, Jodie H.; Muiler, Kristine E.

2005-12-01

This is a report of the adaptation of microwave processing in the preparation of liver biopsies for transmission electron microscopy (TEM) to examine ultrastructural damage of mitochondria in the setting of metabolic stress. Hemorrhagic shock was induced in pigs via 35% total blood volume bleed and a 90-min period of shock followed by resuscitation. Hepatic biopsies were collected before shock and after resuscitation. Following collection, biopsies were processed for TEM by a rapid method involving microwave irradiation (Giberson, 2001). Samples pre- and postshock of each of two animals were viewed and scored using the mitochondrial ultrastructure scoring system (Crouser et al., 2002), a system used to quantify the severity of ultrastructural damage during shock. Results showed evidence of increased ultrastructural damage in the postshock samples, which scored 4.00 and 3.42, versus their preshock controls, which scored 1.18 and 1.27. The results of this analysis were similar to those obtained in another model of shock (Crouser et al., 2002). However, the amount of time used to process the samples was significantly shortened with methods involving microwave irradiation.

Chronic porcine two-hit model with hemorrhagic shock and Pseudomonas aeruginosa sepsis.

PubMed

Eissner, B; Matz, K; Smorodchenko, A; Röschmann, A; v Specht, B U

2002-01-01

Sepsis is still a major cause of death despite well-developed therapeutical strategies such as antibiotics and supportive medication. The aim of this study was to characterize the long-term effects of a two-hit porcine sepsis model with a hemorrhagic shock as 'first hit' followed by a Pseudomonas aeruginosa infusion as 'second hit'. Twelve juvenile healthy pigs were anesthetized and hemodynamically monitored. The two-hit group (n = 6) underwent a hemorrhagic shock with a 50% reduction of the mean arterial pressure and/or cardiac index for 45 min, followed by resuscitation, while the control group (n = 6) received no pretreatment. All chronically catheterized conscious pigs were challenged with a P. aeruginosa infusion (1.6 x 10(7) CFU/kg/h for the first 24 h followed by 1.6 x 10(6) CFU/kg/h for the next 24 h) and observed for another 48 h. The two-hit group showed the following significant differences to the control group: higher APACHE II scores prior to sepsis induction, increased persisting mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance index (PVRI) during bacterial challenge. In contrast, systemic vascular resistance (SVRI) was reduced at the end of the study. Throughout the observation period, the mean arterial pressure (MAP) was significantly reduced. The present study shows that the clinical course and hemodynamic effects of a P. aeruginosa sepsis will be aggravated by a preceding hemorrhagic shock during an observation period of 96 h. This two-hit model represents a valid, clinically relevant experimental protocol in sepsis research. Copyright 2002 S. Karger AG, Basel

Angiotensin (1-7) contributes to nitric oxide tonic inhibition of vasopressin release during hemorrhagic shock in acute ethanol intoxicated rodents

PubMed Central

Whitaker, Annie M.; Molina, Patricia E.

2013-01-01

Aims Acute ethanol intoxication (AEI) attenuates the arginine vasopressin (AVP) response to hemorrhage leading to impaired hemodynamic counter-regulation and accentuated hemodynamic stability. Previously we identified that the ethanol-induced impairment of circulating AVP concentrations in response to hemorrhage was the result of augmented central nitric oxide (NO) inhibition. The aim of the current study was to examine the mechanisms underlying ethanol-induced up-regulation of paraventricular nucleus (PVN) NO concentration. Angiotensin (ANG) (1-7) is an important mediator of NO production through activation of the Mas receptor. We hypothesized that Mas receptor inhibition would decrease central NO concentration and thus restore the rise in circulating AVP levels during hemorrhagic shock in AEI rats. Main Methods Conscious male Sprague Dawley rats (300-325 g) received a 15h intra-gastric infusion of ethanol (2.5g/kg + 300mg/kg/h) or dextrose prior to a fixed-pressure (~40mmHg) 60 minute hemorrhage. The Mas receptor antagonist A-779 was injected through an intracerebroventricular (ICV) cannula 15 min prior to hemorrhage. Key Findings PVN NOS activity and NO were significantly higher in AEI compared to DEX-treated controls at the completion of hemorrhage. ICV A-779 administration decreased NOS activity and NO concentration, partially restoring the rise in circulating AVP levels completion of hemorrhage in AEI rats. Significance These results suggest that Mas receptor activation contributes to the NO-mediated inhibitory tone of AVP release in the ethanol-intoxicated hemorrhaged host. PMID:24002017

Effect of Topical Iloprost and Nitroglycerin on Gastric Microcirculation and Barrier Function during Hemorrhagic Shock in Dogs.

PubMed

Truse, Richard; Hinterberg, Jonas; Schulz, Jan; Herminghaus, Anna; Weber, Andreas; Mettler-Altmann, Tabea; Bauer, Inge; Picker, Olaf; Vollmer, Christian

2017-01-01

Topical drug application is used to avoid systemic side effects. The aim of this study was to analyze whether locally applied iloprost or nitroglycerin influence gastric mucosal perfusion, oxygenation, and barrier function during physiological and hemorrhagic conditions. In repeated experiments, 5 anesthetized dogs received iloprost, nitroglycerin, or normal saline during physiological and hemorrhagic (-20% blood volume) conditions. Macro- and microcirculatory variables were recorded continuously. Gastric barrier function was assessed via translocation of sucrose into the blood. During hemorrhage, gastric mucosal oxygenation decreased from 77 ± 4 to 37 ± 7%. This effect was attenuated by nitroglycerin (78 ± 6 to 47 ± 13%) and iloprost (82 ± 4 to 54 ± 9%). Sucrose plasma levels increased during hemorrhage from 7 ± 4 to 55 ± 15 relative amounts. This was alleviated by nitroglycerin (5 ± 8 to 29 ± 38 relative amounts). These effects were independent of systemic hemodynamic variables. During hemorrhage, topical nitroglycerin and iloprost improve regional gastric oxygenation without affecting perfusion. Nitroglycerin attenuated the shock-induced impairment of the mucosal barrier integrity. Thus, local drug application improves gastric microcirculation without compromising systemic hemodynamic variables, and it may also protect mucosal barrier function. © 2017 S. Karger AG, Basel.

Creating a “Pro-survival Phenotype” Through Histone Deacetylase Inhibition: Past, Present, and Future

PubMed Central

Halaweish, Ihab; Nikolian, Vahagn; Georgoff, Patrick; Li, Yongqing; Alam, Hasan B

2014-01-01

Traumatic injuries and their sequela represent a major source of mortality in the United States and globally. Initial treatment for shock, traumatic brain injury, and polytrauma is limited to resuscitation fluids to replace lost volume. To date, there are no treatments with inherent pro-survival properties. Our lab has investigated the use of histone deacetylase inhibitors (HDACIs) as pharmacological agents to improve survival. This class of drugs acts through posttranslational protein modifications and is a direct regulator of chromatin structure and function, as well as the function of numerous cytoplasmic proteins. In models of hemorrhagic shock and polytrauma, administration of HDACIs offers a significant survival advantage, even in the absence of fluid resuscitation. Positive results have also been shown in two-hit models of hemorrhage and sepsis and in hemorrhagic shock combined with traumatic brain injury. Accumulating data generated by our group and others continue to support the use of HDACIs for creation of a pro-survival phenotype. With further research and clinical trials, HDACIs have the potential to be an integral tool in treatment of trauma, especially in the pre-hospital phase. PMID:25565645

Improving on army field gauze for lethal vascular injuries: a progress report

USDA-ARS?s Scientific Manuscript database

Uncontrolled hemorrhage is the leading cause of death on the battlefield and second leading cause of death in civilian trauma. Recent animal testing using a lethal arterial injury model compared a variety of woven and non woven products with granular products, and found only one product (WoundStat)...

Hemorrhagic Shock and Surgical Stress Alter Distribution of Labile Zinc within High and Low Molecular Weight Plasma Fractions

PubMed Central

Kelly, Edward; Mathew, Jeff; Kohler, Jonathan E.; Blass, Amy L.; Soybel, David I.

2012-01-01

Zinc ions (Zn2+) are essential for tissue repair following injury or stress. We hypothesize that during such stresses Zn2+ is redistributed to labile pools in plasma components. Here we tested this hypothesis utilizing a novel assay to monitor labile Zn2+ in plasma in hemorrhagic shock. Adult rats in the Shock (S) group underwent hemorrhage and resuscitation. Blood samples were drawn at baseline, 1 hr, 4 hrs and 24 hrs. The Surgical Control (SC) group was anesthetized and instrumented, but not bled. Albumin, total Zn2+, and labile Zn2+ levels were assayed in plasma. Binding capacity for Zn2+ was assessed in high (HMW) and low (LMW) molecular weight pools. Significant decreases in total Zn2+ were observed by 24 hrs, in both S and SC groups. Albumin levels were significantly reduced in the S group at 1 hr and 4 hr but restored at 24 hrs; significant changes were not observed in other groups. In whole plasma, labile Zn2+ levels were stable initially in the S and SC groups, but declined at 24 hrs. In the HMW pool, marked and significant impairment of binding was noted throughout all time periods following the shock period in the S group. Such changes were observed in the SC group of less intensity and duration. These experiments suggest that Shock alters affinity of plasma proteins for Zn2+, promoting delivery to peripheral tissues during periods of increased Zn2+ utilization. PMID:22744307

Hemorrhagic shock and surgical stress alter distribution of labile zinc within high- and low-molecular-weight plasma fractions.

PubMed

Kelly, Edward; Mathew, Jeff; Kohler, Jonathan E; Blass, Amy L; Soybel, And David I

2012-08-01

Zinc ions (Zn) are essential for tissue repair following injury or stress. We hypothesize that during such stresses Zn is redistributed to labile pools in plasma components. Here we tested this hypothesis using a novel assay to monitor labile Zn in plasma in hemorrhagic shock. Adult rats in the shock group (S group) underwent hemorrhage and resuscitation. Blood samples were drawn at baseline and at 1, 4, and 24 h. The surgical control group (SC group) was anesthetized and instrumented, but not bled. Albumin, total Zn, and labile Zn levels were assayed in plasma. Binding capacity for Zn was assessed in high- and low-molecular-weight pools. Significant decreases in total Zn were observed by 24 h, in both S and SC groups. Albumin levels were significantly reduced in the S group at 1 and 4 h but restored at 24 h; significant changes were not observed in other groups. In whole plasma, labile Zn levels were stable initially in the S and SC groups, but declined at 24 h. In the high-molecular-weight pool, marked and significant impairment of binding was noted throughout all time periods following the shock period in the S group. Such changes were observed in the SC group of less intensity and duration. These experiments suggest that shock alters affinity of plasma proteins for Zn, promoting delivery to peripheral tissues during periods of increased Zn utilization.

Involvement of connexin 43 phosphorylation and gap junctional communication between smooth muscle cells in vasopressin-induced ROCK-dependent vasoconstriction after hemorrhagic shock.

PubMed

Yang, Guangming; Peng, Xiaoyong; Wu, Yue; Li, Tao; Liu, Liangming

2017-10-01

We examined the roles played by gap junctions (GJs) and the GJ channel protein connexin 43 (Cx43) in arginine vasopressin (AVP)-induced vasoconstriction after hemorrhagic shock and their relationship to Rho kinase (ROCK) and protein kinase C (PKC). The results showed that AVP induced an endothelium-independent contraction in rat superior mesenteric arteries (SMAs). Blocking the GJs significantly decreased the contractile response of SMAs and vascular smooth muscle cells (VSMCs) to AVP after shock and hypoxia. The selective Cx43-mimetic peptide inhibited the vascular contractile effect of AVP after shock and hypoxia. AVP restored hypoxia-induced decrease of Cx43 phosphorylation at Ser 262 and gap junctional communication in VSMCs. Activation of RhoA with U-46619 increased the contractile effect of AVP. This effect was antagonized by the ROCK inhibitor Y27632 and the Cx43-mimetic peptide. In contrast, neither an agonist nor an inhibitor of PKC had significant effects on AVP-induced contraction after hemorrhagic shock. In addition, silencing of Cx43 with siRNA blocked the AVP-induced increase of ROCK activity in hypoxic VSMCs. In conclusion, AVP-mediated vascular contractile effects are endothelium and myoendothelial gap junction independent. Gap junctions between VSMCs, gap junctional communication, and Cx43 phosphorylation at Ser 262 play important roles in the vascular effects of AVP. RhoA/ROCK, but not PKC, is involved in this process. Copyright © 2017 the American Physiological Society.

Impact of hemoglobin nitrite to nitric oxide reductase on blood transfusion for resuscitation from hemorrhagic shock.

PubMed

Brouse, Chad; Ortiz, Daniel; Su, Yan; Oronsky, Bryan; Scicinski, Jan; Cabrales, Pedro

2015-01-01

Transfusion of blood remains the gold standard for fluid resuscitation from hemorrhagic shock. Hemoglobin (Hb) within the red blood cell transports oxygen and modulates nitric oxide (NO) through NO scavenging and nitrite reductase. This study was designed to examine the effects of incorporating a novel NO modulator, RRx-001, on systemic and microvascular hemodynamic response after blood transfusion for resuscitation from hemorrhagic shock in a hamster window chamber model. In addition, to RRx-001 the role of low dose of nitrite (1 × 10(-9) moles per animal) supplementation after resuscitation was studied. Severe hemorrhage was induced by arterial controlled bleeding of 50% of the blood volume (BV) and the hypovolemic state was maintained for 1 h. The animals received volume resuscitation by an infusion of 25% of BV using fresh blood alone or with added nitrite, or fresh blood treated with RRx-001 (140 mg/kg) or RRx-001 (140 mg/kg) with added nitrite. Systemic and microvascular hemodynamics were followed at baseline and at different time points during the entire study. Tissue apoptosis and necrosis were measured 8 h after resuscitation to correlate hemodynamic changes with tissue viability. Compared to resuscitation with blood alone, blood treated with RRx-001 decreased vascular resistance, increased blood flow and functional capillary density immediately after resuscitation and preserved tissue viability. Furthermore, in RRx-001 treated animals, both mean arterial pressure (MAP) and met Hb were maintained within normal levels after resuscitation (MAP >90 mmHg and metHb <2%). The addition of nitrite to RRx-001 did not significantly improve the effects of RRx-001, as it increased methemoglobinemia and lower MAP. RRx-001 alone enhanced perfusion and reduced tissue damage as compared to blood; it may serve as an adjunct therapy to the current gold standard treatment for resuscitation from hemorrhagic shock.

Shock Wave-Stimulated Periosteum for Cartilage Repair

DTIC Science & Technology

2015-03-01

Abscess Hemorrhage was graded with the following scores: 0: No hemorrhage 1: 1 or more small (barely visible through 10x objective) hematomas 2...1-3 or more medium (visible through 10x objective) hematomas 3: >3 or more medium (immediately visible in 10x objective) hematomas 4: 1 or more...large (immediately visible in 10x objective) hematomas The results are shown in Table 3 Table 3. Scores for the degree of inflammation and hemorrhage

Management of massive diffuse alveolar hemorrhage in a child with systemic lupus erythematosus.

PubMed

Kimura, Dai; Shah, Samir; Briceno-Medina, Mario; Sathanandam, Shyam; Haberman, Brent; Zhang, Jie; Myers, Linda; Kumar, Tk Susheel; Knott-Craig, Christopher

2015-01-01

Diffuse alveolar hemorrhage (DAH) from systemic lupus erythematosus (SLE) is a rare but potentially life-threatening condition. We report the case of a 14-year-old female with SLE who developed hypoxia and shock secondary to severe alveolar hemorrhage. She was successfully managed by placement on extracorporeal membrane oxygenation (ECMO) followed by emergent pulmonary lobectomy and medical treatment including high-dose methylprednisolone, cyclophosphamide, intravenous immunoglobulin, and plasmapheresis.

Running Reduces Uncontrollable Stress-Evoked Serotonin and Potentiates Stress-Evoked Dopamine Concentrations in the Rat Dorsal Striatum

PubMed Central

Clark, Peter J.; Amat, Jose; McConnell, Sara O.; Ghasem, Parsa R.; Greenwood, Benjamin N.; Maier, Steven F.; Fleshner, Monika

2015-01-01

Accumulating evidence from both the human and animal literature indicates that exercise reduces the negative consequences of stress. The neurobiological etiology for this stress protection, however, is not completely understood. Our lab reported that voluntary wheel running protects rats from expressing depression-like instrumental learning deficits on the shuttle box escape task after exposure to unpredictable and inescapable tail shocks (uncontrollable stress). Impaired escape behavior is a result of stress-sensitized serotonin (5-HT) neuron activity in the dorsal raphe (DRN) and subsequent excessive release of 5-HT into the dorsal striatum following exposure to a comparatively mild stressor. However, the possible mechanisms by which exercise prevents stress-induced escape deficits are not well characterized. The purpose of this experiment was to test the hypothesis that exercise blunts the stress-evoked release of 5-HT in the dorsal striatum. Changes to dopamine (DA) levels were also examined, since striatal DA signaling is critical for instrumental learning and can be influenced by changes to 5-HT activity. Adult male F344 rats, housed with or without running wheels for 6 weeks, were either exposed to tail shock or remained undisturbed in laboratory cages. Twenty-four hours later, microdialysis was performed in the medial (DMS) and lateral (DLS) dorsal striatum to collect extracellular 5-HT and DA before, during, and following 2 mild foot shocks. We report wheel running prevents foot shock-induced elevation of extracellular 5-HT and potentiates DA concentrations in both the DMS and DLS approximately 24 h following exposure to uncontrollable stress. These data may provide a possible mechanism by which exercise prevents depression-like instrumental learning deficits following exposure to acute stress. PMID:26555633

Effects of hydrogen sulfide on hemodynamics, inflammatory response and oxidative stress during resuscitated hemorrhagic shock in rats

PubMed Central

2010-01-01

Introduction Hydrogen sulfide (H2S) has been shown to improve survival in rodent models of lethal hemorrhage. Conversely, other authors have reported that inhibition of endogenous H2S production improves hemodynamics and reduces organ injury after hemorrhagic shock. Since all of these data originate from unresuscitated models and/or the use of a pre-treatment design, we therefore tested the hypothesis that the H2S donor, sodium hydrosulfide (NaHS), may improve hemodynamics in resuscitated hemorrhagic shock and attenuate oxidative and nitrosative stresses. Methods Thirty-two rats were mechanically ventilated and instrumented to measure mean arterial pressure (MAP) and carotid blood flow (CBF). Animals were bled during 60 minutes in order to maintain MAP at 40 ± 2 mm Hg. Ten minutes prior to retransfusion of shed blood, rats randomly received either an intravenous bolus of NaHS (0.2 mg/kg) or vehicle (0.9% NaCl). At the end of the experiment (T = 300 minutes), blood, aorta and heart were harvested for Western blot (inductible Nitric Oxyde Synthase (iNOS), Nuclear factor-κB (NF-κB), phosphorylated Inhibitor κB (P-IκB), Inter-Cellular Adhesion Molecule (I-CAM), Heme oxygenase 1(HO-1), Heme oxygenase 2(HO-2), as well as nuclear respiratory factor 2 (Nrf2)). Nitric oxide (NO) and superoxide anion (O2-) were also measured by electron paramagnetic resonance. Results At the end of the experiment, control rats exhibited a decrease in MAP which was attenuated by NaHS (65 ± 32 versus 101 ± 17 mmHg, P < 0.05). CBF was better maintained in NaHS-treated rats (1.9 ± 1.6 versus 4.4 ± 1.9 ml/minute P < 0.05). NaHS significantly limited shock-induced metabolic acidosis. NaHS also prevented iNOS expression and NO production in the heart and aorta while significantly reducing NF-kB, P-IκB and I-CAM in the aorta. Compared to the control group, NaHS significantly increased Nrf2, HO-1 and HO-2 and limited O2- release in both aorta and heart (P < 0.05). Conclusions NaHS is protective against the effects of ischemia reperfusion induced by controlled hemorrhage in rats. NaHS also improves hemodynamics in the early resuscitation phase after hemorrhagic shock, most likely as a result of attenuated oxidative stress. The use of NaHS hence appears promising in limiting the consequences of ischemia reperfusion (IR). PMID:20836847

Successful diagnosis and treatment of early splenic ectopic pregnancy: A case report.

PubMed

Wu, Lan; Jiang, Xiaoqin; Ni, Juan

2018-04-01

Splenic ectopic pregnancy (SEP), a special abdominal pregnancy, is extremely rare but carries a high risk of potentially uncontrollable, life-threatening intraperitoneal bleeding at early gestation, which is equivalent to the spontaneous rupture of the spleen. Therefore, early diagnosis of SEP is crucial and may avoid life-threatening situation. A 29-year-old G3P2 woman presented with 50 days of amenorrhea and positive serum β-human gonadotropin (β-HCG) was enrolled into the hospital due to the absence of gestational sac located in the uterine cavity. A pan-abdominal ultrasound scan revealed a 2.6 cm ×1.6 cm hyperechoic mass inferior to the spleen with color Doppler signal surrounding and 0.9 cm anechoic inside. The gynecologist found the gestational sac was located in the dorsal pole of the spleen through the exploratory laparoscopy. Total splenectomy was performed uneventfully to avoid the hemorrhage shock. The patient discharged with no complications and normal 1-month follow-up. It highlights that fully understanding of the knowledge about abdominal pregnancy, especially splenic pregnancy, and early imaging study with ultrasonography could reduce or avoid the misdiagnosis and miss-diagnosis of SEP.

Small-volume resuscitation from hemorrhagic shock with polymerized human serum albumin.

PubMed

Messmer, Catalina; Yalcin, Ozlem; Palmer, Andre F; Cabrales, Pedro

2012-10-01

Human serum albumin (HSA) is used as a plasma expander; however, albumin is readily eliminated from the intravascular space. The objective of this study was to establish the effects of various-sized polymerized HSAs (PolyHSAs) during small-volume resuscitation from hemorrhagic shock on systemic parameters, microvascular hemodynamics, and functional capillary density in the hamster window chamber model. Polymerized HSA size was controlled by varying the cross-link density (ie, molar ratio of glutaraldehyde to HSA). Hemorrhage was induced by controlled arterial bleeding of 50% of the animal's blood volume (BV), and hypovolemic shock was maintained for 1 hour. Resuscitation was implemented in 2 phases, first, by infusion of 3.5% of the BV of hypertonic saline (7.5% NaCl) then followed by infusion of 10% of the BV of each PolyHSA. Resuscitation provided rapid recovery of blood pressure, blood gas parameters, and microvascular perfusion. Polymerized HSA at a glutaraldehyde-to-HSA molar ratio of 60:1 (PolyHSA(60:1)) provided superior recovery of blood pressure, microvascular blood flow, and functional capillary density, and acid-base balance, with sustained volume expansion in relation to the volume infused. The high molecular weight of PolyHSA(60:1) increased the hydrodynamic radius and solution viscosity. Pharmacokinetic analysis of PolyHSA(60:1) indicates reduced clearance and increased circulatory half-life compared with monomeric HSA and other PolyHSA formulations. In conclusion, HSA molecular size and solution viscosity affect central hemodynamics, microvascular blood flow, volume expansion, and circulation persistence during small-volume resuscitation from hemorrhagic shock. In addition, PolyHSA can be an alternative to HSA in pathophysiological situations with compromised vascular permeability. Copyright © 2012 Elsevier Inc. All rights reserved.

Recombinant Factor VIIa Reduces Rebleed Hemorrhage Volume in a Swine Aortotomy Model: A Randomized Double-Blinded Study

DTIC Science & Technology

2008-06-01

Bpops,[ a dose of 90 Hg kgj1 will produce serum concentrations of factor VII high enough to reduce hemorrhage by accelerating thrombin production and...interaction is species-specific, and human FVII seems to have only between 5% and 50% activity when exposed to porcine tissue factor (15). The results...Copyright @ 200 by the Shock Society. Unauthorized reproduction of this article is prohibited.8 RECOMBINANT FACTOR VIIA REDUCES REBLEED HEMORRHAGE

[Prehospital use of haemostatic dressing QuikClot ACS+™ for hemorrhage control of a perineal trauma].

PubMed

Travers, S; Dubourg, O; Ribeiro Parenti, L; Lefort, H; Albarello, S; Domanski, L

2012-12-01

First responders are sometimes confronted with external uncontrolled haemorrhage despite compression, bandages, and tourniquets. Several topical haemostatic agents were developed to try to face these situations. Their application was mainly described and studied in military environment. We report the case of a worker victim of an accident of construction site with hemorrhagic perineal trauma for whom the use of a haemostatic bandage QuikClot ACS+™ (Z-Medica) seemed to us particularly useful in prehospital setting. Copyright © 2012 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

Effects of Bovine Polymerized Hemoglobin in Coagulation in Controlled Hemorrhagic Shock in Swine

DTIC Science & Technology

2005-01-01

continuous blood pressure monitoring. A pulmonary artery catheter was also inserted. To mimic soft tissue injury, the rectus abdominus muscle was crushed in...volume by catheter withdrawal of blood over 15 min (;1.7 mL/kg/min). Time 0 designated initiation of the rectus abdominus crush and concomitant hemorrhage

Recombinant Factor XIII Mitigates Hemorrhagic Shock-Induced Organ Dysfunction

PubMed Central

Zaets, Sergey B.; Xu, Da-Zhong; Lu, Qi; Feketova, Eleonora; Berezina, Tamara L.; Malinina, Inga V.; Deitch, Edwin A.; Olsen, Eva H.

2012-01-01

Background Plasma factor XIII (FXIII) is responsible for stabilization of fibrin clot at the final stage of blood coagulation. Since FXIII has also been shown to modulate inflammation, endothelial permeability, as well as diminish multiple organ dysfunction (MOD) after gut ischemia-reperfusion injury, we hypothesized that FXIII would reduce MOD caused by trauma-hemorrhagic shock (THS). Materials and methods Rats were subjected to a 90 min THS or trauma sham shock (TSS) and treated with either recombinant human FXIII A2 subunit (rFXIII) or placebo immediately after resuscitation with shed blood or at the end of the TSS period. Lung permeability, lung and gut myeloperoxidase (MPO) activity, gut histology, neutrophil respiratory burst, microvascular blood flow in the liver and muscles, and cytokine levels were measured 3 h after the THS or TSS. FXIII levels were measured before THS or TSS and after the 3-h post-shock period. Results THS-induced lung permeability as well as lung and gut MPO activity was significantly lower in rFXIII-treated than in placebo-treated animals. Similarly, rFXIII-treated rats had lower neutrophil respiratory burst activity and less ileal mucosal injury. rFXIII-treated rats also had a higher liver microvascular blood flow compared with the placebo group. Cytokine response was more favorable in rFXIII-treated animals. Trauma-hemorrhagic shock did not cause a drop in FXIII activity during the study period. Conclusions Administration of rFXIII diminishes THS-induced MOD in rats, presumably by preservation of the gut barrier function, limitation of polymorphonuclear leukocyte (PMN) activation, and modulation of the cytokine response. PMID:21276979

Clinical analysis of thoracoscopic surgery combined with intraoperative autologous blood transfusion in the treatment of traumatic hemothorax.

PubMed

Ma, Hu-Sai; Ma, Ju-Hua; Xue, Feng-Lai; Fu, Xiang-Ning; Zhang, Ni

2016-12-01

From January 2013 to January 2015, 19 patients of traumatic hemothorax with hemorrhagic shock were treated in our department by thoracoscopic surgery combined with autologous blood transfusion. This study retrospectively analyzed the therapeutic effect and shared our experience. The average amount of blood transfused back was 662.41 ml ± 269.15 ml. None of the patients developed transfusion reaction and were all discharged uneventfully. Thoracoscopic surgery combined with autologous blood trans- fusion is effective in the rescue of patients with progressive hemothorax and hemorrhagic shock. When corresponding indications are well managed, treatment for these patients is quicker, safer, and more effective.

Intraosseous infusion of blood products and epinephrine in an adult patient in hemorrhagic shock.

PubMed

Burgert, James M

2009-10-01

A 79-year-old woman presented in the postanesthesia care unit with hematemesis following replacement of a jejunostomy tube. Her medical history included recurrent stage IIIC ovarian cancer. The patient rapidly decompensated despite blood products administered through the patient's implanted medication port. The anesthesia service was consulted for resuscitative support. Examination revealed an alert, hypotensive elderly female in hemorrhagic shock. While peripheral intravenous (IV) access was sought, her condition further deteriorated. Attempts at peripheral access were determined futile and central venous access would be required. An intraosseous (IO) catheter was placed in the proximal medial aspect of the left tibia using the EZ-IO device (Vidacare Corp, San Antonio, Texas). Crystalloid and colloid fluids, blood products, and drugs were administered via the IO route, stabilizing the patient's condition during the central access procedure. The IO route was used throughout the resuscitative effort. Hemostasis was achieved, and the patient was admitted to the intensive care unit. Intraosseous infusion is a valuable and underutilized technique in managing patients in hemorrhagic shock with poor IV access. Anesthesia providers should seek education and training from those experienced in IO placement techniques and consider use of the IO route early in the resuscitative process.

Bladder mucosa pH and Pco2 as a minimally invasive monitor of hemorrhagic shock and resuscitation.

PubMed

Clavijo-Alvarez, Julio A; Sims, Carrie A; Menconi, Michael; Shim, Inbo; Ochoa, Christian; Puyana, Juan Carlos

2004-12-01

Continuous monitoring of pH, Pco2, and Po2 using fiberoptic sensor technology has been proposed recently as a clinical monitor of the severity of shock and impaired tissue perfusion. Surrogates of gut tissue perfusion such as gastric tonometry, although cumbersome, have been used to indirectly quantify the degree of gut ischemia. The purpose of this study was to demonstrate the feasibility of monitoring bladder mucosa (BM) and to compare urinary bladder mucosa and proximal jejunum mucosa interstitial pH and Pco2 during hemorrhagic shock and resuscitation. Eleven male miniature swine (25-35 kg) (control, n = 4; shock, n = 7) underwent jejunal tonometry and cystostomy. A multisensor probe was placed adjacent to the BM. Urine was diverted. Normocarbia was maintained. Animals were hemorrhaged and kept at a mean arterial pressure of 40 mm Hg. When a constant infusion was required to maintain the mean arterial pressure at 40 mm Hg (decompensation), animals were resuscitated with shed blood plus two times the shed volume in lactated Ringer's solution (20 minutes) and observed for 2 hours. During decompensation, BM pH values decreased significantly from 7.33 +/- 0.08 to 7.01 +/- 0.2 (p < 0.01) and recovered to 7.11 +/- 0.19 at 120 minutes after completion of resuscitation. During decompensation, BM Pco2 values increased significantly compared with baseline (from 49 +/- 6 mm Hg to 71 +/- 19 mm Hg, p < 0.05) and returned to baseline with resuscitation. Jejunum mucosa and BM interstitial Pco2 correlated throughout shock and resuscitation (r = 0.49). Bland-Altman analysis demonstrated significant differences between jejunum mucosa (intramucosal pH) and BM interstitial pH. Shock-induced changes in the Pco2 of the BM are comparable to tonometric changes in the gut. These data suggest that continuous fiberoptic multisensor probe monitoring of the BM could potentially provide a minimally invasive method for the assessment of impaired tissue perfusion of the splanchnic circulation during shock and resuscitation.

ET-26 hydrochloride (ET-26 HCl) has similar hemodynamic stability to that of etomidate in normal and uncontrolled hemorrhagic shock (UHS) rats.

PubMed

Wang, Bin; Chen, Shouming; Yang, Jun; Yang, Linghui; Liu, Jin; Zhang, Wensheng

2017-01-01

ET-26 HCl is a promising sedative-hypnotic anesthetic with virtually no effect on adrenocortical steroid synthesis. However, whether or not ET-26 HCl also has a sufficiently wide safety margin and hemodynamic stability similar to that of etomidate and related compounds remains unknown. In this study, the effects of ET-26 HCl, etomidate and propofol on therapeutic index, heart rate (HR), mean arterial pressure (MAP), maximal rate for left ventricular pressure rise (Dmax/t), and maximal rate for left ventricular pressure decline (Dmin/t) were investigated in healthy rats and a rat model of uncontrolled hemorrhagic shock (UHS). 50% effective dose (ED50) and 50% lethal dose (LD50) were determined after single bolus doses of propofol, etomidate, or ET-26 HCl using the Bliss method and the up and down method, respectively. All rats were divided into either the normal group and received either etomidate, ET-26 HCl or propofol, (n = 6 per group) or the UHS group and received either etomidate, ET-26 HCl or propofol, (n = 6 per group). In the normal group, after preparation for hemodynamic and heart-function monitoring, rats were administered a dose of one of the test agents twofold-higher than the established ED50, followed by hemodynamic and heart-function monitoring. Rats in the UHS group underwent experimentally induced UHS with a target arterial pressure of 40 mmHg for 1 hour, followed by administration of an ED50 dose of one of the experimental agents. Blood-gas analysis was conducted on samples obtained during equilibration with the experimental setup and at the end of the experiment. In the normal group, no significant differences in HR, MAP, Dmax/t and Dmin/t (all P > 0.05) were observed at any time point between the etomidate and ET-26 HCl groups, whereas HR, MAP and Dmax/t decreased briefly and Dmin/t increased following propofol administration. In the UHS group, no significant differences in HR, MAP, Dmax/t and Dmin/t were observed before and after administration of etomidate or ET-26 HCl at ED50 doses (all P > 0.05). Administration of propofol resulted in brief, statistically significant reductions in HR and Dmax/t, with a brief increase in Dmin/t (P ˂ 0.05), while no significant differences in MAP were observed among the three groups. The blood-lactate concentrations of rats in the ET-26 HCl group were significantly lower than those in etomidate and propofol groups (P ˂ 0.05). ET-26 HCl provides a similar level of hemodynamic stability to that obtained with etomidate in both healthy rats, and rat models of UHS. ET-26 HCl has the potential to be a novel induction anesthetic for use in critically ill patients.

Administration of recombinant interleukin-11 improves the hemodynamic functions and decreases third space fluid loss in a porcine model of hemorrhagic shock and resuscitation.

PubMed

Honma, Kaneatsu; Koles, Nancy L; Alam, Hasan B; Rhee, Peter; Rollwagen, Florence M; Olsen, Cara; Keith, James C; Pollack, Matthew

2005-06-01

We have previously demonstrated that the administration of recombinant human interleukin-11 (rhIL-11) during resuscitation improves the blood pressure in a rodent model of hemorrhagic shock. The purpose of this study was to determine whether the effects of rhIL-11 could be reproduced in a large animal model and to elucidate the impact of rhIL-11 administration on the intravascular volume status and the degree of third space fluid loss after resuscitation. A 40% blood volume hemorrhage was induced in swine (n = 45, weight of 25-35 kg) followed by a 1-h shock period and resuscitation with 0.9% sodium chloride (three times the shed blood volume). The animals were randomized to receive sham hemorrhage (group I, sham); sham hemorrhage and 50 microg/kg rhIL-11 (group II, sham + IL-11); no drug (group III, saline); or 50 microg/kg rhIL-11 (group IV, IL-11). Blood and urine samples were obtained and analyzed at baseline, at the end of hemorrhaging, and thereafter once every hour. The pleural and peritoneal effusions were precisely quantified by using clinically accepted criteria. The mean arterial pressure (MAP) was higher postresuscitation (PR) in groups I, II, and IV (71.4 +/- 7.5 mmHg, 71.0 +/- 8.9 mmHg, and 72.9 +/- 12.3 mmHg, respectively) than in group III (59.9 +/- 10.9 mmHg), and the cardiac output of PR was higher in group IV (3.46 +/- 0.56 L/min) than in group III (2.99 +/- 0.62 L/min; P < 0.01). The difference in MAP between groups I and II became statistically significant at 40 min after rhIL-11 injection and such a difference persisted for 90 min. After resuscitation, the urine output was higher, and the urine specific gravity and third space fluid loss were lower in group IV (1434 +/- 325 mL and 1.0035, 82 +/- 21 mL) than in group III (958 +/- 390 mL and 1.0053, 125 +/- 32 mL; P < 0.05). In a porcine model of hemorrhagic shock, the administration of rhIL-11 at the start of resuscitation significantly improved the cardiac output and blood pressure. This strategy also significantly reduced the extent of third space fluid losses while also having a favorable impact on the intravascular volume status as evidenced by the improved urine output.

Disseminated viridians streptococcus (Streptococcus mitis) infection presenting with toxic shock-like syndrome.

PubMed

Intalapaporn, Poj; Wongcharoen, Sunee; Chinapha, Anongnart; Jariyasethpong, Tavatchai

2013-03-01

The authors report a case of a 35-year-old man with no known underlying disease who presented with fever, cellulitis with hemorrhagic blebs on the left leg, monoarthricular left knee arthritis, multiple organ failure and septic shock. His clinical syndrome was compatible with toxic shock syndrome and his blood grew alpha hemolytic (viridians) Streptococcus mitis. To our knowledge, there are few reported cases of toxic shock syndrome cause by Streptococcus mitis in immune-competent adults.

Effects of C1 Inhibitor on Tissue Damage in a Porcine Model of Controlled Hemorrhage

DTIC Science & Technology

2012-07-01

and cytokine release and improves metabolic acidosis in a porcine model of hemorrhagic shock. Male Yorkshire swine were assigned to experimental groups...damage in a dose-dependent man- ner (100 and 250 IU/kg). In addition, rhC1-INH (250 IU/kg) markedly improved hemorrhage-induced metabolic acidosis ... acidosis , reduced circulating tumor necrosis factor !, and attenuated tissue damage in this model. The observed beneficial effects of rhC1-INH treatment on

HSD is a better resuscitation fluid for hemorrhagic shock with pulmonary edema at high altitude.

PubMed

Liu, Liang-Ming; Hu, De-Yao; Zhou, Xue-Wu; Liu, Jiang-Cang; Li, Ping

2008-12-01

To investigate the fluid tolerance of hemorrhagic shock with pulmonary edema (HSPE) at high altitude in unacclimated rats and the beneficial effect of 7.5% hypertonic saline/6% dextran (HSD). One hundred seventy-six Sprague-Dawley rats, transported to LaSa, Tibet, 3,760 m above the sea level, were anesthetized with sodium pentobarbital (30 mg/kg, i.p.) within 1 week. Hemorrhagic shock with pulmonary edema was induced by bloodletting (50 mmHg for 1 h) plus intravenous injection of oleic acid (50 microL/kg). Seventy-seven rats were equally divided into 11 groups (n = 7/group) including sham-operated control group; hemorrhagic shock control group; HSPE control group; HSPE plus 0.5-, 1.0-, 1.5-, 2.0-, or 3.0-fold volumes of lactated Ringer's solution (LR) groups; and HSPE plus 4, 6, and 8 mL/kg of HSD groups. Hemodynamic parameters including mean arterial blood pressure, left intraventricular systolic pressure, and the maximal change rate of intraventricular pressure rise or decline (+/-dp/dtmax) were observed at baseline and at 15, 30, 60, and 120 min after infusion; blood gases were measured at 30 and 120 min after infusion, and the water content of lung and brain was determined at 120 min after infusion. Additional 99 rats were used to observe the effect of these treatments on the survival time of HSPE rats; 0.5 volume of LR infusion slightly increased the mean arterial blood pressure, left intraventricular systolic pressure, and +/-dp/dtmax and prolonged the survival time of HSPE animals as compared with the HSPE group (P < 0.05 - 0.01); it did not increase the water content of lung and brain and had no marked influences on blood gases. One volume of LR infusion had somewhat improved the hemodynamic parameters for HSPE animals, but had no apparent effect on the survival time and the water content of lung and brain. Lactate Ringer's solution infusion, 1.5, 2, and 3 volumes, significantly deteriorated the hemodynamic parameters, increased the water content of lung, and decreased the survival time of HSPE animals. Hypertonic saline/6% dextran (4 - 8 mL/kg) significantly increased the hemodynamic parameters, improved the blood gases, decreased the water content of lung and brain, and prolonged the survival time of HSPE rats. Among the three dosages of HSD, 6 mL/kg of HSD had the best effect. The tolerance of fluid infusion for hemorrhagic shock with pulmonary edema at high altitude is significantly decreased. More than one volume of LR infusion would aggravate the pulmonary edema and exacerbate the resuscitation effect, but only one volume of LR cannot reach the effective volume resuscitation. Small volume of HSD could better resuscitate hemorrhagic shock with pulmonary edema at high altitude.

Captopril and the intestinal response to hemorrhagic shock.

PubMed

Rosenfeld, L M; Cooper, H S

1982-09-01

In order to help clarify the role of the renin-angiotensin system in the evolution of the post-hemorrhagic circulatory shock syndrome, captopril, a potent inhibitor of the conversion of angiotensin I to angiotensin II, was infused into a hemorrhagic shock model in the cat. The hemorrhage protocol had arterial blood withdrawn until a mean arterial blood pressure (MABP) of 40 mm Hg developed. Oligemia was maintained for a period of 2.5 hr, after which time, all remaining shed blood was reinfused and the cats observed for an additional 2 hr. Coincident with the large reduction in MABP, superior mesenteric artery flow (SMAF) was similarly reduced as recorded by a noncannulating electromagnetic flow probe fitted around the artery. Post-oligemic plasma activities of cathepsin D (CD) and alkaline phosphatase (AP) were elevated 11-fold and 3-fold respectively; intestinal morphological damage was graded at 2.8 +/- 0.6 on a 0-4 scale of increasing severity (control: 0.03 +/- 0.02). Captopril was administered at an initial priming dose of 0.5 mg/kg followed by a continuous infusion of 0.5 mg/kg/hr. Improved post-reinfusion maintenance of MABP and SMAF was noted. Plasma elevations in enzyme activity were more moderate: 8-fold for CD, 1.5-fold for AP. Intestinal morphologic damage was graded at 2.5 +/- 0.3. Blockade of angiotensin II formation by captopril thus demonstrated beneficial effects on post-oligemic hemodynamic status and on the degree of cellular enzyme release without significant improvement in intestinal morphology.

Freewheel running prevents learned helplessness/behavioral depression: role of dorsal raphe serotonergic neurons.

PubMed

Greenwood, Benjamin N; Foley, Teresa E; Day, Heidi E W; Campisi, Jay; Hammack, Sayamwong H; Campeau, Serge; Maier, Steven F; Fleshner, Monika

2003-04-01

Serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) are implicated in mediating learned helplessness (LH) behaviors, such as poor escape responding and expression of exaggerated conditioned fear, induced by acute exposure to uncontrollable stress. DRN 5-HT neurons are hyperactive during uncontrollable stress, resulting in desensitization of 5-HT type 1A (5-HT1A) inhibitory autoreceptors in the DRN. 5-HT1A autoreceptor downregulation is thought to induce transient sensitization of DRN 5-HT neurons, resulting in excessive 5-HT activity in brain areas that control the expression of learned helplessness behaviors. Habitual physical activity has antidepressant/anxiolytic properties and results in dramatic alterations in physiological stress responses, but the neurochemical mediators of these effects are unknown. The current study determined the effects of 6 weeks of voluntary freewheel running on LH behaviors, uncontrollable stress-induced activity of DRN 5-HT neurons, and basal expression of DRN 5-HT1A autoreceptor mRNA. Freewheel running prevented the shuttle box escape deficit and the exaggerated conditioned fear that is induced by uncontrollable tail shock in sedentary rats. Furthermore, double c-Fos/5-HT immunohistochemistry revealed that physical activity attenuated tail shock-induced activity of 5-HT neurons in the rostral-mid DRN. Six weeks of freewheel running also resulted in a basal increase in 5-HT1A inhibitory autoreceptor mRNA in the rostral-mid DRN. Results suggest that freewheel running prevents behavioral depression/LH and attenuates DRN 5-HT neural activity during uncontrollable stress. An increase in 5-HT1A inhibitory autoreceptor expression may contribute to the attenuation of DRN 5-HT activity and the prevention of LH in physically active rats.

A Novel Swine Model for Evaluation of Potential Intravascular Hemostatic Agents

DTIC Science & Technology

2007-06-01

bovine polymerized hemoglobin on coagulation in controlled hemorrhagic shock in swine. Shock 24:145–152. 2. Bellamy RF. 1984. The causes of death in...WZ, Pusateri AE, Uscilowicz JM, Delgado AV, Holcomb JB. 2005. Independent contributions of hypothermia and acidosis to coagulopathy in swine. J

Ion Movements in Shock in Relation to Survival and Its Modifications

DTIC Science & Technology

1985-01-01

from normal to irreversibly injured are initiated and modified by primary and/or secondary effects of ion redistributions taking place between the...reactions to injury by the shock state has become possible. However, spcclflc aspects concerning effects at the cellular and subcellular levels need...to be further clarified. Therefore, the aim of this study was to characterize the cellular and subcellular effects of hemorrhagic and bacteremic shock

NRC/AMRMC Resident Research Associateship Program

DTIC Science & Technology

2013-04-01

Intravital Microscopy was successfully employed for investigating EG shedding in hemorrhagic shock/resuscitation for the very first time; Contract... Intravital microscopy integrated with systemic hemodynamics evaluations may be essential and more accurate tools to identify changes and study...findings in concise form, utilizing key concepts/words. 1) Intravital Microscopy was successfully employed for investigating EG shedding in hemorrhagic

Clinical and clinical laboratory correlates in sea otters dying unexpectedly in rehabilitation centers following the Exxon Valdez oil spill

USGS Publications Warehouse

Rebar, A.H.; Lipscomb, T.P.; Harris, R.K.; Ballachey, Brenda E.

1995-01-01

Following the Exxon Valdez oil spill, 347 oiled sea otters (Enhydra lutris) were treated in rehabilitation centers. Of these, 116 died, 94 within 10 days of presentation. Clinical records of 21 otters dying during the first 10 days of rehabilitation were reviewed to define the laboratory abnormalities and clinical syndromes associated with these unexpected deaths. The most common terminal syndrome was shock characterized by hypothermia, lethargy, and often hemorrhagic diarrhea. In heavily and moderately oiled otters, shock developed within 48 hours of initial presentation, whereas in lightly oiled otters shock generally occurred during the second week of captivity. Accompanying laboratory abnormalities included leukopenia with increased numbers of immature neutrophils (degenerative left shift), lymphopenia, anemia, azotemia (primarily prerenal), hyperkalemia, hypoproteinemia/hypoalbuminemia, elevations of serum transaminases, and hypoglycemia. Shock associated with hemorrhagic diarrhea probably occurred either as a direct primary effect of oiling or as an indirect effect secondary to confinement and handling in the rehabilitation centers. Lightly oiled otters were less likely to die from shock than were heavily oiled otters (22% vs. 72%, respectively). Heavily oiled otters developed shock more rapidly and had greater numbers of laboratory abnormalities, suggesting that exposure to oil was an important contributing factor.

Hypothermia is associated with improved outcomes in a porcine model of hemorrhagic shock.

PubMed

George, Mark E; Mulier, Kristine E; Beilman, Greg J

2010-03-01

: Hypothermia after trauma is, in current medical practice, both avoided and aggressively treated. However, the effects of environmental hypothermia during early resuscitation after hemorrhagic shock have been only poorly characterized. : The objective of our study was to compare normothermia versus mild and severe levels of hypothermia in a porcine model of hemorrhagic shock. In a prospective survival study, we anesthetized 19 juvenile male pigs (Yorkshire-Landrace, 15-25 kg) and caused them to hemorrhage until their systolic blood pressure was 45 mm Hg to 55 mm Hg for a duration of 45 minutes. Then, we randomized them into three groups (all of which underwent an 8-hour limited resuscitation period) as follows: normothermic (39 degrees C), mildly hypothermic (36 degrees C), and severely hypothermic (33 degrees C). We used ice packs to achieve surface cooling that mimicked environmental hypothermia. After 8 hours, we rewarmed the pigs and fully resuscitated them for 16 hours. We extubated the survivors and observed them for an additional 24 hours, before killing them. : Surface cooling resulted in significant reduction in core body temperature. The mortality rate was significantly higher in the normothermic group (60%) than in the two hypothermic groups combined (7%) (p = 0.015) or in the severely hypothermic group (0%) (p = 0.023). Hypothermic animals had significantly lower levels of creatinine kinase, lactate dehydrogenase, and lactate in addition to a lower base deficit after shock. However, severely hypothermic animals required greater volumes of colloid infusion and whole blood transfusion to maintain our target systolic blood pressure and hemoglobin levels when compared with normothermic animals. We saw a strong trend toward decreased oxygen consumption with hypothermia. : In our porcine model, we found that simulating mild and severe levels of environmental hypothermia during early resuscitation after hemorrhage was associated with a significantly decreased mortality rate. Furthermore, markers of cellular stress and organ dysfunction, including lactate levels and the base deficit, were lower in hypothermic animals. Decreasing oxygen consumption with hypothermia may, in part, explain the protective effects observed with hypothermia.

[Effects of granulocyte-macrophage colony stimulating factor on nuclear factor-KappaB activation in multiple organs of hemorrhage-induced acute lung injury in mice].

PubMed

Wang, Qian; Song, Yong; Shi, Yi

2007-05-01

To investigate the effects of nuclear factor-KappaB (NF-KappaB) activation in multiple organs of hemorrhage-induced acute lung injury (ALI) by the specific granulocyte-macrophage colony stimulating factor (GM-CSF)-neutralizing antibody (22E9) and dexamethasone (DEX) in mice. Twenty male C57BL/6 mice were used to reproduce a model of hemorrhagic shock by cardiac puncture. Before cardiac puncture, mice in different groups were transnasally administered with phosphate buffered solution (PBS, PCG group), PBS plus 1 microg 22E9 (HS1 group), PBS plus 10 microg 22E9 (HS10 group) and PBS plus 20 microg DEX (DEX group), respectively. In negative control group (NCG group) received cardiac puncture without shock followed by transnasal administration with PBS without shock. Lungs, hearts, livers and kidneys tissues of mice were harvested at 4 hours after hemorrhagic shock. The activities of NF-KappaB in different organs was determined by electrophoretic mobility shift assay (EMSA). The tumor necrosis factor-alpha (TNF-alpha) in lung and heart were determined by enzyme-linked immunosorbent assay (ELISA). 22E9 in both low or high doses could significantly inhibit NF-KappaB activities in lung, heart and liver, and elevated NF-KappaB activity in kidney compared with those of PCG group (all P<0.05). The effect of 22E9 was much better in HS1 group than in HS10 group (all P<0.05). DEX significantly strengthened NF-KappaB activity in kidney (P<0.05) and didn't significantly inhibit NF-KappaB activities in heart and liver compared with those of PCG group. 22E9 significantly inhibited TNF-alpha in lung and heart, while DEX significantly inhibited TNF-alpha in heart (all P<0.05). 22E9 can inhibit the NF-KappaB activation and inflammatory reaction in multiple organs after hemorrhage-induced ALI and reduce injury in multiple organs, while DEX has no significant effect.

Pathological examination of cerebral amyloid angiopathy in patients who underwent removal of lobar hemorrhages.

PubMed

Lin, Chien-Min; Arishima, Hidetaka; Kikuta, Ken-Ichiro; Naiki, Hironobu; Kitai, Ryuhei; Kodera, Toshiaki; Matsuda, Ken; Hashimoto, Norichika; Isozaki, Makoto; Tsunetoshi, Kenzo; Neishi, Hiroyuki; Higashino, Yoshifumi; Akazawa, Ayumi; Arai, Hiroshi; Yamada, Shinsuke

2018-03-01

Cerebral amyloid angiopathy (CAA) is a degenerative disorder characterized by amyloid-β (Aβ) deposition in the brain microvessels. CAA is also known to contribute not only to cortical microbleeds but also lobar hemorrhages. This retrospective study examined CAA pathologically in patients who underwent direct surgeries for lobar hemorrhage. Thirty-three patients with lobar hemorrhage underwent open surgery with biopsy from 2007 to 2016 in our hospital. Cortical tissues over hematomas obtained surgically were pathologically examined using hematoxylin, eosin stain, and anti-Aβ antibody to diagnose CAA. We also investigated the advanced degree of CAA and clinical features of each patient with lobar hemorrhage. In the 33 patients, 4 yielded specimens that were insufficient to evaluate CAA pathologically. Twenty-four of the remaining 29 patients (82.8%) were pathologically diagnosed with CAA. The majority of CAA-positive patients had moderate or severe CAA based on a grading scale to estimate the advanced degree of CAA. About half of the CAA-positive patients had hypertension, and four took anticoagulant or antiplatelet agents. In five patients who were not pathologically diagnosed with CAA, one had severe liver function disorder, three had uncontrollable hypertension, and one had no obvious risk factor. Our pathological findings suggest that severe CAA with vasculopathic change markedly contributes to lobar hemorrhage. The coexistence of severe CAA and risk factors such as hypertension, anticoagulants or antiplatelets may readily induce lobar hemorrhage.

Strategies of experiment standardization and response optimization in a rat model of hemorrhagic shock and chronic hypertension.

PubMed

Reynolds, Penny S; Tamariz, Francisco J; Barbee, Robert Wayne

2010-04-01

Exploratory pilot studies are crucial to best practice in research but are frequently conducted without a systematic method for maximizing the amount and quality of information obtained. We describe the use of response surface regression models and simultaneous optimization methods to develop a rat model of hemorrhagic shock in the context of chronic hypertension, a clinically relevant comorbidity. Response surface regression model was applied to determine optimal levels of two inputs--dietary NaCl concentration (0.49%, 4%, and 8%) and time on the diet (4, 6, 8 weeks)--to achieve clinically realistic and stable target measures of systolic blood pressure while simultaneously maximizing critical oxygen delivery (a measure of vulnerability to hemorrhagic shock) and body mass M. Simultaneous optimization of the three response variables was performed though a dimensionality reduction strategy involving calculation of a single aggregate measure, the "desirability" function. Optimal conditions for inducing systolic blood pressure of 208 mmHg, critical oxygen delivery of 4.03 mL/min, and M of 290 g were determined to be 4% [NaCl] for 5 weeks. Rats on the 8% diet did not survive past 7 weeks. Response surface regression model and simultaneous optimization method techniques are commonly used in process engineering but have found little application to date in animal pilot studies. These methods will ensure both the scientific and ethical integrity of experimental trials involving animals and provide powerful tools for the development of novel models of clinically interacting comorbidities with shock.

Noninvasive NIR measurement of tissue pH to assess hemorrhagic shock in swine

NASA Astrophysics Data System (ADS)

Soller, Babs R.; Zhang, Songbiao; Micheels, Ronald H.; Puyana, Juan C.

1999-07-01

Body-worn noninvasive physilogical sensors are needed to continuously monitor soldiers for hemorrhage and to provide real-time information for minimally skilled medics to treat the injured. In the hospital intramucosal pHi of the gut is used to monitor shock and its treatment. We hypothesize that abdominal wall muscle (AWM) pH can be measured noninvasively using near infrared (NIR) spectroscopy and partial least squares analysis (PLS) and will correlate with pHi. METHODS: AWM pH was measured with microelectrodes and gastric pHi was measured with a tonometric catheter simultaneously while NIR spectra were collected using prototype LED spectrometers placed on the pig's flanks. Animals were subject to hemorrhagic shock at 45 mm Hg for 45 minutes, then resuscitated with blood and lactated ringers. Relationships between electrode pH, pHi and NIR spectra were developed using PLS with cross validation. RESULTS: NIR spectral changes noninvasively acquired through the skin were shown to be from the muscle, not from changes in skin blood flow. Trending ability (R2) model accuracy (RMSD), and relative error were calculated for individual pigs. Using electrode pH as the reference, average R2 was 0.88 with a predicted accuracy of 0.17 pH units, a 9.3% relative error. Slightly degraded results were observed when pHi was used as a reference. CONCLUSIONS: NIR measurement of tissue pH can be used to noninvasively monitor for shock and guide its treatment in a swine model. These measurements correlate with gastric pHi, a clinically accepted measure of shock, providing an approach to develop similar methodology for humans.

Inhaled, Nebulized Sodium Nitrite Protects In Murine and Porcine Experimental Models Of Hemorrhagic Shock and Resuscitation by Limiting Mitochondrial Injury

PubMed Central

Kautza, Benjamin; Gomez, Hernando; Escobar, Daniel; Corey, Catherine; Ataya, Bilal; Luciano, Jason; Botero, Ana Maria; Gordon, Lisa; Brumfield, John; Martinez, Silvia; Holder, Andre; Ogundele, Olufunmilayo; Pinsky, Michael; Shiva, Sruti; Zuckerbraun, Brian S.

2015-01-01

Objective The cellular injury that occurs in the setting of hemorrhagic shock and resuscitation (HS/R) affects all tissue types and can drive altered inflammatory responses. Resuscitative adjuncts hold the promise of decreasing such injury. Here we test the hypothesis that sodium nitrite (NaNO2), delivered as a nebulized solution via an inhalational route, protects against injury and inflammation from HS/R. Methods Mice underwent HS/R to a mean arterial pressure (MAP) of 20 or 25 mmHg. Mice were resuscitated with Lactated Ringers after 90–120 minutes of hypotension. Mice were randomized to receive nebulized NaNO2 via a flow through chamber (30mg in 5mL PBS). Pigs (30–35 kg) were anesthetized and bled to a MAP of 30–40 mmHg for 90 minutes, randomized to receive NaNO2 (11 mg in 2.5 mL PBS) nebulized into the ventilator circuit starting 60 minutes into the hypotensive period, followed by initial resuscitation with Hextend. Pigs had ongoing resuscitation and support for up to four hours. Hemodynamic data were collected continuously. Results NaNO2 limited organ injury and inflammation in murine hemorrhagic shock. A nitrate/nitrite depleted diet exacerbated organ injury, as well as mortality, and inhaled NaNO2 significantly reversed this effect. Furthermore, NaNO2 limited mitochondrial oxidant injury. In porcine HS/R, NaNO2 had no significant influence on shock induced hemodynamics. NaNO2 limited hypoxia/reoxia or HS/R-induced mitochondrial injury and promoted mitochondrial fusion. Conclusion NaNO2 may be a useful adjunct to shock resuscitation based on its limitation of mitochondrial injury. PMID:26410351

Nonhuman primate model of polytraumatic hemorrhagic shock recapitulates early platelet dysfunction observed following severe injury in humans.

PubMed

Schaub, Leasha J; Moore, Hunter B; Cap, Andrew P; Glaser, Jacob J; Moore, Ernest E; Sheppard, Forest R

2017-03-01

Platelet dysfunction has been described as an early component of trauma-induced coagulopathy. The platelet component of trauma-induced coagulopathy remains to be fully elucidated and translatable animal models are required to facilitate mechanistic investigations. We sought to determine if the early platelet dysfunction described in trauma patients could be recapitulated in a nonhuman primate model of polytraumatic hemorrhagic shock. Twenty-four male rhesus macaques weighting 7 to 14 kg were subjected to 60 minutes (min) of severe pressure-targeted controlled hemorrhagic shock (HS) with and without other injuries. After 60 min, resuscitation with 0.9% NaCl and whole blood was initiated. Platelet counts and platelet aggregation assays were performed at baseline (BSLN), end of shock (EOS; T = 60 min), end of resuscitation (EOR; T = 180 min), and T = 360 min on overall cohort. Results are reported as mean ± standard deviation (SD) or median (interquartile range). Statistical analysis was conducted using Spearmen correlation, one-way analysis of variance, two-way repeated-measures analysis of variance, paired t-test or Wilcoxon nonparametric test, with p < 0.05 considered significant. Platelet count in all injury cohorts decreased over time, but no animals developed thrombocytopenia. Correlations were observed between platelet aggregation and platelet count for all agonists: adenosine diphosphate, thrombin recognition-activating peptide-6, collagen, and arachidonic acid. Overall, compared to BSLN, platelet aggregation decreased for all agonist at EOS, EOR, and T = 360 min. When normalized to platelet count, platelet aggregation in response to agonist thrombin recognition-activating peptide-6 demonstrated no change from BSLN at subsequent time points. Aggregation to adenosine diphosphate was significantly less at EOR but not EOS or T = 360 min compared to BSLN. Platelet aggregation to collagen and arachidonic acid was not significantly different at EOS compared to BSLN but was significantly less at EOR and T = 360 min. Nonhuman primates manifest early platelet dysfunction in response to polytraumatic hemorrhagic shock, consistent with that reported in severely injured human patients. Nonhuman primate models potentially are translationally valuable for understanding the mechanisms and pathophysiology of trauma-induced platelet dysfunction.

Plasmapheresis in severe septic shock with disseminated intravascular coagulation.

PubMed

Zilow, E P; Selle, B; Zilow, G

1994-01-01

An 18-year-old female with CNS relapse of acute lymphoblastic leukemia after previous complete remission of the disease underwent chemotherapy. Due to the therapy she suffered from profound suppression of bone marrow with consecutive thrombocytopenia and leukopenia. Despite prophylactic treatment, severe septicemia occurred with septic shock, hemolysis and disseminated intravascular coagulation (DIC). As the clinical course became uncontrollable by means of conventional therapy, including broad-spectrum antibiotics, substitution of fresh frozen plasma, antithrombin III and heparin therapy, plasma exchange was used as a rescue therapy. This method succeeded in effective replacement of clotting factors and normalization of coagulation, in removal of fibrinogen degradation products and probably of toxins and shock mediators. The patient recovered from shock.

Hemorrhagic Shock-Induced Vascular Hyporeactivity in the Rat: Relationship to Gene Expression of Nitric Oxide Synthase, Endothelin-1, and Select Cytokines in Corresponding Organs

DTIC Science & Technology

2005-01-01

the Selected Genes Sense Antisense Product length (bp) G3PDH 5=-TCCTGCACCACCAACTGCTTAG-3= 5=-TGCTTCACCACCTTCTTGATGTC-3= 341 iNOS 5...GAPDH, as a housekeeping gene, was not affected significantly by the hemorrhage protocol. The results showed that mRNA levels of all enzymes and

NRC/AMRMC Resident Research Associateship Program

DTIC Science & Technology

2013-03-01

Luciana 5/18/2011-8/17/2012 1 Intravital Microscopy was successfully employed for investigating EG shedding in hemorrhagic shock/resuscitation for...05/2013 3/18/2013, 3:21 PM 2 Intravital microscopy integrated with systemic hemodynamics evaluations may be essential and more accurate tools to...concise form, utilizing key concepts/words. 1) Intravital Microscopy was successfully employed for investigating EG shedding in hemorrhagic

Cognitive Function and Heat Shock Protein 70 in Children With Temporal Lobe Epilepsy.

PubMed

Oraby, Azza M; Raouf, Ehab R Abdol; El-Saied, Mostafa M; Abou-Khadra, Maha K; Helal, Suzette I; Hashish, Adel F

2017-01-01

We conducted the present study to examine cognitive function and serum heat shock protein 70 levels among children with temporal lobe epilepsy. The Stanford-Binet Intelligence Test was carried out to examine cognitive function in 30 children with temporal lobe epilepsy and 30 controls. Serum heat shock protein 70 levels were determined with an enzyme-linked immunosorbent assay. The epilepsy group had significantly lower cognitive function testing scores and significantly higher serum heat shock protein 70 levels than the control group; there were significant negative correlations between serum heat shock protein 70 levels and short-term memory and composite scores. Children with uncontrolled seizures had significantly lower verbal reasoning scores and significantly higher serum heat shock protein 70 levels than children with controlled seizures. Children with temporal lobe epilepsy have cognitive dysfunction and elevated levels of serum heat shock protein 70, which may be considered a stress biomarker.

Fluid resuscitation: past, present, and the future.

PubMed

Santry, Heena P; Alam, Hasan B

2010-03-01

Hemorrhage remains a major cause of preventable death following both civilian and military trauma. The goals of resuscitation in the face of hemorrhagic shock are restoring end-organ perfusion and maintaining tissue oxygenation while attempting definitive control of bleeding. However, if not performed properly, resuscitation can actually exacerbate cellular injury caused by hemorrhagic shock, and the type of fluid used for resuscitation plays an important role in this injury pattern. This article reviews the historical development and scientific underpinnings of modern resuscitation techniques. We summarized data from a number of studies to illustrate the differential effects of commonly used resuscitation fluids, including isotonic crystalloids, natural and artificial colloids, hypertonic and hyperoncotic solutions, and artificial oxygen carriers, on cellular injury and how these relate to clinical practice. The data reveal that a uniformly safe, effective, and practical resuscitation fluid when blood products are unavailable and direct hemorrhage control is delayed has been elusive. Yet, it is logical to prevent this cellular injury through wiser resuscitation strategies than attempting immunomodulation after the damage has already occurred. Thus, we describe how some novel resuscitation strategies aimed at preventing or ameliorating cellular injury may become clinically available in the future.

Adiponectin in Fresh Frozen Plasma Contributes to Restoration of Vascular Barrier Function after Hemorrhagic Shock

PubMed Central

Huby, Maria P.; Duan, Chaojun; Baer, Lisa; Peng, Zhanglong; Kozar, Rosemary A.; Doursout, Marie-Francoise; Holcomb, John B.; Wade, Charles E.; Ko, Tien C.

2015-01-01

Hemorrhagic shock is the leading cause of preventable deaths in civilian and military trauma. Use of fresh frozen plasma (FFP) in patients requiring massive transfusion is associated with improved outcomes. FFP contains significant amounts of adiponectin, which is known to have vascular protective function. We hypothesize that FFP improves vascular barrier function largely via adiponectin. Plasma adiponectin levels were measured in 19 severely injured patients in hemorrhagic shock (HS). Compared to normal individuals, plasma adiponectin levels decreased to 49% in HS patients prior to resuscitation (p<0.05) and increased to 64% post resuscitation (but not significant). In a HS mouse model, we demonstrated a similar decrease in plasma adiponectin to 54% but a significant increase to 79% by FFP resuscitation compared to baseline (p<0.05). HS disrupted lung vascular barrier function, leading to an increase in permeability. FFP resuscitation reversed these HS-induced effects. Immunodepletion of adiponectin from FFP abolished FFP's effects on blocking endothelial hyperpermeability in vitro, and on improving lung vascular barrier function in HS mice. Replenishment with adiponectin rescued FFP's effects. These findings suggest that adiponectin is an important component in FFP resuscitation contributing to the beneficial effects on vascular barrier function after HS. PMID:26263440

Defining hypotension in moderate to severely injured trauma patients: raising the bar for the elderly.

PubMed

Edwards, Meghan; Ley, Eric; Mirocha, James; Hadjibashi, Anoushiravan Amini; Margulies, Daniel R; Salim, Ali

2010-10-01

Hypotension, defined as systolic blood pressure less than 90 mm Hg, is recognized as a sign of hemorrhagic shock and is a validated prognostic indicator. The definition of hypotension, particularly in the elderly population, deserves attention. We hypothesized that the systolic blood pressure associated with increased mortality resulting from hemorrhagic shock increases with increasing age. The Los Angeles County Trauma Database was queried for all moderate to severely injured patients without major head injuries admitted between 1998 and 2005. Several fit statistic analyses were performed for each systolic blood pressure from 50 to 180 mm Hg to identify the model that most accurately defined hypotension for three age groups. The optimal definition of hypotension for each group was determined from the best fit model. A total of 24,438 patients were analyzed. The optimal definition of hypotension was systolic blood pressure of 100 mm Hg for patients 20 to 49 years, 120 mm Hg for patients 50 to 69 years, and 140 mm Hg for patients 70 years and older. The optimal systolic blood pressure for improved mortality in hemorrhagic shock increases significantly with increasing age. Elderly trauma patients without major head injuries should be considered hypotensive for systolic blood pressure less than 140 mm Hg.

Optimal Surgical Therapy in a Porcine (Sus scrofa) Model of Extra-Thoracic Penetrating Trauma Resulting in Hemorrhagic Shock: ED Thoracotomy vs. Immediate Trans-Abdominal Vascular Control. A Porcine Model for Evaluating the Management of Non-Compressible Torso Hemorrhage

DTIC Science & Technology

2010-11-08

celiac aortic clamping (n=6), direct vascular control (n=6), and endovascular aortic occlusion n=6). This study presents a large animal model of class...including thoracic aortic clamping, supra- celiac aortic clamping, direct vascular control, and proximal endovascular balloon occlusion. Following vascular...subsequently underwent non-compressible hemorrhage with thoracic aortic clamping (n=6), supra- celiac aortic clamping (n=6), direct vascular control (n=6

Deployable, Field-Sustainable, Reverse Transcription-Polymerase Chain Reaction Assays for Rapid Screening and Serotype Identification of Dengue Virus in Mosquitoes

DTIC Science & Technology

2007-03-01

C, Gottig S, Schiiiing S, et ai: Rapid detection and quantiilcation of RNA of Eboia and Marburg viruses, L.assa virus, Crimean - Congo hemorrhagic fever ...the past two decades, dengue fever (DF) and the poten- tially fatal forms ofthe disease, dengue hemorrhagic fever (DHF) and dengue shock syndrome, have...Viroi 2003; 77: i 1436-47. 5. Gubler DJ: Dengue and dengue hemorrhagic fever . Ciin Microbiol Rev 1998; 11: 480-96. 6. Fonseca BA, Fonseca SN: Dengue virus

Improvement of Blood-Brain Barrier Integrity in Traumatic Brain Injury and Hemorrhagic Shock Following Treatment With Valproic Acid and Fresh Frozen Plasma.

PubMed

Nikolian, Vahagn C; Dekker, Simone E; Bambakidis, Ted; Higgins, Gerald A; Dennahy, Isabel S; Georgoff, Patrick E; Williams, Aaron M; Andjelkovic, Anuska V; Alam, Hasan B

2018-01-01

Combined traumatic brain injury and hemorrhagic shock are highly lethal. Following injuries, the integrity of the blood-brain barrier can be impaired, contributing to secondary brain insults. The status of the blood-brain barrier represents a potential factor impacting long-term neurologic outcomes in combined injuries. Treatment strategies involving plasma-based resuscitation and valproic acid therapy have shown efficacy in this setting. We hypothesize that a component of this beneficial effect is related to blood-brain barrier preservation. Following controlled traumatic brain injury, hemorrhagic shock, various resuscitation and treatment strategies were evaluated for their association with blood-brain barrier integrity. Analysis of gene expression profiles was performed using Porcine Gene ST 1.1 microarray. Pathway analysis was completed using network analysis tools (Gene Ontology, Ingenuity Pathway Analysis, and Parametric Gene Set Enrichment Analysis). Female Yorkshire swine were subjected to controlled traumatic brain injury and 2 hours of hemorrhagic shock (40% blood volume, mean arterial pressure 30-35 mmHg). Subjects were resuscitated with 1) normal saline, 2) fresh frozen plasma, 3) hetastarch, 4) fresh frozen plasma + valproic acid, or 5) hetastarch + valproic acid (n = 5 per group). After 6 hours of observation, brains were harvested for evaluation. Immunofluoroscopic evaluation of the traumatic brain injury site revealed significantly increased expression of tight-junction associated proteins (zona occludin-1, claudin-5) following combination therapy (fresh frozen plasma + valproic acid and hetastarch + valproic acid). The extracellular matrix protein laminin was found to have significantly improved expression with combination therapies. Pathway analysis indicated that valproic acid significantly modulated pathways involved in endothelial barrier function and cell signaling. Resuscitation with fresh frozen plasma results in improved expression of proteins essential for blood-brain barrier integrity. The addition of valproic acid provides significant improvement to these protein expression profiles. This is likely secondary to activation of key pathways related to endothelial functions.

Adverse Effects of Hemorrhagic Shock Resuscitation with Stored Blood are Ameliorated by Inhaled Nitric Oxide in Lambs

PubMed Central

Baron, David M.; Beloiartsev, Arkadi; Nakagawa, Akito; Martyn, Trejeeve; Stowell, Christopher P.; Malhotra, Rajeev; Mayeur, Claire; Bloch, Kenneth D.; Zapol, Warren M.

2013-01-01

Objectives Transfusion of stored red blood cells (RBCs) is associated with increased morbidity and mortality in trauma patients. Plasma hemoglobin scavenges nitric oxide (NO), which can cause vasoconstriction, induce inflammation and activate platelets. We hypothesized that transfusion of RBCs stored for prolonged periods would induce adverse effects (pulmonary vasoconstriction, tissue injury, inflammation, and platelet activation) in lambs subjected to severe hemorrhagic shock, and that concurrent inhalation of NO would prevent these adverse effects. Design Animal study. Setting Research laboratory at the Massachusetts General Hospital, Boston, MA. Subjects Seventeen awake Polypay-breed lambs. Interventions Lambs were subjected to 2 h of hemorrhagic shock by acutely withdrawing 50% of their blood volume. Lambs were resuscitated with autologous RBCs stored for 2 h or less (fresh) or 39±2 (mean±SD) days (stored). Stored RBCs were administered with or without breathing NO (80 ppm) during resuscitation and for 21 h thereafter. Measurements and Main Results We measured hemodynamic and oxygenation parameters, markers of tissue injury and inflammation, plasma hemoglobin concentrations, and platelet activation. Peak pulmonary arterial pressure was higher after resuscitation with stored than with fresh RBCs (24±4 vs. 14±2 mmHg, p<0.001) and correlated with peak plasma hemoglobin concentrations (R2=0.56, p=0.003). At 21 h after resuscitation, pulmonary myeloperoxidase activity was higher in lambs resuscitated with stored than with fresh RBCs (11±2 vs. 4±1 U/g, p=0.007). Furthermore, transfusion of stored RBCs increased plasma markers of tissue injury and sensitized platelets to adenosine diphosphate activation. Breathing NO prevented the pulmonary hypertension, and attenuated the pulmonary myeloperoxidase activity, as well as tissue injury and sensitization of platelets to adenosine diphosphate. Conclusions Our data suggest that resuscitation of lambs from hemorrhagic shock with autologous stored RBCs induces pulmonary hypertension and inflammation, which can be ameliorated by breathing NO. PMID:23887236

Self-Propelled Dressings Containing Thrombin and Tranexamic Acid Improve Short-Term Survival in a Swine Model of Lethal Junctional Hemorrhage.

PubMed

Baylis, James R; St John, Alexander E; Wang, Xu; Lim, Esther B; Statz, Matthew L; Chien, Diana; Simonson, Eric; Stern, Susan A; Liggins, Richard T; White, Nathan J; Kastrup, Christian J

2016-09-01

Hemorrhage is the leading cause of preventable death in trauma, and hemorrhage from noncompressible junctional anatomic sites is particularly difficult to control. The current standard is QuikClot Combat Gauze packing, which requires 3 min of compression. We have created a novel dressing with calcium carbonate microparticles that can disperse and self-propel upstream against flowing blood. We loaded these microparticles with thrombin and tranexamic acid and tested their efficacy in a swine arterial bleeding model without wound compression. Anesthetized immature female swine received 5 mm femoral arteriotomies to induce severe junctional hemorrhage. Wounds were packed with kaolin-based QuikClot Combat Gauze (KG), propelled thrombin-microparticles with protonated tranexamic acid (PTG), or a non-propelling formulation of the same thrombin-microparticles with non-protonated tranexamic acid (NPTG). Wounds were not compressed after packing. Each animal then received one 15 mL/kg bolus of hydroxyethyl starch solution followed by Lactated Ringer as needed for hypotension (maximum: 100 mL/kg) for up to 3 h. Survival was improved with PTG (3-h survival: 8/8, 100%) compared with KG (3/8, 37.5%) and NPTG (2/8, 25%) (P <0.01). PTG animals maintained lower serum lactate and higher hemoglobin concentrations than NPTG (P <0.05) suggesting PTG decreased severity of subsequent hemorrhagic shock. However, total blood loss, Lactated Ringer infusion volumes, and mean arterial pressures of surviving animals were not different between groups (P >0.05). Thus, in this swine model of junctional arterial hemorrhage, gauze with self-propelled, prothrombotic microparticles improved survival and 2 indicators of hemorrhagic shock when applied without compression, suggesting this capability may enable better treatment of non-compressible junctional wounds.

Is gut the "motor" for producing hepatocellular dysfunction after trauma and hemorrhagic shock?

PubMed

Wang, P; Ba, Z F; Cioffi, W G; Bland, K I; Chaudry, I H

1998-02-01

Although studies suggest that the gut may be the "motor" responsible for producing sepsis and multiple organ failure after injury, it is not known whether enterectomy prior to the onset of hemorrhage alters proinflammatory cytokines TNF and IL-6 and, if so, whether hepatocellular dysfunction and damage are prevented or attenuated under such conditions. Under methoxyflurane anesthesia, an enterectomy in the rat was performed by excision of the duodenum, jejunum, and ileum. The rats were then bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximal shed volume was returned in the form of Ringer's lactate. The animals were then resuscitated with four times the volume of shed blood with Ringer's lactate over 1 h. At 1.5 h after the completion of resuscitation, hepatocellular function [i.e., the maximal velocity (Vmax) and transport efficiency (Km) of indocyanine green (ICG) clearance] was assessed by an in vivo ICG clearance technique. Blood samples were taken for the measurement of TNF, IL-6, and liver enzymes (i.e., SGPT and SGOT). Cardiac output and microvascular blood flow were determined by ICG dilution and laser Doppler flowmetry, respectively. The increase in circulating levels of TNF but not IL-6 was prevented by enterectomy prior to hemorrhage. The reduced Vmax and K(m) and elevated SGPT and SGOT following hemorrhage and resuscitation, however, were not significantly affected by prior enterectomy. Moreover, enterectomy before hemorrhage further reduced hepatic perfusion. Since enterectomy prior to the onset of hemorrhage does not prevent or attenuate the reduced ICG clearance and elevated liver enzymes despite downregulation of TNF production, it appears that the small intestine does not play a significant role in producing hepatocellular dysfunction and injury following trauma and hemorrhagic shock.

Systemic Effects of Shock and Resuscitation Monitored by Visible Hyperspectral Imaging

DTIC Science & Technology

2003-01-01

organs. Its causes include hemorrhage, cardiac failure, sepsis, hypoglycemia , and burns; the pathophysiology of these various shock states is quite...different. Depending on the cause of shock, the skin is one organ that readily manifests its ef- fects. The importance of skin oxygenation is well known...attachment of a 7.5-cm-diameter plate to the bolt, was used to cause a blunt right chest injury. A tube thora- costomy was immediately performed. After a

76 FR 64223 - Cardiovascular Devices; Reclassification of External Pacemaker Pulse Generator Devices

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-17

... arrhythmias; and 4. Micro/macro shocks--Uncontrolled leakage currents or patient auxiliary currents can cause...); Medtronic, Inc. v. Lohr, 518 U.S. 470 (1996); and Riegel v. Medtronic, Inc. 128 S. Ct. 999 (2008)). If this...

Hypertonic Saline Resuscitation Restores Inflammatory Cytokine Balance in Post-Traumatic Hemorrhagic Shock Patients

DTIC Science & Technology

2004-09-01

hypertonic saline with 6% dextran-70 (HSD) has been shown in experimental studies to reduce shock/resuscitation-induced inflammatory reactions and...hemodynamics and reestablishing inflammatory equilibrium [12]. Various immunoinflammatory alterations have been described in clinical and experimental ...ultimately causing greater morbidity and mortality [4]. Moreover, convincing experimental evidence indicates that conventional large-volume fluid

A Comparison of the Effects of Intraosseous and Intravenous 5% Albumin on Infusion Time and Hemodynamic Measures in a Swine Model of Hemorrhagic Shock.

PubMed

Muir, Stacy L; Sheppard, Lance B; Maika-Wilson, Anne; Burgert, James M; Garcia-Blanco, Jose; Johnson, Arthur D; Coyner, Jennifer L

2016-08-01

Introduction Obtaining intravenous (IV) access in patients in hemorrhagic shock is often difficult and prolonged. Failed IV attempts delay life-saving treatment. Intraosseous (IO) access may often be obtained faster than IV access. Albumin (5%) is an option for prehospital volume expansion because of the absence of interference with coagulation and platelet function. Hypothesis/Problem There are limited data comparing the performance of IO and IV administered 5% albumin. The aims of this study were to compare the effects of tibial IO (TIO) and IV administration of 500 mL of 5% albumin on infusion time and hemodynamic measurements of heart rate (HR), mean arterial pressure (MAP), cardiac output (CO), and stroke volume (SV) in a swine model of hemorrhagic shock. Sixteen male swine were divided into two groups: TIO and IV. All subjects were anesthetized and a Class III hemorrhage was achieved by exsanguination of 31% of estimated blood volume (EBV) from a femoral artery catheter. Following exsanguination, 500 mL of 5% albumin was administered under pressurized infusion (300 mmHg) by the TIO or IV route and infusion time was recorded. Hemodynamic measurements of HR, MAP, CO, and SV were collected before and after exsanguination and every 20 seconds for 180 seconds during 5% albumin infusion. An independent t-test determined that IV 5% albumin infusion was significantly faster compared to IO (P=.01). Mean infusion time for TIO was seven minutes 35 seconds (SD=two minutes 44 seconds) compared to four minutes 32 seconds (SD=one minute 08 seconds) in the IV group. Multivariate Analysis of Variance was performed on hemodynamic data collected during the 5% albumin infusion. Analyses indicated there were no significant differences between the TIO and IV groups relative to MAP, CO, HR, or SV (P>.05). While significantly longer to infuse 5% albumin by the TIO route, the longer TIO infusion time may be negated as IO devices can be placed more quickly compared to repeated IV attempts. The lack of significant difference between the TIO and IV routes relative to hemodynamic measures indicate the TIO route is a viable route for the infusion of 5% albumin in a swine model of Class III hemorrhage. Muir SL , Sheppard LB , Maika-Wilson A , Burgert JM , Garcia-Blanco J , Johnson AD , Coyner JL . A comparison of the effects of intraosseous and intravenous 5% albumin on infusion time and hemodynamic measures in a swine model of hemorrhagic shock. Prehosp Disaster Med. 2016;31(4):436-442.

Public Health Surveillance: A Local Health Department Perspective

DTIC Science & Technology

2002-04-03

vomiting – Diarrhea (+/-bloody) • Rash and fever – Vesicular – Petechial • Neurologic – cranial nerve palsies, HA, fever , confusion • Septic Shock...Francisella tularensis (tularemia) • Viral hemorrhagic fever Agents of Concern: CDC Category B • Coxiella burnetti (Q fever ) • Brucella species...Concern: CDC Category C • Nipah virus • hantaviruses • tickborne hemorrhagic fever viruses • yellow fever • multidrug-resistant tuberculosis

Novel Resuscitation from Lethal Hemorrhage Suspended Animation for Delayed Resuscitation

DTIC Science & Technology

2005-10-01

hypothermia on rat hippocampal proteomic profiles after 30 minutes of complete cerebral ischemia. American Stroke Association; Fellows’ Research Day, Hilton...well as traumatic brain injury , stroke , hemorrhagic shock, myocardial infarction, hepatic failure, and even pulmonary failure with sepsis. Additional...specific secondary injury 64 Chapter 5 mechanisms, such as local cerebral inflammation, were shown. State-of-the- art reviews by central nervous system

Oxygen Flow Rate Requirements of Critically Injured Patients

DTIC Science & Technology

2015-04-08

2.0 BACKGROUND Supplemental oxygen is required to correct hypoxemia and is often used to augment tissue oxygen delivery following hemorrhagic ...least 6 months after enrollment to determine mortality status. 3.4 Outcome Measurements The primary outcomes were the proportion of subjects...and 53/204 (26%) with hemorrhagic shock (systolic blood pressure (SBP) ៊ or blood transfusion). There were 33/142 (23%) patients with an indication

Changes in the interstitial fluid and the muscle water in rabbits in hemorrhagic shock.

PubMed Central

Wolcott, M W; Malinin, T I; Wu, N M

1976-01-01

Dynamics and changes in the biochemical composition in the interstitial fluid and the muscle water were studied in hemorrhagic shock. The interstitial fluid was collected from implanted perforated capsules. Muscle biopsies were examined with regard to their water content by the steady state magnetic nuclear resonance spectroscopy. The consistent and what appears to be the most significant changes were the fall in the interstitial fluid pressures, the quantitative reduction of muscle water, a sharp fall in the blood and interstitial blood pH, the moderate hyperkalemia and lack of change in blood an interstitial fluid sodium, and the rise in blood glucose levels not accompanied by a rise in the interstitial fluid glucose levels. PMID:11754

A Sphingosine-1 Phosphate agonist (FTY720) limits trauma/hemorrhagic shock induced multiple organ dysfunction syndrome

PubMed Central

Bonitz, Joyce A.; Son, Julie Y.; Chandler, Benjamin; Tomaio, Jacquelyn N.; Qin, Yong; Prescott, Lauriston M.; Feketeova, Eleonora; Deitch, Edwin A.

2014-01-01

BACKGROUND Trauma/hemorrhagic shock is one of the major consequences of battlefield injury as well as civilian trauma. FTY720 (sphingosine-1 phosphate agonist) has the capability to decrease the activity of the innate and adaptive immune systems and, at the same time, maintain endothelial cell barrier function and vascular homeostasis during stress. For this reason, we hypothesize that FTY720, as part of resuscitation therapy, would limit T/HS induced multiple organ dysfunction syndrome (MODS) in a rodent trauma-hemorrhagic shock (T/HS) model. METHODS Rats subjected to trauma/sham-shock (T/SS) or T/HS (30 mm Hg × 90 min), were administered FTY720 (1 mg/kg) post-T/HS during volume resuscitation. Lung injury (permeability to Evans Blue dye), PMN priming (respiratory burst activity), and RBC rigidity were measured. In addition, lymph duct cannulated rats were used to quantify the effect of FTY720 on gut injury (permeability and morphology) and the biologic activity of T/HS vs. T/SS lymph on PMN-RB and RBC deformability. RESULTS T/HS-induced increased lung permeability, PMN priming and RBC rigidity were all abrogated by FTY720. The systemic protective effect of FTY720 was only partially at the gut level, since FTY720 did not prevent T/HS-induced gut injury (morphology or permeability,) however, it did abrogate T/HS lymph-induced increased respiratory burst and RBC rigidity. CONCLUSION FTY720 limited T/HS-induced MODS (lung injury, red cell injury, and neutrophil priming) as well as T/HS lymph bioactivity, although it did not limit gut injury. PMID:25004059

A Prospective, Randomized Investigation of Plasma First Resuscitation for Traumatic Hemorrhage and Attenuation of Acute Coagulopathy of Trauma

DTIC Science & Technology

2016-05-01

TL, Silliman, CC, and Banerjee, A: Tranexamic Acid Inhibited Thromboelastography is a More Sensitive and Rapid Predictor of Hyperfibrinolytic...A: Alpha-enolase, A Glycolytic Enzyme Elevated in Hemorrhagic Shock, Potentiates Fibrinolysis, and is Reversible by Tranexamic Acid (Presented at the...Silliman, CC. Rationale for the Selective Administration of Tranexamic Acid to Inhibit-Fibrinolysis in the Injured Patient. (Presented at Trauma

Battlefield Trauma Care Research, Development, Test and Evaluation Priorities

DTIC Science & Technology

2011-06-14

approved them by unanimous vote on March 8, 2011. FINDINGS Non-Compressible Hemorrhage Control-Follow-Up Tranexamic Acid Studies 5. Hemorrhagic shock...received tranexamic acid demonstrated a significant decrease in mortality without any increase in venous occlusive events either accompanied by or at...occlusive events. 8. Tranexarnic acid is a low-cost, FDA-approved agent. 9. The potential benefit and optimal use of tranexamic acid are not yet

NK1.1+ cells promote sustained tissue injury and inflammation after trauma with hemorrhagic shock.

PubMed

Chen, Shuhua; Hoffman, Rosemary A; Scott, Melanie; Manson, Joanna; Loughran, Patricia; Ramadan, Mostafa; Demetris, Anthony J; Billiar, Timothy R

2017-07-01

Various cell populations expressing NK1.1 contribute to innate host defense and systemic inflammatory responses, but their role in hemorrhagic shock and trauma remains uncertain. NK1.1 + cells were depleted by i.p. administration of anti-NK1.1 (or isotype control) on two consecutive days, followed by hemorrhagic shock with resuscitation and peripheral tissue trauma (HS/T). The plasma levels of IL-6, MCP-1, alanine transaminase (ALT), and aspartate aminotransferase (AST) were measured at 6 and 24 h. Histology in liver and gut were examined at 6 and 24 h. The number of NK cells, NKT cells, neutrophils, and macrophages in liver, as well as intracellular staining for TNF-α, IFN-γ, and MCP-1 in liver cell populations were determined by flow cytometry. Control mice subjected to HS/T exhibited end organ damage manifested by marked increases in circulating ALT, AST, and MCP-1 levels, as well as histologic evidence of hepatic necrosis and gut injury. Although NK1.1 + cell-depleted mice exhibited a similar degree of organ damage as nondepleted animals at 6 h, NK1.1 + cell depletion resulted in marked suppression of both liver and gut injury by 24 h after HS/T. These findings indicate that NK1.1 + cells contribute to the persistence of inflammation leading to end organ damage in the liver and gut. © Society for Leukocyte Biology.

Nano- and micro-materials in the treatment of internal bleeding and uncontrolled hemorrhage.

PubMed

Gaston, Elizabeth; Fraser, John F; Xu, Zhi Ping; Ta, Hang T

2018-02-01

Internal bleeding is defined as the loss of blood that occurs inside of a body cavity. After a traumatic injury, hemorrhage accounts for over 35% of pre-hospital deaths and 40% of deaths within the first 24 hours. Coagulopathy, a disorder in which the blood is not able to properly form clots, typically develops after traumatic injury and results in a higher rate of mortality. The current methods to treat internal bleeding and coagulopathy are inadequate due to the requirement of extensive medical equipment that is typically not available at the site of injury. To discover a potential route for future research, several current and novel treatment methods have been reviewed and analyzed. The aim of investigating different potential treatment options is to expand available knowledge, while also call attention to the importance of research in the field of treatment for internal bleeding and hemorrhage due to trauma. Copyright © 2017 Elsevier Inc. All rights reserved.

Cerebral effects of resuscitation with hypertonic saline and a new low-sodium hypertonic fluid in hemorrhagic shock and head injury.

PubMed

Sheikh, A A; Matsuoka, T; Wisner, D H

1996-07-01

A 2400-mOsm/L hypertonic solution (isosal) with a lower sodium content, compared with conventional 7.5% hypertonic saline, was formulated using a mixture of sodium chloride, glucose, and mixed amino acids. This solution was developed to minimize hypernatremia during resuscitation. We assessed the effects of isosal on hemodynamics, brain edema, and plasma sodium concentration after head injury associated with hemorrhagic shock. DESIGN. Prospective, randomized laboratory study. University research laboratory. Twenty-one adult female Suffolk sheep, weighing 39 to 49 kg. Animals were subjected to a 2-hr period of hemorrhagic shock to a mean arterial pressure (MAP) of 40 to 45 mm Hg in the presence of a freeze injury to the cerebral cortex. The hemorrhagic shock/head injury phase was followed by 2 hrs of resuscitation with isosal, a new 2400-mosm/L low-sodium hypertonic fluid, 2400 mosm/L of 7.5% hypertonic saline, or lactated Ringer's solution. Initial resuscitation was with a bolus injection of 8 mL/kg of the study solution; subsequent resuscitation in all three groups was with lactated Ringer's solution as needed to maintain baseline cardiac output. Serial hemodynamics, intracranial pressure, electrolytes, and osmolarity were measured. AT the end of resuscitation, the animals were killed and brain water content (mL H2O/g dry weight) of the injured and uninjured areas was determined. Resuscitation volumes were significantly lower in the isosal (19 +/- 5 mL/kg) and 7.5% hypertonic saline (14 +/- 2 mL/mg) groups compared with the lactated Ringer's solution (35 +/- 5 mL/kg) group. Intracranial pressure after 2 hrs of resuscitation was significantly lower in the isosal (7 +/- 1 mm Hg) and hypertonic saline groups (4 +/- 1 mm Hg). Water content in all areas of the brain was significantly lower in the hypertonic saline group compared with the lactated Ringer's solution group. Brain water content in the isosal group was lower than in the lactated Ringer's solution group only in the cerebellum. Plasma sodium content was lower in the isosal group than in the hypertonic saline group. After combined head injury and shock, isosal and 7.5% hypertonic saline have similar effects on hemodynamics and intracranial pressure. Hypertonic saline induces a greater degree of brain dehydration; isosal resuscitation results in smaller increases in plasma sodium.

Hemorrhagic shock-induced cerebral bioenergetic imbalance is corrected by pharmacologic treatment with EF24 in a rat model.

PubMed

Rao, Geeta; Xie, Jun; Hedrick, Andria; Awasthi, Vibhudutta

2015-12-01

Maintenance of cerebral viability and function is an important goal of critical care in victims of injury due to ischemia and hypovolemia. As part of the multiple organ dysfunction syndrome, the brain function after trauma is influenced by the systemic inflammatory response. We investigated the effect of EF24, an anti-inflammatory bis-chalcone, on cerebral bioenergetics in a rat model of 45% hemorrhagic shock. The rats were treated with EF24 (0.4 mg/kg) or EF24 with an artificial oxygen carrier liposome-encapsulated hemoglobin (LEH). The volume of LEH administered was equal to the shed blood. The brain was collected after 6 h of shock for biochemical assays. EF24 treatment showed significant recovery of ATP, phosphocreatine, and NAD/NADH ratio. It also increased citrate synthase activity and cytochrome c oxidase subunit IV expression which were reduced in shock brain. Furthermore, it reduced the shock-induced accumulation of pyruvate and pyruvate dehydrogenase kinase-1 expression, suggesting that EF24 treatment improves cerebral energetics by restoring perturbed pyruvate metabolism in the mitochondria. These effects of EF24 were associated with reduced poly(ADP-ribose) polymerase cleavage and a significant improvement in the levels of nerve growth factor and brain-derived neurotrophic factor in shock brain. Co-administration of LEH with EF24 was only marginally more effective as compared to the treatment with EF24 alone. These results show that EF24 treatment sets up a pro-survival phenotype in shock by resurrecting cerebral bioenergetics. Since EF24 was effective in the absence of accompanying fluid resuscitation, it has potential utility as a pre-hospital pharmacotherapy in shock due to accidental blood loss. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hemorrhagic shock-induced cerebral bioenergetic imbalance is corrected by pharmacologic treatment with EF24 in a rat model

PubMed Central

Rao, Geeta; Xie, Jun; Hedrick, Andria; Awasthi, Vibhudutta

2015-01-01

Maintenance of cerebral viability and function is an important goal of critical care in victims of injury due to ischemia and hypovolemia. As part of the multiple organ dysfunction syndrome, the brain function after trauma is influenced by systemic inflammatory response. We investigated the effect of EF24, an anti-inflammatory bis-chalcone, on cerebral bioenergetics in a rat model of 45% hemorrhagic shock. The rats were treated with EF24 (0.4 mg/kg) or EF24 with an artificial oxygen carrier liposome-encapsulated hemoglobin (LEH). The volume of LEH administered was equal to the shed blood. The brain was collected after 6 h of shock for biochemical assays. EF24 treatment showed significant recovery of ATP, phosphocreatine, and NAD/NADH ratio. It also increased citrate synthase activity and cytochrome c oxidase subunit IV expression which were reduced in shock brain. Furthermore, it reduced the shock-induced accumulation of pyruvate and pyruvate dehydrogenase kinase-1 expression, suggesting that EF24 treatment improves cerebral energetics by restoring perturbed pyruvate metabolism in the mitochondria. These effects of EF24 were associated with reduced poly(ADP-ribose) polymerase cleavage and a significant improvement in the levels of nerve growth factor and brain-derived neurotrophic factor in shock brain. Co-administration of LEH with EF24 was only marginally more effective as compared to the treatment with EF24 alone. These results show that EF24 treatment sets up a pro-survival phenotype in shock by resurrecting cerebral bioenergetics. Since EF24 was effective in the absence of accompanying fluid resuscitation, it has potential utility as a pre-hospital pharmacotherapy in shock due to accidental blood loss. PMID:26232641

IDENTIFICATION AND DESCRIPTION OF A NOVEL MURINE MODEL FOR POLYTRAUMA AND SHOCK

PubMed Central

Gentile, Lori F; Nacionales, Dina C; Cuenca, Alex G; Armbruster, Michael; Ungaro, Ricardo F; Abouhamze, Amer S; Lopez, Cecelia; Baker, Henry V; Moore, Frederick A; Ang, Darwin N; Efron, Philip A

2013-01-01

Objective To develop a novel polytrauma model that better recapitulates the immunological response of the severely injured patient by combining long-bone fracture, muscle tissue damage and cecectomy with hemorrhagic shock, resulting in an equivalent Injury Severity Score of greater than 15. We compared this new polytrauma/shock model to historically-used murine trauma-hemorrhage models. Design Pre-clinical controlled in vivo laboratory study. Setting Laboratory of Inflammation Biology and Surgical Science. Subjects 6–10 wk old C57BL/6 (B6) mice Interventions Mice underwent 90 minutes of shock (MAP 30 mmHg) and resuscitation via femoral artery cannulation followed by either laparotomy (TH), laparotomy with femur fracture (H+FFx), or laparotomy with cecetomy and femur fracture with muscle tissue damage (PT). Mice were euthanized at two hours, one day and three days post injury. Measurements and Main Results The spleen, bone marrow, blood, and serum were collected from mice for analysis at the above time points. None of the models were lethal. Mice undergoing PT exhibited a more robust inflammatory response with significant elevations in cytokine/chemokine concentrations when compared to traditional models. PT was the only model to induce neutrophilia (Ly6G+CD11b+ cells) on days 1 and 3 (p<0.05). PT, as compared to TH and H+FFx, induced a loss of circulating CD4+ T cell with simultaneous increased cell activation (CD69+ and CD25+), similar to human trauma. There was a prolonged loss of MHCII expression on monocytes in the PT model (p<0.05). Results were confirmed by genome-wide expression analysis which revealed a greater magnitude and duration of blood leukocyte gene expression changes in the PT model than the TH and sham models. Conclusions This novel polytrauma model better replicates the human leukocyte, cytokine, and overall inflammatory response following injury and hemorrhagic shock. PMID:23399937

Aortic occlusion balloon catheter technique is useful for uncontrollable massive intraabdominal bleeding after hepato-pancreato-biliary surgery.

PubMed

Miura, Fumihiko; Takada, Tadahiro; Ochiai, Takenori; Asano, Takehide; Kenmochi, Takashi; Amano, Hodaka; Yoshida, Masahiro

2006-04-01

Massive intraabdominal hemorrhage sometimes requires urgent hemostatic surgical intervention. In such cases, its rapid stabilization is crucial to reestablish a general hemodynamic status. We used an aortic occlusion balloon catheter in patients with massive intraabdominal hemorrhage occurring after hepato-pancreato-biliary surgery. An 8-French balloon catheter was percutaneously inserted into the aorta from the femoral artery, and the balloon was placed just above the celiac artery. Fifteen minutes inflation and 5 minutes deflation were alternated during surgery until the bleeding was surgically controlled. An aortic occlusion balloon catheter was inserted on 13 occasions in 10 patients undergoing laparotomy for hemostasis of massive hemorrhage. The aorta was successfully occluded on 12 occasions in nine patients. Both systolic pressure and heart rate were normalized during aortic occlusion, and the operative field became clearly visible after adequate suction of leaked blood. Bleeding sites were then easily found and controlled. Hemorrhage was successfully controlled in 7 of 10 patients (70%), and they were discharged in good condition. The aortic occlusion balloon catheter technique was effective for easily controlling massive intraabdominal bleeding by hemostatic procedure after hepato-pancreato-biliary surgery.

Role of transfused red blood cells for shock and coagulopathy within remote damage control resuscitation.

PubMed

Spinella, Philip C; Doctor, Allan

2014-05-01

The philosophy of damage control resuscitation (DCR) and remote damage control resuscitation (RDCR) can be summarized by stating that the goal is to prevent death from hemorrhagic shock by "staying out of trouble instead of getting out of trouble." In other words, it is preferred to arrest the progression of shock, rather than also having to reverse this condition after significant tissue damage and organ injury cascades are established. Moreover, to prevent death from exsanguination, a balanced approach to the treatment of both shock and coagulopathy is required. This was military doctrine during World War II, but seemed to be forgotten during the last half of the 20th century. Damage control resuscitation and RDCR have revitalized the approach, but there is still more to learn about the most effective and safe resuscitative strategies to simultaneously treat shock and hemorrhage. Current data suggest that our preconceived notions regarding the efficacy of standard issue red blood cells (RBCs) during the hours after transfusion may be false. Standard issue RBCs may not increase oxygen delivery and may in fact decrease it by disturbing control of regional blood flow distribution (impaired nitric oxide processing) and failing to release oxygen, even when perfusing hypoxic tissue (abnormal oxygen affinity). Standard issue RBCs may assist with hemostasis but appear to have competing effects on thrombin generation and platelet function. If standard issue or RBCs of increased storage age are not optimal, then are there alternatives that will allow for an efficacious and safe treatment of shock while also supporting hemostasis? Studies are required to determine if fresh RBCs less than 7 to 10 days provide an outcome advantage. A resurgence in the study of whole blood stored at 4°C for up to 10 days also holds promise. Two randomized controlled trials in humans have indicated that following transfusion with either whole blood stored at 4°C or platelets stored at 4°C there was less clinical bleeding than when blood was reconstituted with components or when platelets were stored at 22°C. Early reversal of shock is essential to prevent exacerbation of coagulopathy and progression of cell death cascades in patients with severe traumatic injuries. Red blood cell storage solutions have evolved to accommodate the needs of non-critically ill patients yet may not be optimal for patients in hemorrhagic shock. Continued focus on the recognition and treatment of shock is essential for continued improvement in outcomes for patients who require damage control resuscitation and RDCR.

Resuscitation with Lyophilized Plasma Is Safe and Improves Neurological Recovery in a Long-Term Survival Model of Swine Subjected to Traumatic Brain Injury, Hemorrhagic Shock, and Polytrauma.

PubMed

Georgoff, Patrick E; Nikolian, Vahagn C; Halaweish, Ihab; Chtraklin, Kiril; Bruhn, Peter J; Eidy, Hassan; Rasmussen, Monica; Li, Yongqing; Srinivasan, Ashok; Alam, Hasan B

2017-07-01

We have shown previously that fresh frozen plasma (FFP) and lyophilized plasma (LP) decrease brain lesion size and improve neurological recovery in a swine model of traumatic brain injury (TBI) and hemorrhagic shock (HS). In this study, we examine whether these findings can be validated in a clinically relevant model of severe TBI, HS, and polytrauma. Female Yorkshire swine were subjected to TBI (controlled cortical impact), hemorrhage (40% volume), grade III liver and splenic injuries, rib fracture, and rectus abdominis crush. The animals were maintained in a state of shock (mean arterial pressure 30-35 mm Hg) for 2 h, and then randomized to resuscitation with normal saline (NS), FFP, or LP (n = 5 swine/group). Animals were recovered and monitored for 30 d, during which time neurological recovery was assessed. Brain lesion sizes were measured via magnetic resonance imaging (MRI) on post-injury days (PID) three and 10. Animals were euthanized on PID 30. The severity of shock and response to resuscitation was similar in all groups. When compared with NS-treated animals, plasma-treated animals (FFP and LP) had significantly lower neurologic severity scores (PID 1-7) and a faster return to baseline neurological function. There was no significant difference in brain lesion sizes between groups. LP treatment was well tolerated and similar to FFP. In this clinically relevant large animal model of severe TBI, HS, and polytrauma, we have shown that plasma-based resuscitation strategies are safe and result in neurocognitive recovery that is faster than recovery after NS-based resuscitation.

Low-volume binary drug therapy for the treatment of hypovolemia.

PubMed

Bhattacharjee, Himanshu; Nadipuram, Asha; Kosanke, Stanley; Kiani, Mohammad F; Moore, Bob M

2011-06-01

The selective regulation of total peripheral circulation in hypovolemic crisis offers a unique approach for treating and preventing hemorrhagic shock. Ideally, such a therapeutic intervention would require targeting of the striated muscle vascular beds without altering the vascular resistance in vital organ vascular beds. We discovered that a combination of cannabinoid receptor agonist, THC (Δ-tetrahydrocannabinol), and cyclooxygenase 2 inhibitor, NS-398, caused selective microvascular constriction in the mouse cremaster muscle manifested by a pronounced and significant 27.4% ± 7.9% decrease in vessel diameter relative to control (P < 0.01). This observation, and the reported lack of microvascular response in the mesentery and brain, led us to hypothesize that the drug combination could favorably redistribute blood volume in hypovolemia and prolong survival. To test the hypothesis, male Sprague-Dawley rats were subjected to a pressure-controlled hemorrhage (mean arterial pressure reduced to 30 ± 13.73 mmHg) then randomly assigned to one of six treatment groups (n = 6 per group). The untreated, NS-398-treated, and THC-treated groups manifested an insignificant difference in survival between groups after shock. The group treated with a combination of THC and NS-398 manifested a significant increase in mean survival from 53 ± 12 to 227 ± 23 min after shock (P < 0.001). The drug combination significantly reduced IL-1α, IL-1β, IFN-γ, and IL-10 production compared with the group resuscitated with normal saline. In addition, histological evaluation indicated that the therapy protects the lungs and liver against hemorrhagic shock-induced damage. The combination of cannabinoid receptor agonist and cyclooxygenase 2 inhibitor represents a potentially new approach to low-volume therapeutic intervention for hypovolemia.

Obesity-induced hepatic hypoperfusion primes for hepatic dysfunction after resuscitated hemorrhagic shock.

PubMed

Matheson, Paul J; Hurt, Ryan T; Franklin, Glen A; McClain, Craig J; Garrison, R Neal

2009-10-01

Obese patients (BMI>35) after blunt trauma are at increased risk compared to non-obese for organ dysfunction, prolonged hospital stay, infection, prolonged mechanical ventilation, and mortality. Obesity and non-alcoholic fatty liver disease (NAFLD) produce a low grade systemic inflammatory response syndrome (SIRS) with compromised hepatic blood flow, which increases with body mass index. We hypothesized that obesity further aggravates liver dysfunction by reduced hepatic perfusion following resuscitated hemorrhagic shock (HEM). Age-matched Zucker rats (Obese, 314-519 g & Lean, 211-280 g) were randomly assigned to 4 groups (n = 10-12/group): (1) Lean-Sham; (2) Lean, HEM, and resuscitation (HEM/RES); (3) Obese-Sham; and (4) Obese-HEM/RES. HEM was 40% of mean arterial pressure (MAP) for 60 min; RES was return of shed blood/5 min and 2 volumes of saline/25 min. Hepatic blood flow (HBF) using galactose clearance, liver enzymes and complete metabolic panel were measured over 4 h after completion of RES. Obese rats had increased MAP, heart rate, and fasting blood glucose and BUN concentrations compared to lean controls, required less blood withdrawal (mL/g) to maintain 40% MAP, and RES did not restore BL MAP. Obese rats had decreased HBF at BL and during HEM/RES, which persisted 4 h post RES. ALT and BUN were increased compared to Lean-HEM/RES at 4 h post-RES. These data suggest that obesity significantly contributes to trauma outcomes through compromised vascular control or through fat-induced sinusoidal compression to impair hepatic blood flow after HEM/RES resulting in a greater hepatic injury. The pro-inflammatory state of NAFLD seen in obesity appears to prime the liver for hepatic ischemia after resuscitated hemorrhagic shock, perhaps intensified by insidious and ongoing hepatic hypoperfusion established prior to the traumatic injury or shock.

Interventional Vitamin C-A Strategy for Attenuation of Coagulopathy and Inflammation in Hemorrhagic Trauma and Shock

DTIC Science & Technology

2017-10-01

edema, protein leak and exuberant infiltration of inflammatory cells. Significant hemorrhage and cellular damage were also evident in liver and kidney ...Treatment with VitC also reduced the expression of pro-inflammatory mediators in lungs, liver and kidneys . Preliminary lipidomic analysis showed that VitC at...Histological changes to lung, liver and kidney f. Proteomic analysis of plasma for identification of novel circulating proteins, and g. Lipidomic

Lethal Hemorrhage Caused by Aortoesophageal Fistula Secondary to Stent-Graft Repair of the Thoracic Aorta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sager, Hendrik B., E-mail: hendrik.sager@uk-sh.de; Wellhoener, Peter; Wermelt, Johanna A.

Aortoesophageal fistula (AEF) is a rare but life-threatening complication after endovascular or surgical aortic repair. Here we report a patient with AEF secondary to aortic stent-placement 2 years earlier who presented with hematemesis and died from hemorrhagic shock. By means of this case and the literature, we highlight potential bleeding sources in such a scenario because this is of crucial importance for the management strategy.

Efforts and Programs of the Department of Defense Relating to the Prevention, Mitigation, and Treatment of Blast Injuries

DTIC Science & Technology

2007-01-01

Combat Critical Care Engineering: Evaluation of Closed Loop Control of Ventilation and Oxygen Flow During Resuscitation in the Compensatory and...Decompensatory Phases of Hemorrhagic Shock: This effort evaluated closed loop control of ventilation and oxygen flow during resuscitation in the...Cerebral Injury Volume, Cerebral Edema, Cerebral Blood Flow and Reactivity, and Histopathology in a Rat Model of Traumatic Brain Injury and Hemorrhagic

Lung and Diaphragm Damage at Varying Oxygen Levels and Ventilator Modes Pst Hemorrhagic

DTIC Science & Technology

2011-12-20

scavenging in prenatal neonates (Vento et al., 2009). In addition, Lee et al. found that mice breathing 40% oxygen had elevated tissue levels of...pulmonary mechanics. Another limitation was that we did not administer any fluid resuscitation to correct the hemorrhagic shock during mechanical... resuscitation . Testing only a controlled mode of mechanical ventilation was a limitation to our study. Most mechanical ventilations offer a mixed mode of

Impaired gut contractility following hemorrhagic shock is accompaied by IL-6 and G-CSF production and neutrophil infiltration.

PubMed

Hierholzer, C; Kalff, J C; Chakraborty, A; Watkins, S C; Billiar, T R; Bauer, A J; Tweardy, D J

2001-02-01

Recovery from hemorrhagic shock (HS) is frequently accompanied by bowel stasis. The aim of this study was to examine whether or not HS initiates an inflammatory response that includes production of cytokines, specifically G-CSF and interleukin-6 (IL-6), and recruitment of leukocytes within the intestinal muscularis which contribute to impaired muscle contractility. Sprague-Dawley rats were subjected to HS (MAP 40 mm Hg for 156 min) followed by resuscitation, and then they were killed at 4 hr. Shock animals demonstrated accumulation of PMNs in the jejunal muscularis and decreased spontaneous and bethanechol-stimulated muscle contractility. Semiquantitative RT-PCR demonstrated elevated levels of IL-6 and G-CSF mRNA in shock animals in full-thickness jejunum and in mucosa and muscularis layers compared to sham controls. Immunostaining demonstrated increased IL-6 protein production within the muscularis externa and submucosa. In situ hybridization studies localized G-CSF mRNA production to the submucosa. Gel shift assays revealed increased NF-kappaB and Stat3 activity in full-thickness jejunum and jejunal layers of shock animals. Activation of Stat3 also was demonstrated in normal muscularis tissue exposed to IL-6 and G-CSF in vitro. IL-6 and G-CSF are produced in the muscularis and mucosa layers of the gut in HS where they may contribute to PMN recruitment and smooth muscle dysfunction.

Extracorporeal Shock Wave Therapy for Nonunion of the Tibia

DTIC Science & Technology

2010-03-01

osseous biology evident as diminished callus formation or osteopenia on radiographs. Infected nonunions were defined by clinical presentation ( fever ...to the epiphyseal growth plate, malignant nnnor in the shock wave focus. active infection ( fever greater than 38°C, C-reactive protein greater than 5...infrequently and appeared to be dose-related: local edema, cutaneous petechial hemorrhage, and subcutaneous hematoma (range, 1-5 mm in greatest

Novel insights for systemic inflammation in sepsis and hemorrhage.

PubMed

Cai, Bolin; Deitch, Edwin A; Ulloa, Luis

2010-01-01

The inflammatory responses in sepsis and hemorrhage remain a major cause of death. Clinically, it is generally accepted that shock in sepsis or hemorrhage differs in its mechanisms. However, the recognition of inflammatory cytokines as a common lethal pathway has become consent. Proinflammatory cytokines such as tumor necrosis factor (TNF) or high-mobility group box1 (HMGB1) are fanatically released and cause lethal multiorgan dysfunction. Inhibition of these cytokines can prevent the inflammatory responses and organ damage. In seeking potential anti-inflammatory strategies, we reported that ethyl pyruvate and alpha7 nicotinic acetylcholine receptor (alpha7nAChR) agonists effectively restrained cytokine production to provide therapeutic benefits in both experimental sepsis and hemorrhage. Here, we review the inflammatory responses and the anti-inflammatory strategies in experimental models of sepsis and hemorrhage, as they may have a consistent inflammatory pathway in spite of their different pathophysiological processes.

Dengue Hemorrhagic Fever Virus in Saudi Arabia: A Review.

PubMed

Al-Tawfiq, Jaffar A; Memish, Ziad A

2018-02-01

Dengue fever is a global disease with a spectrum of clinical manifestation ranging from mild febrile disease to a severe disease in the form of dengue hemorrhagic fever and dengue shock syndrome. Dengue virus is one viral hemorrhagic fever that exists in the Kingdom of Saudi Arabia in addition to Alkhurma (Alkhurma) Hemorrhagic Fever, Chikungunya virus, Crimean-Congo Hemorrhagic Fever, and Rift Valley Fever. The disease is limited to the Western and South-western regions of Saudi Arabia, where Aedes aegypti exists. The majority of the cases in Saudi Arabia had mild disease and is related to serotypes 1-3 but not 4. The prospect for Dengue virus control relies on vector control, health education, and possibly vaccine use. Despite extensive collaborative efforts between multiple governmental sectors, including Ministry of Health, Ministry of Municipalities and Rural Affairs, and Ministry of Water, dengue remains a major public health concern in the regions affected.

Inescapable Stress Changes Walking Behavior in Flies - Learned Helplessness Revisited.

PubMed

Batsching, Sophie; Wolf, Reinhard; Heisenberg, Martin

2016-01-01

Like other animals flies develop a state of learned helplessness in response to unescapable aversive events. To show this, two flies, one 'master', one 'yoked', are each confined to a dark, small chamber and exposed to the same sequence of mild electric shocks. Both receive these shocks when the master fly stops walking for more than a second. Behavior in the two animals is differently affected by the shocks. Yoked flies are transiently impaired in place learning and take longer than master flies to exit from the chamber towards light. After the treatment they walk more slowly and take fewer and shorter walking bouts. The low activity is attributed to the fly's experience that its escape response, an innate behavior to terminate the electric shocks, does not help anymore. Earlier studies using heat pulses instead of electric shocks had shown similar effects. This parallel supports the interpretation that it is the uncontrollability that induces the state.

The clinical effectiveness of permissive hypotension in blunt abdominal trauma with hemorrhagic shock but without head or spine injuries or burns: a systematic review

PubMed Central

Alsawadi, Abdulrahman

2012-01-01

Background Trauma is a major cause of death and disability. The current trend in trauma management is the rapid administration of fluid as per the Advanced Trauma Life Support guidelines, although there is no evidence to support this and even some to suggest it might be harmful. Some guidelines, protocols, and recommendations have been established for the use of permissive hypotension although there is reluctance concerning its application in blunt injuries. Objectives The aim of this review is to determine whether there is evidence of the use of permissive hypotension in the management of hemorrhagic shock in blunt trauma patients. This review also aims to search for any reason for the reluctance to apply permissive hypotension in blunt injuries. Methods This systematic review has followed the steps recommended in the Cochrane Handbook for Systematic Reviews of Interventions. It is also being reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement and checklist. Database searches of MEDLINE, EMBASE, the Centre for Reviews and Dissemination databases and the Cochrane Library were made for eligible studies as well as journal searches. Inclusion criteria included systematic reviews that have similar primary questions to this review and randomized controlled trials where patients with blunt torso injuries and hemorrhagic shock were not excluded. Rapid or early fluid administration was compared with controlled or delayed fluid resuscitation and a significant outcome was obtained. Results No systematic reviews attempting to answer similar questions were found. Two randomized controlled trials with mixed types of injuries in the included patients found no significant difference between the groups used in each study. Data concerning the question of this review was sought after these papers were appraised. Conclusion The limited available data are not conclusive. However, the supportive theoretical concept and laboratory evidence do not show any reason for treating blunt injuries differently from other traumatic injuries. Moreover, permissive hypotension is being used for some nontraumatic causes of hemorrhagic shock and in theater. Therefore, this should encourage interested researchers to continue clinical work in this important field. PMID:27147860

Clinical Study of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for Severe Pelvic Fracture and Intra-Abdominal Hemorrhagic Shock Using Continuous Vital Signs

DTIC Science & Technology

2017-03-01

University of Maryland, Baltimore Baltimore, MD 21201 REPORT DATE: March 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research ...ongoing. After FDA approval of a new novel REBOA catheter (ER-REBOATM (Prytime Medical , Boerne, TX )) in October 2015, we incorporated this catheter into...Scalea, MD 39th Annual CONFERENCE ON SHOCK – June 11-14th, Austin , TX 2. REBOA IMPROVES MEAN BLOOD PRESSURE (MBP) AND SHOCK INDEX (SI) AS MEASURED

Minocycline and Doxycycline, but not Tetracycline, Mitigate Liver and Kidney Injury after Hemorrhagic Shock/Resuscitation*

PubMed Central

Kholmukhamedov, Andaleb; Czerny, Christoph; Hu, Jiangting; Schwartz, Justin; Zhong, Zhi; Lemasters, John J.

2014-01-01

Background Despite recovery of hemodynamics by fluid resuscitation after hemorrhage, development of the systemic inflammatory response and multiple organ dysfunction syndromes can nonetheless lead to death. Minocycline and doxycycline are tetracycline derivatives that are protective in models of hypoxic, ischemic and oxidative stress. Our Aim was to determine whether minocycline and doxycycline protect liver and kidney and improve survival in a mouse model of hemorrhagic shock and resuscitation. Methods Mice were hemorrhaged to 30 mm Hg for 3 h and then resuscitated with shed blood followed by half the shed volume of lactated Ringer's solution containing tetracycline (10 mg/kg), minocycline (10 mg/kg), doxycycline (5 mg/kg) or vehicle. For pre-plus post-treatment, drugs were administered intraperitoneally prior to hemorrhage followed by second equal dose in Ringer's solution after blood resuscitation. Blood and tissue were harvested after 6 h. Results Serum alanine aminotransferase (ALT) increased to 1988 and 1878 U/L after post-treatment with vehicle and tetracycline, respectively, whereas minocycline and doxycycline post-treatment decreased ALT to 857 and 863 U/L. Pre-plus post-treatment with minocycline and doxycycline also decreased ALT to 849 and 834 U/L. After vehicle, blood creatinine increased to 279 μM, which minocycline and doxycycline post-treatment decreased to 118 and 112 μM. Minocycline and doxycycline pre- plus post-treatment decreased creatinine similarly. Minocycline and doxycycline also decreased necrosis and apoptosis in liver and apoptosis in both liver and kidney, the latter assessed by TUNEL and caspase-3 activation. Lastly after 4.5 h of hemorrhage followed by resuscitation, minocycline and doxycycline (but not tetracycline) post-treatment improved 1-week survival from 38%(vehicle) to 69% and 67%, respectively. Conclusion Minocycline and doxycycline were similarly protective when given before as after blood resuscitation and might therefore have clinical efficacy to mitigate liver and kidney injury after resuscitated hemorrhage. PMID:24978888

Dehydroepiandrosterone restores hepatocellular function and prevents liver damage in estrogen-deficient females following trauma and hemorrhage.

PubMed

Kuebler, J F; Jarrar, D; Wang, P; Bland, K I; Chaudry, I H

2001-05-15

Recent studies have shown that administration of the sex steroid dehydroepiandrosterone (DHEA) in males following trauma-hemorrhagic shock has salutary effects on the depressed cardiovascular and immunological functions under those conditions. Since the effects of sex steroids are gender specific, we examined whether administration of DHEA has any beneficial effects on hepatocellular function in female rats with low estrogen levels following trauma-hemorrhage. Ovariectomy was performed in female Sprague-Dawley rats 14 days prior to the experiments. The animals then underwent a 5-cm midline laparotomy and were subjected to hemorrhagic shock (40 mm Hg for 90 min). This was followed by fluid resuscitation (Ringer's lactate over 60 min) and administration of DHEA (30 mg/kg BW) or vehicle subcutaneously at the end of resuscitation. At 24 h after resuscitation hepatocellular function, i.e., clearance of indocyanine green (ICG), and hepatocyte damage (serum alanine aminotransferase) were measured. Plasma levels of DHEA and 17beta-estradiol were also assayed. Vehicle-treated rats had significantly reduced hepatocellular function, increased ALT activity, and decreased levels of 17beta-estradiol following trauma-hemorrhage compared to sham-operated animals (P < 0.05, ANOVA and Student-Newman-Keuls test). In animals receiving DHEA following trauma-hemorrhage, hepatocellular function and ALT activity were similar to those of shams. However, administration of DHEA did not influence the plasma levels of 17beta-estradiol. Administration of DHEA following trauma-hemorrhage restored hepatocellular function and reduced hepatic damage that was observed in ovariectomized female rats under such conditions. This salutary effect of DHEA did not appear to be due to elevated levels of plasma 17beta-estradiol. We therefore propose that DHEA should be considered a novel, safe, and useful adjunct in the treatment of trauma-induced hepatocellular dysfunction in ovariectomized and postmenopausal females. Copyright 2001 Academic Press.

Delayed Esophageal Hemorrhage Caused by a Metal Stent: Treatment with Embolization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kos, Xavier; Trotteur, Genevieve; Dondelinger, Robert F.

We report a case of life-threatening esophageal hemorrhage after metal stent implantation successfully treated by arterial embolization. An 85-year-old woman was admitted in shock secondary to massive hematemesis and melena. Recent medical history revealed esophageal cancer treated 8 weeks previously by endoesophageal radiotherapy (40 Gy) and endoscopic placement of a covered Wallstent prosthesis. Selective arteriography of the fifth posterior right intercostal artery showed massive contrast extravasation in the esophagus. Embolization was performed with 150-250-{mu}m polyvinyl alcohol particles. Follow-up at 5 months was uneventful. Arteriography and embolization are advised when severe hemorrhage occurs after esophageal implantation of metal stents.

Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance.

PubMed

Rasmussen, Angela L; Okumura, Atsushi; Ferris, Martin T; Green, Richard; Feldmann, Friederike; Kelly, Sara M; Scott, Dana P; Safronetz, David; Haddock, Elaine; LaCasse, Rachel; Thomas, Matthew J; Sova, Pavel; Carter, Victoria S; Weiss, Jeffrey M; Miller, Darla R; Shaw, Ginger D; Korth, Marcus J; Heise, Mark T; Baric, Ralph S; de Villena, Fernando Pardo-Manuel; Feldmann, Heinz; Katze, Michael G

2014-11-21

Existing mouse models of lethal Ebola virus infection do not reproduce hallmark symptoms of Ebola hemorrhagic fever, neither delayed blood coagulation and disseminated intravascular coagulation nor death from shock, thus restricting pathogenesis studies to nonhuman primates. Here we show that mice from the Collaborative Cross panel of recombinant inbred mice exhibit distinct disease phenotypes after mouse-adapted Ebola virus infection. Phenotypes range from complete resistance to lethal disease to severe hemorrhagic fever characterized by prolonged coagulation times and 100% mortality. Inflammatory signaling was associated with vascular permeability and endothelial activation, and resistance to lethal infection arose by induction of lymphocyte differentiation and cellular adhesion, probably mediated by the susceptibility allele Tek. These data indicate that genetic background determines susceptibility to Ebola hemorrhagic fever. Copyright © 2014, American Association for the Advancement of Science.

Topically Applied AaeIAP1 Double-Stranded RNA Kills Female Adults of Aedes aegypti

DTIC Science & Technology

2008-05-01

L. Barreto, and E. Mota. 2005. Dengue and dengue hemorrhagic fever epidemics in Brazil : what research is needed based on trends, sur- veillance...disease in the world andcancause anundifferentiated fever , dengue fever , dengue hemorrhagic fever , or dengue shock syndrome (Malavige et al. 2004...Para State, Amazon region of Brazil , 1998Ð1999: entomologic and epidemiologic Þnd- ings. Emerg. Infect. Dis. 7: 565Ð569. Vaux, D. L., G. Haecker, and A

Comparative Testing of New Hemostatic Agents in a Swine Model of Extremity Arterial and Venous Hemorrhage

DTIC Science & Technology

2010-01-01

by the Institutional Animal Care and Use Committee and all animals received humane care in com- pliance with the Guide for the Care and Use of...diminished markedly in recent military operations, due to sev- eral factors including routine vi-ear of hody armor, judicious use of tourniquets for...extremity hemorrhage, rapid casualty evacuation, and aggressive use of blood products in hemor- rhagic shock.’’ Advanced hemostatic agents further reduce

Temporary Percutaneous Aortic Balloon Occlusion to Enhance Fluid Resuscitation Prior to Definitive Embolization of Post-Traumatic Liver Hemorrhage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsuoka, Shin; Uchiyama, Katsuhiro; Shima, Hideki

2001-07-15

We successfully stabilized severe hemorrhagic shock following traumatic liver injury by percutaneous transcarotid supraceliac aortic occlusion with a 5 Fr balloon catheter. Then we were able to perform transfemoral embolization therapy of the hepatic arterial bleeding source. Transient aortic occlusion using a balloon catheter appears to be a useful adjunct in select cases where stabilization of the patient is necessary to allow successful selective embolization of the bleeding source.

Vasopressin for Hemorrhagic Shock Management: Revisiting the Potential Value in Civilian and Combat Casualty Care

DTIC Science & Technology

2010-07-01

get rid of weight relevant infusion bags . The rationale behind vasopressor drugs for cardiocirculatory stabilization in hemorrhage is based on our...Ringer’s and hydroxyethyl starch solu- tions were applied at this point in time, hepatic blood loss rapidly increased. These animals died of protracted...norepinephrine (20 g/kg followed by 1 g/kg/min) was combined with hypertonic starch solution, CPP and cerebral oxygenation were significantly increased and

Abstracts of the International Conference on Hypertonic Resuscitation (5th) Held in Galveston, Texas on 3-5 June 1992

DTIC Science & Technology

1992-08-01

Dextran Metabolism in Dehydrated, Hemorrhaged Sheep Infused with Hypertonic Saline/Dextran (HSD). 3 J. Eaker (Davis, U.S.A.): Small Volume Intraosseous ...S. Majluf (Mexico City, Mexico): Eualuation of an Intraosseous Function versus Intrauenous and Central Catheter in Patients with Hemorrhagic Shock. W...between the traumatized brain parenchyma and the skull bone followed by closure of the cranium by dental cement. At 20 hrs later the animals were

21 CFR 862.1130 - Blood volume test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... shock, hemorrhage, and polycythemia vera (a disease characterized by an absolute increase in erythrocyte... the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9. [52...

Crocin attenuates hemorrhagic shock-induced oxidative stress and organ injuries in rats.

PubMed

Yang, Long; Dong, Xiujuan

2017-06-01

We aimed to evaluate the effect of natural antioxidant crocin in alleviating hemorrhagic shock (HS)-induced organ damages. HS rats were treated with crocin during resuscitation. Mortality at 12h and 24h post resuscitation was documented. HS and resuscitation induced organ injuries, as characterized by elevated wet/dry ratio, quantitative assessment ratio, blood urea nitrogen, creatinine, aspartate aminotransferase and alanine aminotransferase, whereas rats received crocin treatment demonstrated improvements in all the above characteristics. This protective effect coincided with reduced malondialdehyde and increased glutathione in both serum and lung tissues, indicating attenuated oxidative stress in crocin-treated rats. Myeloperoxide levels in lung, kidney and liver were also reduced. Crocin can potentially be used to protect organs from HS-induced damages during resuscitation due to its anti-oxidative role. Copyright © 2017 Elsevier B.V. All rights reserved.

Traumatic hemorrhage of occult phaeochromocytoma in a patient with septic shock

PubMed Central

Moazzam, Mohammad Shahnawaz; Ahmed, Syed Moied; Bano, Shahjahan

2010-01-01

Phaeochromocytoma can have a variety of presentations; however, traumatic hemorrhage into a phaeochromocytoma is a very rare presentation. Diagnosing and managing a critically ill, septic patient with a Phaeochromocytoma can be very challenging. We report a case of 53 years old man with a previously undiagnosed Phaeochromocytoma, who presented initially with bowel perforation following an assault. Following a laparotomy for bowel resection and anastomosis, whilst on the intensive care unit, he developed paroxysmal severe hypertension overlying septic shock. Phaeochromocytoma was confirmed using a computed tomography scan and urinary assay of metanephrine and catecholamines. We managed the haemodynamic instability using labetalol and noradrenaline infusions. As his septic state improved he was convention therapy and following control of his symptoms over the next few weeks, he underwent an uncomplicated right sided adrenalectomy. He made a full recovery. PMID:20930983

Intrinsic Cholinergic Mechanisms Regulating Cerebral Blood Flow as a Target for Organophosphate Action

DTIC Science & Technology

1988-10-01

autoregulation, render the cerebral circulation dependent upon systemic circulation exposing brain to ischernic damage or edema in shock or stress...Thus, sharp reductions of arterial pressure, as might occur in hemorrhagic or traumatic shock, will render the cerebral circulation vulnerable to...autoregulated range, rendering local areas of the brain vulnerable to cerebral edema and breakdown of the blood brain barrier. -2- 8. Cerebral blood

Alcohol abuse and the injured host; Dysregulation of counteregulatory mechanisms Review

PubMed Central

Molina, Patricia E.; Sulzer, Jesse K.; Whitaker, Annie

2013-01-01

Traumatic injury ranks as the number one cause of death for the under 44 year old age group and 5th leading cause of death overall (www.nationaltraumainstitute.org/home/trauma_statistics.html). Although improved resuscitation of trauma patients has dramatically reduced immediate mortality from hemorrhagic shock, long-term morbidity and mortality continue to be unacceptably high during the post-resuscitation period, particularly as a result of impaired host immune responses to subsequent challenges such as surgery or infection. Acute alcohol intoxication (AAI) is a significant risk factor for traumatic injury; with intoxicating blood alcohol levels present in more than 40% of injured patients (1–5). Severity of trauma, hemorrhagic shock and injury is higher in intoxicated individuals than that of sober victims, resulting in higher mortality rates in this patient population. Necessary invasive procedures (surgery, anesthesia) and subsequent challenges (infection) that intoxicated trauma victims are frequently subjected to are additional stresses to an already compromised inflammatory and neuroendocrine milieu and further contribute to their morbidity and mortality. Thus, dissecting the dynamic imbalance produced by AAI during trauma is of critical relevance for a significant proportion of injured victims. This review outlines how AAI at the time of hemorrhagic shock not only prevents adequate responses to fluid resuscitation but also impairs the ability of the host to overcome a secondary infection. Moreover, it discusses the neuroendocrine mechanisms underlying alcohol-induced hemodynamic dysregulation and its relevance to host defense restoration of homeostasis following injury. PMID:23416555

Pyruvate dose response studies targeting the vital signs following hemorrhagic shock

PubMed Central

Sharma, Pushpa; Vyacheslav, Makler; Carissa, Chalut; Vanessa, Rodriguez; Bodo, Mike

2015-01-01

Objectives: To determine the optimal effective dose of sodium pyruvate in maintaining the vital signs following hemorrhagic shock (HS) in rats. Materials and Methods: Anesthetized, male Sprague-Dawley rats underwent computer-controlled HS for 30 minute followed by fluid resuscitation with either hypertonic saline, or sodium pyruvate solutions of 0.5 M, 1.0 M, 2.0 M, and 4.0 M at a rate of 5ml/kg/h (60 minute) and subsequent blood infusion (60 minute). The results were compared with sham and non- resuscitated groups. The animals were continuously monitored for mean arterial pressure, systolic and diastolic pressure, heart rate, pulse pressure, temperature, shock index and Kerdo index (KI). Results: The Sham group remained stable throughout the experiment. Non-resuscitated HS animals did not survive for the entire experiment due to non-viable vital signs and poor shock and KI. All fluids were effective in normalizing the vital signs when shed blood was used adjunctively. Sodium pyruvate 2.0 M was most effective, and 4.0 M solution was least effective in improving the vital signs after HS. Conclusions: Future studies should be directed to use 2.0 M sodium pyruvate adjuvant for resuscitation on multiorgan failure and survival rate in HS. PMID:26229300

Hypertensive emergency due to pheochromocytoma crisis complicated with refractory hemodynamic collapse.

PubMed

Hayıroğlu, Mert İlker; Yıldırımtürk, Özlem; Bozbay, Mehmet; Eren, Mehmet; Pehlivanoğlu, Seçkin

2015-12-01

Hypertensive emergency usually appears in older patients with previous recurrent episodes, and is among the most frequent admissions to emergency departments. A 29-year-old woman was referred to our clinic with the diagnosis of hypertensive emergency. The patient complained of severe headache, dyspnea, palpitation, diaphoresis, and confusion due to hypertensive encephalopathy. Her blood pressure was 250/150 mmHg on admission. At the referral hospital, the patient had undergone cranial CT because of her confused state and this excluded acute cerebral hemorrhage. Also at that hospital, thoracoabdominal CT for differential diagnosis depicted an adrenal mass with a necrotic core. After admission to our clinic, initial control of excessive blood pressure was not achieved despite high dose intravenous nitrate therapy. Thereafter intravenous esmolol treatment was initiated simultaneously with oral alpha blocker therapy in order to counterbalance the unopposed alpha adrenergic activity with beta blocker therapy. After 12 hours, sudden onset of hypotension developed and deepened despite IV saline, inotropic and vasopressor agents such as IV dopamine, noradrenaline and adrenaline. The patient died at the 24th hour due to hemodynamic collapse as a result of hyperadrenergic state due to possible pheochromocytoma crisis. This case is an exceptional example of hypertensive emergency secondary to fulminant pheochromocytoma crisis failing to respond to intensive antihypertensive treatment, and in which patient death was unavoidable due to uncontrolled excessive adrenergic activity which led to profound cardiogenic shock.

Stent-Grafts in the Management of Hemorrhagic Complications Related to Hemostatic Closure Devices: Report of Two Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giansante Abud, Daniel; Mounayer, Charbel; Saint-Maurice, Jean Pierre

We report 2 cases of hemorrhagic complications related to use of the Angio-Seal hemostatic closure device that were successfully managed with stent-grafts. Two patients with subarachnoid hemorrhage were referred to our departments for endovascular treatment of ruptured intracranial aneurysms. The treatment was performed through a femoral access; the sheaths were removed immediately after the procedures, and the punctures sites closed by Angio-Seals. Both patients presented clinical signs of hypovolemic shock after treatment. The diagnosis of active bleeding through the puncture site was made by emergency digital subtraction angiography. The lesions were managed with stent-grafts. The use of stent-grafts proved tomore » be efficient in the management of these life-threatening hemorrhagic complications following the use of the Angio-Seal hemostatic closure device.« less

A Prospective, Randomized Trial of Intravenous Hydroxocobalamin Versus Whole Blood Transfusion Compared to No Treatment for Class III Hemorrhagic Shock Resuscitation in a Prehospital Swine Model

DTIC Science & Technology

2015-03-01

statistically significant increase in systemic vascular resistance compared to control, but not whole blood, with a concomitant decrease in cardiac...increasing blood pressure as well as sys- temic vascular resistance in a hypovolemic hemorrhagic swine model.18 The primary hypothesis of this study is...output, sys- temic vascular resistance , mixed venous oxygen satura- tion, central venous pressure, pulmonary artery pressure, and core temperature. The

Physiologic Mechanisms Underlying the Failure of the Shock Index as a Tool for Accurate Assessment of Patient Status during Progressive Simulated Hemorrhage

DTIC Science & Technology

2013-08-01

in central blood volume similar to hemorrhage in humans. Lower-body negative- pressure (LBNP) is a unique physiologic model that has been adopted to...relatively high tolerance (HT) to reduced blood volume, while 30% to 35% display low toler- ance (LT), with earlier onset of cardiovascular instability (i.e... pressure were recorded by infrared finger photoplethysmography (Finometer Blood Pressure Mon- itor, TNO-TPD Biomedical Instrumentation, Amsterdam

Specific Cardiovascular Drugs Utilized in the Critically Ill

DTIC Science & Technology

1985-11-01

has been demonstrated to improve survival following hemorrhagic shock" " in rats and pigs. It is believed that ATP- MgCL treatment reverses a marked ...L.: Action of ghacagon on canine left ventricular performance and coronary hemodynamics. Circ. Shock, 11:45, 1963. 2. Allwood, M. J., Cobbold , A. F...and phenylephrine. Anesthesiology, 45;570-573, 1975. 101.- Mark , A. L., lizuka, T., Wendling, M. C., et al.: Responses of saphenous and mnesenteric

Hemorrhagic and necrotizing hepatitis associated with administration of a modified live canine adenovirus-2 vaccine in a maned wolf (Chrysocyon brachyurus).

PubMed

Swenson, Julie; Orr, Kathryn; Bradley, Gregory A

2012-06-01

A 15-yr-old, female, maned wolf (Chrysocyon brachyurus) was euthanized after presenting semicomatose with severe, uncontrolled frank hemorrhage from her rectum 6 days following a routine physical examination and vaccination. Histopathology indicated severe hemorrhagic and necrotizing hepatitis with intranuclear basophilic inclusion bodies in the liver that were thought to be consistent with adenoviral infection. Further classification by polymerase chain reaction, immunohistochemical staining, virus isolation, and electron microscopy confirmed the etiologic agent to be canine adenovirus-2. A representative sample of the vaccine that had been used was submitted and sequenced along with the virus isolated from the maned wolf. The sequencing of the etiologic agent that had been isolated from the maned wolf was determined to be the same as the strain of virus used in the production of the modified live vaccine that had been administered 6 days prior to death. From this information, the diagnosis of vaccine-induced adenoviral hepatitis was made. This is the first confirmed case of vaccine-induced canine adenoviral hepatitis in a maned wolf.

Severe postpartum hemorrhage from uterine atony: a multicentric study.

PubMed

Montufar-Rueda, Carlos; Rodriguez, Laritza; Jarquin, José Douglas; Barboza, Alejandra; Bustillo, Maura Carolina; Marin, Flor; Ortiz, Guillermo; Estrada, Francisco

2013-01-01

Postpartum hemorrhage (PPH) is an important cause of maternal mortality (MM) around the world. Seventy percent of the PPH corresponds to uterine atony. The objective of our study was to evaluate multicenter PPH cases during a 10-month period, and evaluate severe postpartum hemorrhage management. The study population is a cohort of vaginal delivery and cesarean section patients with severe postpartum hemorrhage secondary to uterine atony. The study was designed as a descriptive, prospective, longitudinal, and multicenter study, during 10 months in 13 teaching hospitals. Total live births during the study period were 124,019 with 218 patients (0.17%) with severe postpartum hemorrhage (SPHH). Total maternal deaths were 8, for mortality rate of 3.6% and a MM rate of 6.45/100,000 live births (LB). Maternal deaths were associated with inadequate transfusion therapy. In all patients with severe hemorrhage and subsequent hypovolemic shock, the most important therapy is intravascular volume resuscitation, to reduce the possibility of target organ damage and death. Similarly, the current proposals of transfusion therapy in severe or massive hemorrhage point to early transfusion of blood products and use of fresh frozen plasma, in addition to packed red blood cells, to prevent maternal deaths.

Initial Resuscitation with Plasma and Other Blood Components Reduced Bleeding Compared to Hetastarch in Anesthetized Swine with Uncontrolled Splenic Hemorrhage

DTIC Science & Technology

2011-04-01

products and Hextend. The fluid with the highest amount of coagulation factors , FFP resulted in the lowest blood loss. The FFP treatment had the highest...compared to humans and have higher concentrations of many of the clotting factors (FV, FVII , FVIII, F IX, and FXII).44 Although we have confirmed the higher...utilizing plasma early in treatment is to prevent dilution of remaining coagulation factors or reverse the coagulopathy that has been observed in

Warm Fresh Whole Blood Is Independently Associated With Improved Survival for Patients With Combat-Related Traumatic Injuries

DTIC Science & Technology

2009-04-01

2 US Military reports estimate that 15% to 20% of traumatic deaths are preventable , and 66% to 80% of these deaths occur from hemorrhage.3,4 Rural...civilian data indicates that approximately 10% of deaths are preventable .5,6 If 10% to 20% of 150,000 US civilian traumatic deaths are preventable , and...66% to 80% of these preventable deaths are due to uncontrolled bleeding this translates to between 10,000 and 24,000 potentially preventable

Technique Refinement and Validation of Variable Aortic Occlusion via Extracorporeal Flow Circuit in a Pig Model (Sus scrofa) of Uncontrolled Hemorrhage with Subsequent Resuscitation and Critical Care

DTIC Science & Technology

2016-07-24

60th Medical Group (AMC), Travis AFB, CA INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE (IACUC) FINAL REPORT SUMMARY (Please type all information. Use...TRIENNIAL REVISION DATE: N/A FUNDING SOURCE: HQ USAF SG 1. RECORD OF ANIMAL USAGE: Animal Species: Total # Approved # Used this FY Total # Used to...Restraint Training: non-Live Animal Health Promotion Research: Survival (chronic) Prevention x_ Research: non-Survival (acute) Utilization Mgt. Other

Hemoglobin-based Oxygen Carrier (HBOC-201) and Escalating Doses of Recombinant Factor VIla (rFVIIa) as a Novel Pre-hospital Resuscitation Fluid in a Swine Model of Severe Uncontrolled Hemorrhage

DTIC Science & Technology

2011-01-01

challenge [ 16]. Trauma-associated co- agulopathy is attributed to the dilutional effect of fluid resus- citation and transfusion, hypothermia, acidosis ...alongside with correcting acidosis and hypothermia [ 18]. These steps, however, often fail to control life-threatening bleeding in trauma [ 19...ispurified,filtered,stroma-freeandheat-treated bovine hemoglobin that is polymerized by gluteraldehyde- crosslinking to form polymers ranging from 130-500

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

PubMed

Jiang, Wenhua; Bian, Yuzhu; Wang, Zhenghui; Chang, Thomas Ming Swi

2017-02-01

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.

G6PC3, ALDOA and CS induction accompanies mir-122 down-regulation in the mechanical asphyxia and can serve as hypoxia biomarkers.

PubMed

Zeng, Yan; Lv, Yehui; Tao, Li; Ma, Jianlong; Zhang, Heng; Xu, Hongmei; Xiao, Bi; Shi, Qun; Ma, Kaijun; Chen, Long

2016-10-26

Hypoxia influences different cellular biological processes. To reveal the dynamics of hypoxia's effects on miRNA regulation in vivo, we examined the expression levels of all miRNAs in human brain and heart specimens from cases of mechanical asphyxia compared with those from cases of craniocerebral injury and hemorrhagic shock. We further validated differently expressed miRNAs in another 84 human specimens and rat models. We found that mir-122 was significantly down-regulated and that its putative targets G6PC3, ALDOA and CS were increased in the brain and cardiac tissues in cases of mechanical asphyxia compared with craniocerebral injury and hemorrhagic shock. Our data indicate that mir-122 and its targets G6PC3, ALDOA and CS play roles in the hypoxia responses that regulate glucose and energy metabolism and can serve as hypoxia biomarkers.

G6PC3, ALDOA and CS induction accompanies mir-122 down-regulation in the mechanical asphyxia and can serve as hypoxia biomarkers

PubMed Central

Zeng, Yan; Lv, Yehui; Tao, Li; Ma, Jianlong; Zhang, Heng; Xu, Hongmei; Xiao, Bi; Shi, Qun; Ma, Kaijun; Chen, Long

2016-01-01

Hypoxia influences different cellular biological processes. To reveal the dynamics of hypoxia's effects on miRNA regulation in vivo, we examined the expression levels of all miRNAs in human brain and heart specimens from cases of mechanical asphyxia compared with those from cases of craniocerebral injury and hemorrhagic shock. We further validated differently expressed miRNAs in another 84 human specimens and rat models. We found that mir-122 was significantly down-regulated and that its putative targets G6PC3, ALDOA and CS were increased in the brain and cardiac tissues in cases of mechanical asphyxia compared with craniocerebral injury and hemorrhagic shock. Our data indicate that mir-122 and its targets G6PC3, ALDOA and CS play roles in the hypoxia responses that regulate glucose and energy metabolism and can serve as hypoxia biomarkers. PMID:27793029

Detection of occult pericardial hemorrhage early after open-heart surgery using technetium-99m red blood cell radionuclide ventriculography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bateman, T.M.; Czer, L.S.; Gray, R.J.

1984-11-01

Pericardial or mediastinal hemorrhage requiring reoperation occurs in 2% to 5% of patients, usually early (0 to 48 hours), after open-heart surgery. This hemorrhage may be occult, and resulting cardiac tamponade may easily be misinterpreted as ventricular dysfunction, common early postoperatively. In such cases, appropriate and timely intervention may not occur. Of 50 patients evaluated by technetium-99m red blood cell gated equilibrium radionuclide ventriculography (RNV) because of early postoperative cardiogenic shock of uncertain etiology, 17 had unique scintigraphic images suggestive of intrathoracic hemorrhage. Of these 17, 5 had a generalized halo of abnormal radioactivity surrounding small hyperdynamic right and leftmore » ventricles, 11 had localized regions of intense blood pool activity outside the cardiac chambers (two with compression of single chambers), and one demonstrated marked radionuclide activity in the right hemithorax (2000 ml of blood at reoperation). Twelve patients had exploratory reoperation for control of hemorrhage as a direct result of the scintigraphic findings, three were successfully treated with fresh frozen plasma and platelet infusions along with medical interventions to optimize cardiac performance, and two patients died in cardiogenic shock (presumed tamponade) without reoperation. In the 12 reoperated patients, all were confirmed to have active pericardial bleeding. Scintigraphic localization of abnormal blood pools within the pericardium corresponded to the sites at which active bleeding was witnessed at reoperation. The abnormal bleeding was etiologically related to the tamponade state, with marked improvement in hemodynamics after reoperation. Nine additional patients were reoperated for presumed tamponade after RNV revealed an exaggerated halo of photon deficiency surrounding the cardiac chambers.« less

[Massive hemorrhage of upper gastrointestinal tract caused by gastrointestinal stromal tumor of the stomach--case report].

PubMed

Lalović, Nenad; Dukić Vladicić, Nikolina; Marić, Radmil; Cuk, Mirjana; Simatović, Milan; Jokanović, Dragana

2012-01-01

Acute bleeding from the upper gastrointestinal system is a medical emergency which is followed by high mortality rate, ranging from 6 to 15% in spite of modern diagnostic methods and treatment. Bleeding from the upper gastrointestinal system may be caused by gastrointestinal stromal tumors of the stomach, which are mainly characterized by occult bleeding, while profuse bleeding rarely occurs accompanied by hemorrhagic shock. Gastrointestinal stromal tumors of stomach are the most common mesenchimal tumors of the gastrointestinal tract. In our study we showed a 60-year-old female patient with profuse bleeding from the stomach and the clinical picture of severe hemorrhagic shock, caused by gastrointestinal stromal tumor. An ovoid junction, raised towards the lumen, covered with ulcerated mucosa in several places and followed by massive arterial bleeding was found intraoperatively, after the performed gastrotomy. Histopathological examination with immunohistochemical analysis confirmed that this was a gastrointestinal stromal tumor of the stomach. Acute bleeding from the digestive system is a sudden and serious condition of the body. Urgent esophagogastroduodenoscopy is a sensitive and specific diagnostic and therapeutic method of choice. Massive bleeding from the upper gastrointestinal tract is very rarely caused by gastrointestinal stromal tumors, whose clinical picture is very heterogeneous and depends on tumor size and location. Abundant bleeding from the tumor is an indication for urgent surgical intervention. According to the literature massive hemorrhage of the upper digestive system can rarely be caused by gastrointestinal stromal tumor of the stomach. It is shown that abundant hemorrhage of the upper digestive tract can be caused with gastric gastrointestinal stromal tumor. Surgical resection is the main form of treatment of gastrointestinal stromal tumors of the digestive system and bleeding from these tumors caused by failure of endoscopic hemostasis.

Inescapable Stress Changes Walking Behavior in Flies - Learned Helplessness Revisited

PubMed Central

Batsching, Sophie; Wolf, Reinhard; Heisenberg, Martin

2016-01-01

Like other animals flies develop a state of learned helplessness in response to unescapable aversive events. To show this, two flies, one 'master', one 'yoked', are each confined to a dark, small chamber and exposed to the same sequence of mild electric shocks. Both receive these shocks when the master fly stops walking for more than a second. Behavior in the two animals is differently affected by the shocks. Yoked flies are transiently impaired in place learning and take longer than master flies to exit from the chamber towards light. After the treatment they walk more slowly and take fewer and shorter walking bouts. The low activity is attributed to the fly's experience that its escape response, an innate behavior to terminate the electric shocks, does not help anymore. Earlier studies using heat pulses instead of electric shocks had shown similar effects. This parallel supports the interpretation that it is the uncontrollability that induces the state. PMID:27875580

Effects of a Single Dose of Parecoxib on Inflammatory Response and Ischemic Tubular Injury Caused by Hemorrhagic Shock in Rats.

PubMed

Takaku, Mariana; da Silva, Andre Carnevali; Iritsu, Nathalie Izumi; Vianna, Pedro Thadeu Galvao; Castiglia, Yara Marcondes Machado

2018-01-01

Parecoxib, a selective COX-2 inhibitor, is used to improve analgesia in postoperative procedures. Here we evaluated whether pretreatment with a single dose of parecoxib affects the function, cell injury, and inflammatory response of the kidney of rats subjected to acute hemorrhage. Inflammatory response was determined according to serum and renal tissue cytokine levels (IL-1 α , IL-1 β , IL-6, IL-10, and TNF- α ). Forty-four adult Wistar rats anesthetized with sevoflurane were randomized into four groups: placebo/no hemorrhage (Plc/NH); parecoxib/no hemorrhage (Pcx/NH); placebo/hemorrhage (Plc/H); and parecoxib/hemorrhage (Pcx/H). Pcx groups received a single dose of intravenous parecoxib while Plc groups received a single dose of placebo (isotonic saline). Animals in hemorrhage groups underwent bleeding of 30% of blood volume. Renal function and renal histology were then evaluated. Plc/H showed the highest serum levels of cytokines, suggesting that pretreatment with parecoxib reduced the inflammatory response in rats subjected to hemorrhage. No difference in tissue cytokine levels between groups was observed. Plc/H showed higher percentage of tubular dilation and degeneration, indicating that parecoxib inhibited tubular injury resulting from renal hypoperfusion. Our findings indicate that pretreatment with a single dose of parecoxib reduced the inflammatory response and tubular renal injury without altering renal function in rats undergoing acute hemorrhage.

Evaluation of contralateral kidney, liver and lung after extracorporeal shock wave lithotripsy in rabbits.

PubMed

Senyucel, M F; Boybeyi, O; Ayva, S; Aslan, M K; Soyer, T; Demet, A I; Kısa, U; Basar, M; Cakmak, M A

2013-10-01

An experimental study was carried out to evaluate the effects of extracorporeal shock wave lithotripsy (ESWL) on contralateral kidney, liver and lung by histopathological and biochemical methods. Twelve New Zealand rabbits were allocated to two groups (n = 6). Tissues of control group (CG, n = 6) were harvested without any intervention. In ESWL group (EG), right kidneys were exposed to 3,000 shock waves at 14 kV energy using electro-hydraulic type ESWL device three times every other day. Both kidneys, liver, and right lobe of lung tissues in EG were harvested on seventh day. Kidneys were examined histopathologically for presence of glomerular and tubular injury, interstitial edema, congestion, inflammation and fibrosis. Livers were examined for hepatocyte vacuolization, congestion, portal inflammation and fibrosis. Lung tissues were examined for loss of normal structure, emphysema, interstitial congestion-edema, prominent alveolar septal vessels, interstitial inflammation, intra-alveolar hemorrhage, intraluminal hemorrhage, peribronchial edema, congestion, inflammation in bronchial wall and epithelial desquamation. Biochemical analysis of tissue samples was performed for oxidative injury markers. Histopathological evaluations revealed that tubular injury was found in both shocked and contralateral kidneys (p < 0.05). EG showed higher grades of portal fibrosis in liver and higher grades of peribronchial congestion in lung when compared to CG (p < 0.05). Biochemical evaluations of both kidneys showed that malondialdehyde levels were higher in EG than in CG (p < 0.05). ESWL causes histopathologic alterations both in shocked and contralateral kidneys. Extrarenal tissues such as liver and lung can be affected by shock waves histopathologically and oxidative injury of contralateral kidney may occur acutely after ESWL.

Effect of liposome-encapsulated hemoglobin resuscitation on proteostasis in small intestinal epithelium after hemorrhagic shock

PubMed Central

Rao, Geeta; Yadav, Vivek R.; Awasthi, Shanjana; Roberts, Pamela R.

2016-01-01

Gut barrier dysfunction is the major trigger for multiorgan failure associated with hemorrhagic shock (HS). Although the molecular mediators responsible for this dysfunction are unclear, oxidative stress-induced disruption of proteostasis contributes to the gut pathology in HS. The objective of this study was to investigate whether resuscitation with nanoparticulate liposome-encapsulated hemoglobin (LEH) is able to restore the gut proteostatic mechanisms. Sprague-Dawley rats were recruited in four groups: control, HS, HS+LEH, and HS+saline. HS was induced by withdrawing 45% blood, and isovolemic LEH or saline was administered after 15 min of shock. The rats were euthanized at 6 h to collect plasma and ileum for measurement of the markers of oxidative stress, unfolded protein response (UPR), proteasome function, and autophagy. HS significantly increased the protein and lipid oxidation, trypsin-like proteasome activity, and plasma levels of IFNγ. These effects were prevented by LEH resuscitation. However, saline was not able to reduce protein oxidation and plasma IFNγ in hemorrhaged rats. Saline resuscitation also suppressed the markers of UPR and autophagy below the basal levels; the HS or LEH groups showed no effect on the UPR and autophagy. Histological analysis showed that LEH resuscitation significantly increased the villus height and thickness of the submucosal and muscularis layers compared with the HS and saline groups. Overall, the results showed that LEH resuscitation was effective in normalizing the indicators of proteostasis stress in ileal tissue. On the other hand, saline-resuscitated animals showed a decoupling of oxidative stress and cellular protective mechanisms. PMID:27288424

Outcomes of transconjunctival sutureless 27-gauge micro-incision vitrectomy surgery in diabetic vitreous haemorrhage

PubMed Central

Shahzadi, Bashiran; Rizwi, Syed Fawad; Qureshi, Faisal Murtaza; Latif, Kanwal; Mahmood, Syed Asaad

2017-01-01

Objective: To evaluate the visual outcomes of 27-gauge transconjunctival sutureless vitrectomy surgery and its complications in patients with diabetic vitreous hemorrhage. Methods: A quasi-experimental study was conducted where eighty seven eyes of 87 uncontrolled type II diabetes mellitus patients presenting with diabetic vitreous hemorrhage were selected to undergo 27-gauge transconjunctival sutureless micro-incision vitrectomy surgery. Main outcome measured was best corrected visual acuity (BCVA). Post-operative complications were also screened for at each visit. The follow ups were at post-operative day one, one month, three months and six months respectively. Results: Out of 87 patients, 52 (59.8%) were males and 35 (40.2%) were females. The mean age of the patients was 52.32 ± 6.78 years (95% CI: 53.13 - 55.57). For most of the patients, the BCVA improved progressively with each subsequent follow up visit. Pre-operative BCVA was 1.01 ± 0.206 logMar, compared to BCVA at final follow up of 0.44 ± 0.231 (p-value < 0.001). Six (6.9%) patients developed recurrent vitreous hemorrhage during the study period, four (4.6%) developed cataract, one (1.1%) had increased intraocular pressure and sub conjunctival hemorrhage was present in two (2.3%). Conclusion: 27-gauge micro-incision vitrectomy surgery is an effective sutureless surgery with favorable outcomes, in terms of vision, in patients with diabetic vitreous hemorrhage. The associated complications are few which can be easily managed. PMID:28367178

Investigating Non-Invasive Hemodynamic Monitoring Devices Using Severe Dengue as a Surrogate for Trauma-Induced Shock

DTIC Science & Technology

2014-12-01

dengue hemorrhagic fever. In future work we will continue to evaluate the use of pulse wave forms to predict shock and will assess other...Index Three laboratory Phase I clinical trials have been completed to support a 510(k) application for FDA approval of the first prototype Pulse ... Oximeter with the CRI algorithm and capability for real-time continuous collection of photoplethymographic (PPG) analog signals. An FDA-cleared

Prevention of Trauma/Hemorrhagic Shock-Induced Mortality,Apoptosis, Inflammation and Mitochondrial Dysfunction

DTIC Science & Technology

2013-12-01

suggesting another mechanism for the apoptosis-reduction benefit of IL-6 signaling, and 7) Stat3. can substitute for Stat3. to restore mitochondrial...Rats subjected to femur fracture and T-HS (AIM 2) and 3) Swine subjected to laparotomy, splenectomy, tissue injury and controlled HS (AIM 3). Aim...unacceptable mortality during the shock phase, the second was that there was variable amounts of bleeding from the femoral fracture site. We opted based on

Complexity and Animal Models

DTIC Science & Technology

2015-01-01

ventricular fibrillation and cardiopulmonary resuscitation . The second presentation will be summarized below. doi:10.1016/j.jcrc.2010.05.013 Neural dynamics...hemorrhagic shock, resuscitation , trauma, inhalation injury, apnea, and other critical states. This research serves as a test bed for discovery

Early identification of patients requiring massive transfusion, embolization, or hemostatic surgery for traumatic hemorrhage: a systematic review protocol.

PubMed

Tran, Alexandre; Matar, Maher; Steyerberg, Ewout W; Lampron, Jacinthe; Taljaard, Monica; Vaillancourt, Christian

2017-04-13

Hemorrhage is a major cause of early mortality following a traumatic injury. The progression and consequences of significant blood loss occur quickly as death from hemorrhagic shock or exsanguination often occurs within the first few hours. The mainstay of treatment therefore involves early identification of patients at risk for hemorrhagic shock in order to provide blood products and control of the bleeding source if necessary. The intended scope of this review is to identify and assess combinations of predictors informing therapeutic decision-making for clinicians during the initial trauma assessment. The primary objective of this systematic review is to identify and critically assess any existing multivariable models predicting significant traumatic hemorrhage that requires intervention, defined as a composite outcome comprising massive transfusion, surgery for hemostasis, or angiography with embolization for the purpose of external validation or updating in other study populations. If no suitable existing multivariable models are identified, the secondary objective is to identify candidate predictors to inform the development of a new prediction rule. We will search the EMBASE and MEDLINE databases for all randomized controlled trials and prospective and retrospective cohort studies developing or validating predictors of intervention for traumatic hemorrhage in adult patients 16 years of age or older. Eligible predictors must be available to the clinician during the first hour of trauma resuscitation and may be clinical, lab-based, or imaging-based. Outcomes of interest include the need for surgical intervention, angiographic embolization, or massive transfusion within the first 24 h. Data extraction will be performed independently by two reviewers. Items for extraction will be based on the CHARMS checklist. We will evaluate any existing models for relevance, quality, and the potential for external validation and updating in other populations. Relevance will be described in terms of appropriateness of outcomes and predictors. Quality criteria will include variable selection strategies, adequacy of sample size, handling of missing data, validation techniques, and measures of model performance. This systematic review will describe the availability of multivariable prediction models and summarize evidence regarding predictors that can be used to identify the need for intervention in patients with traumatic hemorrhage. PROSPERO CRD42017054589.

Time Course of Septic Shock in Immunocompromised and Nonimmunocompromised Patients.

PubMed

Jamme, Matthieu; Daviaud, Fabrice; Charpentier, Julien; Marin, Nathalie; Thy, Michaël; Hourmant, Yannick; Mira, Jean-Paul; Pène, Frédéric

2017-12-01

To address the impact of underlying immune conditions on the course of septic shock with respect to both mortality and the development of acute infectious and noninfectious complications. An 8-year (2008-2015) monocenter retrospective study. A medical ICU in a tertiary care center. Patients diagnosed for septic shock within the first 48 hours of ICU admission were included. Patients were classified in four subgroups with respect to their immune status: nonimmunocompromised and immunocompromised distributed into hematologic or solid malignancies and nonmalignant immunosuppression. Outcomes were in-hospital death and the development of ischemic and hemorrhagic complications and ICU-acquired infections. The determinants of death and complications were addressed by multivariate competing risk analysis. None. Eight hundred one patients were included. Among them, 305 (38%) were immunocompromised, distributed into solid tumors (122), hematologic malignancies (106), and nonmalignant immunosuppression (77). The overall 3-day, in-ICU, and in-hospital mortality rates were 14.1%, 37.3%, and 41.3%, respectively. Patients with solid tumors displayed increased in-hospital mortality (cause-specific hazard, 2.20 [95% CI, 1.64-2.96]; p < 0.001). ICU-acquired infections occurred in 211 of the 3-day survivors (33%). In addition, 95 (11.8%) and 70 (8.7%) patients exhibited severe ischemic or hemorrhagic complications during the ICU stay. There was no association between the immune status and the occurrence of ICU-acquired infections. Nonmalignant immunosuppression and hematologic malignancies were independently associated with increased risks of severe ischemic events (cause-specific hazard, 2.12 [1.14-3.96]; p = 0.02) and hemorrhage (cause-specific hazard, 3.17 [1.41-7.13]; p = 0.005), respectively. The underlying immune status impacts on the course of septic shock and on the susceptibility to ICU-acquired complications. This emphasizes the complexity of sepsis syndromes in relation with comorbid conditions and raises the question of the relevant endpoints in clinical studies.

N-acetylcysteine reduces the renal oxidative stress and apoptosis induced by hemorrhagic shock.

PubMed

Moreira, Miriam Aparecida; Irigoyen, Maria Claudia; Saad, Karen Ruggeri; Saad, Paulo Fernandes; Koike, Marcia Kiyomi; Montero, Edna Frasson de Souza; Martins, José Luiz

2016-06-01

Renal ischemia/reperfusion injury induced by hemorrhagic shock (HS) and subsequent fluid resuscitation is a common cause of acute renal failure. The objective of this study was to evaluate the effect of combining N-acetylcysteine (NAC) with fluid resuscitation on renal injury in rats that underwent HS. Two groups of male Wistar rats were induced to controlled HS at 35 mm Hg mean arterial pressure for 60 min. After this period, the HS and fluid resuscitation (HS/R) group was resuscitated with lactate containing 50% of the blood that was withdrawn. The HS/R + NAC group was resuscitated with Ringer's lactate combined with 150 mg/kg of NAC and blood. The sham group animals were catheterized but were not subjected to shock. All animals were kept under anesthesia and euthanized after 120 min of fluid resuscitation or observation. Animals treated with NAC presented attenuation of histologic lesions, reduced oxidative stress, and apoptosis markers when compared with animals from the HS/R group. The serum creatinine was similar in all the groups. NAC is a promising drug for combining with fluid resuscitation to attenuate the kidney injury associated with HS. Copyright © 2016 Elsevier Inc. All rights reserved.

Skin test performed with highly purified Mycobacterium tuberculosis recombinant protein triggers tuberculin shock in infected guinea pigs.

PubMed

Reece, Stephen T; Stride, Nicole; Ovendale, Pamela; Reed, Steven G; Campos-Neto, Antonio

2005-06-01

Tuberculin shock due to inoculation of Mycobacterium tuberculosis antigens in patients with tuberculosis is a serious syndrome originally described over 100 years ago by Robert Koch. Here, we present experimental evidence that a single M. tuberculosis recombinant protein, CFP-10, triggers this syndrome. Intradermal inoculation of CFP-10 elicits in M. tuberculosis-infected mice high levels of serum tumor necrosis factor alpha and causes tuberculin shock in infected guinea pigs characterized by hypothermia and death within 6 to 48 h after the antigen inoculation. Autopsies of these animals revealed intense polycythemia and hemorrhagic patches in the lung parenchyma, a pathological observation consistent with tuberculin shock. These results point to the possible occurrence of tuberculin shock in sensitive individuals inoculated with highly purified M. tuberculosis recombinant proteins as vaccine candidates or skin test reagents.

Association between sex, nutritional status, severity of dengue hemorrhagic fever, and immune status in infants with dengue hemorrhagic fever.

PubMed

Nguyen, Thanh Hung; Nguyen, Trong Lan; Lei, Huan-Yao; Lin, Yee-Shin; Le, Bich Lien; Huang, Kao-Jean; Lin, Chiou-Feng; Do, Quang Ha; Vu, Thi Que Huong; Lam, Thi My; Yeh, Trai-Ming; Huang, Jyh-Hsiung; Liu, Ching-Chuan; Halstead, Scott B

2005-04-01

The association between sex, nutritional status, and the severity of dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), and immune status was investigated in 245 Vietnamese infants with predominantly primary infections with dengue virus. Male and female infants were at equal risk of developing DHF/DSS. However, infants of low height and weight for age were under-represented among DHF/DSS cases compared with 533 healthy baby clinic infant controls. Acute illness phase blood levels of selected cytokines (interferon-gamma and tumor necrosis factor-alpha) and serum levels of antibodies to dengue virus were elevated in the same range in male and female infants with DHF/DSS, as well as in infants with and without malnutrition.

When Pain Hurts: Nociceptive Stimulation Induces a State of Maladaptive Plasticity and Impairs Recovery after Spinal Cord Injury.

PubMed

Grau, James W; Huang, Yung-Jen; Turtle, Joel D; Strain, Misty M; Miranda, Rajesh C; Garraway, Sandra M; Hook, Michelle A

2017-05-15

Spinal cord injury (SCI) is often accompanied by other tissue damage (polytrauma) that provides a source of pain (nociceptive) input. Recent findings are reviewed that show SCI places the caudal tissue in a vulnerable state that exaggerates the effects nociceptive stimuli and promotes the development of nociceptive sensitization. Stimulation that is both unpredictable and uncontrollable induces a form of maladaptive plasticity that enhances nociceptive sensitization and impairs spinally mediated learning. In contrast, relational learning induces a form of adaptive plasticity that counters these adverse effects. SCI sets the stage for nociceptive sensitization by disrupting serotonergic (5HT) fibers that quell overexcitation. The loss of 5HT can enhance neural excitability by reducing membrane-bound K + -Cl - cotransporter 2, a cotransporter that regulates the outward flow of Cl - . This increases the intracellular concentration of Cl - , which reduces the hyperpolarizing (inhibitory) effect of gamma-aminobutyric acid. Uncontrollable noxious stimulation also undermines the recovery of locomotor function, and increases behavioral signs of chronic pain, after a contusion injury. Nociceptive stimulation has a greater effect if experienced soon after SCI. This adverse effect has been linked to a downregulation in brain-derived neurotrophic factor and an upregulation in the cytokine, tumor necrosis factor. Noxious input enhances tissue loss at the site of injury by increasing the extent of hemorrhage and apoptotic/pyroptotic cell death. Intrathecal lidocaine blocks nociception-induced hemorrhage, cellular indices of cell death, and its adverse effect on behavioral recovery. Clinical implications are discussed.

Heparin use in a rat hemorrhagic shock model induces biologic activity in mesenteric lymph separate from shock.

PubMed

Qin, Yong; Prescott, Lauriston M; Deitch, Edwin A; Kaiser, Vicki L

2011-04-01

Experimental data have shown that mesenteric lymph from rats subjected to trauma-hemorrhagic shock (THS) but not trauma-sham shock induces neutrophil activation, cytotoxicity, decreased red blood cell (RBC) deformability, and bone marrow colony growth suppression. These data have led to the hypothesis that gut factors produced from THS enter the systemic circulation via the mesenteric lymphatics and contribute to the progression of multiple organ failure after THS. Ongoing studies designed to identify bioactive lymph agents implicated factors associated with the heparin use in the THS procedure. We investigated if heparin itself was responsible for reported toxicity to human umbilical vein endothelial cells (HUVECs). Human umbilical vein endothelial cell toxicity was not induced by lymph when alternate anticoagulants (citrate and EDTA) were used in THS. Human umbilical vein endothelial cell toxicity was induced by lymph after heparin but not saline or citrate injection into trauma-sham shock and naive animals and was dose dependent. Activities of both heparin-releasable lipases (lipoprotein and hepatic) were detected in the plasma and lymph from THS and naive animals receiving heparin but not citrate or saline. Lymph-induced HUVEC toxicity correlated with lymph lipase activities. Finally, incubation of HUVECs with purified lipoprotein lipase added to naive lymph-induced toxicity in vitro. These data show that heparin, not THS, is responsible for the reported lymph-mediated HUVEC toxicity through its release of lipases into the lymph. These findings can provide alternative explanations for several of the THS effects reported in the literature using heparin models, thus necessitating a review of previous work in this field.

A Syrian golden hamster model recapitulating ebola hemorrhagic fever.

PubMed

Ebihara, Hideki; Zivcec, Marko; Gardner, Donald; Falzarano, Darryl; LaCasse, Rachel; Rosenke, Rebecca; Long, Dan; Haddock, Elaine; Fischer, Elizabeth; Kawaoka, Yoshihiro; Feldmann, Heinz

2013-01-15

Ebola hemorrhagic fever (EHF) is a severe viral infection for which no effective treatment or vaccine is currently available. While the nonhuman primate (NHP) model is used for final evaluation of experimental vaccines and therapeutic efficacy, rodent models have been widely used in ebolavirus research because of their convenience. However, the validity of rodent models has been questioned given their low predictive value for efficacy testing of vaccines and therapeutics, a result of the inconsistent manifestation of coagulopathy seen in EHF. Here, we describe a lethal Syrian hamster model of EHF using mouse-adapted Ebola virus. Infected hamsters displayed most clinical hallmarks of EHF, including severe coagulopathy and uncontrolled host immune responses. Thus, the hamster seems to be superior to the existing rodent models, offering a better tool for understanding the critical processes in pathogenesis and providing a new model for evaluating prophylactic and postexposure interventions prior to testing in NHPs.

A Syrian Golden Hamster Model Recapitulating Ebola Hemorrhagic Fever

PubMed Central

Ebihara, Hideki; Zivcec, Marko; Gardner, Donald; Falzarano, Darryl; LaCasse, Rachel; Rosenke, Rebecca; Long, Dan; Haddock, Elaine; Fischer, Elizabeth; Kawaoka, Yoshihiro; Feldmann, Heinz

2013-01-01

Ebola hemorrhagic fever (EHF) is a severe viral infection for which no effective treatment or vaccine is currently available. While the nonhuman primate (NHP) model is used for final evaluation of experimental vaccines and therapeutic efficacy, rodent models have been widely used in ebolavirus research because of their convenience. However, the validity of rodent models has been questioned given their low predictive value for efficacy testing of vaccines and therapeutics, a result of the inconsistent manifestation of coagulopathy seen in EHF. Here, we describe a lethal Syrian hamster model of EHF using mouse-adapted Ebola virus. Infected hamsters displayed most clinical hallmarks of EHF, including severe coagulopathy and uncontrolled host immune responses. Thus, the hamster seems to be superior to the existing rodent models, offering a better tool for understanding the critical processes in pathogenesis and providing a new model for evaluating prophylactic and postexposure interventions prior to testing in NHPs. PMID:23045629

Kv7 voltage-activated potassium channel inhibitors reduce fluid resuscitation requirements after hemorrhagic shock in rats.

PubMed

Nassoiy, Sean P; Byron, Kenneth L; Majetschak, Matthias

2017-01-17

Recent evidence suggests that drugs targeting Kv7 channels could be used to modulate vascular function and blood pressure. Here, we studied whether Kv7 channel inhibitors can be utilized to stabilize hemodynamics and reduce resuscitation fluid requirements after hemorrhagic shock. Anesthetized male Sprague-Dawley rats were instrumented with arterial and venous catheters for blood pressure monitoring, hemorrhage and fluid resuscitation. Series 1: Linopirdine (Kv7 channel blocker, 0.1-6 mg/kg) or retigabine (Kv7 channel activator, 0.1-12 mg/kg) were administered to normal animals. Series 2: Animals were hemorrhaged to a MAP of 25 mmHg for 30 min, followed by fluid resuscitation with normal saline (NS) to a MAP of 70 mmHg until t = 75 min. Animals were treated with single bolus injections of vehicle, linopirdine (1-6 mg/kg), XE-991 (structural analogue of linopirdine with higher potency for channel blockade, 1 mg/kg) prior to fluid resuscitation. Series 3: Animals were resuscitated with NS alone or NS supplemented with linopirdine (1.25-200 μg/mL). Data were analyzed with 2-way ANOVA/Bonferroni post-hoc testing. Series 1: Linopirdine transiently (10-15 min) and dose-dependently increased MAP by up to 15%. Retigabine dose-dependently reduced MAP by up to 60%, which could be reverted with linopirdine. Series 2: Fluid requirements to maintain MAP at 70 mmHg were 65 ± 34 mL/kg with vehicle, and 57 ± 13 mL/kg, 22 ± 8 mL/kg and 22 ± 11 mL/kg with intravenous bolus injection of 1, 3 and 6 mg/kg linopirdine, respectively. XE-991 (1 mg/kg), reduced resuscitation requirements comparable to 3 mg/kg linopirdine. Series 3: When resuscitation was performed with linopirdine-supplemented normal saline (NS), fluid requirements to stabilize MAP were 73 ± 12 mL/kg with NS alone and 72 ± 24, 61 ± 20, 36 ± 9 and 31 ± 9 mL/kg with NS supplemented with 1.25, 6.25, 12.5 and 200 μg/mL linopirdine, respectively. Our data suggest that Kv7 channel blockers could be used to stabilize blood pressure and reduce fluid resuscitation requirements after hemorrhagic shock.

The Effect of Diazoxide Upon Heat Shock Protein and Physiological Response to Hemorrhagic Shock and Cerebral Stroke

DTIC Science & Technology

2006-06-16

ischemic kidney model [121]. Photothrombic brain injury elicits the expression of HSP70 and HSP27 . HSP70 expression as early as one hour post-trauma...delineated the area of necrosis at 24 hours post-thrombic injury in ipsilateral cortex. HSP27 expression also was found to be upregulated and in fact...more globally expressed in the entire ipsilateral cerebral cortex, primarily in astrocytes [122]. 25 HSP25 and HSP27 Research demonstrates

248: Resuscitative Endovascular Balloon Occlusion of the Aorta Improves Survival in Lethal Hemorrhage

DTIC Science & Technology

2014-01-01

analyzed to evaluate for nonconvulsvie status epilepticus (NCSE) as defined in previous studies. Results: Out of the thirty patients that underwent...and oxygenation failure in 2,000 (38%) as indications for TI. In univariate analysis, shock status (OR 6.1 95%CI: 3.8-9.7, pɘ.0001) and...attempt, shock status remained associated with CAs (OR 6.2, 95%CI: 3.9-9.7, pɘ.0001) while oxygenation fa lure and resident providers were not (p=0.54

Evaluation of Coagulation Stages of Hemorrhaged Swine: Comparison of Thromboelastography and Rotational Elastometry

DTIC Science & Technology

2010-01-01

this article is prohibited. TEG and ROTEM comparison Tomori et al . 23 Table 2 Blood loss and survival in three Injury models Blood loss at injury...Shock Society, Cologne, Germany; June 2008, Shock 2008; 29:14. 8 Stern S, Rice J, Philbin N, McGwin G, Arnaud F, Johnson T, et al . Resuscitation...commonly used as measures of hemostasis for a variety of 0957·5235 C 2010 Wolters Kluwer Health 1 Lippincott Williams & Wilkins extremely

Severe Postpartum Hemorrhage from Uterine Atony: A Multicentric Study

PubMed Central

Montufar-Rueda, Carlos; Rodriguez, Laritza; Jarquin, José Douglas; Barboza, Alejandra; Bustillo, Maura Carolina; Marin, Flor; Ortiz, Guillermo; Estrada, Francisco

2013-01-01

Objective. Postpartum hemorrhage (PPH) is an important cause of maternal mortality (MM) around the world. Seventy percent of the PPH corresponds to uterine atony. The objective of our study was to evaluate multicenter PPH cases during a 10-month period, and evaluate severe postpartum hemorrhage management. Study Design. The study population is a cohort of vaginal delivery and cesarean section patients with severe postpartum hemorrhage secondary to uterine atony. The study was designed as a descriptive, prospective, longitudinal, and multicenter study, during 10 months in 13 teaching hospitals. Results. Total live births during the study period were 124,019 with 218 patients (0.17%) with severe postpartum hemorrhage (SPHH). Total maternal deaths were 8, for mortality rate of 3.6% and a MM rate of 6.45/100,000 live births (LB). Maternal deaths were associated with inadequate transfusion therapy. Conclusions. In all patients with severe hemorrhage and subsequent hypovolemic shock, the most important therapy is intravascular volume resuscitation, to reduce the possibility of target organ damage and death. Similarly, the current proposals of transfusion therapy in severe or massive hemorrhage point to early transfusion of blood products and use of fresh frozen plasma, in addition to packed red blood cells, to prevent maternal deaths. PMID:24363935

Subgaleal hemorrhage in the newborn infant associated with silicone elastomer vacuum extractor.

PubMed

Florentino-Pineda, I; Ezhuthachan, S G; Sineni, L G; Kumar, S P

1994-01-01

Subgaleal hemorrhage in the newborn infant has been reported worldwide, but despite the efforts of previous authors, this entity has not received the necessary attention in pediatric literature, and continues to represent a potentially fatal problem. Although the association of subgaleal hemorrhage with the use of the metal cup vacuum extractor has clearly been documented, its association with the silicone elastomer version has not been previously reported. We describe two cases in newborn infants where silicone elastomer cup vacuum extractor was used. The diagnosis of subgaleal hemorrhage must be considered in any infant with a scalp swelling and a falling hematocrit, and coagulation studies should be performed in all infants with a diagnosis of subgaleal hemorrhage. Complications include shock and death if subgaleal hemorrhage is massive and acute, and anemia and hyperbilirubinemia if it is slowly progressive. The familiarity with and ability of care givers to recognize the signs and symptoms of subgaleal hemorrhage are essential in preventing fatalities. A systematic approach to diagnosis with close monitoring of vital signs, hematocrit, blood gases, head circumference, and signs of tissue hypoperfusion is recommended for infants after instrument deliveries. Pathogenesis of this lesion needs to be emphasized in pediatric literature so that early recognition and prompt treatment may avoid a fatal outcome.

Treatment of shock.

PubMed

Hardaway, R M

1979-03-01

In order to effectively treat shock the physician must understand the physiology of shock. Shock patients may have a low, normal, or high arterial blood pressure, and the blood volume may be below normal, normal, or above normal. Shock is not necessarily accompanied by low arterial pH or low peripheral resistance. Most cases of acute traumatic and hemorrhagic shock show a high arterial pH, partly due to the blowing off of CO2, despite an elevated blood lactic acid level. Most patients also show a very high resistance. A factor that all shock patients have in common is a deficient capillary perfusion, or an insufficient amount of blood flowing through the capillaries. The cornerstone of the treatment of hypovolemic shock is the administration of adequate amounts of the right kinds of intravenous fluids. Focus is on classification of shock (reversible shock, irreversible or fatal shock, hypovolemia), the heart in shock, respiration, drugs (steroids, vasoactive drugs), and disseminated intravascular coagulation. If edema is a problem, diuretics may be helpful. Antibiotics for infection are very important in sepsis and septic shock. Supportive drugs are also important. Steroids and vasoactive drugs have a secondary place in the treatment of shock, and they should be used when these treatments have failed to produce an adequate blood pressure and urinary output.

Far Forward Treatment of Hemorrhagic Shock

DTIC Science & Technology

2007-02-01

Ringer’s solutions on human leukocytes. J Trauma 52(5):872-878, 2002 6. Alam HB, Punzalan CM, Koustova E, Bowyer MW, Rhee P. Hypertonic Saline: Intraosseous ...Fluid Resuscitation. 17. February 2006- Anesthesia Grand Rounds. Massachusetts General Hospital, Boston, MA. Topic: Trauma Resuscitation: New

To shunt or not to shunt? An experimental study comparing temporary vascular shunts and venous ligation as damage control techniques for vascular trauma.

PubMed

Marinho de Oliveira Góes Junior, Adenauer; de Campos Vieira Abib, Simone; de Seixas Alves, Maria Teresa; Venerando da Silva Ferreira, Paulo Sérgio; Carvalho de Andrade, Mariseth

2014-04-01

To evaluate vascular flow through temporary vascular shunts inserted into peripheral arteries and veins and the repercussion, on the arterial perfusion, of venous ligation and venous shunt insertion in an experimental model for damage control. Experimental study in pigs. Animals were distributed in 5 groups: group 1, right external iliac artery (EIA) shunting and right external iliac vein (EIV) ligation; group 2, right EIA shunting and right EIV shunting; group 3, right EIV ligation; group 4, right EIV shunting; group 5, no vascular shunting and no venous ligation. Flowmeters were used to measure vascular flow on right and left external iliac vessels, and blood samples were collected from the EIVs for biochemical analysis. A right anterior limb biopsy was performed before shock. Hemorrhagic shock was induced through the external right jugular vein, until the vascular flow through right iliac external artery shunt or right iliac external vein shunt (group 4) ceased or until the animal's death. After the end of the experiments, biopsies of bilateral hind limb were obtained for histologic analysis. For statistical analysis, Microsoft Office Excel 2007 and BioEstat 5.0 (2007) were used. In the absence of hemorrhagic shock, venous ligation (group 1) was associated with a 38.8% reduction (P < 0.05) and venous shunting with a 28.4% reduction on the vascular flow through the arterial shunt. When associated with hemorrhagic shock, the mean vascular flow on the right EIA was 13 mL/min and on the left EIA was 41.2 mL/min; on group 2, the right EIA flow was 8.5 mL/min and the left EIA flow was 8.1 mL/min. When associated with hemorrhagic shock, the pO2 was 25.8 mm Hg on right EIV and 33.8 mm Hg on the left EIV for group 1 (P < 0.05), whereas for group 2, the pO2 was 22.6 mm Hg on right EIV and 22.8 mm Hg on the left EIV. On group 1, serum potassium was 3.84 mEq/L on the right EIV and 3.96 mEq/L on the left EIV, whereas on group 2, it was 7.1 mEq/L on the right EIV and 5.88 mEq/L on the left EIV (P < 0.05). In the developed experimental model, venous shunting, when compared with venous ligation, offered less resistance to vascular flow through the arterial shunt and allowed a more efficient limb venous drainage than simple vein ligature. Copyright © 2014 Elsevier Inc. All rights reserved.

Parameters of hormetic stress and resilience to trauma in rats.

PubMed

Plumb, Traci N; Cullen, Patrick K; Minor, Thomas R

2015-01-01

Hormesis is the process by which small stresses build resilience to large stresses. We pre-exposed rats to various parameters of mild-to-moderate stress prior to traumatic stress in the present experiments to assess the potential benefits of hormetic training on resilience to traumatic, uncontrollable stress. Rats underwent varying stress pre-training parameters prior to exposure to uncontrollable traumatic stress in the learned helplessness procedure. The ability to prevent the exaggerated fear responding and escape deficits that normally follow experience with traumatic stress were used as a measure of the benefits of hormetic training. Four experiments examined the effects of number of training sessions, stressor severity and pattern of rest between pre-training stress sessions. Repeated exposure to mild restraint stress or moderate shock stress eliminated both the enhanced fear conditioning and shuttle-escape deficits that result from exposure to traumatic, inescapable shock. The pattern of rest did not contribute to resilience when the pre-exposure stressor was mild, but was vital when the pre-exposure stressor was moderate, with an alternation of stress and rest being the most effective procedure. The data also suggest that the level of resilience may increase with the number of pre-exposure sessions.

Effects of hemorrhagic hypotension on tyrosine concentrations in rat spinal cord and plasma

NASA Technical Reports Server (NTRS)

Conlay, L. A.; Maher, T. J.; Roberts, C. H.; Wurtman, R. J.

1988-01-01

Tyrosine is the precursor for catecholamine neurotransmitters. When catecholamine-containing neurons are physiologically active (as sympathoadrenal cells are in hypotension), tyrosine administration increases catecholamine synthesis and release. Since hypotension can alter plasma amino acid composition, the effects of an acute hypotensive insult on tyrosine concentrations in plasma and spinal cord were examined. Rats were cannulated and bled until the systolic blood pressure was 50 mmHg, or were kept normotensive for 1 h. Tyrosine and other large neutral amino acids (LNAA) known to compete with tyrosine for brain uptake were assayed in plasma and spinal cord. The rate at which intra-arterial (H-3)tyrosine disappeared from the plasma was also estimated in hemorrhaged and control rats. In plasma of hemorrhaged animals, both the tyrosine concentration and the tyrosine/LNAA ratio was elevated; moreover, the disappearance of (H-3)tyrosine was slowed. Tyrosine concentrations also increased in spinal cords of hemorrhaged-hypotensive rats when compared to normotensive controls. Changes in plasma amino acid patterns may thus influence spinal cord concentrations of amino acid precursors for neurotransmitters during the stress of hemorrhagic shock.

Experimental Study on the Efficacy of Site-Specific PEGylated Human Serum Albumins in Resuscitation From Hemorrhagic Shock.

PubMed

Song, Xinlei; Zhang, Shu; Cheng, Yanna; Zhao, Ting; Lian, Qianqian; Lu, Lu; Wang, Fengshan

2016-11-01

To evaluate the resuscitative efficacy and the effect on reperfusion injury of two site-specific PEGylated human serum albumins modified with linear or branched PEG20kDa, compared with saline, 8% human serum albumin and 25% human serum albumin, in a hemorrhagic shock model. Laboratory. Male Wistar rats. Prospective study. Rats were bled to hemorrhagic hypovolemic shock and resuscitated with different resuscitation fluids. The mean arterial pressure and blood gas variables were measured. Hemorheology analysis was performed to evaluate the influence of resuscitation on RBCs and blood viscosity. The microvascular state was indirectly characterized in terms of monocyte chemotactic protein-1 and endothelial nitric oxide synthase that related to shear stress and vasodilation, respectively. The levels of inflammation-related factors and apoptosis-related proteins were used to evaluate the reperfusion injury in lungs. The results showed that PEGylated human serum albumin could improve the level of mean arterial pressure and blood gas variables more effectively at the end of resuscitation. poly(ethylene glycol) modification was able to increase the viscosity of human serum albumin to the level of effectively enhancing the expression of monocyte chemotactic protein-1 and endothelial nitric oxide synthase, which could promote microvascular perfusion. The hyperosmotic resuscitative agents including both 25% human serum albumin and PEGylated human serum albumins could greatly attenuate lung injury. No significant therapeutic advantages but some disadvantages were found for Y shaped poly(ethylene glycol) modification over linear poly(ethylene glycol) modification, such as causing the decrease of erythrocyte deformability. Linear high molecular weight site-specific PEGylated human serum albumin is recommended to be used as a hyperosmotic resuscitative agent.

A Nonerythropoietic Peptide that Mimics the 3D Structure of Erythropoietin Reduces Organ Injury/Dysfunction and Inflammation in Experimental Hemorrhagic Shock

PubMed Central

Patel, Nimesh SA; Nandra, Kiran K; Brines, Michael; Collino, Massimo; Wong, WS Fred; Kapoor, Amar; Benetti, Elisa; Goh, Fera Y; Fantozzi, Roberto; Cerami, Anthony; Thiemermann, Christoph

2011-01-01

Recent studies have shown that erythropoietin, critical for the differentiation and survival of erythrocytes, has cytoprotective effects in a wide variety of tissues, including the kidney and lung. However, erythropoietin has been shown to have a serious side effect—an increase in thrombovascular effects. We investigated whether pyroglutamate helix B-surface peptide (pHBSP), a nonerythropoietic tissue-protective peptide mimicking the 3D structure of erythropoietin, protects against the organ injury/ dysfunction and inflammation in rats subjected to severe hemorrhagic shock (HS). Mean arterial blood pressure was reduced to 35 ± 5 mmHg for 90 min followed by resuscitation with 20 mL/kg Ringer Lactate for 10 min and 50% of the shed blood for 50 min. Rats were euthanized 4 h after the onset of resuscitation. pHBSP was administered 30 min or 60 min into resuscitation. HS resulted in significant organ injury/dysfunction (renal, hepatic, pancreas, neuromuscular, lung) and inflammation (lung). In rats subjected to HS, pHBSP significantly attenuated (i) organ injury/dysfunction (renal, hepatic, pancreas, neuromuscular, lung) and inflammation (lung), (ii) increased the phosphorylation of Akt, glycogen synthase kinase-3β and endothelial nitric oxide synthase, (iii) attenuated the activation of nuclear factor (NF)-κB and (iv) attenuated the increase in p38 and extracellular signal-regulated kinase (ERK)1/2 phosphorylation. pHBSP protects against multiple organ injury/dysfunction and inflammation caused by severe hemorrhagic shock by a mechanism that may involve activation of Akt and endothelial nitric oxide synthase, and inhibition of glycogen synthase kinase-3β and NF-κB. PMID:21607291

Protective Role of Cytotoxic T Lymphocytes in Filovirus Hemorrhagic Fever

PubMed Central

Warfield, Kelly Lyn; Olinger, Gene Garrard

2011-01-01

Infection with many emerging viruses, such as the hemorrhagic fever disease caused by the filoviruses, Marburg (MARV), and Ebola virus (EBOV), leaves the host with a short timeframe in which to mouse a protective immune response. In lethal cases, uncontrolled viral replication and virus-induced immune dysregulation are too severe to overcome, and mortality is generally associated with a lack of notable immune responses. Vaccination studies in animals have demonstrated an association of IgG and neutralizing antibody responses against the protective glycoprotein antigen with survival from lethal challenge. More recently, studies in animal models of filovirus hemorrhagic fever have established that induction of a strong filovirus-specific cytotoxic T lymphocyte (CTL) response can facilitate complete viral clearance. In this review, we describe assays used to discover CTL responses after vaccination or live filovirus infection in both animal models and human clinical trials. Unfortunately, little data regarding CTL responses have been collected from infected human survivors, primarily due to the low frequency of disease and the inability to perform these studies in the field. Advancements in assays and technologies may allow these studies to occur during future outbreaks. PMID:22253531

Molecular pathogenesis of viral hemorrhagic fever.

PubMed

Basler, Christopher F

2017-07-01

The clinical syndrome referred to as viral hemorrhagic fever (VHF) can be caused by several different families of RNA viruses, including select members of the arenaviruses, bunyaviruses, filoviruses, and flaviviruses. VHF is characterized by malaise, fever, vascular permeability, decreased plasma volume, coagulation abnormalities, and varying degrees of hemorrhage. Study of the filovirus Ebola virus has demonstrated a critical role for suppression of innate antiviral defenses in viral pathogenesis. Additionally, antigen-presenting cells are targets of productive infection and immune dysregulation. Among these cell populations, monocytes and macrophages are proposed to produce damaging inflammatory cytokines, while infected dendritic cells fail to undergo proper maturation, potentially impairing adaptive immunity. Uncontrolled virus replication and accompanying inflammatory responses are thought to promote vascular leakage and coagulopathy. However, the specific molecular pathways that underlie these features of VHF remain poorly understood. The arenavirus Lassa virus and the flavivirus yellow fever virus exhibit similar molecular pathogenesis suggesting common underlying mechanisms. Because non-human primate models that closely mimic VHF are available for Ebola, Lassa, and yellow fever viruses, we propose that comparative molecular studies using these models will yield new insights into the molecular underpinnings of VHF and suggest new therapeutic approaches.

Inner myometrial laceration - an unusual presentation of antepartum and postpartum hemorrhage: case reports and review of the literature.

PubMed

Kaplanoglu, Mustafa; Kaplanoglu, Dilek; Bulbul, Mehmet; Dilbaz, Berna

2016-01-01

The aim of this study is to evaluate the diagnostic criteria, treatment options and progression of cases who have antenatal or postpartum hemorrhage due to internal myometrial laceration (IML) and to review the literature. The files of eight patients who were diagnosed to have IML between August 2012 and July 2015 were evaluated retrospectively. The patient group consisted of four patients who had an emergency c-section due to massive bleeding during labor and four patients who had an emergency laparotomy due to uncontrolled bleeding after vaginal delivery after evaluation of the patient for signs of 4Ts (trauma, tissue retention, uterine tonus, and trombin). Primary suturation was the first-line treatment in all patients. In two of the patients, hysterectomy was performed after the defined surgical procedures were not successful in controling the bleeding. The presented case series is a pioneering study that describes IM which is a poorly defined reason of postpartum hemorrhage, as the cause of bleeding during labor. Primary suturation is the first-step, further surgery might be required in order to treat this life-threathening condition and the decision should be based on the age and the fertility status of the patient.

The Role and Use of Estrogens Following Trauma.

PubMed

Weniger, Maximilian; Angele, Martin K; Chaudry, Irshad H

2016-09-01

Several lines of evidence indicate that female sex is a protective factor in trauma and hemorrhage. In both clinical and experimental studies, proestrus females have been shown to have better chances of survival and reduced rates of posttraumatic sepsis. Estrogen receptors are expressed in a variety of tissues and exert genomic, as well as nongenomic effects. By improving cardiac, pulmonary, hepatic, and immune function, estrogens have been shown to prolong survival in animal models of hemorrhagic shock. Despite encouraging results from experimental studies, retrospective clinical studies have not clearly pointed to advantages of estrogens following trauma-hemorrhage, which may be due to insufficient study design. Therefore, this review aims to give an overview on the current evidence and emphasizes on the importance of further clinical investigation on estrogens following trauma.

Optoacoustic monitoring of central and peripheral venous oxygenation during simulated hemorrhage

NASA Astrophysics Data System (ADS)

Petrov, Andrey; Kinsky, Michael; Prough, Donald S.; Petrov, Yuriy; Petrov, Irene Y.; Henkel, S. Nan; Seeton, Roger; Salter, Michael G.; Khan, Muzna N.; Esenaliev, Rinat O.

2014-03-01

Circulatory shock may be fatal unless promptly recognized and treated. The most commonly used indicators of shock (hypotension and tachycardia) lack sensitivity and specificity. In the initial stages of shock, the body compensates by reducing blood flow to the peripheral (skin, muscle, etc.) circulation in order to preserve vital organ (brain, heart, liver) perfusion. Characteristically, this can be observed by a greater reduction in peripheral venous oxygenation (for instance, the axillary vein) compared to central venous oxygenation (the internal jugular vein). While invasive measurements of oxygenation are accurate, they lack practicality and are not without complications. We have developed a novel optoacoustic system that noninvasively determines oxygenation in specific veins. In order to test this application, we used lower body negative pressure (LBNP) system, which simulates hemorrhage by exerting a variable amount of suction on the lower body, thereby reducing the volume of blood available for central circulation. Restoration of normal blood flow occurs promptly upon cessation of LBNP. Using two optoacoustic probes, guided by ultrasound imaging, we simultaneously monitored oxygenation in the axillary and internal jugular veins (IJV). LBNP began at -20 mmHg, thereafter was reduced in a step-wise fashion (up to 30 min). The optoacoustically measured axillary oxygenation decreased with LBNP, whereas IJV oxygenation remained relatively constant. These results indicate that our optoacoustic system may provide safe and rapid measurement of peripheral and central venous oxygenation and diagnosis of shock with high specificity and sensitivity.

Autologous blood transfusion in dogs with thoracic or abdominal hemorrhage: 25 cases (2007-2012).

PubMed

Higgs, Veronica A; Rudloff, Elke; Kirby, Rebecca; Linklater, Andrew K J

2015-01-01

To describe the use and outcome following autologous blood transfusion (ABT) in dogs. Retrospective study (January 2007-July 2012). Private veterinary referral center. Twenty-five dogs that underwent ABT secondary to thoracic or abdominal hemorrhage. None. The hospital transaction database was searched using the keyword "autotransfusion" from January 2007 to July 2012. Data collected included signalment, body weight, etiology of hemorrhage, source and method of collection, volumes and method of ABT administration, use of anticoagulant, reported complications, and outcome. Twenty-five dogs were included for a total of 27 ABTs. Causes of hemorrhage included vascular trauma (14/25 dogs, 56%), ruptured tumor (8/25, 32%), and coagulopathy attributed to brodifacoum toxicosis (3/25, 12%). Autologous blood was collected from the abdominal (19/25, 76%), thoracic (5/25, 20%), or abdominal and thoracic cavities (1/25, 4%). Anticoagulant was added to the ABT blood in 13 of 25 (52%) cases. A median ABT volume of 29.3 mL/kg (range 2.9-406.9 mL/kg) was infused through either a 210 μm blood administration filter (21/27, 78%) or an 18 μm hemonate filter (6/27, 22%). Reported complications that may have been associated with ABT included hypocalcemia (4/17, 24%), hemolyzed serum (5/19, 26%), and prolonged coagulation times (4/5, 80%). These complications were considered of minimal clinical significance. Additional blood products were administered in 17 of 25 (68%) dogs. Seventeen (68%) dogs survived to discharge. Cause of death in the remaining cases was euthanasia or cardiac arrest secondary to uncontrollable hemorrhage. ABT is an adjunct to volume replacement in dogs with thoracic or abdominal hemorrhage secondary to vascular trauma, ruptured tumor, or anticoagulant rodenticide toxicosis. ABT may be used as bridge to definitive hemorrhage control, particularly when other blood products are not available or affordable. Complications may include hypocalcemia, prolonged coagulation times, and hemolysis. © Veterinary Emergency and Critical Care Society 2015.

Systemic thrombolysis increases hemorrhagic stroke risk without survival benefit compared with catheter-directed intervention for the treatment of acute pulmonary embolism.

PubMed

Liang, Nathan L; Avgerinos, Efthymios D; Singh, Michael J; Makaroun, Michel S; Chaer, Rabih A

2017-03-01

Systemic thrombolysis (ST) and catheter-directed intervention (CDI) are both used in the treatment of acute pulmonary embolism (PE), but the comparative outcomes of these two therapies remain unclear. The objective of this study was to compare short-term mortality and safety outcomes between the two treatments using a large national database. Patients presenting with acute PE were identified in the National Inpatient Sample (NIS) from 2009 to 2012. Comorbidities, clinical characteristics, and invasive procedures were identified using International Classification of Diseases, Ninth Revision (ICD) codes and the Elixhauser comorbidity index. To adjust for anticipated baseline differences between the two treatment groups, propensity score matching was used to create a matched ST cohort with clinical and comorbid characteristics similar to those of the CDI cohort. Subgroups of patients with and without hemodynamic shock were analyzed separately. Primary outcomes were in-hospital mortality, overall bleeding risk, and hemorrhagic stroke risk. Of 263,955 subjects with acute PE, 1.63% (n = 4272) received ST and 0.55% (n = 1455) received CDI. ST subjects were older, had more chronic comorbidities, and had higher rates of respiratory failure (ST, 27.9% [n = 1192]; CDI, 21.2% [n = 308]; P < .001) and shock (ST, 18.2% [n = 779]; CDI, 12% [n = 174]; P < .001). CDI subjects had higher rates of concurrent deep venous thrombosis (ST, 35.8% [n = 1530]; CDI, 45.9% [n = 668]; P < .001) and vena cava filter placement (ST, 31.1% [n = 1328]; CDI, 57% [n = 830]; P < .001). In the unmatched cohort, ST subjects had higher in-hospital mortality (ST, 16.7% [n = 714]; CDI, 9.4% [n = 136]; P < .001) and hemorrhagic stroke rates (ST, 2.2% [n = 96]; CDI, 1.4% [n = 20]; P = .041). After propensity matching, 1430 patients remained in each cohort; baseline characteristics of the matched cohorts did not differ significantly using standardized difference comparisons. Analysis of the matched cohorts did not demonstrate a significant effect of CDI on in-hospital mortality or overall bleeding risk but did show a significant protective effect against hemorrhagic stroke compared with ST (odds ratio, 0.47; 95% confidence interval, 0.27-0.82; P = .01). Subgroup analysis showed decreased odds of hemorrhagic stroke for CDI in the nonshock subgroup and increased procedural bleeding for CDI but no difference in hemorrhagic stroke risk in the shock subgroup. ST for acute PE may not improve in-hospital mortality compared with CDI but increases the overall risk of hemorrhagic stroke compared with CDI. Further prospective studies should examine the comparative effectiveness and safety of these two treatments. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Treatment outcomes of open pelvic fractures associated with extensive perineal injuries.

PubMed

Hasankhani, Ebrahim Ghayem; Omidi-Kashani, Farzad

2013-12-01

The main causes of death in patients with open pelviperineal injuries are uncontrollable bleeding and pelvic sepsis. The aim of this study was to evaluate the management outcomes of open pelvic fractures associated with extensive perineal injuries. We retrospectively studied 15 cases with open pelvic fractures associated with extensive perineal injuries (urethral and anal canal laceration) admitted between August 2006 and September 2010. Mechanism of injury, Injury Severity Score, associated injuries, hemodynamic status on arrival, resuscitation and transfusion requirements, operative techniques, intra- and postoperative complications, length of intensive care unit and hospital stay, and mortality were recorded in a computerised database for further evaluation and analysis. The male to female ratio was 12:3 with an average age of 38.6 years (ranged, 11 to 65 years). The average packed red blood cell units used were 8 units (ranged, 4 to 21 units). All patients were initially transferred to the operating room for colostomy, radical debridement and fixation of the pelvic fracture by an external fixator. One patient had acute renal failure, which improved with medical treatment and 2 patients (13.3%) died, one with type III anteroposterior compression fracture due to hemorrhagic shock and the other due to septicemia. Open pelvic fractures with extensive perineal injuries are associated with high mortality rates. Early diagnosis and appropriate treatment, including reanimation, colostomy, cystostomy, vigorous and repeated irrigation and debridement, and fixation by an external fixator can improve the outcomes and reduce the mortality rate.

Early Support of Intracranial Perfusion

DTIC Science & Technology

2011-10-01

combination of both controlled cortical impact plus hemorrhagic shock with adult male Sprague Dawley rats and with adult male Hanford miniature swine...surface without causing ruptured dura and non-survivable injury. Methods: Ten male miniature Hanford swine weighing 38-45 kg were fasted 8 hours prior to

Role of cognitive parameters in dengue hemorrhagic fever and dengue shock syndrome

PubMed Central

2013-01-01

Dengue is becoming recognized as one of the most important vector-borne human diseases. It is predominant in tropical and subtropical zones but its geographical distribution is progressively expanding, making it an escalating global health problem of today. Dengue presents with spectrum of clinical manifestations, ranging from asymptomatic, undifferentiated mild fever, dengue fever (DF), to dengue hemorrhagic fever (DHF) with or without shock (DSS), a life-threatening illness characterized by plasma leakage due to increased vascular permeability. Currently, there are no antiviral modalities or vaccines available to treat and prevent dengue. Supportive care with close monitoring is the standard clinical practice. The mechanisms leading to DHF/DSS remains poorly understood. Multiple factors have been attributed to the pathological mechanism, but only a couple of these hypotheses are popular in scientific circles. The current discussion focuses on underappreciated factors, temperature, natural IgM, and endotoxin, which may be critical components playing roles in dengue pathogenesis. PMID:24305068

Hemorrhagic shock caused by sigmoid colon volvulus: An autopsy case

PubMed Central

Sato, Hiroaki; Tanaka, Toshiko; Tanaka, Noriyuki

2011-01-01

Summary Background Many reports have described sigmoid volvulus, but fatal hemorrhagic shock resulting from the rupture of the involved artery has not been reported as a complication of a sigmoid volvulus. Case Report A 71-year-old man with slight abdominal pain and obstipation in hypotension died at a nursing home without seeing a doctor. At autopsy, a mesenteric hematoma and hemoperitoneum was observed with approximately 1,000 ml of blood in the abdominal cavity. The sigmoid colon and the mesentery were twisted at an adhesion site of a sigmoid colon to an ileum, and the condition was determined to be a sigmoid volvulus. The volvulus was observed to be loosened. The inferior mesenteric artery was incorporated into the twisted part of the mesentery, but remained patent, and its peripheral branch near the hematoma ruptured without histological abnormality. Conclusions Since ischemic-reperfusion injury occurs with a temporarily occluded artery, the acute re-loading of blood flow may injure the distal vessels after spontaneous reduction of compression by loosening of the volvulus. PMID:22129905

Red blood cell transfusion in newborn infants

PubMed Central

Whyte, Robin K; Jefferies, Ann L

2014-01-01

Red blood cell transfusion is an important and frequent component of neonatal intensive care. The present position statement addresses the methods and indications for red blood cell transfusion of the newborn, based on a review of the current literature. The most frequent indications for blood transfusion in the newborn are the acute treatment of perinatal hemorrhagic shock and the recurrent correction of anemia of prematurity. Perinatal hemorrhagic shock requires immediate treatment with large quantities of red blood cells; the effects of massive transfusion on other blood components must be considered. Some guidelines are now available from clinical trials investigating transfusion in anemia of prematurity; however, considerable uncertainty remains. There is weak evidence that cognitive impairment may be more severe at follow-up in extremely low birth weight infants transfused at lower hemoglobin thresholds; therefore, these thresholds should be maintained by transfusion therapy. Although the risks of transfusion have declined considerably in recent years, they can be minimized further by carefully restricting neonatal blood sampling. PMID:24855419

Integrating Medical Simulation Into the Physician Assistant Physiology Curriculum.

PubMed

Li, Lixin; Lopes, John; Zhou, Joseph Yi; Xu, Biao

2016-12-01

Medical simulation has recently been used in medical education, and evidence indicates that it is a valuable tool for teaching and evaluation. Very few studies have evaluated the integration of medical simulation in medical physiology education, particularly in PA programs. This study was designed to assess the value of integrating medical simulation into the PA physiology curriculum. Seventy-five students from the PA program at Central Michigan University participated in this study. Mannequin-based simulation was used to simulate a patient with hemorrhagic shock and congestive heart failure to demonstrate the Frank-Starling force and cardiac function curve. Before and after the medical simulation, students completed a questionnaire as a self-assessment. A knowledge test was also delivered after the simulation. Our study demonstrated a significant improvement in student confidence in understanding congestive heart failure, hemorrhagic shock, and the Frank-Starling curve after the simulation. Medical simulation may be an effective way to enhance basic science learning experiences for students and an ideal supplement to traditional, lecture-based teaching in PA education.

Ebola virus: the role of macrophages and dendritic cells in the pathogenesis of Ebola hemorrhagic fever.

PubMed

Bray, Mike; Geisbert, Thomas W

2005-08-01

Ebola hemorrhagic fever is a severe viral infection characterized by fever, shock and coagulation defects. Recent studies in macaques show that major features of illness are caused by effects of viral replication on macrophages and dendritic cells. Infected macrophages produce proinflammatory cytokines, chemokines and tissue factor, attracting additional target cells and inducing vasodilatation, increased vascular permeability and disseminated intravascular coagulation. However, they cannot restrict viral replication, possibly because of suppression of interferon responses. Infected dendritic cells also secrete proinflammatory mediators, but cannot initiate antigen-specific responses. In consequence, virus disseminates to these and other cell types throughout the body, causing multifocal necrosis and a syndrome resembling septic shock. Massive "bystander" apoptosis of natural killer and T cells further impairs immunity. These findings suggest that modifying host responses would be an effective therapeutic strategy, and treatment of infected macaques with a tissue-factor inhibitor reduced both inflammation and viral replication and improved survival.

Continuous cytokine haemoadsorption incorporated into a venoarterial ECMO circuit for the management of postcardiotomy cardiogenic and septic shock - a case report.

PubMed

Nemeth, Endre; Szigeti, Szabolcs; Varga, Tamas; Daroczi, Laszlo; Barati, Zoltan; Merkely, Bela; Gal, Janos

2018-05-01

The acute surgical treatment of infective endocarditis (IE) carries a high risk of postoperative mortality. Most complications are linked to uncontrolled sepsis and inflammatory processes. Cytokine haemoadsorption is an extracorporeal technique which has benefits reported in haemodynamic stability and inflammatory response. A 46-year-old male patient underwent emergency cardiac surgery due to progressive IE. Postcardiotomy cardiogenic shock associated with cardiac surgery required the implantation of venoarterial (VA)-ECMO. Three days later, the patient developed secondary septic shock. The novel application of continuous CytoSorb TM treatment installed in the VA-ECMO circuit is demonstrated in this case during the management of simultaneous shocks. Advanced intensive care led to an improvement in the patient's condition, which facilitated successful weaning from mechanical ventilation. However, the patient died from a new onset fulminant septic shock two months after his initial cardiac surgery. VA-ECMO is suitable for installation of the CytoSorb TM cartridge. This modality could be an option for high-volume, continuous cytokine haemoadsorption when VA-ECMO is employed without renal replacement therapy. This specific application of CytoSorb TM was safe, feasible and contributed to the optimal management of simultaneous shocks.

The role of nitric oxide in the reversal of hemorrhagic shock by oxotremorine.

PubMed

Gören, M Z; Akici, A; Karaalp, A; Aker, R; Oktay, S

2001-10-05

In the present study, the effect of the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methylester (L-NAME), on the antishock actions of oxotremorine was investigated in rats subjected to hemorrhagic shock under urethane anesthesia. L-citrulline production in the AV3V region, as an indicator of nitric oxide (NO) synthesis, was assayed by high-performance liquid chromatography (HPLC) with fluorescent detection throughout the experiment. The rats were pretreated with either intravenous (i.v.) physiological saline or L-NAME (2.5 mg/kg) before bleeding. L-NAME potentiated the reversal of hypotension by oxotremorine (25 microg/kg, i.v.). However, oxotremorine either alone or in combination with L-NAME did not produce any significant change in 60-min survival rate at this low dose. Analysis of microdialysis samples collected from the AV3V region showed that L-citrulline concentration increased during bleeding and that this increase was abolished by L-NAME pretreatment. These results may suggest that nitric oxide production contributes to hypotension in rats bled to shock since nitric oxide levels in the AV3V region increased in response to bleeding and nitric oxide synthase (NOS) inhibition abolished this increase and potentiated the oxotremorine-induced reversal of hypotension.

Long-term outcome and risk factors for uncontrolled seizures after a first seizure in children with hematological malignancies.

PubMed

Khan, Raja B; Morris, E Brannon; Pui, Ching-Hon; Hudson, Melissa M; Zhou, Yinmei; Cheng, Cheng; Ledet, Davonna S; Howard, Scott C

2014-06-01

Long-term outcomes of seizures that develop during treatment of childhood hematological malignancies have not been described. We analyzed seizure outcome in 62 children with leukemia or lymphoma treated at our institution. There was a median follow-up of 6.5 years since first seizure. Seizure etiology included intrathecal or systemic methotrexate in 24, leucoencephalopathy in 11, brain hemorrhage or thrombosis in 11, meningitis in 4, and no identifiable cause in 12. Seizures remained uncontrolled in 18, and risk factors for poor control included female sex (P = .02), no seizure control with first antiseizure drug (P = .08), and longer interval between cancer diagnosis and seizure onset (P = .09). Poor seizure control after initial antiseizure drug also predicted recurrent seizure after drug withdrawal (P = .04). In conclusion, seizures are controlled with medications in a majority of patients with hematological cancer. After a period without seizures, antiseizure drug withdrawal in appropriately selected patient has a high success rate. © The Author(s) 2013.

Recombinant human erythropoietin improves gut barrier function in a hemorrhagic shock and resuscitation rat model.

PubMed

Kao, N Raymond L C; Xenocostas, Anargyros; Driman, David K; Rui, Tao; Huang, Weixiong; Jiao, Xiujun; Martin, Claudio M

2011-11-01

Gut injury and bacterial translocation develop and persist after limited periods of hemorrhagic shock. Erythropoietin (EPO) can exert hemodynamic, anti-inflammatory, and tissue protective effects. We tested the hypothesis that EPO given at the time of resuscitation with saline will reduce functional ileal injury 24 hours after shock. Sprague-Dawley rats (n = 6 per group) were randomized to sham surgery or hemorrhagic shock maintained at mean arterial pressure 40 mm Hg for 60 minutes and then treated with either saline resuscitation (three times the volume of shed blood) or saline + recombinant human EPO (rHuEPO) resuscitation. Intravenous rHuEPO (1,000 U/kg) was given at the start of saline resuscitation, and at 24 hours ileal function was evaluated using quantitative cultures of mesenteric lymph nodes to assess for bacterial translocation (colony-forming units per gram of tissue [CFU/g]), determination of portal vein plasma endotoxin levels and histopathological evaluation using semi-thin plastic sections of the distal ileum. In a second series of animals, fluorescein isothiocyanate-dextran 4000 (FD-4) was used to assess mucosal permeability of the distal ileum to macromolecules. At 24 hours, the saline group had morphologic evidence of intestinal injury when compared with the sham group, and the degree of mucosal injury was less in the saline + rHuEPO when compared with the saline group, which demonstrated significantly reduced bacterial translocation to the mesenteric lymph nodes (383 CFU/g ± 111 CFU/g vs. 1130 CFU/g ± 297 CFU/g; p < 0.05) and decreased terminal ileum permeability to FD-4 (3.08 μg/mL ± 0.31 μg/mL vs. 5.14 μg/mL ± 0.88 μg/mL; p < 0.05). No significant difference was found in the portal vein endotoxin levels between the two groups. Histopathological evaluation demonstrated a trend for decreased enterocyte disarray or disruption and vacuolization in the saline + rHuEPO versus saline group. Using rHuEPO at time of saline resuscitation resulted in decreased bacterial translocation and permeability to macromolecules 24 hours after shock. These observations suggest that rHuEPO can mediate a protective effect on intestinal mucosal barrier function during ischemic injury.

Critical role of oxygen radicals in the initiation of hepatic depression after trauma hemorrhage.

PubMed

Jarrar, D; Wang, P; Cioffi, W G; Bland, K I; Chaudry, I H

2000-11-01

Although depression in hepatocellular function occurs early after trauma and severe hemorrhage and persists despite fluid resuscitation, it remains unknown whether reactive oxygen species (ROS) play any role in the initiation of hepatocellular depression and damage under those conditions. We hypothesized that administration of a ROS scavenger at the beginning of resuscitation will attenuate organ injury after severe shock. Male Sprague-Dawley rats (275-325 g) underwent laparotomy (i.e., induction of soft tissue trauma) and were then bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the maximal bleed-out volume was returned in the form of Ringer's lactate. The animals were then resuscitated with four times the volume of maximal bleed-out with RL over 60 minutes. The ROS scavenger 2-mercaptopropionyl glycine (30 mg/kg) or vehicle was administered intravenously as a bolus at the beginning of resuscitation. At 2 hours after the completion of crystalloid resuscitation or the equivalent interval after sham-operation, cardiac index was measured by a dye dilution technique. Hepatocellular function, i.e., the maximum velocity of indocyanine green clearance (Vmax) and the efficiency of the active transport (Km), was determined using an in vivo hemoreflectometer. Serum levels of tumor necrosis factor (TNF)-alpha and alanine aminotransferase were determined with ELISA and colorimetrically, respectively. The results indicate that at 2 hours after trauma hemorrhage and resuscitation, cardiac index and hepatocellular function were markedly depressed with concomitantly increased serum levels of TNF-alpha and alanine aminotransferase (p < 0.05). Administration of 2-mercaptopropionyl glycine, however, restored the depressed cardiac and hepatic function and markedly attenuated liver enzyme release and serum levels of TNF-alpha (p < 0.05). Our data suggest that ROS play a role in producing the depression in organ functions after severe hemorrhagic shock. Thus, adjuncts that attenuate the detrimental effects of ROS may be useful for improving the depressed cardiac and hepatocellular functions after trauma hemorrhage and resuscitation.

European experience of 573 liver resections for hepatocellular adenoma: a cross-sectional study by the AFC-HCA-2013 study group.

PubMed

Laurent, Alexis; Dokmak, Safi; Nault, Jean-Charles; Pruvot, François-René; Fabre, Jean-Michel; Letoublon, Christian; Bachellier, Philippe; Capussotti, Lorenzo; Farges, Olivier; Mabrut, Jean-Yves; Le Treut, Yves-Patrice; Ayav, Ahmet; Suc, Bertrand; Soubrane, Olivier; Mentha, Gilles; Popescu, Irinel; Montorsi, Marco; Demartines, Nicolas; Belghiti, Jacques; Torzilli, Guido; Cherqui, Daniel; Hardwigsen, Jean

2016-09-01

Hepatocellular adenoma (HCA) is a benign hepatic lesion that may be complicated by bleeding and malignant transformation. The aim of the present study is to report on large series of liver resections for HCA and assess the incidence of hemorrhage and malignant transformation. A retrospective cross-sectional study, from 27 European high-volume HPB units. 573 patients were analyzed. The female: male gender ratio was 8:2, mean age: 37 ± 10 years. Of the 84 (14%) patients whose initial presentation was hemorrhagic shock (Hemorrhagic HCAs), hemostatic intervention was urgently required in 25 (30%) patients. No patients died after intervention. Tumor size was >5 cm in 74% in hemorrhagic HCAs and 64% in non-hemorrhagic HCAs (p < 0.001). In non-hemorrhagic HCAs (n = 489), 5% presented with malignant transformation. Male status and tumor size >10 cm were the two predictive factors. Liver resections included major hepatectomy in 25% and a laparoscopic approach in 37% of the patients. In non-hemorrhagic HCAs, there was no mortality and major complications occurred in 9% of patients. Liver resection for HCA is safe. Presentation with hemorrhage was associated with larger tumor size. In males with a HCA >10 cm, a HCC should be suspected. In such situation, a preoperative biopsy is preferable and an oncological liver resection should be considered. Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Portable Low-Volume Therapy for Severe Blood Loss

DTIC Science & Technology

2012-06-01

be reflected in Htc as well. Classic changes in plasma electrolyte concentration during hemorrhagic shock include hyperkalemia [17, 18] and...comparison with treatment no. 1 (pɘ.05), treatment no. 2 (pɘ.05), and treatment no. 3 (pɘ.05). Because the hyperkalemia and hyponatremia in

The Postconditioning Effects Of Diazoxide in the Brain Following Hemorrhagic Shock and Cerebral Hypoperfusion

DTIC Science & Technology

2009-10-13

ERK to promote cell survival. RISK can be activated by insulin, urocortin, atorvastatin , adenosine, bradykinin, opioid agonists, volatile...Bell, R.M. and D.M. Yellon, Atorvastatin , administered at the onset of reperfusion, and independent of lipid lowering, protects the myocardium by

Real-time 3-dimensional contrast-enhanced ultrasound in detecting hemorrhage of blunt renal trauma.

PubMed

Xu, Rui-Xue; Li, Ye-Kuo; Li, Ting; Wang, Sha-Sha; Yuan, Gui-Zhong; Zhou, Qun-Fang; Zheng, Hai-Rong; Yan, Fei

2013-10-01

The objective of this study is to evaluate the diagnostic value of real-time 3-dimensional contrast-enhanced ultrasound in the hemorrhage of blunt renal trauma. Eighteen healthy New Zealand white rabbits were randomly divided into 3 groups. Blunt renal trauma was performed on each group by using minitype striker. Ultrasonography, color Doppler flow imaging, and contrast-enhanced 2-dimensional and real-time 3-dimensional ultrasound were applied before and after the strike. The time to shock and blood pressure were subjected to statistical analysis. Then, a comparative study of ultrasound and pathology was carried out. All the struck kidneys were traumatic. In the ultrasonography, free fluid was found under the renal capsule. In the color Doppler flow imaging, active hemorrhage was not identified. In 2-dimensional contrast-enhanced ultrasound, active hemorrhage of the damaged kidney was characterized. Real-time 3-dimensional contrast-enhanced ultrasound showed a real-time and stereoscopic ongoing bleeding of the injured kidney. The wider the hemorrhage area in 4-dimensional contrast-enhanced ultrasound was, the faster the blood pressure decreased. Real-time 3-dimensional contrast-enhanced ultrasound is a promising noninvasive tool for stereoscopically and vividly detecting ongoing hemorrhage of blunt renal trauma in real time. © 2013.

Persistent pit viper envenomation in a cat.

PubMed

Yankin, Igor; Schaer, Michael; Johnson, Matthew; Meland, Tessa; Londoño, Leonel A

2017-01-01

A 4-year-old female spayed, indoor/outdoor domestic mediumhair cat presented with multiple bleeding puncture wounds and hemorrhagic shock. The cat was diagnosed with suspected pit viper envenomation based on the location and appearance of the bite wounds, as well as the presence of severe coagulopathy with prolonged activated coagulation time (762 s), which responded to antivenom administration. The clinical course of the cat was unique owing to the prolonged clinical signs of envenomation that appeared as intermittent coagulopathy and hemorrhage over a 2 week period. Five vials of antivenom were administered and three units of packed red blood cells were transfused over a 7 day period. The cat made a complete recovery with cessation of hemorrhage and normalization of clotting times. This is the first report of persistent pit viper venom-induced coagulopathy in the feline veterinary literature.

Traumatic brain injury and hemorrhagic shock: evaluation of different resuscitation strategies in a large animal model of combined insults.

PubMed

Jin, Guang; DeMoya, Marc A; Duggan, Michael; Knightly, Thomas; Mejaddam, Ali Y; Hwabejire, John; Lu, Jennifer; Smith, William Michael; Kasotakis, Georgios; Velmahos, George C; Socrate, Simona; Alam, Hasan B

2012-07-01

Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of trauma-related mortality and morbidity. Combination of TBI and HS (TBI + HS) is highly lethal, and the optimal resuscitation strategy for this combined insult remains unclear. A critical limitation is the lack of suitable large animal models to test different treatment strategies. We have developed a clinically relevant large animal model of TBI + HS, which was used to evaluate the impact of different treatments on brain lesion size and associated edema. Yorkshire swine (42-50 kg) were instrumented to measure hemodynamic parameters and intracranial pressure. A computer-controlled cortical impact device was used to create a TBI through a 20-mm craniotomy: 15-mm cylindrical tip impactor at 4 m/s velocity, 100-ms dwell time, and 12-mm penetration depth. Volume-controlled hemorrhage was started (40% blood volume) concurrent with the TBI. After 2 h of shock, animals were randomized to one of three resuscitation groups (n = 5/group): (a) normal saline (NS); (b) 6% hetastarch, Hextend (Hex); and (c) fresh frozen plasma (FFP). Volumes of Hex and FFP matched the shed blood, whereas NS was three times the volume. After 6 h of postresuscitation monitoring, brains were sectioned into 5-mm slices and stained with TTC (2,3,5-triphenyltetrazolium chloride) to quantify the lesion size and brain swelling. Combination of 40% blood loss with cortical impact and a period of shock (2 h) resulted in a highly reproducible brain injury. Total fluid requirements were lower in the Hex and FFP groups. Lesion size and brain swelling in the FFP group (2,160 ± 202.63 mm and 22% ± 1.0%, respectively) were significantly smaller than those in the NS group (3,285 ± 130.8 mm3 and 37% ± 1.6%, respectively) (P < 0.05). Hex treatment decreased the swelling (29% ± 1.6%) without reducing the lesion size. Early administration of FFP reduces the size of brain lesion and associated swelling in a large animal model of TBI + HS. In contrast, artificial colloid (Hex) decreases swelling without reducing the actual size of the brain lesion.

Sympathetic Nerve Activity and Heart Rate Variability During Severe Hemorrhagic Shock in Sheep

DTIC Science & Technology

2007-01-01

2000, Boebingen, Germany). 2.3. Experimental protocol After a steady nerve signal was obtained (verified visually and by auscultation ) the experimental...both visually and by auscultation . Automatic amplitude-based detection of sym- pathetic bursts was performed with WinCPRS software (Absolute Aliens Oy

Pre-Hospital Resuscitation of Traumatic Hemorrhagic Shock with Hypertonic Solutions Worsen Hypocoagulation and Hyperfibrinolysis

DTIC Science & Technology

2015-07-01

coagulation defects using fresh plasma and other blood prod- ucts in near equivalent ratios (38), along with prohemostatic agents such as tranexamic ... acid (39). This approach also rec- ommends restricting fluids to limit hemodilution (40) and other deleterious effects of the lethal triad (41). Still

Neurotransmitter Amines in Hemorrhagic Shock.

DTIC Science & Technology

1984-03-02

and synthesis for future studies. Crit Care Med 11:202-207, 1983. 7. Gelmer HJ: Effect of ninodipine (Bay e 9736) on post-ischaemic- cerebro - vascular...the calcium antagonist, nimodipine on cerebral blood flow and metabolism in the primate . JCereb Blood Flow and Metabol 1:349-356, 1981. 9. Edvinsson L

Agreement of Bioreactance Cardiac Output Monitoring With Thermodilution During Hemorrhagic Shock and Resuscitation in Adult Swine.

PubMed

Berlin, David A; Peprah-Mensah, Harrison; Manoach, Seth; Heerdt, Paul M

2017-02-01

The study tests the hypothesis that noninvasive cardiac output monitoring based upon bioreactance (Cheetah Medical, Portland, OR) has acceptable agreement with intermittent bolus thermodilution over a wide range of cardiac output in an adult porcine model of hemorrhagic shock and resuscitation. Prospective laboratory animal investigation. Preclinical university laboratory. Eight ~ 50 kg Yorkshire swine with a femoral artery catheter for blood pressure measurement and a pulmonary artery catheter for bolus thermodilution. With the pigs anesthetized and mechanically ventilated, 40 mL/kg of blood was removed yielding marked hypotension and a rise in plasma lactate. After 60 minutes, pigs were resuscitated with shed blood and crystalloid. Noninvasive cardiac output monitoring and intermittent thermodilution cardiac output were simultaneously measured at nine time points spanning baseline, hemorrhage, and resuscitation. Simultaneous noninvasive cardiac output monitoring and thermodilution measurements of cardiac output were compared by Bland-Altman analysis. A plot was constructed using the difference of each paired measurement expressed as a percentage of the mean of the pair plotted against the mean of the pair. Percent bias was used to scale the differences in the measurements for the magnitude of the cardiac output. Method concordance was assessed from a four-quadrant plot with a 15% zone of exclusion. Overall, noninvasive cardiac output monitoring percent bias was 1.47% (95% CI, -2.5 to 5.4) with limits of agreement of upper equal to 33.4% (95% CI, 26.5-40.2) and lower equal to -30.4% (95% CI, -37.3 to -23.6). Trending analysis demonstrated a 97% concordance between noninvasive cardiac output monitoring and thermodilution cardiac output. Over the wide range of cardiac output produced by hemorrhage and resuscitation in large pigs, noninvasive cardiac output monitoring has acceptable agreement with thermodilution cardiac output.

Heparin use in a rat hemorrhagic shock model induces biologic activity in mesenteric lymph separate from shock

PubMed Central

Qin, Yong; Prescott, Lauriston M.; Deitch, Edwin A.; Kaiser, Vicki L.

2011-01-01

Experimental data has shown that mesenteric lymph from rats subjected to trauma-hemorrhagic shock (THS) but not trauma-sham shock (TSS) induces neutrophil activation, cytotoxicity, decreased red blood cell deformability and bone marrow colony growth suppression. These data have lead to the hypothesis that gut factors produced from THS enter the systemic circulation via the mesenteric lymphatics and contribute to the progression of Multiple Organ Failure (MOF) following THS. Ongoing studies designed to identify bioactive lymph agents implicated factors associated with the heparin use in the THS procedure. We investigated if heparin itself was responsible for reported toxicity to human umbilical vein endothelial cells (HUVECs). HUVEC toxicity was not induced by lymph when alternate anti-coagulants (citrate and EDTA) were used in THS. HUVEC toxicity was induced by lymph after heparin but not saline or citrate injection into TSS and naïve animals and was dose dependent. Activities of both heparin-releasable lipases (lipoprotein (LPL) and hepatic (HL)) were detected in the plasma and lymph from THS and naïve animals receiving heparin but not citrate or saline. Lymph-induced HUVEC toxicity correlated with lymph lipase activities. Finally, incubation of HUVECs with purified LPL added to naïve lymph induced toxicity in vitro. These data show that heparin, not THS, is responsible for the reported lymph-mediated HUVEC toxicity through its release of lipases into the lymph. These findings can provide alternative explanations for several of the THS effects reported in the literature using heparin models thus necessitating a review of previous work in this field. PMID:21063238

[Use of "NovoSeven" (rFVIIa) hemostatic in patients operated with extracorporeal blood circulation].

PubMed

Dement'eva, I I; Sandrikov, V A; Charnaia, M A; Morozov, Iu A; Trekova, N A; Eremenko, A A

2004-01-01

The "NovoSeven" drug was used in 25 patients (male - 18, female - 7) operated on the heart and main vessels including with artificial extracorporeal circulation (AEC). Patients did not have any clinically significant impairment in blood circulation before surgery. Perioperatively, all of them and, immediately after surgery, 4 them had uncontrollable hemorrhages at 10-25 ml/min in spite of extensive hemostatic therapy, including freshly frozen plasma, cryoprecipitate, thromboconcentrate, trasilol and ?-amine acid. Yet in 30 min after "NovoSeven" administration, hemorrhages seized virtually in all patients irrespective of a surgical intervention. It normalized the hemostasis by it differential action on an impairment depending on an activated or suppressed coagulation. Thus, the conclusion is that the "NovoSeven" (rFVIIa) is an effective hemostatic ensuring the correction of massive intra- and postoperative blood losses in cardiosurgery patients. The drug cuts the need in using the donor-blood components, thus, diminishing the risk of multi organ failure that can develop immediately after surgery.

Hemorrhagic Tamponade as Initial Manifestation of Systemic Lupus with Subsequent Refractory and Progressive Lupus Myocarditis Resulting in Cardiomyopathy and Mitral Regurgitation.

PubMed

Marijanovich, Nicole; Halalau, Alexandra

2018-01-01

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a wide range of clinical and serological manifestations. Cardiac disease among patients with SLE is common and can involve the pericardium, myocardium, valves, conduction system, and coronary arteries. We are reporting a case of SLE in a young woman that is unique is unique in that initial symptoms consisted of pericarditis and hemorrhagic tamponade which remained progressive and resistant to aggressive immunosuppressive treatment and led to severe cardiomyopathy (ejection fraction of 25%) and severe (+4) mitral regurgitation. Her immunosuppressive treatment included hydroxychloroquine, high-dose steroids, intravenous immunoglobulins, azathioprine, and mycophenolate mofetil. Her disease progression was felt to be due to underlying uncontrolled SLE because the complement levels remained persistently low throughout the entire course and PET Myocardial Perfusion and Viability study showed stable persistent active inflammation. Eventually, she was treated with cyclophosphamide which led to improvement in ejection fraction to 55% with only mild mitral regurgitation.

Hemorrhagic Tamponade as Initial Manifestation of Systemic Lupus with Subsequent Refractory and Progressive Lupus Myocarditis Resulting in Cardiomyopathy and Mitral Regurgitation

PubMed Central

Marijanovich, Nicole

2018-01-01

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a wide range of clinical and serological manifestations. Cardiac disease among patients with SLE is common and can involve the pericardium, myocardium, valves, conduction system, and coronary arteries. We are reporting a case of SLE in a young woman that is unique is unique in that initial symptoms consisted of pericarditis and hemorrhagic tamponade which remained progressive and resistant to aggressive immunosuppressive treatment and led to severe cardiomyopathy (ejection fraction of 25%) and severe (+4) mitral regurgitation. Her immunosuppressive treatment included hydroxychloroquine, high-dose steroids, intravenous immunoglobulins, azathioprine, and mycophenolate mofetil. Her disease progression was felt to be due to underlying uncontrolled SLE because the complement levels remained persistently low throughout the entire course and PET Myocardial Perfusion and Viability study showed stable persistent active inflammation. Eventually, she was treated with cyclophosphamide which led to improvement in ejection fraction to 55% with only mild mitral regurgitation. PMID:29610699

Selective inhibition of iNOS attenuates trauma-hemorrhage/resuscitation-induced hepatic injury.

PubMed

Kan, Wen-Hong; Hsu, Jun-Te; Schwacha, Martin G; Choudhry, Mashkoor A; Raju, Raghavan; Bland, Kirby I; Chaudry, Irshad H

2008-10-01

Although trauma-hemorrhage produces tissue hypoxia, systemic inflammatory response and organ dysfunction, the mechanisms responsible for these alterations are not clear. Using a potent selective inducible nitric oxide (NO) synthase inhibitor, N-[3-(aminomethyl) benzyl]acetamidine (1400W), and a nonselective NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), we investigated whether inducible NO synthase plays any role in producing hepatic injury, inflammation, and changes of protein expression following trauma-hemorrhage. To investigate this, male Sprague-Dawley rats were subjected to midline laparotomy and hemorrhagic shock (mean blood pressure 35-40 mmHg for approximately 90 min) followed by fluid resuscitation. Animals were treated with either vehicle (DMSO) or 1400W (10 mg/kg body wt ip), or L-NAME (30 mg/kg iv), 30 min before resuscitation and killed 2 h after resuscitation. Trauma-hemorrhage/resuscitation induced a marked hypotension and increase in markers of hepatic injury (i.e., plasma alpha-glutathione S-transferase, tissue myeloperoxidase activity, and nitrotyrosine formation). Hepatic expression of iNOS, hypoxia-inducible factor-1alpha, ICAM-1, IL-6, TNF-alpha, and neutrophil chemoattractant (cytokine-induced neutrophil chemoattractant-1 and macrophage inflammatory protein-2) protein levels were also markedly increased following trauma-hemorrhage/resuscitation. Administration of the iNOS inhibitor 1400W significantly attenuated hypotension and expression of these mediators of hepatic injury induced by trauma-hemorrhage/resuscitation. However, administration of L-NAME could not attenuate hepatic dysfunction and tissue injury mediated by trauma-hemorrhage, although it improved mean blood pressure as did 1400W. These results indicate that increased expression of iNOS following trauma-hemorrhage plays an important role in the induction of hepatic damage under such conditions.

Diagnosis of hantavirus infection in humans.

PubMed

Mattar, Salim; Guzmán, Camilo; Figueiredo, Luis Tadeu

2015-08-01

Rodent-borne hantaviruses (family Bunyaviridae, genus Hantavirus) cause hantavirus pulmonary syndrome in the Americas and hemorrhagic fever with renal syndrome in Europe and Asia. The viruses are transmitted to humans mainly by inhalation of virus-contaminated aerosols of rodent excreta and secreta. Classic clinical hemorrhagic fever with renal syndrome occurs in five phases: fever, hypotension, oliguria, polyuria, and convalescence. Hantavirus pulmonary syndrome is a severe acute disease that is associated with respiratory failure, pulmonary edema and cardiogenic shock. The diagnosis of hantavirus infections in humans is based on clinical and epidemiological information as well as laboratory tests. We review diagnosis for hantavirus infections based on serology, PCR, immunochemistry and virus culture.

Osthole attenuates hepatic injury in a rodent model of trauma-hemorrhage.

PubMed

Yu, Huang-Ping; Liu, Fu-Chao; Tsai, Yung-Fong; Hwang, Tsong-Long

2013-01-01

Recent evidences show that osthole possesses anti-inflammatory properties and protective effects following shock-like states, but the mechanism of these effects remains unknown. The p38 mitogen-activated protein kinase (p38 MAPK) pathway exerts anti-inflammatory effects in injury. The aim of this study was to investigate whether p38 MAPK plays any role in the osthole-mediated attenuation of hepatic injury after trauma-hemorrhage. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35-40 mmHg for 90 minutes), followed by fluid resuscitation. During resuscitation, a single dose of osthole (3 mg/kg, intravenously) with and without a p38 MAPK inhibitor SB-203580 (2 mg/kg, intravenously), SB-203580 or vehicle was administered. Plasma alanine aminotransferase (ALT) with aspartate aminotransferase (AST) concentrations and various hepatic parameters were measured (n = 8 rats/group) at 24 hours after resuscitation. The results showed that trauma-hemorrhage increased hepatic myeloperoxidase activity, intercellular adhesion molecule-1 and interleukin-6 levels, and plasma ALT and AST concentrations. These parameters were significantly improved in the osthole-treated rats subjected to trauma-hemorrhage. Osthole treatment also increased hepatic phospho-p38 MAPK expression compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of SB-203580 with osthole abolished the osthole-induced beneficial effects on the above parameters and hepatic injury. These results suggest that the protective effect of osthole administration on alleviation of hepatic injury after trauma-hemorrhage, which is, at least in part, through p38 MAPK-dependent pathway.

Trauma Hemostasis and Oxygenation Research Network position paper on the role of hypotensive resuscitation as part of remote damage control resuscitation.

PubMed

Woolley, Thomas; Thompson, Patrick; Kirkman, Emrys; Reed, Richard; Ausset, Sylvain; Beckett, Andrew; Bjerkvig, Christopher; Cap, Andrew P; Coats, Tim; Cohen, Mitchell; Despasquale, Marc; Dorlac, Warren; Doughty, Heidi; Dutton, Richard; Eastridge, Brian; Glassberg, Elon; Hudson, Anthony; Jenkins, Donald; Keenan, Sean; Martinaud, Christophe; Miles, Ethan; Moore, Ernest; Nordmann, Giles; Prat, Nicolas; Rappold, Joseph; Reade, Michael C; Rees, Paul; Rickard, Rory; Schreiber, Martin; Shackelford, Stacy; Skogran Eliassen, Håkon; Smith, Jason; Smith, Mike; Spinella, Philip; Strandenes, Geir; Ward, Kevin; Watts, Sarah; White, Nathan; Williams, Steve

2018-06-01

The Trauma Hemostasis and Oxygenation Research (THOR) Network has developed a consensus statement on the role of permissive hypotension in remote damage control resuscitation (RDCR). A summary of the evidence on permissive hypotension follows the THOR Network position on the topic. In RDCR, the burden of time in the care of the patients suffering from noncompressible hemorrhage affects outcomes. Despite the lack of published evidence, and based on clinical experience and expertise, it is the THOR Network's opinion that the increase in prehospital time leads to an increased burden of shock, which poses a greater risk to the patient than the risk of rebleeding due to slightly increased blood pressure, especially when blood products are available as part of prehospital resuscitation.The THOR Network's consensus statement is, "In a casualty with life-threatening hemorrhage, shock should be reversed as soon as possible using a blood-based HR fluid. Whole blood is preferred to blood components. As a part of this HR, the initial systolic blood pressure target should be 100 mm Hg. In RDCR, it is vital for higher echelon care providers to receive a casualty with sufficient physiologic reserve to survive definitive surgical hemostasis and aggressive resuscitation. The combined use of blood-based resuscitation and limiting systolic blood pressure is believed to be effective in promoting hemostasis and reversing shock".

Spontaneous heparin-induced thrombocytopenia presenting as bilateral adrenal hemorrhages and pulmonary embolism after total knee arthroplasty.

PubMed

Elshoury, Amro; Khedr, Maha; Abousayed, Mostafa M; Mehdi, Syed

2015-09-01

Heparin-induced thrombocytopenia syndrome is an acquired potentially life-threatening prothrombotic disorder caused by antibodies that recognize complexes of platelet factor 4 bound to heparin or heparin-like molecules. It typically occurs after exposure to unfractionated heparin, to a lesser extent after exposure to low-molecular-weight heparins, and rarely after exposure to fondaparinux. Herein, we report the case of a 48-year-old woman who developed severe thrombocytopenia, bilateral pulmonary embolism, and bilateral adrenal hemorrhages after total knee arthroplasty without evidence of heparin exposure. Antibodies to the heparin-platelet factor 4 complex and serotonin-release assay were positive. Spontaneous heparin-induced thrombocytopenia syndrome should be considered in patients with unexplained thrombocytopenia after knee replacement surgery even without heparin exposure, and a high index of suspicion for adrenal hemorrhage is needed in patients with fever, abdominal pain, and shock.

Effect of isolated hepatic ischemia on organic anion clearance and oxidative metabolism.

PubMed

Minard, G; Bynoe, R; Wood, G C; Fabian, T C; Croce, M; Kudsk, K A

1992-04-01

Hepatic failure is frequently seen following severe hemorrhagic shock, sepsis, and trauma. Clearance of various drugs has been used to evaluate hepatocellular dysfunction, including indocyanine green (ICG), an organic anionic dye that is transported similarly to bilirubin, and antipyrine (AP), a marker of oxidative phosphorylation. Previous investigators have noted a decrease in ICG excretion following systemic hemorrhage. The effect of isolated hepatic ischemia on the clearances of ICG and AP was studied in 16 pigs after 90 minutes of vascular occlusion to the liver. Antipyrine clearance decreased almost 50% from baseline values at 24 and 72 hours after the ischemia procedure, indicating a significant depression in the cytochrome P-450 system. On the other hand, ICG clearance did not change significantly. In conclusion, ICG clearance is not depressed after isolated hepatic ischemia in pigs. Changes in organic anion clearance after systemic hemorrhage may be because of release of toxic products from ischemic peripheral tissue.

Effects of Pharmacologic Intervention on Oxygenation, Lung Water and Protein Leak in the Pseudomonas ARDS Procine Model

DTIC Science & Technology

1993-07-01

they displayed varying degrees of congestion and edema, often with petechial or larger hemorrhages and more or less widespread bronchopneumonia in...Chemow, B. (1990) Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever . J. Infect. Dis., 161:79-84

Optimizing the use of Limb Tourniquets in Tactical Combat Casualty Care: TCCC Guidelines Change 14-02

DTIC Science & Technology

2014-02-01

Sebesta JA, Blackbourne LH, Herbert GS, Kauvar DS, Baer DG, Walters TJ, Mullenix PS, Holcomb JB, 31 st Combat Support Hospital Research Group...K, Dixon P, Cowart J, Spencer J, Rasmussen TE. Hemorrhagic shock worsens neuromuscular recovery in a porcine model of hind limb vascular injury and

Altered Signal Transduction in Renal Cell Injury Following Hemorrhagic Shock or Anoxia

DTIC Science & Technology

1989-07-01

Camal ter, R. F. ; Saffiotti, U. Effects of serum and serum-derved factors on growth and differentiation of mouse keratinocytes. In Vitro 22: 423-428...growth and differentiation of mouse epidermal cells in culture. Cell 19: 245-254; 1980. 19. Kaighn, M. E.; Camaller , R. F.; Bertolero, F.; SaffLotti, U

Standard First Aid Training Course. Naval Education and Training Command Rate Training Manual.

ERIC Educational Resources Information Center

Naval Education and Training Command, Washington, DC.

This first aid manual is designed to serve as basic first aid instructional materials for all nonmedical naval personnel. Chapters are included on the following topics: basic life support, hemorrhage, shock, wounds, injuries, drug abuse, poisoning, common medical emergencies, NBC (nuclear, biological, chemical) agent casualties, and rescue and…

Electrical Burns and Late Spontaneous Artery Ruptures: About Three Cases.

PubMed

Reinbold, C; Serror, K; Mimoun, M; Chaouat, M; Marco, O; Boccara, D

2018-05-15

Electrical burns are responsible for arterial and venous thrombosis, as well as weakening of the arteries. Immediate or delayed arterial occlusions, secondary to the aggression of the intima, or aneurysms, secondary to the aggression of the media, sometimes lead to artery ruptures without any warning signs. Such ruptures may trigger a hemorrhagic shock whose period of onset is variable and unpredictable. We are presenting here three cases treated in our department for electrical burns, whose complications were marked by hemorrhagic shock, secondary to late artery ruptures, sometimes occurring several months following the event. These case reports required performance of emergency hemostasis in order to control sudden bleeding, with first approach being placement of a tourniquet at the base of the limb and/or a compression point. Through these cases, we thought it is crucial to closely monitor for a few weeks all patients who were victims of electrical injury, even more so if it was associated with a compartment syndrome of one or more limbs and high rhabdomyolysis, which seem to be predictive factors of late artery ruptures in our case reports.

[Cardiogenic shock associated with inappropriate nutritional regimen: refeeding syndrome].

PubMed

Campos-Ferrer, C; Cervera-Montes, M; Romero, A; Borrás, S; Gómez, E; Ricart, C

2004-01-01

Situations of cardiac arrest have been reported in under-nourished patients with protein and calorie deficits when the provision of nutrients was initiated in an uncontrolled manner. The recognition of the association between the provision of food in these circumstances and the serious clinical consequences, generally heartbeat disorders, has led this condition to be described as "re-feeding syndrome". The case presented here is of severe acute respiratory failure and cardiogenic shock in a 44-year-old female patient with severe protein and calorie malnutrition associated with the start of hyperproteic nutritional support. Treatment with inotropic-vasoactive drugs and diuretics together with a progressive nutritional programme brought about the complete reversal of her heart failure and the concomitant endocrine-metabolic syndrome.

Ethyl pyruvate reduces acute lung damage following trauma and hemorrhagic shock via inhibition of NF-κB and HMGB1.

PubMed

Relja, Borna; Wagner, Nils; Franz, Niklas; Dieteren, Scott; Mörs, Katharina; Schmidt, Julia; Marzi, Ingo; Perl, Mario

2018-03-01

After blunt thoracic trauma (TxT) and hemorrhagic shock with resuscitation (H/R) intense local inflammatory response and cell loss frequently impair the pulmonary function. Ethyl pyruvate (EP) has been reported to improve the pathophysiologic derangements in models of acute inflammation. Here, we studied the effects of EP on inflammation and lung damage after TxT+H/R. Twenty four female Lewis rats (180-240g) were randomly divided into 3 groups: two groups underwent TxT followed by hemorrhagic shock (35±3mmHg) for 60min and resuscitation with either Ringers-Lactat (RL) alone or RL supplemented with EP (EP, 50mg/kg). Sham operated animals underwent surgical procedures. Two hours later bronchoalveolar lavage fluid (BAL), lung tissue and blood were collected for analyses. EP significantly improved pO 2 levels compared to RL after TxT+H/R. TxT+H/R induced elevated levels of lactate dehydrogenase, total protein concentration in BAL and lung damage as evidenced by lung histology; these effects were significantly reduced by EP. Local inflammatory markers, lung TNF-alpha protein levels and infiltration with polymorphonuclear leukocytes (PMNL) significantly decreased in EP vs. RL group after TxT+H/R. Indicators of apoptosis as reduced BCL-2 and increased FAS gene expression after TxT+H/R were significantly increased or decreased, respectively, by EP after TxT+H/R. EP reduced TxT+H/R-induced p65 phosphorylation, which was concomitant with reduced HMGB1 levels in lung sections. Taken together, TxT+H/R induced strong inflammatory response and apoptotic changes as well as lung injury which were markedly diminished by EP. Our results suggest that this might be mediated via NF-κB and/or HMGB1 dependent mechanism. Copyright © 2017 Elsevier GmbH. All rights reserved.

Estradiol improves cardiac and hepatic function after trauma-hemorrhage: role of enhanced heat shock protein expression.

PubMed

Szalay, László; Shimizu, Tomoharu; Suzuki, Takao; Yu, Huang-Ping; Choudhry, Mashkoor A; Schwacha, Martin G; Rue, Loring W; Bland, Kirby I; Chaudry, Irshad H

2006-03-01

Although studies indicate that 17beta-estradiol administration after trauma-hemorrhage (T-H) improves cardiac and hepatic functions, the underlying mechanisms remain unclear. Because the induction of heat shock proteins (HSPs) can protect cardiac and hepatic functions, we hypothesized that these proteins contribute to the salutary effects of estradiol after T-H. To test this hypothesis, male Sprague-Dawley rats ( approximately 300 g) underwent laparotomy and hemorrhagic shock (35-40 mmHg for approximately 90 min) followed by resuscitation with four times the shed blood volume in the form of Ringer lactate. 17beta-estradiol (1 mg/kg body wt) was administered at the end of the resuscitation. Five hours after T-H and resuscitation there was a significant decrease in cardiac output, positive and negative maximal rate of left ventricular pressure. Liver function as determined by bile production and indocyanine green clearance was also compromised after T-H and resuscitation. This was accompanied by an increase in plasma alanine aminotransferase (ALT) levels and liver perfusate lactic dehydrogenase levels. Furthermore, circulating levels of TNF-alpha, IL-6, and IL-10 were also increased. In addition to decreased cardiac and hepatic function, there was an increase in cardiac HSP32 expression and a reduction in HSP60 expression after T-H. In the liver, HSP32 and HSP70 were increased after T-H. There was no change in heart HSP70 and liver HSP60 after T-H and resuscitation. Estradiol administration at the end of T-H and resuscitation increased heart/liver HSPs expression, ameliorated the impairment of heart/liver functions, and significantly prevented the increase in plasma levels of ALT, TNF-alpha, and IL-6. The ability of estradiol to induce HSPs expression in the heart and the liver suggests that HSPs, in part, mediate the salutary effects of 17beta-estradiol on organ functions after T-H.

Fluid resuscitation with isotonic or hypertonic saline solution avoids intraneural calcium influx after traumatic brain injury associated with hemorrhagic shock.

PubMed

Balbino, Marcos; Capone Neto, Antonio; Prist, Ricardo; Ferreira, Alice Teixeira; Poli-de-Figueiredo, Luiz F

2010-04-01

Calcium is one of the triggers involved in ischemic neuronal death. Because hypotension is a strong predictor of outcome in traumatic brain injury (TBI), we tested the hypothesis that early fluid resuscitation blunts calcium influx in hemorrhagic shock associated to TBI. Fifteen ketamine-halothane anesthetized mongrel dogs (18.7 kg +/- 1.4 kg) underwent unilateral cryogenic brain injury. Blood was shed in 5 minutes to a target mean arterial pressure of 40 mm Hg to 45 mm Hg and maintained at these levels for 20 minutes (shed blood volume = 26 mL/kg +/- 7 mL/kg). Animals were then randomized into three groups: CT (controls, no fluid resuscitation), HS (7.5% NaCl, 4 mL/kg, in 5 minutes), and LR (lactate Ringer's, 33 mL/kg, in 15 minutes). Twenty minutes later, a craniotomy was performed and cerebral biopsies were obtained next to the lesion ("clinical penumbra") and from the corresponding contralateral side ("lesion's mirror") to determine intracellular calcium by fluorescence signals of Fura-2-loaded cells. Controls remained hypotensive and in a low-flow state, whereas fluid resuscitation improved hemodynamic profile. There was a significant increase in intracellular calcium in the injured hemisphere in CT (1035 nM +/- 782 nM), compared with both HS (457 nM +/- 149 nM, p = 0.028) and LR (392 nM +/- 178 nM, p = 0.017), with no differences between HS and LR (p = 0.38). Intracellular calcium at the contralateral, uninjured hemisphere was 438 nM +/- 192 nM in CT, 510 nM +/- 196 nM in HS, and 311 nM +/- 51 nM in LR, with no significant differences between them. Both small volume hypertonic saline and large volume lactated Ringer's blunts calcium influx in early stages of TBI associated to hemorrhagic shock. No fluid resuscitation strategy promotes calcium influx and further neural damage.

Transmural Intestinal Wall Permeability in Severe Ischemia after Enteral Protease Inhibition

PubMed Central

Altshuler, Angelina E.; Lamadrid, Itze; Li, Diana; Ma, Stephanie R.; Kurre, Leena; Schmid-Schönbein, Geert W.; Penn, Alexander H.

2014-01-01

In intestinal ischemia, inflammatory mediators in the small intestine's lumen such as food byproducts, bacteria, and digestive enzymes leak into the peritoneal space, lymph, and circulation, but the mechanisms by which the intestinal wall permeability initially increases are not well defined. We hypothesize that wall protease activity (independent of luminal proteases) and apoptosis contribute to the increased transmural permeability of the intestine's wall in an acutely ischemic small intestine. To model intestinal ischemia, the proximal jejunum to the distal ileum in the rat was excised, the lumen was rapidly flushed with saline to remove luminal contents, sectioned into equal length segments, and filled with a tracer (fluorescein) in saline, glucose, or protease inhibitors. The transmural fluorescein transport was determined over 2 hours. Villi structure and epithelial junctional proteins were analyzed. After ischemia, there was increased transmural permeability, loss of villi structure, and destruction of epithelial proteins. Supplementation with luminal glucose preserved the epithelium and significantly attenuated permeability and villi damage. Matrix metalloproteinase (MMP) inhibitors (doxycycline, GM 6001), and serine protease inhibitor (tranexamic acid) in the lumen, significantly reduced the fluorescein transport compared to saline for 90 min of ischemia. Based on these results, we tested in an in-vivo model of hemorrhagic shock (90 min 30 mmHg, 3 hours observation) for intestinal lesion formation. Single enteral interventions (saline, glucose, tranexamic acid) did not prevent intestinal lesions, while the combination of enteral glucose and tranexamic acid prevented lesion formation after hemorrhagic shock. The results suggest that apoptotic and protease mediated breakdown cause increased permeability and damage to the intestinal wall. Metabolic support in the lumen of an ischemic intestine with glucose reduces the transport from the lumen across the wall and enteral proteolytic inhibition attenuates tissue breakdown. These combined interventions ameliorate lesion formation in the small intestine after hemorrhagic shock. PMID:24805256

Using 300 Pretreatment Shock Waves in a Voltage Ramping Protocol Can Significantly Reduce Tissue Injury During Extracorporeal Shock Wave Lithotripsy.

PubMed

Connors, Bret A; Evan, Andrew P; Handa, Rajash K; Blomgren, Philip M; Johnson, Cynthia D; Liu, Ziyue; Lingeman, James E

2016-09-01

Pretreating a pig kidney with 500 low-energy shock waves (SWs) before delivering a clinical dose of SWs (2000 SWs, 24 kV, 120 SWs/min) has been shown to significantly reduce the size of the hemorrhagic lesion produced in that treated kidney, compared with a protocol without pretreatment. However, since the time available for patient care is limited, we wanted to determine if fewer pretreatment SWs could be used in this protocol. As such, we tested if pretreating with 300 SWs can initiate the same reduction in renal lesion size as has been observed with 500 SWs. Fifteen female farm pigs were placed in an unmodified Dornier HM-3 lithotripter, where the left kidney of each animal was targeted for lithotripsy treatment. The kidneys received 300 SWs at 12 kV (120 SWs/min) followed immediately by 2000 SWs at 24 kV (120 SWs/min) focused on the lower pole. These kidneys were compared with kidneys given a clinical dose of SWs with 500 SW pretreatment, and without pretreatment. Renal function was measured both before and after SW exposure, and lesion size analysis was performed to assess the volume of hemorrhagic tissue injury (% functional renal volume, FRV) created by the 300 SW pretreatment regimen. Glomerular filtration rate fell significantly in the 300 SW pretreatment group by 1 hour after lithotripsy treatment. For most animals, low-energy pretreatment with 300 SWs significantly reduced the size of the hemorrhagic injury (to 0.8% ± 0.4%FRV) compared with the injury produced by a typical clinical dose of SWs. The results suggest that 300 pretreatment SWs in a voltage ramping treatment regimen can initiate a protective response in the majority of treated kidneys and significantly reduce tissue injury in our model of lithotripsy injury.

Resuscitation with Pooled and Pathogen-Reduced Plasma Attenuates the Increase in Brain Water Content following Traumatic Brain Injury and Hemorrhagic Shock in Rats.

PubMed

Genét, Gustav Folmer; Bentzer, Peter; Ostrowski, Sisse Rye; Johansson, Pär Ingemar

2017-03-01

Traumatic brain injury and hemorrhagic shock is associated with blood-brain barrier (BBB) breakdown and edema formation. Recent animal studies have shown that fresh frozen plasma (FFP) resuscitation reduces brain swelling and improves endothelial function compared to isotonic NaCl (NS). The aim of this study was to investigate whether pooled and pathogen-reduced plasma (OctaplasLG ® [OCTA]; Octapharma, Stockholm, Sweden) was comparable to FFP with regard to effects on brain water content, BBB permeability, and plasma biomarkers of endothelial glycocalyx shedding and cell damage. After fluid percussion brain injury, hemorrhage (20 mL/kg), and 90-min shock, 48 male Sprague-Dawley rats were randomized to resuscitation with OCTA, FFP, or NS (n = 16/group). Brain water content (wet/dry weight) and BBB permeability (transfer constant for 51 Cr-EDTA) were measured at 24 h. Plasma osmolality, oncotic pressure, and biomarkers of systemic glycocalyx shedding (syndecan-1) and cell damage (histone-complexed DNA) were measured at 0 and 23 h. At 24 h, brain water content was 80.44 ± 0.39%, 80.82 ± 0.82%, and 81.15 ± 0.86% in the OCTA, FFP, and NS groups (lower in OCTA vs. NS; p = 0.026), with no difference in BBB permeability. Plasma osmolality and oncotic pressures were highest in FFP and OCTA resuscitated, and osmolality was further highest in OCTA versus FFP (p = 0.027). In addition, syndecan-1 was highest in FFP and OCTA resuscitated (p = 0.010). These results suggest that pooled solvent-detergent (SD)-treated plasma attenuates the post-traumatic increase in brain water content, and that this effect may, in part, be explained by a high crystalloid and colloid osmotic pressure in SD-treated plasma.

Ethyl pyruvate ameliorates hepatic injury following blunt chest trauma and hemorrhagic shock by reducing local inflammation, NF-kappaB activation and HMGB1 release.

PubMed

Wagner, Nils; Dieteren, Scott; Franz, Niklas; Köhler, Kernt; Mörs, Katharina; Nicin, Luka; Schmidt, Julia; Perl, Mario; Marzi, Ingo; Relja, Borna

2018-01-01

The treatment of patients with multiple trauma including blunt chest/thoracic trauma (TxT) and hemorrhagic shock (H) is still challenging. Numerous studies show detrimental consequences of TxT and HS resulting in strong inflammatory changes, organ injury and mortality. Additionally, the reperfusion (R) phase plays a key role in triggering inflammation and worsening outcome. Ethyl pyruvate (EP), a stable lipophilic ester, has anti-inflammatory properties. Here, the influence of EP on the inflammatory reaction and liver injury in a double hit model of TxT and H/R in rats was explored. Female Lewis rats were subjected to TxT followed by hemorrhage/H (60 min, 35±3 mm Hg) and resuscitation/R (TxT+H/R). Reperfusion was performed by either Ringer`s lactated solution (RL) alone or RL supplemented with EP (50 mg/kg). Sham animals underwent all surgical procedures without TxT+H/R. After 2h, blood and liver tissue were collected for analyses, and survival was assessed after 24h. Resuscitation with EP significantly improved haemoglobin levels and base excess recovery compared with controls after TxT+H/R, respectively (p<0.05). TxT+H/R-induced significant increase in alanine aminotransferase levels and liver injury were attenuated by EP compared with controls (p<0.05). Local inflammation as shown by increased gene expression of IL-6 and ICAM-1, enhanced ICAM-1 and HMGB1 protein expression and infiltration of the liver with neutrophils were also significantly attenuated by EP compared with controls after TxT+H/R (p<0.05). EP significantly reduced TxT+H/R-induced p65 activation in liver tissue. Survival rates improved by EP from 50% to 70% after TxT+H/R. These data support the concept that the pronounced local pro-inflammatory response in the liver after blunt chest trauma and hemorrhagic shock is associated with NF-κB. In particular, the beneficial anti-inflammatory effects of ethyl pyruvate seem to be regulated by the HMGB1/NF-κB axis in the liver, thereby, restraining inflammatory responses and liver injury after double hit trauma in the rat.

Clinical experience of infective endocarditis complicated by acute cerebrovascular accidents.

PubMed

Hsu, Chan-Yang; Chi, Nai-Hsin; Wang, Shoei-Shen; Chen, Yih-Sharng; Yu, Hsi-Yu

2017-04-01

To evaluate the clinical results of patients with infective endocarditis (IE) complicated by acute cerebrovascular accidents (CVAs). A total of 44 patients with IE complicated by CVA at admission were retrospectively analyzed in a single medical institute from 2005 to 2011. At the time of admission, 18 patients were diagnosed with hemorrhagic stroke, and 26 patients were diagnosed with ischemic stroke. Fifteen patients received surgical intervention during hospitalization. The hospital mortality rate was 38.9% for the hemorrhagic stroke group and 42.3% for the ischemic stroke group (p = 0.821). The mortality rate was 33.3% for the surgical group and 44.8% for the nonsurgical group (p = 0.531). At 30 days of hospitalization, 45.8% of the patients experienced an adverse event (defined as death due to organ failure, restroke, cardiogenic shock, or septic shock during the treatment period), and the attrition rate was 1.5% per day. Surgery performed after the adverse events increased mortality (80.0%) compared with surgery performed on patients with no adverse events (10.0%; p = 0.017). A Cox regression analysis revealed that creatinine > 2 mg/dL, diabetes, and staphylococcal infection were the risk factors of the adverse events. Early surgical intervention for IE with ischemic stroke may prevent adverse events, particularly in patients with impaired renal function, diabetes, or staphylococcal infection. A delay in operation of > 30 days is recommended after hemorrhagic stroke. Copyright © 2017. Published by Elsevier Taiwan.

Severe Blunt Hepatic Trauma in Polytrauma Patient - Management and Outcome.

PubMed

Doklestić, Krstina; Djukić, Vladimir; Ivančević, Nenad; Gregorić, Pavle; Lončar, Zlatibor; Stefanović, Branislava; Jovanović, Dušan; Karamarković, Aleksandar

2015-01-01

Despite the fact that treatment of liver injuries has dramatically evolved, severe liver traumas in polytraumatic patients still have a significant morbidity and mortality. The purpose of this study was to determine the options for surgical management of severe liver trauma as well as the outcome. In this retrospective study 70 polytraumatic patients with severe (American Association for the Surgery of Trauma [AAST] grade III-V) blunt liver injuries were operated on at the Clinic for Emergency Surgery. Mean age of patients was 48.26±16.80 years; 82.8% of patients were male. Road traffic accident was the leading cause of trauma, seen in 63 patients (90.0%). Primary repair was performed in 36 patients (51.4%), while damage control with perihepatic packing was done in 34 (48.6%). Complications related to the liver occurred in 14 patients (20.0%). Liver related mortality was 17.1%. Non-survivors had a significantly higher AAST grade (p=0.0001), higher aspartate aminotransferase level (p=0.01), lower hemoglobin level (p=0.0001), associated brain injury (p=0.0001), perioperative complications (p=0.001) and higher transfusion score (p=0.0001). The most common cause of mortality in the "early period" was uncontrolled bleeding, in the "late period" mortality was caused by sepsis and acute respiratory distress syndrome. Patients with high-grade liver trauma who present with hemorrhagic shock and associated severe injury should be managed operatively. Mortality from liver trauma is high for patients with higher AAST grade of injury, associated brain injury and massive transfusion score.

Association Between MC-2 Peptide and Hepatic Perfusion and Liver Injury Following Resuscitated Hemorrhagic Shock.

PubMed

Matheson, Paul J; Fernandez-Botran, Rafael; Smith, Jason W; Matheson, Samuel A; Downard, Cynthia D; McClain, Craig J; Garrison, Richard N

2016-03-01

Hemorrhagic shock (HS) due to trauma remains a major cause of morbidity and mortality in the United States, despite continuing progression of advanced life support and treatment. Trauma is the third most common cause of death worldwide and is the leading cause of death in the 1- to 44-year-old age group. Hemorrhagic shock often progresses to multiple organ failure despite conventional resuscitation (CR) that restores central hemodynamics. To examine whether MC-2 would bind glycosaminoglycans to decrease proinflammatory cytokines' influence in the liver, minimize organ edema, prevent liver injury, and improve hepatic perfusion. MC-2, a synthetic octapeptide derived from the heparin-binding domain of murine interferon gamma (IFN-γ), binds glycosaminoglycans to modulate serum and interstitial cytokine levels and activity. A controlled laboratory study of 3y male Sprague-Dawley rats that were randomized to 4 groups of 8 each: sham, sham+MC-2 (50 mg/kg), HS/CR, or HS/CR+MC-2 (HS = 40% of baseline mean arterial pressure for 60 minutes; CR = return of shed blood and 2 volumes of saline). The study began in March, 2013. Effective hepatic blood flow (EHBF) by galactose clearance, wet-dry weights, cytokines, histopathology, complete metabolic panel, and complete blood cell count were performed at 4 hours after CR. MC-2 partially reversed the HS/CR-induced hepatic hypoperfusion at 3 and 4 hours postresuscitation compared with HS/CR alone. Effective hepatic blood flow decreased during the HS period from a mean (SD) of 7.4 (0.3) mL/min/100 g and 7.5 (0.5) mL/min/100g at baseline to 3.7 (0.4) mL/min/100g and 5.9 (0.5) mL/min/100g for the HS/CR and HS/CR+MC-2 groups, respectively (P <.05). Effective hepatic blood flow remained constant in the sham groups throughout the experimental protocol. Organ edema was increased in the ileum and liver in the HS/CR vs sham group, and MC-2 decreased edema in the ileum vs the HS/CR group. MC-2 in HS also decreased levels of alanine aminotransferase, zonula occludens-1, and interleukin-1β compared with HS/CR alone. MC-2 was associated with decreased liver injury, enhanced effective hepatic blood flow, decreased cytokines, and prevention of edema formation in the ileum when administered with CR following HS. These data suggest that the MC-2 peptide could be a potential therapeutic approach to target cytokine and chemokine interactions, which might limit multiple organ failure and decrease mortality in hemorrhagic shock.

Reperfusion does not induce oxidative stress but sustained endoplasmic reticulum stress in livers of rats subjected to traumatic-hemorrhagic shock.

PubMed

Duvigneau, Johanna Catharina; Kozlov, Andrey V; Zifko, Clara; Postl, Astrid; Hartl, Romana T; Miller, Ingrid; Gille, Lars; Staniek, Katrin; Moldzio, Rudolf; Gregor, Wolfgang; Haindl, Susanne; Behling, Tricia; Redl, Heinz; Bahrami, Soheyl

2010-03-01

Oxidative stress is believed to accompany reperfusion and to mediate dysfunction of the liver after traumatic-hemorrhagic shock (THS). Recently, endoplasmic reticulum (ER) stress has been suggested as an additional factor. This study investigated whether reperfusion after THS leads to increased oxidative and/or ER stress in the liver. In a rat model, including laparotomy, bleeding until decompensation, followed by inadequate or adequate reperfusion phase, three time points were investigated: 40 min, 3 h, and 18 h after shock. The reactive oxygen and nitrogen species and its scavenging capacity (superoxide dismutase 2), the nitrotyrosine formation in proteins, and the lipid peroxidation together with the status of endogenous antioxidants (alpha-tocopherylquinone-alpha-tocopherol ratio) were investigated as markers for oxidative or nitrosylative stress. Mitochondrial function and cytochrome P450 isoform 1A1 activity were analyzed as representatives for hepatocyte function. Activation of the inositol-requiring enzyme 1/X-box binding protein pathway and up-regulation of the 78-kDa glucose-regulated protein were recorded as ER stress markers. Plasma levels of alanine aminotransferase and Bax/Bcl-XL messenger RNA (mRNA) ratio were used as indicators for hepatocyte damage and apoptosis induction. Oxidative or nitrosylative stress markers or representatives of hepatocyte function were unchanged during and short after reperfusion (40 min, 3 h after shock). In contrast, ER stress markers were elevated and paralleled those of hepatocyte damage. Incidence for sustained ER stress and subsequent apoptosis induction were found at 18 h after shock. Thus, THS or reperfusion induces early and persistent ER stress of the liver, independent of oxidative or nitrosylative stress. Although ER stress was not associated with depressed hepatocyte function, it may act as an early trigger of protracted cell death, thereby contributing to delayed organ failure after THS.

Pharmacologic Suppression of Inflammation by a Diphenyldifluoroketone, EF24, in a Rat Model of Fixed-Volume Hemorrhage Improves Survival

PubMed Central

Yadav, Vivek R.; Sahoo, Kaustuv; Roberts, Pamela R.

2013-01-01

An exaggerated release of proinflammatory cytokines and accompanying inflammation contributes to the development of multiple organ failure after hemorrhagic shock. Here, we tested the nuclear factor (NF) κ-light-chain-enhancer of activated B cell (NF-κB)–mediated transcriptional control of inflammatory pathways as a target in the management of hemorrhage-induced inflammation. We performed a study in a rat model of fixed-volume hemorrhage to investigate the anti-inflammatory effects of the diphenyldifluoroketone EF24 [3,5-bis(2-fluorobenzylidene)piperidin-4-one], an NF-κB inhibitor, in lung tissue. EF24 treatment (0.4 mg/kg) significantly prevented the upregulation of inflammatory biomarkers in rats subjected to 50% hemorrhage and preserved the pulmonary histology in hemorrhaged rats. The lung tissue from treated rats showed marked suppression of the hemorrhage-mediated induction of Toll-like receptor 4, phospho-p65 NF-κB, inducible nitric-oxide synthase, heme oxygenase–1, and cyclooxygenase-2 (COX-2). The hemorrhage-induced COX-2 activity was also significantly inhibited by the EF24 treatment. At the same time, EF24 induced nuclear factor (erythroid-derived 2)-like 2–mediated protective mechanisms against oxidative stress. EF24 also reduced hemorrhage-induced lung myeloperoxidase activity. The plasma levels of proinflammatory tumor necrosis factor-α, interleukin (IL)-6, IL-1α, and IL-1β were lower in EF24-treated rats than in untreated rats. Moreover, there was a significant reduction in the pulmonary expression of high-mobility group B1 protein. These biochemical effects were accompanied by a significant improvement in the survival of rats administered with EF24 as compared with the rats receiving vehicle control (P < 0.05). Overall, the results suggest that EF24 attenuates hemorrhage-induced inflammation and could serve as a salutary anti-inflammatory agent in resuscitation strategies. PMID:23995597

Histone deacetylase inhibitors: Isoform selectivity improves survival in a hemorrhagic shock model.

PubMed

Chang, Panpan; Weykamp, Michael; Dennahy, Isabel S; Williams, Aaron M; Bhatti, Umar F; Liu, Baoling; Nikolian, Vahagn C; Li, Yongqing; Alam, Hasan B

2018-05-01

Hemorrhage is a leading preventable cause of death. Nonselective histone deacetylase inhibitors (HDACIs), such as valproic acid (VPA), have been shown to improve outcomes in hemorrhagic shock (HS). The HDACs can be divided into four functional classes (I, IIa/IIb, III, and IV). Classes I, IIa/IIb, and III have previously been implicated in the pathophysiology of HS. This study aimed to determine which HDAC class, or classes, are responsible for the survival benefit observed with nonselective HDACIs. Survival study: Sprague-Dawley rats were subjected to lethal HS (50% hemorrhage) and randomized to the following groups (n = 8): (1) no treatment, (2) normal saline vehicle, (3) cyclodextrin vehicle, (4) MS275 (class I HDACI), (5) VPA (class I/IIa HDACI), (6) MC1568 (class IIa HDACI), (7) ACY1083 (class IIb HDACI), and (8) EX527 (class III HDACI). Survival was monitored for 24 hours. Mechanistic study: Sprague-Dawley rats were subjected to sublethal HS (40% hemorrhage) and randomized to the same groups (n = 3), excluding EX527, based on results of the survival study. Tissues were harvested at 3 hours posttreatment, and expression of phosphorylated-AKT, β-catenin, acetylated histones H3 and H4, and acetylated α-tubulin were analyzed in myocardial tissue. Survival rate was 12.5% in the untreated group, and did not improve with vehicle or MS275 treatment. EX527 improved survival to 50%, although this did not achieve statistical significance (p = 0.082). However, treatment with VPA, MC1568, and ACY1083 improved survival rates to 87.5%, 75%, and 75%, respectively (p < 0.05). The VPA-induced acetylation of both histones H3 and H4, while MC1568 and ACY1083 increased acetylation of histone H4. ACY1083 also induced acetylation of α-tubulin. All treatment groups, except MS275, increased phosphorylated-AKT, and β-catenin. Inhibition of HDAC classes IIa or IIb, but not class I, activates prosurvival pathways, which may be responsible for the improved outcomes in rodent models of HS.

Thirty-Day Readmission Among Patients With Non-variceal Upper Gastrointestinal Hemorrhage and Effects on Outcomes.

PubMed

Abougergi, Marwan S; Peluso, Heather; Saltzman, John R

2018-03-28

We aimed to determine the rate of hospital readmission within 30 days of non-variceal upper gastrointestinal hemorrhage and its impact on mortality, morbidity, and health care use in the United States. We performed a retrospective study using the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project Nationwide Readmission Database for the year 2014 (data on 14.9 million hospital stays at 2048 hospitals in 22 states). We collected data on hospital readmissions of 203,220 adults who were hospitalized for urgent non-variceal upper gastrointestinal hemorrhage and discharged. The primary outcome was rate of all-cause readmission within 30 days of discharge. Secondary outcomes were reasons for readmission, readmission mortality rate, morbidity (shock and prolonged mechanical ventilation) and resource use (length of stay and total hospitalization costs and charges). Independent risk factors for readmission were identified using Cox regression analysis. The 30-day rate of readmission was 13%. Only 18% of readmissions were due to recurrent non-variceal upper gastrointestinal bleeding. The rate of death among patients readmitted to the hospital (4.7%) was higher than that for index admissions (1.9%) (P < .01). A higher proportion of readmitted patients had morbidities requiring prolonged mechanical ventilation (1.5%) compared with index admissions (0.8%) (P < .01). A total of 133,368 hospital days was associated with readmission, and the total health care in-hospital economic burden was $30.3 million (in costs) and $108 million (in charges). Independent predictors of readmission were Medicaid insurance, higher Charlson comorbidity score, lower income, residence in a metropolitan area, hemorrhagic shock, and longer stays in the hospital. Older age, private or no insurance, upper endoscopy, and prolonged mechanical ventilation were associated with lower odds for readmission. In a retrospective study of patients hospitalized for non-variceal upper gastrointestinal hemorrhage, 13% are readmitted to the hospital within 30 days of discharge. Readmission is associated with higher mortality, morbidity, and resource use. Most readmissions are not for recurrent gastrointestinal bleeding. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Edward D. Churchill as a combat consultant: lessons for the senior visiting surgeons and today's military medical corps.

PubMed

Cannon, Jeremy W; Fischer, Josef E

2010-03-01

In World War II, Edward D. Churchill volunteered as a combat consultant. In this role, he mentored many junior surgeons and challenged the Army leadership to treat hemorrhagic shock with blood rather than plasma. These lessons have continued relevance for today's Senior Visiting Surgeons and our military medical corps.

Emergency Preservation and Resuscitation for Cardiac Arrest from Trauma (EPR-CAT)

DTIC Science & Technology

2013-10-01

proceed with the formal Department of the Army review. 15. SUBJECT TERMS Trauma, hemorrhagic shock, cardiac arrest, cardiopulmonary resuscitation ...n/a Introduction Cardiopulmonary resuscitation (CPR) can save victims of normovolemic cardiac arrest (CA), e.g., ventricular...delayed resuscitation with cardiopulmonary bypass. The primary outcome variable will be survival to hospital discharge with minimal neurologic dysfunction

Hibernation-Based Therapy to Improve Survival of Severe Blood Loss

DTIC Science & Technology

2015-10-01

improve outcomes for injured casualties suffering from polytrauma and blast injuries. 2   Key Words: Beta-hydroxybutyrate Melatonin Poly-trauma...Safety  of  D-­‐ß-­‐Hydroxybutyrate  and  Melatonin  for  the   Treatment  of  Hemorrhagic  Shock  with   Polytrauma ”  has

The Lack of Consistent Diaspirin Cross-Linked Hemoglobin Infusion Blood Pressure Effects in the US and EU Traumatic Hemorrhagic Shock Clinical Trials

DTIC Science & Technology

2009-04-01

Jackson Foundation. Dr. Sloan provided consultation to Northfield Inc on February 29, 2009, regarding Poly Heme and to Biopure Inc on May 2006 as part of...Professor Payen (Principal Investigator, Hopiatl Lariboisiere, Paris Cedex I 0); Docteur Rouvier, MD (Principal Investigator, Hopital Percy , Clamart

Diaspirin Cross-Linked Hemoglobin Infusion Did Not Influence Base Deficit and Lactic Acid Levels in Two Clinical Trials of Traumatic Hemorrhagic Shock Patient Resuscitation

DTIC Science & Technology

2010-05-01

Program, University of Illinois School of Public Health (W.G.), Chicago, Illinois. Supported by a contract with the Henry M. Jackson Foundation...fessor Payen (Principal Investigator, Hopiatl Lariboisiere, Paris Cedex 1 0); Docteur Rouvier, MD (Principal Investiga- tor, Hopital Percy , Clamart

Osthole Attenuates Hepatic Injury in a Rodent Model of Trauma-Hemorrhage

PubMed Central

Yu, Huang-Ping; Liu, Fu-Chao; Tsai, Yung-Fong; Hwang, Tsong-Long

2013-01-01

Recent evidences show that osthole possesses anti-inflammatory properties and protective effects following shock-like states, but the mechanism of these effects remains unknown. The p38 mitogen-activated protein kinase (p38 MAPK) pathway exerts anti-inflammatory effects in injury. The aim of this study was to investigate whether p38 MAPK plays any role in the osthole-mediated attenuation of hepatic injury after trauma-hemorrhage. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35–40 mmHg for 90 minutes), followed by fluid resuscitation. During resuscitation, a single dose of osthole (3 mg/kg, intravenously) with and without a p38 MAPK inhibitor SB-203580 (2 mg/kg, intravenously), SB-203580 or vehicle was administered. Plasma alanine aminotransferase (ALT) with aspartate aminotransferase (AST) concentrations and various hepatic parameters were measured (n = 8 rats/group) at 24 hours after resuscitation. The results showed that trauma-hemorrhage increased hepatic myeloperoxidase activity, intercellular adhesion molecule-1 and interleukin-6 levels, and plasma ALT and AST concentrations. These parameters were significantly improved in the osthole-treated rats subjected to trauma-hemorrhage. Osthole treatment also increased hepatic phospho-p38 MAPK expression compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of SB-203580 with osthole abolished the osthole-induced beneficial effects on the above parameters and hepatic injury. These results suggest that the protective effect of osthole administration on alleviation of hepatic injury after trauma-hemorrhage, which is, at least in part, through p38 MAPK-dependent pathway. PMID:23755293

An Autopsy Case of a Pregnant Woman With Severe Placental and Fetal Damage From Domestic Violence.

PubMed

Kanawaku, Yoshimasa; Takahashi, Shirushi; Kanetake, Jun; Funayama, Masato

2015-09-01

We present an autopsy case of a pregnant woman who was a victim of domestic violence. The deceased showed injuries mainly to her head and abdomen. Postmortem examination revealed 1400 mL of abdominal hemorrhage, ablation of the perimetrium, placental avulsion, and intracranial hematoma. The cause of death was diagnosed as hemorrhagic shock. The uterus contained a fetus of 7 months' gestational age. Fetal autopsy revealed laceration of the lungs, laceration and avulsion of the liver, and 15 mL of hemoperitoneum. Both placental and fetal injuries suggested repeated severe attacks to the abdomen, such as those expected to result from kicking or hitting.

AICAR Administration Attenuates Hemorrhagic Hyperglycemia and Lowers Oxygen Debt in Anesthetized Male Rabbits.

PubMed

Huang, Yi; Ratz, Paul H; Miner, Amy S; Locke, Victoria A; Chen, Grace; Chen, Yang; Barbee, Robert W

2017-01-01

Background: Many strategies have been utilized to treat traumatic shock via improved oxygen delivery (DO 2 ), while fewer have been used to in an attempt to reduce oxygen demand (VO 2 ). The cellular energy sensor 5' adenosine monophosphate-activated protein kinase (AMPK) has the potential to modulate both whole-body DO 2 and VO 2 . Therefore, we determined the effect of the AMPK activator AICAR (5-aminoimidazole-4-carboxamide 1-β-D-ribonucleoside) given acutely or chronically on key metabolites, hemodynamics, and oxygen consumption/delivery before and during hemorrhage in anesthetized male rabbits. Methods: Chronically treated animals received AICAR (40 mg/kg/day, IV) for 10 days prior to hemorrhage, while rabbits in the acute study were infused with AICAR (7.5 mg/kg bolus, 2 mg/kg/min infusion) or vehicle (0.3 ml/kg saline bolus, 0.03 ml/kg/min infusion) IV for 2 h prior to severe hemorrhage. Both acutely and chronically treated animals were sedated (ketamine/xylazine cocktail) the morning of the terminal experiment and surgically prepared for hemorrhage, including the implantation of arterial and venous catheters (for blood removal/sampling and drug/vehicle administration) and thoracotomy for implantation of transit-time flow transducers (for cardiac output determination). Results: AICAR given acutely lowered arterial blood glucose and increased blood lactate levels before hemorrhage, and abolished the well-documented hemorrhage-induced hyperglycemia seen in vehicle treated animals. Animals given AICAR chronically had blunted hemorrhage-induced hyperglycemia without prior baseline changes. Chronically treated AICAR animals showed significantly lower lactate levels during hemorrhage. Rabbits receiving AICAR both acutely and chronically experienced similar falls in mean arterial pressure, cardiac output and hence DO 2 to their vehicle counterparts throughout the hemorrhage period. However, rabbits treated either acutely or chronically with AICAR accumulated lower oxygen deficits and debt during hemorrhage compared to vehicle-infused controls. Conclusions: The oxygen debt data suggest that AMPK activation could decrease trauma associated morbidity and mortality, perhaps by mechanisms related to increased glucose utilization. Additional studies are needed to investigate the effects of AICAR and associated mechanisms of action when given during resuscitation from hemorrhage.

Earlier Endpoints Are Required for Hemorrhagic Shock Trials among Severely Injured Patients

PubMed Central

Fox, Erin E.; Holcomb, John B.; Wade, Charles E.; Bulger, Eileen M.; Tilley, Barbara C.

2016-01-01

Background Choosing the appropriate endpoint for a trauma hemorrhage control trial can determine the likelihood of its success. Recent Phase 3 trials and observational studies have used 24-hour and/or 30-day all-cause mortality as the primary endpoint and some have not used exception from informed consent (EFIC), resulting in multiple failed trials. Five recent high-quality prospective studies among 4,064 hemorrhaging trauma patients provide new evidence to support earlier primary endpoints. Methods The goal of this project was to determine the optimal endpoint for hemorrhage control trials using existing literature and new analyses of previously published data. Results Recent studies among bleeding trauma patients show that hemorrhagic deaths occur rapidly, at a high rate, and in a consistent pattern. Early preventable deaths among trauma patients are largely due to hemorrhage and the median time to hemorrhagic death from admission is 2.0-2.6 hours. Approximately 85% of hemorrhagic deaths occur within 6 hours. The hourly mortality rate due to traumatic injury decreases rapidly after enrollment from 4.6% per hour at 1 hour post-enrollment to 1% per hour at 6 hours to <0.1% per hour by 9 hours and thereafter. Early primary endpoints (within 6 hours) have critically important benefits for hemorrhage control trials, including being congruent with the median time to hemorrhagic death, biologic plausibility, and enabling the use of all-cause mortality, which is definitive and objective. Conclusions Primary endpoints should be congruent with the timing of the disease process. Therefore, if a resuscitation/hemorrhage control intervention is under study, a primary endpoint of all-cause mortality evaluated within the first 6 hours is appropriate. Before choosing the timing of the primary endpoint for a large multicenter trial, we recommend performing a Phase 2 trial under EFIC to better understand the effects of the hemorrhage control intervention and distribution of time to death. When early primary endpoints are used, patients should be monitored for multiple subsequent secondary safety endpoints, including 24 hour and 30 day all-cause mortality as well as the customary safety endpoints. PMID:28207628

Mechanism of salutary effects of melatonin-mediated liver protection after trauma-hemorrhage: p38 MAPK-dependent iNOS/HIF-1α pathway.

PubMed

Hsu, Jun-Te; Le, Puo-Hsien; Lin, Chun-Jung; Chen, Tsung-Hsing; Kuo, Chia-Jung; Chiang, Kun-Chun; Yeh, Ta-Sen

2017-05-01

Although melatonin attenuates the increases in inflammatory mediators and reduces organ injury during trauma-hemorrhage, the mechanisms remain unclear. This study explored whether melatonin prevents liver injury after trauma-hemorrhage through the p38 mitogen-activated protein kinase (MAPK)-dependent, inducible nitrite oxide (iNOS)/hypoxia-inducible factor (HIF)-1α pathway. After a 5-cm midline laparotomy, male rats underwent hemorrhagic shock (mean blood pressure ~40 mmHg for 90 min) followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, melatonin (2 mg/kg), melatonin plus p38 MAPK inhibitor SB203580 (2 mg/kg), or melatonin plus the melatonin receptor antagonist luzindole (2.5 mg/kg). At 2 h after trauma-hemorrhage, histopathology score of liver injury, liver tissue myeloperoxidase activity, malondialdehyde, adenosine triphosphate, serum alanine aminotransferase, and asparate aminotransferase levels were significantly increased compared with sham-operated control. Trauma-hemorrhage resulted in a significant decrease in the p38 MAPK activation compared with that in the sham-treated animals. Administration of melatonin after trauma-hemorrhage normalized liver p38 MAPK phosphorylation and iNOS and HIF-1α expression and attenuated cleaved caspase 3 and receptor interacting protein kinase-1 levels. Coadministration of SB203580 or luzindole abolished the melatonin-mediated attenuation of the trauma-hemorrhage-induced increase of iNOS/HIF-1α protein expression and liver injury markers. Taken together, our results suggest that melatonin prevents trauma-hemorrhage-induced liver injury in rats, at least in part, through melatonin receptor-related, p38 MAPK-dependent iNOS/HIF-1α pathway. NEW & NOTEWORTHY Trauma-hemorrhage resulted in a significant decrease in liver p38 MAPK activation and increase in nitrite oxide synthase (iNOS) and hypoxia-inducible factor (HIF)-1α expression. Administration of melatonin after trauma-hemorrhage normalized liver p38 MAPK phosphorylation and iNOS and HIF-1α expression, which was abolished by coadministration of SB203580 or luzindole. Melatonin prevents trauma-hemorrhage-induced liver injury in rats via the melatonin receptor-related, p38 MAPK-dependent iNOS/HIF-1α pathway. Copyright © 2017 the American Physiological Society.

Embolic Brain Infarcts: A Rare Fatal Complication of Preoperative Embolization of a Massive Solitary Fibrous Tumor of the Pleura

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patel, Shreyas R., E-mail: Shrey000@gmail.com; Vachhani, Prasann; Moeslein, Fred

Solitary fibrous tumor of the pleura (SFTP) is a rare intrathoracic neoplasm, often giant in size and highly vascular, which can make surgical resection very challenging. Preoperative percutaneous embolization before surgical removal can significantly reduce the risk of uncontrollable intraoperative hemorrhage. However, a rare potential life threatening complication could result from embolization of SFTP and must be taken into consideration. This report describes a 69-year-old female with a large right thoracic SFTP, who underwent preoperative angiography and embolization and developed diffuse embolic brain infarcts immediately after the administration of polyvinyl alcohol particles.

Endogenous hydrogen sulfide regulates histone demethylase JMJD3-mediated inflammatory response in LPS-stimulated macrophages and in a mouse model of LPS-induced septic shock.

PubMed

Liu, Siyu; Wang, Xiling; Pan, Lilong; Wu, Weijun; Yang, Di; Qin, Ming; Jia, Wanwan; Xiao, Chenxi; Long, Fen; Ge, Junbo; Liu, Xinhua; Zhu, YiZhun

2018-03-01

Overproduction of inflammatory mediators contributes to uncontrolled inflammation during endotoxin shock. Cystathionine-γ-lyase (CSE), an enzyme involved in hydrogen sulfide (H 2 S) biosynthesis, has potential anti-inflammatory activity in a variety of inflammatory diseases. Jumonji domain-containing protein 3 (JMJD3), a histone 3 Lys27 (H3K27) demethylase, has been implicated in macrophage activation, but its function in CSE-mediated anti-inflammatory activities remains unknown. In the present study CSE was found to be upregulated in macrophages and mouse lipopolysaccharide (LPS) challenge models. LPS stimulation also enhanced the activation of JMJD3 and decreased H3K27me3 levels. JMJD3 knockdown upregulated H3K27me3 levels and attenuated the LPS-mediated inflammatory response. CSE knockout amplified the inflammatory cascade by increasing JMJD3 expression in septic mice. Similarly, enhanced production of inflammatory mediators by macrophages was mitigated by CSE overexpression via inhibition of JMJD3 expression. This is the first report indicating that inflammation enhanced CSE/H 2 S system biosynthesis, that in turn attenuated the LPS-triggered inflammatory response by regulating JMJD3 expression. Thus, the CSE/H 2 S system represents an epigenetic-based modification mechanism to prevent uncontrolled inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

Survival, quality of life and impact of right heart failure in patients with acute cardiogenic shock treated with ECMO.

PubMed

Schoenrath, Felix; Hoch, Dennis; Maisano, Francesco; Starck, Christoph T; Seifert, Burkhardt; Wenger, Urs; Ruschitzka, Frank; Wilhelm, Markus J

2016-01-01

Mechanical circulatory support is increasingly used in acute cardiogenic shock. To assess treatment strategies for cardiogenic shock. Data of 57 patients in acute intrinsic cardiogenic shock treated with ECMO were analyzed. Different subsequent strategies (weaning, VAD, transplantation) were followed.​ Overall 1, 2, and 4-year survival was 36.8 ± 6.4%, 32.2 ± 6.4%, 29.8 ± 6.3%. Elevated lactate and hemorrhagic complications (all p in patients with right heart failure prior to ECMO implantation, BVAD therapy showed a trend (p=0.058) towards superior survival compared with LVAD therapy. Seven of the BVAD patients received successful transplantation, with a 1-year survival of 71%. Among survivors Short Form 36 reported significantly lower combined physical scores (p=0.004). Right heart assessment prior to ECMO implantation may be beneficial to provide tailored therapy if ECMO weaning fails. Survival after cardiogenic shock requiring ECMO seems to be associated with impaired long-term quality of life. Copyright © 2016 Elsevier Inc. All rights reserved.

The Role of Endorphins in the Pathophysiology of Hemorrhagic and Endotoxic Shock in the Subhuman Primate.

DTIC Science & Technology

1985-03-15

by either a- or e-adrenergic blockade (phenoxybenzamine or metoprolol , respectively) and potentiated by cholinergic receptor *blockade with...which was blocked by e-adrenergic blockade with metoprolol . Naloxone had no effect on plasma catecholamine levels (Table V). The sustained cardiovascular...58±8 213±134 57:5C Shock Saline 19.3:3.7 8.6±2.8 1.4:0.2 Metoprolol 21.1±7.0 5.2t1.3 1.0:0.2 Phenox y- benzamine 9.4:1.5 4.2±0.5 1.0:0.2 Both 14.1±3.5

Vasopressin: Its current role in anesthetic practice

PubMed Central

Mitra, Jayanta K.; Roy, Jayeeta; Sengupta, Saikat

2011-01-01

Vasopressin or antidiuretic hormone is a potent endogenous hormone, which is responsible for regulating plasma osmolality and volume. In high concentrations, it also raises blood pressure by inducing moderate vasoconstriction. It acts as a neurotransmitter in the brain to control circadian rhythm, thermoregulation and adrenocorticotropic hormone release. The therapeutic use of vasopressin has become increasingly important in the critical care environment in the management of cranial diabetes insipidus, bleeding abnormalities, esophageal variceal hemorrhage, asystolic cardiac arrest and septic shock. After 10 years of ongoing research, vasopressin has grown to a potential component as a vasopressor agent of the anesthesiologist's armamentarium in the treatment of cardiac arrest and severe shock states. PMID:21814369

Extracorporeal shock wave lithotripsy (ESWL) of a renal calculus in a liver transplant recipient: report of a severe complication--a case report.

PubMed

Friedersdorff, F; Buckendahl, J; Fuller, T F; Cash, H

2010-11-01

Extracorporeal shock wave lithotripsy (ESWL) has evolved as a standard treatment modality for calculi of the upper urinary tract. Noninvasive ESWL shows rare life-threatening complications. Herein we have reported the case of a liver transplant recipient who developed severe renal hemorrhage after ESWL of a renal calculus. Transfusion of erythrocytes and platelets led to anaphylactic shock with acute renal failure requiring intensive care. The patient fully recovered shortly thereafter and was discharged home with a residual left kidney stone measuring 8 mm. A 55-year-old man with a single left kidney underwent ESWL due to symptomatic left nephrolithiasis. He had undergone successful liver transplantation 11 years earlier. At the time of ESWL his liver functions were normal and his serum creatinine level was 1.3 mg/dL. Two weeks before the treatment a double pigtail ureteral stent was inserted because of a symptomatic left hydronephrosis. Several hours after ESWL treatment the patient complained of left-sided flank pain. An ultrasound revealed a large subcapsular hematoma of the left kidney, which was confirmed using abdominal computed tomography (CT). With the patient being hemodynamically stable, we opted for conservative management. Despite postinterventional complications, the patient made a fast recovery. ESWL is a noninvasive, safe, and efficient method to treat renal calculi. Patients who are at risk for hemorrhage should undergo close postinterventional monitoring, including red blood cell count and renal ultrasound. Copyright © 2010 Elsevier Inc. All rights reserved.

Recanalization after successful occlusion by transcatheter arterial embolization with N-butyl cyanoacrylate for traumatic splenic artery injury.

PubMed

Ishikawa, Masaki; Kakizawa, Hideaki; Yamasaki, Wataru; Date, Syuji; Hieda, Masashi; Kajiwara, Kenji; Awai, Kazuo

2011-12-01

A 70-year-old male with advanced pancreatic cancer went into shock after sustaining a traumatic abdominal injury. Computed tomography (CT) showed a hematoma with extravasation around the pancreas and hemorrhagic ascites. After direct catheterization failed due to angiospasm, the ruptured splenic artery was successfully occluded by transcatheter arterial embolization (TAE) using an N-butyl cyanoacrylate (NBCA)-lipiodol mixture and the patient recovered from shock without complications. A follow-up CT obtained 20 days later showed a recurrent splenic artery pseudoaneurysm without extravasation. A repeat angiogram demonstrated recanalization of the splenic artery and pseudoaneurysm via antegrade. We embolized the recanalized pseudoaneurysm using metallic coils for isolation. Our experience indicates that adequate concentration and volume of the NBCA-lipiodol mixture should be considered depending on the vascular spasm in a patient with hypovolemic shock.

Transarterial embolization for the treatment of massive bleeding in gynecologic and obstetric emergencies: a single center experience.

PubMed

Hongsakul, Keerati; Songjamrat, Apiradee; Rookkapan, Sorracha

2014-08-01

Delayed treatment of the massive bleeding in gynecologic and obstetric conditions can cause high morbidity and mortality. The aim of this study is to assess the angiographic findings and outcomes of transarterial embolization in cases of massive hemorrhage from underlying gynecological and obstetrical conditions. This is a retrospective study of 18 consecutive patients who underwent transarterial embolization of uterine and/or hypogastric arteries due to massive bleeding from gynecological and obstetrical causes from January 2006 to December 2011. The underlying causes of bleeding, angiographic findings, technical success rates, clinical success rates, and complications were evaluated. Massive gynecological and obstetrical bleeding occurred in 12 cases and 6 cases, respectively. Gestational trophoblastic disease was the most common cause of gynecological bleeding. The most common cause of obstetrical hemorrhage was primary post-partum hemorrhage. Tumor stain was the most frequent angiographic finding (11 cases) in the gynecological bleeding group. The most common angiographic findings in obstetrical patients were extravasation (2 cases) and pseudoaneurysm (2 cases). Technical and final clinical success rates were found in all 18 cases and 16 cases. Collateral arterial supply, severe metritis, and unidentified cervical laceration were causes of uncontrolled bleeding. Only minor complications occurred, which included pelvic pain and groin hematoma. Percutaneous transarterial embolization is a highly effective and safe treatment to control massive bleeding in gynecologic and obstetric emergencies.

Hemostatic granules and dressing prepared from formulations of carboxymethyl cellulose, kappa-carrageenan and polyethylene oxide crosslinked by gamma radiation

NASA Astrophysics Data System (ADS)

Barba, Bin Jeremiah D.; Aranilla, Charito T.; Relleve, Lorna S.; Cruz, Veriza Rita C.; Vista, Jeanina Richelle; Abad, Lucille V.

2018-03-01

Uncontrolled hemorrhage remains a persistent problem especially in anatomical areas where compression and tourniquet cannot be applied. Hemostatic agents are materials which can achieve control of bleeding in acute, life-threatening traumatic coagulopathy. In this study, we prepared biocompatible hydrogel-based hemostat crosslinked by ionizing radiation. Granules made from carboxymethyl cellulose and dressing from kappa carrageenan and polyethylene oxide were characterized by FT-IR, SEM, and gel analysis. Gamma radiation with a dose of 25 kGy was used for sterilization process. Stability studies indicate that the products remain effective with a shelf life of up to 18 months based on accelerated aging. Both hemostatic agents were demonstrated to be effective in vitro blood clotting assays showing a low blood clotting index, high platelet adhesion capacity and accelerated clotting time. Hemostat granules and dressing were also used in a femoral artery rat bleeding model where hemorrhage control was achieved in 90 s without compression and resulted in 100% survival rate after a 7 and 14-day observation.

Structure-Property Relationships in Tough, Superabsorbent Thermoplastic Elastomers for Hemorrhage Control

NASA Astrophysics Data System (ADS)

Beyer, Frederick; Bain, Erich; Long, Tyler; Mrozek, Randy; Savage, Alice; Martin, Halie; Dadmun, Mark; Lenhart, Joseph

Between 2001 and 2009, uncontrolled hemorrhaging from major trauma accounted for the deaths of roughly 80% of wounded soldiers with potentially survivable injuries. Modern hemostatic materials are limited in their ability to deliver therapeutic agents, causing tissue damage themselves, or being difficult to remove intact. The goal of this study is to create a mechanically robust polymer that takes up as much as 1000 wt% water in seconds while maintaining sufficient toughness to be removed intact from the wound intact. A thermoplastic elastomer scaffold in which physical crosslinks provide mechanical toughness might provide an appropriate combination of fast swelling and excellent toughness if the matrix material can be engineered to be strongly hydrophilic and swell rapidly. In this work, a commercial SBS triblock copolymer has been modified with poly(acrylic acid) side chains, resulting in materials that are superabsorbent but retain good mechanical properties when saturated. Although SAXS experiments failed to show any significant changes in morphology, even with 800 wt% water uptake, preliminary SANS experiments using selectively deuterated materials and swelling with D2O show significant changes in morphology. Our most recent findings will be presented.

Alcohol Intoxication Impact on Outcome from Traumatic Injury

DTIC Science & Technology

2008-05-01

emergency department. Previously we have demonstrated that ICV choline increased basal MABP (+17%) and produced a similar increase in basal MABP in...alcohol intoxicated. However, ICV choline did not alter the initial % decrease in blood pressure nor did it improve MABP throughout hemorrhagic...shock or fluid resuscitation in alcohol-treated animals. These studies showed that intracerebroventricular (ICV) choline (acetylcholine precursor

Effects of Early Altitude Exposure Following Traumatic Injury and Hemorrhagic Shock

DTIC Science & Technology

2017-06-27

chemokines by multiplex enzyme-linked immunosorbent assay ( ELISA ) (Quansys, Logan, UT), including the following: interleukin 1 alpha and beta (IL...Tissue Cytokine Profiles Fourteen cytokines and chemokines were analyzed from serum and intestinal tissues via multiplex ELISA . There were no...2017-3567, 25 Jul 2017. LIST OF ABBREVIATIONS AND ACRONYMS AE aeromedical evacuation BCA bicinchoninic acid ELISA enzyme-linked immunosorbent

Assessment of renal injury with a clinical dual head lithotriptor delivering 240 shock waves per minute.

PubMed

Handa, Rajash K; McAteer, James A; Evan, Andrew P; Connors, Bret A; Pishchalnikov, Yuri A; Gao, Sujuan

2009-02-01

Lithotriptors with 2 treatment heads deliver shock waves along separate paths. Firing 1 head and then the other in alternating mode has been suggested as a strategy to treat stones twice as rapidly as with conventional shock wave lithotripsy. Because the shock wave rate is known to have a role in shock wave lithotripsy induced injury, and given that treatment using 2 separate shock wave sources exposes more renal tissue to shock wave energy than treatment with a conventional lithotriptor, we assessed renal trauma in pigs following treatment at rapid rate (240 shock waves per minute and 120 shock waves per minute per head) using a Duet lithotriptor (Direx Medical Systems, Petach Tikva, Israel) fired in alternating mode. Eight adult female pigs (Hardin Farms, Danville, Indiana) each were treated with sham shock wave lithotripsy or 2,400 shock waves delivered in alternating mode (1,200 shock waves per head, 120 shock waves per minute per head and 240 shock waves per minute overall at a power level of 10) to the lower renal pole. Renal functional parameters, including glomerular filtration rate and effective renal plasma flow, were determined before and 1 hour after shock wave lithotripsy. The kidneys were perfusion fixed in situ and the hemorrhagic lesion was quantified as a percent of functional renal volume. Shock wave treatment resulted in no significant change in renal function and the response was similar to the functional response seen in sham shock wave treated animals. In 6 pigs treated with alternating mode the renal lesion was small at a mean +/- SEM of 0.22% +/- 0.09% of functional renal volume. Kidney tissue and function were minimally affected by a clinical dose of shock waves delivered in alternating mode (120 shock waves per minute per head and 240 shock waves per minute overall) with a Duet lithotriptor. These observations decrease concern that dual head lithotripsy at a rapid rate is inherently dangerous.

Bone marrow hematopoietic stem cells behavior with or without growth factors in trauma hemorrhagic shock

PubMed Central

Kumar, Manoj; Bhoi, Sanjeev; Mohanty, Sujata; Kamal, Vineet Kumar; Rao, D. N.; Mishra, Pravas; Galwankar, Sagar

2016-01-01

Background: Hemorrhagic shock (HS) is the major leading cause of death after trauma. Up to 50% of early deaths are due to massive hemorrhage. Excessive release of pro-inflammatory cytokine and hypercatecholamine induces hematopoietic progenitor cells (HPCs) apoptosis, leading to multiorgan failure and death. However, still, result remains elusive for hematopoietic stem cells (HSCs) behavior in trauma HS (T/HS). Objectives: Therefore, our aim was to evaluate the in vitro HSCs behavior with or without recombinant human erythropoietin (rhEPO), recombinant human granulocyte macrophage-colony-stimulating factor (rhGM-CSF), recombinant human interleukin-3 (rhIL-3) alone, and combination with rhEPO + rhGM-CSF + rhIL-3 (EG3) in T/HS patients. Methodology: Bone marrow (BM) aspirates (n = 14) were collected from T/HS patients, those survived on day 3. BM cells were cultured for HPCs: Colony-forming unit-erythroid (CFU-E), burst-forming unit-erythroid (BFU-E), and colony-forming unit-granulocyte, monocyte/macrophage colonies growth. HPCs were counted with or without rhEPO, rhGM-CSF, rhIL-3 alone, and combination with EG3 in T/HS patients. Results: BM HSCs growth significantly suppressed in T/HS when compared with control group (P < 0.05). In addition, CFU-E and BFU-E colony growth were increased with additional growth factor (AGF) (rhEPO, rhGM-CSF, and rhIL-3) as compared to baseline (without AGF) (P < 0.05). Conclusion: Suppressed HPCs may be reactivated by addition of erythropoietin, GM-CSF, IL-3 alone and with combination in T/HS. PMID:27722113

Pathologic highlights of dengue hemorrhagic fever in 13 autopsy cases from Myanmar.

PubMed

Aye, Khin Saw; Charngkaew, Komgrid; Win, Ne; Wai, Kyaw Zin; Moe, Kyaw; Punyadee, Nuntaya; Thiemmeca, Somchai; Suttitheptumrong, Aroonroong; Sukpanichnant, Sanya; Prida, Malasit; Halstead, Scott B

2014-06-01

Vascular permeability, thrombocytopenia, liver pathology, complement activation, and altered hemostasis accompanying a febrile disease are the hallmarks of the dengue hemorrhagic fever/dengue shock syndrome, a major arthropod-borne viral disease that causes significant morbidity and mortality throughout tropical countries. We studied tissues from 13 children who died of acute dengue hemorrhagic fever/dengue shock syndrome at the Childrens' Hospital, Yangon, Myanmar. Dengue viral RNA from each of the 4 dengue viruses (DENVs) was detected by reverse transcriptase polymerase chain reaction in 11 cases, and dengue viral proteins (envelope, NS1, or NS3) were detected in 1 or more tissues from all 13 cases. Formalin-fixed and frozen tissues were studied for evidence of virus infection using monoclonal antibodies against DENV structural and nonstructural antigens (E, NS1, and nonsecreting NS3). In the liver, DENV infection occurred in hepatocytes and Kupffer cells but not in endothelial cells. Liver damage was associated with deposition on hepatocytes of complement components of both classical and alternative pathways. Evidence of dengue viral replication was observed in macrophage-like cells in spleens and lymph nodes. No dengue antigens were detected in endothelial cells in any organ. Germinal centers of the spleen and lymph nodes showed a marked reduction in the number of lymphocytes that were replaced by eosinophilic deposits, which contained dengue antigens as well as immunoglobulins, and complement components (C3, C1q, and C9). The latter findings had previously been reported but overlooked as a diagnostic feature. Copyright © 2014 Elsevier Inc. All rights reserved.

A Rare Case: Rupture of Internal Pudendal and Uterine Artery in a Vaginal Delivery.

PubMed

Chughtai, Novera G; Rizvi, Raheela Mohsin

2018-03-01

The management of puerperal hematomas after normal delivery has always been challenging for obstetricians. Vulvar, vulvovaginal, or paravaginal hematomas are common. On the other hand, retroperitoneal hematomas are uncommon and can be life-threatening. The diagnosis of vascular injury is rarely made preoperatively as atonic or traumatic postpartum hemorrhage (PPH), uterine rupture and amniotic fluid embolism are more common differential diagnoses. Injury to internal pudendal and uterine vessels is extremely rare in cases of vaginal delivery and, therefore, the literature on this topic is very scarce. We present a rare case of both internal pudendal and uterine artery rupture in a normal vaginal delivery, which led to massive postpartum hemorrhage. The diagnosis was made on Magnetic Resonance imaging (MRI) and arterial embolization was performed. This case stresses on the need for careful post-delivery monitoring for revealed postpartum hemorrhage. Vascular injury is a rare life-threatening cause of obstetric shock, and active; and timely operative intervention can prevent morbidity and mortality.

Learned helplessness in the rat: effect of response topography in a within-subject design.

PubMed

dos Santos, Cristiano Valerio; Gehm, Tauane; Hunziker, Maria Helena Leite

2011-02-01

Three experiments investigated learned helplessness in rats manipulating response topography within-subject and different intervals between treatment and tests among groups. In Experiment 1, rats previously exposed to inescapable shocks were tested under an escape contingency where either jumping or nose poking was required to terminate shocks; tests were run either 1, 14 or 28 days after treatment. Most rats failed to jump, as expected, but learned to nose poke, regardless of the interval between treatment and tests and order of testing. The same results were observed in male and female rats from a different laboratory (Experiment 2) and despite increased exposure to the escape contingencies using a within-subject design (Experiment 3). Furthermore, no evidence of helplessness reversal was observed, since animals failed to jump even after having learned to nose-poke in a previous test session. These results are not consistent with a learned helplessness hypothesis, which claims that shock (un)controllability is the key variable responsible for the effect. They are nonetheless consistent with the view that inescapable shocks enhance control by irrelevant features of the relationship between the environment and behavior. Copyright © 2010 Elsevier B.V. All rights reserved.

Peripheral Venous Waveform Analysis for Detecting Hemorrhage and Iatrogenic Volume Overload in a Porcine Model.

PubMed

Hocking, Kyle M; Sileshi, Ban; Baudenbacher, Franz J; Boyer, Richard B; Kohorst, Kelly L; Brophy, Colleen M; Eagle, Susan S

2016-10-01

Unrecognized hemorrhage and unguided resuscitation is associated with increased perioperative morbidity and mortality. The authors investigated peripheral venous waveform analysis (PIVA) as a method for quantitating hemorrhage as well as iatrogenic fluid overload during resuscitation. The authors conducted a prospective study on Yorkshire Pigs (n = 8) undergoing hemorrhage, autologous blood return, and administration of balanced crystalloid solution beyond euvolemia. Intra-arterial blood pressure, electrocardiogram, and pulse oximetry were applied to each subject. Peripheral venous pressure was measured continuously through an upper extremity standard peripheral IV catheter and analyzed with LabChart. The primary outcome was comparison of change in the first fundamental frequency (f1) of PIVA with standard and invasive monitoring and shock index (SI). Hemorrhage, return to euvolemia, and iatrogenic fluid overload resulted in significantly non-zero slopes of f1 amplitude. There were no significant differences in heart rate or mean arterial pressure, and a late change in SI. For the detection of hypovolemia the PIVA f1 amplitude change generated an receiver operator curves (ROC) curve with an area under the curve (AUC) of 0.93; heart rate AUC = 0.61; mean arterial pressure AUC = 0.48, and SI AUC = 0.72. For hypervolemia the f1 amplitude generated an ROC curve with an AUC of 0.85, heart rate AUC = 0.62, mean arterial pressure AUC = 0.63, and SI AUC = 0.65. In this study, PIVA demonstrated a greater sensitivity for detecting acute hemorrhage, return to euvolemia, and iatrogenic fluid overload compared with standard monitoring and SI. PIVA may provide a low-cost, minimally invasive monitoring solution for monitoring and resuscitating patients with perioperative hemorrhage.

Hemorrhagic fever of bunyavirus etiology: disease models and progress towards new therapies.

PubMed

Gowen, Brian B; Hickerson, Brady T

2017-03-01

A growing number of bunyaviruses are known to cause viral hemorrhagic fever (VHF), a severe febrile illness which can progress to hypovolemic shock and multi-organ failure and is characterized by hematologic abnormalities and vascular leak. At present, there are no approved vaccines or antiviral therapies to effectively prevent or treat VHF caused by pathogenic bunyaviruses. Advances in the modeling of bunyaviral infections have facilitated efforts towards the development of novel post-exposure prophylactic and therapeutic countermeasures, several of which may some day be approved for human use. Here, we review recent progress in animal models of severe bunyaviral infections essential to this mission, as well as promising antivirals and biologicals that are at various stages of the development process.

Coagulation challenges after severe injury with hemorrhagic shock.

PubMed

Ledgerwood, Anna M; Blaisdell, William

2012-06-01

During the past 50 years, there have been huge changes in the approach to coagulopathic bleeding following the treatment of traumatic hemorrhagic shock (HS). Treatment during the 1960s consisted primarily of physiologic saline (balanced electrolyte solution [BES]) and whole blood supported with sodium bicarbonate for acidosis. Subsequent coagulopathy was assumed to be caused by lack of the labile factors (FV and FVIII) which were then replaced by fresh whole blood. The decade of 1970s saw the implementation of component therapy by the American Blood Banking Association so that HS was treated with BES and packed red blood cells (RBC). A new paradigm had to be learned to determine when and how much fresh frozen plasma (FFP) was needed to restore all coagulation factors. By the end of 1970s, most trauma centers were supplementing BES and RBC with FFP in patients with severe injuries requiring massive transfusion of more than one circulating blood volume. By the 1980s, the use of FFP skyrocketed, creating a crisis for the American Blood Banking Association. This led to a National Institute of Health Consensus Development Conference which concluded that FFP should be given to only those patients who had a documented coagulopathy as evidenced by a prolongation of the prothrombin time and the partial thromboplastin time. Restriction of FFP replacement to patients with proven coagulopathy after treatment for HS led to postoperative bleeding which was sometimes fatal. During the 1990s, uncontrolled clinical studies and rigorously controlled animal studies showed that FFP should be administered before the onset of proven coagulopathy with prolongation of the prothrombin time and partial thromboplastin time. Later during the 1990s, recombinant-activated factor VII (FVIIa) was purported to provide quicker hemostasis in patients treated with HS. The efficacy of FVIIa supplementation is still being assessed. During the 2010s, the military surgeons promoted the use of a hemostatic regimen which consists of platelets, RBC, and FFP in a 1:1:1 ratio. This recommendation is still being assessed with different authors reporting benefits and detriments. Throughout these years, an unusual entity of disseminated intravascular coagulation (DIC) was known to complicate the resuscitation of seriously injured patients with HS. This syndrome was typically seen after treatment of HS and was associated with abnormal bleeding plus respiratory failure and renal failure thought to be caused by a combination of micro- and macrothromboses. The early studies suggested that the best therapy for breaking this viscous cycle of bleeding and intravascular coagulation was by infusing fresh whole blood. The theoretical benefits of administering heparin to prevent the thrombosis and epsilon-aminocaproic acid to enhance lysis have not proven beneficial. DIC is also seen in association with toxic exposures, including snake bites. Epsilon-aminocaproic acid may be beneficial in that setting. Many of the intricate understandings of DIC remain elusive and are still being studied. Copyright © 2012 by Lippincott Williams & Wilkins.

[The effect of the membrane attack complex C5b-9 on liver cells during traumatic hemorrhagic shock in rat].

PubMed

Zhao, Zhi-ling; Cao, Shu-hua; Wang, Yong-qiang

2011-03-01

To observe whether the membrane attack complex C5b-9 would accumulate in the rats' liver after receiving the assault of traumatic hemorrhagic shock, and whether the membrane attack complex deals an impact on liver apoptosis. Fifty male healthy Wistar rats were randomly divided into five groups: normal group, 1, 3, 6, 24 hour model groups. The model of traumatic hemorrhagic shock was reproduced by withdrawal of blood from carotid artery after a bone fracture till the blood pressure lowered to 40 mm Hg (1 mm Hg=0.133 kPa). Plasma membrane attack complex C5b-9 concentration was assayed using enzyme linked immunoadsorbent assay. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in blood was determined by Rate method. Immunohistochemistry was used to detect C5b-9 deposition in the liver. Apoptosis of liver cells was then detected by the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay. The pathological changes in paraffin sections stained with hematoxylin eosin (HE) were observed under light microscope. A small amount of C5b 9 in plasma was found in normal group, and the values (ng/L) of 1, 3, 6 hour models were significantly higher than those of the normal group (272.91 ± 9.56, 192.01 ± 9.04, 156.78 ± 8.37 vs. 25.98 ± 5.87, all <0.05 ). ALT (U/L) in 3 hour model group and AST (U/L) in 1 hour model group were increased significantly (92.90 ± 8.83, 264.83 ± 31.4), peaked at 24 hours (184.30 ± 12.98, 647.36 ± 60.02), and there was significant difference compared with normal group (38.75 ± 5.40, 66.69 ± 19.95, all P <0.05). In the normal group and the 1 hour and 6 hour model groups, no C5b 9 was found in liver, but in the 3 hour model group a large number of liver parenchymal cells in the portal area were found to contain C5b 9 22.60 ± 1.06), however the number decreased significantly in the 24 hour model (2.20 ± 0.60, P<0.05). In normal group there was no apoptotic cell, and in 1, 6, 24 hour model groups there were scattered apoptotic cells (1.20 ± 0.25, 5.60 ± 0.37, 1.60 ± 0.26). In the 3 hour model group apoptosis of hepatic cells around the central vein was increased to the peak (20.60 ± 0.47), and there was significant difference compared with other groups (all P <0.05) . In the model groups the liver cells became edematous, and the integrity of the membrane was lost, and some cells were even lysed.The pathological damage is most serious in 24 hour model group. The membrane attack complex C5b-9 insulted the rats' liver after a traumatic hemorrhagic shock, and apoptosis of hepatic cells and the content of C5b-9 peaked in 3 hour model , though they do not occur in the same site. A low level of C5b-9 in blood 3 hours after shock predict a poor prognosis.

A Rare Case of Gastric Ulcer Penetrating the Pancreas that was Successfully Managed by Conservative Therapy.

PubMed

Shibukawa, Narihiro; Ouchi, Shohei; Wakamatsu, Shuji; Wakahara, Yuhei; Tatsumi, Nobuyuki; Kaneko, Akira

2017-09-01

A 62-year-old woman was admitted to our hospital with septic shock due to left submandibular osteomyelitis and cellulitis. Her condition improved following tooth extraction, drainage, and the administration of antibiotics. However, on the 4th day of hospitalization, she went into hemorrhagic shock after defecating a massive tarry stool. Emergency esophagogastroduodenoscopy (EGD) was performed. We found a giant ulcer at the antral greater curvature of the stomach. Computed tomography (CT) revealed that the gastric ulcer had penetrated the pancreas. She had no signs of peritonitis and had a bad general condition. She was therefore managed solely by conservative therapy. She recovered within days.

Adult Wilms tumor: Case report.

PubMed

Morabito, V; Guglielmo, N; Melandro, F; Mazzesi, G; Alesini, F; Bosco, S; Berloco, P B

2015-01-01

Wilms tumor (WT) occurs infrequently in adults. Even rarer is adult WT with extension by direct intravascular spread into the right side of the heart. The present report describes a WT with intracaval and intracardiac extension in a 38-year-young man. In addition, thrombus extension above the infrahepatic IVC represents a major technical topic for surgeons because of the possible occurrence of uncontrollable hemorrhages and tumor fragmentation. We report the results of a surgical approach to caval thrombosis including the isolation of the IVC from the liver as routinely performed during liver harvesting. The morphologic and immune-histochemical findings confirmed the diagnosis. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Aedes aegypti in south Vietnam: ecology, genetic structure, vectorial competence and resistance to insecticides.

PubMed

Huber, Karine; Le Loan, Luu; Hoang, Tran Huu; Tien, Tran Khanh; Rodhain, François; Failloux, Anna-Bella

2003-03-01

In Vietnam, dengue hemorrhagic fever has been detected since the 1950s. In Southeast Asia, urban centers expanded rapidly in an uncontrolled and unplanned way. The Aedes aegypti populations and dengue viruses thrived in these new ecological and demographic settings. The result of these changes was a greatly extended geographic distribution, increased densities of Ae. aegypti and the maintenance of the four dengue serotypes leading to a dramatic increase in dengue transmission. To assess the role of the vector in the changing pattern of the disease in Southeast Asia, we studied the ecology of Ae. aegypti, genetic differentiation, variability in competence as a vector for dengue 2 virus, and resistance to insecticides.

Optimization of Lyophilized Plasma for Use in Combat Casualties

DTIC Science & Technology

2013-01-21

SD. (Fib: fibrinogen, FII: Factor II, FV: Factor V, FVII : Factor VII, FVIII: Factor VIII, FIX: Factor IX, FX: Factor X, FXI: Factor XI, FXII...coagulation factor activity. Twenty swine were anesthetized and subjected to a validated model of polytrauma and hemorrhagic shock. They were...to assess inflammatory markers. Major Findings: 50%LP had higher electrolyte concentrations, osmolarity, and increased coagulation factor activity

Early Treatment in Shock. Addendum

DTIC Science & Technology

2012-08-01

from gardenia root (Gardenia jasminoides Ellis). It is com- monly sold in the United States as an herbal supplement . In terms of crocetin’s fundamental...but results of 14 the available literature collectively allow the conclusion that L-arginine supplementation 15 can be beneficial in ameliorating the...were designed to test two 19 hypotheses. First, L-arginine supplementation during resuscitation will improve survival 20 from lethal hemorrhagic

The Inflammatory Sequelae of Aortic Balloon Occlusion in Hemorrhagic Shock

DTIC Science & Technology

2014-04-13

circulating volume) and 30, 60, or 90 min of REBOA. Data are plotted as mean value. (A) MAP (B) SVR (C) CO. j o u r n a l o f s u r g i c a l r e s...could be included within an extracorporeal circuit merged with a REBOA system. Equally, a perfusion capable REBOA catheter [36] could be used to

Emergency Preservation and Resuscitation for Cardiac Arrest from Trauma (EPR-CAT)

DTIC Science & Technology

2014-12-01

SUBJECT TERMS Trauma, hemorrhagic shock, cardiac arrest, cardiopulmonary resuscitation, hypothermia 16. SECURITY CLASSIFICATION OF: 17...EPR) was developed to rapidly preserve the organism during ischemia, using hypothermia , drugs, and fluids, to “buy time” for transport and...resuscitative surgery. The purpose of this study is to test the feasibility of rapidly inducing profound hypothermia (< 10oC) with an aortic flush in trauma

Determining the Cardiovascular Effect of Partial versus Complete REBOA in a Porcine (Sus scrofa) Model of Hemorrhagic Shock.

DTIC Science & Technology

2018-03-09

all information . Use additional pages if necessary.) PROTOCOL #: FDG20170005A DATE: 9 March 2018 PROTOCOL TITLE: Determining...Investigator Attachments: Attachment 1: Defense Technical Information Center (DTIC) Abstract Submission (Mandatory) 4 FDG20170005A...Attachment 1 Defense Technical Information Center (DTIC) Abstract Submission This abstract requires a brief (no more than 200 words) factual summary of the

[EBOLA HEMORRHAGIC FEVER; ETIOLOGY, EPIDEMIOLOGY, PATHOGENESIS, AND CLINICAL SYMPTOMS].

PubMed

Zhdanov, K W; Zakharenko, S M; Kovalenko, A N; Semenov, A V; Fusin, A Ya

2015-01-01

The data on the prevalence of disease caused by Ebola virus, biological features of its pathogen, character of the epidemiological process, pathogenesis and clinical symptoms are presented. The disease is characterized by suppression of protective immunological mechanisms and systemic inflammatory reaction accounting for the lesions of vascular endothelium, hemostatic and immune systems. It eventually leads to polyorgan insufficiency and severe shock. Lethality amounts to 50%.

The Effect of Hypobaria on Muscle Inflammation and Regeneration After Injury and Hemorrhagic Shock

DTIC Science & Technology

2017-08-01

including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and...significant bleeding. This situation may affect recovery following combat injuries, especially if wounded service members are traveling from Asia to... time from the battlefield to a medical care facility. While injury recovery in low oxygen environments requires further analysis, military operations

Feasibility Study of Pharmacological Treatment to Reduce Morbidity and Mortality After Brain Injury

DTIC Science & Technology

1991-04-02

1976). Long-term effects of electroconvulsive shock therapy on synthesis, turnover and uptake of brain monoamines. Psvchopharmacol. 49: 179-185. 30...tissue, and relieving concomitant effects, such as hemorrhage, edema, or elevated intracranial pressure. These therapies have not resulted in...and antagonists, and 3) electroconvulsive seizures on funztional recovery from hemiplegia. In addition, the extent of cortical neci otic cavitation was

Diagnostic and Predictive Values of Thirst, Angiotensin II, and Vasopressin During Trauma Resuscitation

DTIC Science & Technology

2010-09-01

and plasma AVP and AT2 levels across a broader spectrum of hemorrhagic shock severity may be warranted. The authors wish to thank the medical, nursing ...301. 2. Olsson K. Central control of vasopressin release and thirst. Acta Paediatr Scand Suppl. 1983;305:36–9. Pr eh os p E m er g C ar e D ow nl oa

A SOF Damage Control Resuscitation Cocktail

DTIC Science & Technology

2015-05-01

include Hextend for volume resuscitation and tissue perfusion, fibrinogen concentrate for hemostasis, and tranexamic acid for hemostasis. These...for hemostasis, and tranexamic acid for hemostasis. These components are tested in a combat-relevant swine polytrauma model of hemorrhagic shock with...HexVasoCntl HexVasoAlb Ctrl 4 4 would not allow adequate blood loss from the aortic tear, preventing testing of fibrinogen and tranexamic acid as

Freeze-dried plasma enhances clot formation and inhibits fibrinolysis in the presence of tissue plasminogen activator similar to pooled liquid plasma.

PubMed

Huebner, Benjamin R; Moore, Ernest E; Moore, Hunter B; Sauaia, Angela; Stettler, Gregory; Dzieciatkowska, Monika; Hansen, Kirk; Banerjee, Anirban; Silliman, Christopher C

2017-08-01

Systemic hyperfibrinolysis is an integral part of trauma-induced coagulopathy associated with uncontrolled bleeding. Recent data suggest that plasma-first resuscitation attenuates hyperfibrinolysis; however, the availability, transport, storage, and administration of plasma in austere environments remain challenging and have limited its use. Freeze-dried plasma (FDP) is a potential alternative due to ease of storage, longer shelf life, and efficient reconstitution. FDP potentially enhances clot formation and resists breakdown better than normal saline (NS) and albumin and similar to liquid plasma. Healthy volunteers underwent citrated blood draw followed by 50% dilution with NS, albumin, pooled plasma (PP), or pooled freeze-dried plasma (pFDP). Citrated native and tissue plasminogen activator (t-PA)-challenge (75 ng/mL) thrombelastography were done. Proteins in PP, pFDP, and albumin were analyzed by mass spectroscopy. pFDP and PP had superior clot-formation rates (angle) and clot strength (maximum amplitude) compared with NS and albumin in t-PA-challenge thrombelastographies (angle: pFDP, 67.9 degrees; PP, 67.8 degrees; NS, 40.6 degrees; albumin, 35.8 degrees; maximum amplitude: pFDP, 62.4 mm; PP, 63.5 mm; NS, 44.8 mm; albumin, 41.1 mm). NS and albumin dilution increased susceptibility to t-PA-induced hyperfibrinolysis compared with pFDP and PP (NS, 62.4%; albumin, 62.6%; PP, 8.5%; pFDP, 6.7%). pFDP was similar to PP in the attenuation of t-PA-induced fibrinolysis. Most proteins (97%) were conserved during the freeze-dry process, with higher levels in 12% of pFDP proteins compared with PP. pFDP enhances clot formation and attenuates hyperfibrinolysis better than NS and albumin and is a potential alternative to plasma resuscitation in the treatment of hemorrhagic shock. © 2017 AABB.

Mesenchymal Stem Cells Increase T-Regulatory Cells and Improve Healing Following Trauma and Hemorrhagic Shock (MSCs Increase Tregs and Improve Healing After T/HS)

PubMed Central

Gore, Amy V.; Bible, Letitia E.; Song, Kimberly; Livingston, David H.; Mohr, Alicia M.; Sifri, Ziad C.

2015-01-01

Background Rodent lungs undergo full histologic recovery within one week following unilateral lung contusion (LC). However, when LC is followed by hemorrhagic shock (HS), healing is impaired. We hypothesize that the intravenous administration of mesenchymal stem cells (MSC) to animals undergoing combined LC followed by HS (LCHS) will improve wound healing. Methods Male Sprague-Dawley rats (n=5-6/group) were subjected to LCHS with or without the injection of a single iv dose of 5 × 106 MSCs following return of shed blood after HS. Rats were sacrificed seven days following injury. Flow cytometry was used to determine the T regulatory (Treg) cell population in peripheral blood (PB). Lung histology was graded using a well-established lung injury score (LIS). Components of the LIS include average inflammatory cells/high power field (hpf) over 30 fields, interstitial edema, pulmonary edema, and alveolar integrity with total scores ranging from 0-11. Data analyzed by ANOVA followed by Tukey's multiple comparison test, expressed as mean ± SD. p<0.05 considered significant. Results Seven days following isolated LC animals demonstrate lung healing with a LIS unchanged from naive. The addition of HS results in a persistently elevated LIS score, whereas addition of MSC to LCHS decreased the LIS score back to naïve levels. The change in LIS was driven by a significant decrease in edema scores. In rats undergoing LC alone, 10.5 ± 3.3% of CD4+ cells were Tregs. The addition of HS caused no significant change in Treg population (9.3±0.7%), whereas LCHS+MSC significantly increased the population to 18.2±6.8% in PB (p<0.05 vs LCHS). Conclusion Impaired wound healing following trauma and hemorrhagic shock is improved by a single dose of MSCs given immediately after injury. This enhanced healing is associated with an increase in the T regulatory cell population and a significant decrease in lung edema score as compared to animals undergoing LCHS. Further study into the role of Tregs in MSC-mediated wound healing is warranted. PMID:26091313

The flow dependency of Tie2 expression in endotoxemia.

PubMed

Kurniati, Neng F; Jongman, Rianne M; vom Hagen, Franziska; Spokes, Katherine C; Moser, Jill; Regan, Erzsébet Ravasz; Krenning, Guido; Moonen, Jan-Renier A J; Harmsen, Martin C; Struys, Michel M R F; Hammes, Hans-Peter; Zijlstra, Jan G; Aird, William C; Heeringa, Peter; Molema, Grietje; van Meurs, Matijs

2013-07-01

Tie2 is predominantly expressed by endothelial cells and is involved in vascular integrity control during sepsis. Changes in Tie2 expression during sepsis development may contribute to microvascular dysfunction. Understanding the kinetics and molecular basis of these changes may assist in the development of therapeutic intervention to counteract microvascular dysfunction. To investigate the molecular mechanisms underlying the changes in Tie2 expression upon lipopolysaccharide (LPS) challenge. Studies were performed in LPS and pro-inflammatory cytokine challenged mice as well as in mice subjected to hemorrhagic shock, primary endothelial cells were used for in vitro experiments in static and flow conditions. Eight hours after LPS challenge, Tie2 mRNA loss was observed in all major organs, while loss of Tie2 protein was predominantly observed in lungs and kidneys, in the capillaries. A similar loss could be induced by secondary cytokines TNF-α and IL-1β. Ang2 protein administration did not affect Tie2 protein expression nor was Tie2 protein rescued in LPS-challenged Ang2-deficient mice, excluding a major role for Ang2 in Tie2 down regulation. In vitro, endothelial loss of Tie2 was observed upon lowering of shear stress, not upon LPS and TNF-α stimulation, suggesting that inflammation related haemodynamic changes play a major role in loss of Tie2 in vivo, as also hemorrhagic shock induced Tie2 mRNA loss. In vitro, this loss was partially counteracted by pre-incubation with a pharmacologically NF-кB inhibitor (BAY11-7082), an effect further substantiated in vivo by pre-treatment of mice with the NF-кB inhibitor prior to the inflammatory challenge. Microvascular bed specific loss of Tie2 mRNA and protein in vivo upon LPS, TNFα, IL-1β challenge, as well as in response to hemorrhagic shock, is likely an indirect effect caused by a change in endothelial shear stress. This loss of Tie2 mRNA, but not Tie2 protein, induced by TNFα exposure was shown to be controlled by NF-кB signaling. Drugs aiming at restoring vascular integrity in sepsis could focus on preventing the Tie2 loss.

Resveratrol ameliorates mitochondrial dysfunction but increases the risk of hypoglycemia following hemorrhagic shock.

PubMed

Wang, Hao; Guan, Yuxia; Widlund, Anne Lykkegaard; Becker, Lance B; Baur, Joseph A; Reilly, Patrick M; Sims, Carrie A

2014-12-01

Hemorrhagic shock (HS) may contribute to organ failure, by profoundly altering mitochondrial function. Resveratrol (RSV), a naturally occurring polyphenol, has been shown to promote mitochondrial function and regulate glucose homeostasis in diabetes. We hypothesized that RSV during resuscitation would ameliorate HS-induced mitochondrial dysfunction and improve hyperglycemia following acute blood loss. With the use a decompensated HS model, male Long-Evans rats (n = 6 per group) were resuscitated with lactated Ringer's solution with or without RSV (30 mg/kg) and were killed before hemorrhage (sham), at severe shock, following resuscitation, and 18 hours after resuscitation. At each time point, the liver and kidney mitochondria were isolated to assess individual respiratory complexes (CI, CII, and CIV) and the production of reactive oxygen species (ROS). Blood samples were assayed for glucose, insulin, corticosterone, total glucagon-like peptide (GLP-1), glucagon, and serum cytokine levels. The Homeostatic Model Assessment-Insulin Resistance index was used to quantify insulin resistance. RSV supplementation following HS significantly improved mitochondrial function and decreased mitochondrial ROS production in both liver and kidney. RSV-treated animals had significantly lower blood glucose levels following resuscitation when compared with sham animals (116.0 ± 20.2 mg/dL vs. 227.7 ± 8.3 mg/dL, p < 0.05) or those resuscitated with lactated Ringer's solution (116.0 ± 20.2 mg/dL vs. 359.0 ± 79.5 mg/dL, p < 0.05). RSV supplementation was associated with significantly decreased plasma insulin levels (1.0 ± 0.4 ng/mL vs. 6.5 ± 3.7 ng/mL, p < 0.05), increased total GLP-1 levels (385.8 ± 56.6 ng/mL vs. 187.3 ± 11.1 ng/mL, p < 0.05), and a lower natural Log Homeostatic Model Assessment-Insulin Resistance index (1.30 ± 0.42 vs. 4.18 ± 0.68, p < 0.05) but had minimal effect on plasma corticosterone, glucagon, or cytokine levels. Resuscitation with RSV restores mitochondrial function and decreases insulin resistance but may be associated with increased hypoglycemia. The observed antiglycemic effects of RSV may be mediated by decreased mitochondrial ROS and increased GLP-1 secretion.

Protective Effect of Tropisetron on Rodent Hepatic Injury after Trauma-Hemorrhagic Shock through P38 MAPK-Dependent Hemeoxygenase-1 Expression

PubMed Central

Hwang, Tsong-Long; Tsai, Yung-Fong

2012-01-01

Tropisetron can decrease inflammatory cell responses and alleviate organ damage caused by trauma-hemorrhage, but the mechanism of these effects remains unknown. The p38 mitogen-activated protein kinase/hemeoxygenase-1 (p38 MAPK/HO-1) pathway exerts anti-inflammatory effects on different tissues. The aim of this study was to investigate whether p38 MAPK/HO-1 plays any role in the tropisetron-mediated attenuation of hepatic injury after trauma-hemorrhage. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35–40 mmHg for 90 min), followed by fluid resuscitation. During resuscitation, several treatment regimens were administered: four doses of tropisetron alone (0.1, 0.3, 1, 3 mg/kg body weight), or a single dose of tropisetron (1 mg/kg body weight) with and without a p38 MAPK inhibitor (SB-203580, 2 mg/kg body weight) or HO antagonist (chromium-mesoporphyrin, 2.5 mg/kg body weight). Various parameters were measured, and the animals were sacrificed at 24 h post-resuscitation. The results showed that trauma-hemorrhage increased the following parameters: plasma concentrations of aspartate (AST) and alanine aminotransferases (ALT), hepatic myeloperoxidase (MPO) activity, and levels of cytokine-induced neutrophil chemoattractant-1 and -3 (CINC-1 and CINC-3), intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein-1α (MIP-1α). These parameters were significantly improved in the tropisetron-treated rats subjected to trauma-hemorrhage. Tropisetron treatment also increased hepatic p38 MAPK and HO-1 expression compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of SB-203580 or chromium-mesoporphyrin with tropisetron abolished the tropisetron-induced beneficial effects on the above parameters and hepatic injury. These results suggest that the protective effect of tropisetron administration on alleviation of hepatic injury after trauma-hemorrhage is likely mediated through p38 MAPK-dependent HO-1 expression. PMID:23285267

Protective effect of tropisetron on rodent hepatic injury after trauma-hemorrhagic shock through P38 MAPK-dependent hemeoxygenase-1 expression.

PubMed

Liu, Fu-Chao; Yu, Huang-Ping; Hwang, Tsong-Long; Tsai, Yung-Fong

2012-01-01

Tropisetron can decrease inflammatory cell responses and alleviate organ damage caused by trauma-hemorrhage, but the mechanism of these effects remains unknown. The p38 mitogen-activated protein kinase/hemeoxygenase-1 (p38 MAPK/HO-1) pathway exerts anti-inflammatory effects on different tissues. The aim of this study was to investigate whether p38 MAPK/HO-1 plays any role in the tropisetron-mediated attenuation of hepatic injury after trauma-hemorrhage. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35-40 mmHg for 90 min), followed by fluid resuscitation. During resuscitation, several treatment regimens were administered: four doses of tropisetron alone (0.1, 0.3, 1, 3 mg/kg body weight), or a single dose of tropisetron (1 mg/kg body weight) with and without a p38 MAPK inhibitor (SB-203580, 2 mg/kg body weight) or HO antagonist (chromium-mesoporphyrin, 2.5 mg/kg body weight). Various parameters were measured, and the animals were sacrificed at 24 h post-resuscitation. The results showed that trauma-hemorrhage increased the following parameters: plasma concentrations of aspartate (AST) and alanine aminotransferases (ALT), hepatic myeloperoxidase (MPO) activity, and levels of cytokine-induced neutrophil chemoattractant-1 and -3 (CINC-1 and CINC-3), intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein-1α (MIP-1α). These parameters were significantly improved in the tropisetron-treated rats subjected to trauma-hemorrhage. Tropisetron treatment also increased hepatic p38 MAPK and HO-1 expression compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of SB-203580 or chromium-mesoporphyrin with tropisetron abolished the tropisetron-induced beneficial effects on the above parameters and hepatic injury. These results suggest that the protective effect of tropisetron administration on alleviation of hepatic injury after trauma-hemorrhage is likely mediated through p38 MAPK-dependent HO-1 expression.

Massive retroperitoneal haemorrhage after extracorporeal shock wave lithotripsy (ESWL).

PubMed

Inoue, Hiromasa; Kamphausen, Thomas; Bajanowski, Thomas; Trübner, Kurt

2011-01-01

A 76-year-old male suffering from nephrolithiasis developed a shock syndrome 5 days after extracorporal shock wave lithotripsy (ESWL). CT scan of the abdomen showed massive haemorrhage around the right kidney. Although nephrectomy was performed immediately, the haemorrhage could not be controlled. Numerous units of erythrocytes were transfused, but the patient died. The autopsy revealed massive retroperitoneal haemorrhage around the right kidney. The kidney showed a subcapsular haematoma and a rupture of the capsule. The right renal artery was dissected. The inferior vena cava was lacerated. Accordingly, a hemorrhagic shock as the cause of death was determined, which might mainly have resulted from the laceration of the inferior vena cava due to ESWL. ESWL seems to be a relatively non-invasive modality, but one of its severe complications is perirenal hematoma. The injuries of the blood vessels might have been caused by excessive shock waves. Subsequently, anticoagulation therapy had been resumed 3 days after EWSL, which might have triggered the haemorrhage. Physicians should note that a haemorrhage after an ESWL can occur and they should pay attention to the postoperative management in aged individuals especially when they are under anticoagulation therapy.

Direct peritoneal resuscitation improves obesity-induced hepatic dysfunction after trauma.

PubMed

Matheson, Paul J; Franklin, Glen A; Hurt, Ryan T; Downard, Cynthia D; Smith, Jason W; Garrison, Richard N

2012-04-01

The metabolic syndrome and associated fatty liver disease are thought to contribute to poor outcomes in trauma patients. Experimentally, obesity compromises liver blood flow. We sought to correlate the effect of obesity, injury severity, and liver dysfunction with trauma outcomes. We hypothesized that obesity-related liver dysfunction could be mitigated with the novel technique of adjunctive direct peritoneal resuscitation (DPR). This study has clinical and experimental arms. The clinical study was a case-controlled retrospective analysis of ICU trauma patients (n = 72 obese, n = 187 nonobese). The experimental study was a hemorrhagic shock model in obese rats to assess the effect of DPR on liver blood flow, liver function, and inflammatory mediators. In trauma patients, univariate and multivariate analyses demonstrated increasing mortality (p < 0.05), septic complications (p < 0.05), liver dysfunction (p < 0.001), and renal impairment (p < 0.05) with increasing body mass index and injury severity score. Obesity in rats impairs liver blood flow, liver function, renal function, and inflammation (interleukin [IL]-1β, IL-6, high mobility group protein B1[HMGB-1]). The addition of DPR to shock resuscitation restores liver blood flow, improves organ function, and reverses the systemic proinflammatory response. Our clinical review substantiates that obesity worsens trauma outcomes regardless of injury severity. Obesity-related liver and renal dysfunction is aggravated by injury severity. In an obese rat model of resuscitated hemorrhagic shock, the addition of DPR abrogates trauma-induced liver, renal, and inflammatory responses. We conclude that the addition of DPR to the clinical resuscitation regimen will benefit the obese trauma patient. Published by Elsevier Inc.

The superoxide dismutase (SOD)-mimic manganese-deferoxamine (Mn-DFO) improves survival following hemorrhagic and endotoxic shock

DOE Office of Scientific and Technical Information (OSTI.GOV)

de Garavilla, L.; Chermak, T.; Valentine, H.L.

1990-02-26

The novel, low-molecular weight, organo-metallic complex Mn-DFO functions in vitro as an SOD-mimic effectively dismutating the superoxide radical. Oxygen-derived free radicals appear to be involved in the pathology of both endotoxic (ENDO) and hemorrhagic (HEM) shock whereby treatment with SOD is associated with improvements in survival. Therefore, the following models were utilized to evaluate the in vivo activity of Mn-DFO. Male rats (350-450g) were anesthetized with ketamine (100mg/kg, ip) and subjected to HEM hypotension by withdrawing approximately 40% of the animals' blood volume over a 10 minute period. MABP was maintained constant at 40mmHg for 60 minutes, followed by completemore » autoreinfusion. Survival was reduced to 20% in the control group at 24 hour post-reinfusion. A single post-shock dose of Mn-DFO (10mg/kg, iv) more than doubled the survival rate for up to 24 hour post-reinfusion as compared to control. Female mice (CFmal and-1, 20-25g) were challenged with 500ug of ENDO and 0.8ug of actinomycin/animal and dosed 1 hour pre and post with Mn-DFO (30mg/kg/dose, iv). Survival improved from 60% in the control group to 100% in the Mn-DFO group at 18 hours post ENDO challenge. Using a multiple dosing regimen, Mn-DFO significantly improved survival for up to 48 hours post-ENDO. Thus, unlike other SOD-mimics, Mn-DFO appears to exhibit in vivo activity.« less

Hyperoxygenated hydrogen-rich solution suppresses shock- and resuscitation-induced liver injury.

PubMed

Dang, Yangjie; Liu, Ting; Mei, Xiaopeng; Meng, Xiangzhong; Gou, Xingchun; Deng, Bin; Xu, Hao; Xu, Lixian

2017-12-01

It is not known whether simultaneous delivery of hydrogen and oxygen can reduce injury caused by hemorrhagic shock and resuscitation (HSR). This study investigated the therapeutic potential of hyperoxygenated hydrogen-rich solution (HHOS), a combined hydrogen/oxygen carrier, in a rat model of HSR-induced liver injury. Rats (n = 60) were randomly divided into 5 groups (n = 6 per group at each time point). One group underwent sham operation, and the others were subjected to severe hemorrhagic shock and then treated with lactated Ringer's solution (LRS), hydrogen-rich solution, hyperoxygenated solution, or HHOS. At 2 and 6 h after resuscitation, blood samples (n = 6) were collected from the femoral artery and serum concentrations of alanine aminotransferase and aspartate aminotransferase (AST) were measured. Rats were then sacrificed, and histopathological changes in the liver were evaluated by quantifying the percentage of apoptotic cells by caspase-3 immunohistochemistry and terminal deoxynucleotidyl transferase dUTP nick-end labeling. Inflammation was assessed by assessing malondialdehyde content and tumor necrosis factor-α, and interleukin (IL)-6 expression. Compared to lactated Ringer's solution, hydrogen-rich solution, or hyperoxygenated solution groups, serum AST and alanine aminotransferase levels and IL-6, tumor necrosis factor-α, and malondialdehyde expression in liver tissue were decreased by HHOS treatment. The number of caspase-3- and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells was decreased (P < 0.05) by HHOS treatment, 2 and 6 h after resuscitation. HHOS has protective effects against liver injury in a rat model of HSR. Copyright © 2017 Elsevier Inc. All rights reserved.

The redox status of experimental hemorrhagic shock as measured by cyclic voltammetry.

PubMed

Mittal, Anubhav; Göke, Friederike; Flint, Richard; Loveday, Benjamin P T; Thompson, Nichola; Delahunt, Brett; Kilmartin, Paul A; Cooper, Garth J S; MacDonald, Julia; Hickey, Anthony; Windsor, John A; Phillips, Anthony R J

2010-05-01

Hemorrhagic shock (HS) leads to reactive oxygen species production. However, clinicians do not have access to bedside measurements of the redox status during HS. Cyclic voltammetry (CyV) is a simple electrochemical method of measuring redox status. The aims of this study were to 1) report the first application of cyclic voltammetry to measure the acute changes in serum redox status after HS, 2) to contrast it with another severe systemic disease with a different redox pathology (acute pancreatitis [AP]), and 3) to describe the response of CyV over time in a resolving model of AP. In the acute study, 24 male Wistar rats were randomized into three groups: groups 1 (control), 2 (AP), and 3 (HS). In the time-course study, 28 rats were randomized to a sham-control as well as 6 and 24 h post-AP cohorts, respectively.Cyclic voltammetry was performed using a three-electrode system. In the acute study, the first and second voltammetric peaks increased significantly in HS. In contrast, within the AP group, only the first voltammetric peak showed a significant increase. The first voltammetric peak correlated with plasma protein carbonyls (PCs) and with thiobarbituric acid-reactive substances, whereas the second voltammetric peak correlated positively with plasma protein carbonyls. In the second study, the first voltammetric peak correlated with physiological improvements. Here, we showed that serum CyV could respond to the serum redox change in HS and AP. Cyclic voltammetry warrants evaluation as a potential real-time beside measure of a patient's redox status during shock.

Shock Index Correlates with Extravasation on Angiographs of Gastrointestinal Hemorrhage: A Logistics Regression Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakasone, Yutaka, E-mail: n-yutaka@cd5.so-net.ne.jp; Ikeda, Osamu; Yamashita, Yasuyuki

We applied multivariate analysis to the clinical findings in patients with acute gastrointestinal (GI) hemorrhage and compared the relationship between these findings and angiographic evidence of extravasation. Our study population consisted of 46 patients with acute GI bleeding. They were divided into two groups. In group 1 we retrospectively analyzed 41 angiograms obtained in 29 patients (age range, 25-91 years; average, 71 years). Their clinical findings including the shock index (SI), diastolic blood pressure, hemoglobin, platelet counts, and age, which were quantitatively analyzed. In group 2, consisting of 17 patients (age range, 21-78 years; average, 60 years), we prospectively appliedmore » statistical analysis by a logistics regression model to their clinical findings and then assessed 21 angiograms obtained in these patients to determine whether our model was useful for predicting the presence of angiographic evidence of extravasation. On 18 of 41 (43.9%) angiograms in group 1 there was evidence of extravasation; in 3 patients it was demonstrated only by selective angiography. Factors significantly associated with angiographic visualization of extravasation were the SI and patient age. For differentiation between cases with and cases without angiographic evidence of extravasation, the maximum cutoff point was between 0.51 and 0.0.53. Of the 21 angiograms obtained in group 2, 13 (61.9%) showed evidence of extravasation; in 1 patient it was demonstrated only on selective angiograms. We found that in 90% of the cases, the prospective application of our model correctly predicted the angiographically confirmed presence or absence of extravasation. We conclude that in patients with GI hemorrhage, angiographic visualization of extravasation is associated with the pre-embolization SI. Patients with a high SI value should undergo study to facilitate optimal treatment planning.« less

Severe progressive scoliosis due to huge subcutaneous cavernous hemangioma: A case report

PubMed Central

2011-01-01

Cavernous hemangioma consists mainly of congenital vascular malformations present before birth and gradually increasing in size with skeletal growth. A small number of patients with cavernous hemangioma develop scoliosis, and surgical treatment for the scoliosis in such cases has not been reported to date. Here we report a 12-year-old male patient with severe progressive scoliosis due to a huge subcutaneous cavernous hemangioma, who underwent posterior correction and fusion surgery. Upon referral to our department, radiographs revealed a scoliosis of 85° at T6-L1 and a kyphosis of 58° at T4-T10. CT and MR images revealed a huge hemangioma extending from the subcutaneous region to the paraspinal muscles and the retroperitoneal space and invading the spinal canal. Posterior correction and fusion surgery using pedicle screws between T2 and L3 were performed. Massive hemorrhage from the hemangioma occurred during the surgery, with intraoperative blood loss reaching 2800 ml. The scoliosis was corrected to 59°, and the kyphosis to 45° after surgery. Seven hours after surgery, the patient suffered from hypovolemic shock and disseminated intravascular coagulation due to postoperative hemorrhage from the hemangioma. The patient developed sensory and conduction aphasia caused by cerebral hypoxia during the shock on the day of the surgery. At present, two years after the surgery, although the patient has completely recovered from the aphasia. This case illustrates that, in correction surgery for scoliosis due to huge subcutaneous cavernous hemangioma, intraoperative and postoperative intensive care for hemodynamics should be performed, since massive hemorrhage can occur during the postoperative period as well as the intraoperative period. PMID:21414205

Horizontal traumatic laceration of the pancreas head: A rare case report.

PubMed

Nanashima, Atsushi; Imamura, Naoya; Tsuchimochi, Yuki; Hamada, Takeomi; Yano, Kouichi; Hiyoshi, Masahide; Fujii, Yoshiro; Kawano, Fumiaki; MitsuruTamura

2017-01-01

This case report is intended to inform acute care surgeons about treating rare horizontal laceration of the pancreas head caused by blunt trauma. A 57-year-old woman who sustained blunt abdominal trauma during a car crash was transported to the emergency center of our hospital with unstable vital signs due to hemorrhagic shock. Computed tomography showed transection of the pancreas head and massive intra-abdominal hemorrhage. She was referred for emergency surgery because of a transient response. Laparotomy at five hours after the accident initially revealed consistent massive bleeding from branches of the superior mesenteric artery and vein, which we resolved by suturing the vessels without damaging the main trunks. A horizontal laceration and complete transection of the pancreatic head were then confirmed but the main pancreatic duct remained intact. The lower part of the pancreatic head including the uncus with the attached part of the duodenum was resected, and the pancreatic stump remaining after transection was fixed by suturing. The jejunal limb was attached to the remnant duodenum by side-to-side functional anastomosis. Although gastric emptying was delayed for one month after surgery, the postoperative course was good and the patient recovered at three months thereafter. The embryonic border of pancreas head accompanied with pancreatic divisum was considered for this laceration without disruption of the main pancreatic duct. Blunt pancreatic trauma usually causes vertical transection and thus, horizontal transection is considered rare. The embryological anatomical border between the ventral and dorsal pancreas due to pancreatic divisum was supposed to be transected and therefore the main pancreatic duct was not damaged. Hemorrhagic shock and rare pancreatic head trauma were treated by appropriate intraoperative management. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Recurrent secondary postpartum hemorrhages due to placental site vessel subinvolution and local uterine tissue coagulopathy

PubMed Central

2014-01-01

Background Postpartum hemorrhage (PPH) represents a serious problem for women and obstetricians. Because of its association with hemorrhagic shock and predisposition to disseminated coagulopathy, it is a leading cause of maternal deaths worldwide. Furthermore, the jeopardy of PPH is rising with the secondary form of PPH occurring between 24 hours and 6 weeks postpartum, when women are already discharged home. The causes of this pathology are severe inflammation (endometritis), inherited coagulation disorders, consumptive coagulopathy, and retained products of conceptions. Others are of rare occurrence, such as vessel subinvolution (VSI) of the placental implantation site, uterine artery pseudoaneurysm, or trauma. Case presentation We present a rare form of recurrent secondary postpartum hemorrhage in a woman after uncomplicated cesarean delivery, with review of the literature linked to the management of this situation originating in the rare local VSI in the placental implantation site, defective decidual homeostasis, and coagulopathy confined to the uterus. Conclusion The placental site VSI is one of the rare causes of secondary PPH, and this situation is frequently underdiagnosed by clinicians. The histological confirmation of dilated “clustered”-shaped myometrial arteries partially occluded by thrombi of variable “age” together with the presence of endovascular extravillous trophoblasts confirms the diagnosis. PMID:24558972

Clostridium septicum myositis in a western lowland gorilla (Gorilla gorilla gorilla).

PubMed

Fontenot, Deidre K; Terrell, Scott P; Miller, Michele; Robbins, Patricia K; Stetter, Mark; Weber, Martha

2005-09-01

A 10-yr-old male gorilla (Gorilla gorilla gorilla) with a history of conspecific bite wounds was evaluated for acute onset of depression, anorexia, and right hemiparesis. The animal was immobilized for diagnostic examination and treatment for suspected toxic shock from a necrotizing, emphysematous wound infection, but was euthanized due to complications during recovery. Gross and histopathologic examination revealed acute necrotizing myositis, fasciitis, cellulitis, and emphysema in the affected wound area, with large numbers of large Gram-positive rods among necrotic muscle fibers. Severe pulmonary edema with airways containing fibrin, acute hemorrhage in multiple body sites, thrombosis in blood vessels in the skeletal muscle, liver, and lung, and lymph node hyperplasia with lymphoid necrosis and hemorrhage. Immunohistochemical fluorescent antibody staining of muscle from the wound site was positive for

A review of dengue fever: a resurging tropical disease.

PubMed

Mangold, Karen A; Reynolds, Sally L

2013-05-01

Dengue is a resurging mosquito-borne disease that is often contracted in U.S. travelers to Latin America, Asia, and the Caribbean. The clinical symptoms range from a simple febrile illness to hemorrhagic fever or shock. The clinical course has a wide range of outcomes, and adequate supportive care can reduce mortality rates dramatically. Repeated exposures to the virus can lead to a more complicated clinical course.

Polyethylene Glycol Polymers in Low Volume Resuscitation

DTIC Science & Technology

2017-10-01

peripheral vascular disease and chronic heart failure, and space medicine. What as the impact on technology transfer? Technology transfer is a very...patterns were almost identical in volunteers and trauma patients. The significantly lower clot strength in blood diluted with 10% PEG-20k could be...lost in the US, compared to cancer (16%), heart disease (12%), and HIV (2%) (1). For all traumatic injuries, hemorrhagic shock is responsible for

Naval Medical Research and Development News: Volume 8, Issue 2,February 2016

DTIC Science & Technology

2016-02-01

yellow fever , viral encephalitides, leishmaniasis, Chagas’ disease, and enteric diseases such as shigellosis and typhoid fever . NAMRU-6 partners with...clothing with permethrin, and reducing mosquito breeding grounds such as standing water. If someone develops sudden fever , rash, joint aches, or...headache, fever , muscle and bone aches and skin rash. The terms Dengue Fever (DF), Dengue Hemorrhagic Fever (DHF), and Dengue Shock Syndrome (DSS) are

Summary Report: Workshop on the Potential Risks of Antibody-Dependent Enhancement in Human HIV Vaccine Trials

DTIC Science & Technology

1993-01-01

the possible role of ADE of infection are not understood. Immune-mediated disease enhancement in several viral dis- Animal viral diseases. Feline ...hemorrhagic fever/ more, in vitro FIPV infection of primary feline peritoneal dengue shock syndrome (DHF/DSS). Such severe manifesta- macrophages is...in vivo immune enhancement has these cells. The enhancing (or neutralizing) activity measured not been reported in simian immunodeficiency viruses

Left Gastric Artery Aneurysm: Successful Embolization with Ethylene Vinyl Alcohol Copolymer (Onyx)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vargas, Hebert Alberto, E-mail: alberto.vargas@addenbrookes.nhs.uk; Cousins, Claire; Higgins, J. Nicholas

2008-03-15

Patients with left gastric artery aneurysms present with hemorrhagic shock due to rupture or occasionally it is an incidental finding on abdominal CT examinations. Due to the increased morbidity and mortality from this condition, adequate diagnosis and treatment are essential. In this article we present a patient with a left gastric artery aneurysm treated with a new embolization agent, ethylene vinyl alcohol copolymer (Onyx)

Inspiratory Resistance as a Potential Treatment for Orthostatic Intolerance and Hemorrhagic Shock

DTIC Science & Technology

2005-04-01

central blood volume by forcing the thoracic muscles to develop increased negative pressure , thus drawing venous blood from extrathoracic cavi- ties...cardiac baroreflex sensitivity associated with re- ductions of central blood volume during lower body negative pressure (LBNP) are reversed with...9:621–26. 8. Chapleau MW, Abboud FM. Contrasting effects of static and pulsatile pressure on carotid baroreceptor activity in dogs. Circ Res 1987; 61

A Hemoglobin-based Oxygen Carrier, Bovine Polymerized Hemoglobin (HBOC-201) Versus Hetastarch (HEX) in a Moderate Severity Hemorrhagic Shock Swine Model with Delayed Evacuation

DTIC Science & Technology

2005-03-23

esuscitation The Kocher clamp was closed for 5 min to crush the por- ion of the rectus abdominus muscle to create a soft tissue njury, and pigs were...continuously monitored. A 3–5 cm lower abdominal incision was made and the left rectus abdomi- nus muscle located. The rectus sheath was mobilized

Effects of n-3 PUFAs on Intestinal Mucosa Innate Immunity and Intestinal Microbiota in Mice after Hemorrhagic Shock Resuscitation.

PubMed

Tian, Feng; Gao, Xuejin; Zhang, Li; Wang, Xinying; Wan, Xiao; Jiang, Tingting; Wu, Chao; Bi, Jingcheng; Lei, Qiucheng

2016-09-29

n -3 polyunsaturated fatty acids (PUFAs) can improve the function of the intestinal barrier after damage from ischemia-reperfusion or hemorrhagic shock resuscitation (HSR). However, the effects of n -3 PUFAs on intestinal microbiota and the innate immunity of the intestinal mucosa after HSR remain unclear. In the present study, 40 C57BL/6J mice were randomly assigned to five groups: control, sham, HSR, HSR + n -3 PUFAs and HSR + n -6 PUFAs. Mice were sacrificed 12 h after HSR. Liver, spleen, mesenteric lymph nodes and terminal ileal tissues were collected. Intestinal mucosae were scraped aseptically. Compared with the HSR group, the number of goblet cells increased, expression of mucin 2 was restored and disturbed intestinal microbiota were partly stabilized in the PUFA-administered groups, indicating that both n -3 and n -6 PUFAs reduced overproliferation of Gammaproteobacteria while promoting the growth of Bacteroidetes. Notably, n -3 PUFAs had an advantage over n -6 PUFAs in improving ileal tissue levels of lysozyme after HSR. Thus, PUFAs, especially n -3 PUFAs, partly improved the innate immunity of intestinal mucosa in mice after HSR. These findings suggest a clinical rationale for providing n -3 PUFAs to patients recovering from ischemia-reperfusion.

Successful treatment of ciguatera fish poisoning with intravenous mannitol.

PubMed

Palafox, N A; Jain, L G; Pinano, A Z; Gulick, T M; Williams, R K; Schatz, I J

1988-05-13

Twenty-four patients with acute ciguatera fish poisoning were treated with intravenous mannitol, and each patient's condition improved dramatically. All exhibited marked lessening of neurologic and muscular dysfunction within minutes of the administration of mannitol. Gastrointestinal symptoms disappeared more slowly. Two patients in coma and one in shock responded within minutes, with full recovery after infusion. Although these observations were empiric and uncontrolled and the mechanism of action of mannitol in this disease is unclear, mannitol should be considered for initial use in patients with significant illness and morbidity from ciguatera fish poisoning.

Physiologic Tolerance of Descending Thoracic Aortic Balloon Occlusion in a Swine Model of Hemorrhagic Shock

DTIC Science & Technology

2013-01-10

Nitrogen (BUN), Creatinine , Potassium and Creatine Kinase. Brain, spinal cord, heart, lung, kidney and liver were also examined histologically at the...significantly greater in the Shock groups than in the REBOA groups. There were no significant differences detected in Creatinine level amongst all groups...2.0 10.2±2.4 12.3±7.6 11.5±4.6 0.884 Creatinine , mg/dL 1.6±0.3 1.4±0.2 1.7±0.6 1.7±0.4 0.613 K + , mmol/l 4.4±0.3 4.3±0.2 4.6±0.7 4.6±0.5 0.548 CK

Substance P is a determinant of lethality in diet-induced hemorrhagic pancreatitis in mice.

PubMed

Maa, J; Grady, E F; Yoshimi, S K; Drasin, T E; Kim, E H; Hutter, M M; Bunnett, N W; Kirkwood, K S

2000-08-01

The neuropeptide substance P (SP) induces plasma extravasation and neutrophil infiltration by activating the neurokinin 1-receptor (NK1-R). SP-induced neurogenic inflammation is terminated by the cell surface enzyme neutral endopeptidase (NEP), which degrades SP. We determined whether genetic deletion of the NK1-R reduces mortality and, conversely, whether genetic deletion of NEP increases mortality in a lethal model of hemorrhagic pancreatitis. Necrotizing pancreatitis was induced by feeding mice a diet deficient in choline and supplemented with ethionine. We determined the length of survival, the severity of pancreatitis (by measuring the neutrophil enzyme myeloperoxidase [MPO] and by histologic evaluation), and the severity of pancreatitis-associated lung injury (lung MPO and histology) in NK1-R (+/+)/(-/-) and NEP (+/+)/(-/-) mice. Genetic deletion of the NK1-R significantly improved survival (100% vs 8% at 120 hours, P <.001) and reduced pancreatic MPO and acinar cell necrosis. Conversely, genetic deletion of NEP significantly worsened survival (0% vs 90% at 120 hours, P <.001) and exacerbated pancreatic MPO and pancreatitis-associated lung injury. Substance P is an important determinant of lethality in this model of necrotizing pancreatitis. Defects in NEP expression could lead to uncontrolled inflammation.

Viral hemorrhagic septicemia virus (VHSV IVb) risk factors and association measures derived by expert panel

USGS Publications Warehouse

,

2010-01-01

Viral hemorrhagic septicemia virus (VHSV) is an OIE-listed pathogen of fish, recently expanding in known host and geographic range in North America. Through a group process designed for subjective probability assessment, an international panel of fish health experts identified and weighted risk factors perceived important to the emergence and spread of the viral genotype, VHSV IVb, within and from the Great Lakes region of the US and Canada. Identified factors included the presence of known VHSV-susceptible species, water temperatures conducive for disease, hydrologic connectivity and proximity to known VHSV-positive areas, untested shipments of live or frozen fish from known positive regions, insufficient regulatory infrastructure for fish health oversight, and uncontrolled exposure to fomites associated with boat and equipment or fish wastes from known VHSV-positive areas. Results provide qualitative insights for use in VHSV surveillance and risk-management planning, and quantitative estimates of contextual risk for use in a Bayesian model combining multiple evidence streams for joint probability assessment of disease freedom status. Consistency checks suggest that the compiled factors positively reflect expert judgment of watershed risk for acquiring VHSV IVb. External validation is recommended as the availability of empirical data permits.

Investigation and suppression of high dynamic response encountered on an elastic supercritical wing

NASA Technical Reports Server (NTRS)

Seidel, David A.; Adams, William M., Jr.; Eckstrom, Clinton V.; Sandford, Maynard C.

1989-01-01

The DAST Aeroelastic Research Wing had been previously in the NASA Langley TDT and an unusual instability boundary was predicted based upon supercritical response data. Contrary to the predictions, no instability was found during the present test. Instead a region of high dynamic wing response was observed which reached a maximum value between Mach numbers 0.92 and 0.93. The amplitude of the dynamic response increased directly with dynamic pressure. The reponse appears to be related to chordwise shock movement in conjunction with flow separation and reattachment on the upper and lower wing surfaces. The onset of flow separation coincided with the occurrence of strong shocks on a surface. A controller was designed to suppress the wing response. The control law attenuated the response as compared with the uncontrolled case and added a small but significant amount of damping for the lower density condition.

mRNA quality control is bypassed for immediate export of stress-responsive transcripts.

PubMed

Zander, Gesa; Hackmann, Alexandra; Bender, Lysann; Becker, Daniel; Lingner, Thomas; Salinas, Gabriela; Krebber, Heike

2016-12-12

Cells grow well only in a narrow range of physiological conditions. Surviving extreme conditions requires the instantaneous expression of chaperones that help to overcome stressful situations. To ensure the preferential synthesis of these heat-shock proteins, cells inhibit transcription, pre-mRNA processing and nuclear export of non-heat-shock transcripts, while stress-specific mRNAs are exclusively exported and translated. How cells manage the selective retention of regular transcripts and the simultaneous rapid export of heat-shock mRNAs is largely unknown. In Saccharomyces cerevisiae, the shuttling RNA adaptor proteins Npl3, Gbp2, Hrb1 and Nab2 are loaded co-transcriptionally onto growing pre-mRNAs. For nuclear export, they recruit the export-receptor heterodimer Mex67-Mtr2 (TAP-p15 in humans). Here we show that cellular stress induces the dissociation of Mex67 and its adaptor proteins from regular mRNAs to prevent general mRNA export. At the same time, heat-shock mRNAs are rapidly exported in association with Mex67, without the need for adapters. The immediate co-transcriptional loading of Mex67 onto heat-shock mRNAs involves Hsf1, a heat-shock transcription factor that binds to heat-shock-promoter elements in stress-responsive genes. An important difference between the export modes is that adaptor-protein-bound mRNAs undergo quality control, whereas stress-specific transcripts do not. In fact, regular mRNAs are converted into uncontrolled stress-responsive transcripts if expressed under the control of a heat-shock promoter, suggesting that whether an mRNA undergoes quality control is encrypted therein. Under normal conditions, Mex67 adaptor proteins are recruited for RNA surveillance, with only quality-controlled mRNAs allowed to associate with Mex67 and leave the nucleus. Thus, at the cost of error-free mRNA formation, heat-shock mRNAs are exported and translated without delay, allowing cells to survive extreme situations.

Pathophysiological roles of peroxynitrite in circulatory shock

PubMed Central

Szabó, Csaba; Módis, Katalin

2014-01-01

Summary Peroxynitrite is a reactive oxidant produced from nitric oxide (NO) and superoxide, which reacts with proteins, lipids and DNA and promotes cytotoxic and pro-inflammatory responses. Here we overview the role of peroxynitrite in various forms of circulatory shock. Immunohistochemical and biochemical evidence demonstrate the production of peroxynitrite in various experimental models of endotoxic and hemorrhagic shock, both in rodents and in large animals. In addition, biological markers of peroxynitrite have been identified in human tissues after circulatory shock. Peroxynitrite can initiate toxic oxidative reactions in vitro and in vivo. Initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3-phosphate dehydrogenase, inhibition of membrane Na+/K+ ATP-ase activity, inactivation of membrane sodium channels, and other oxidative protein modifications contribute to the cytotoxic effect of peroxynitrite. In addition, peroxynitrite is a potent trigger of DNA strand breakage, with subsequent activation of the nuclear enzyme poly (ADP-ribose) polymerase (PARP), which promotes cellular energetic collapse and cellular necrosis. Additional actions of peroxynitrite that contribute to the pathogenesis of shock include inactivation of catecholamines and catecholamine receptors (leading to vascular failure), endothelial and epithelial injury (leading to endothelial and epithelial hyper-permeability and barrier dysfunction) as well as myocyte injury (contributing to loss of cardiac contractile function). Neutralization of peroxynitrite with potent peroxynitrite decomposition catalysts provides cytoprotective and beneficial effects in rodent and large animal models of circulatory shock. PMID:20523270

Examining platelet-fibrin interactions during traumatic shock in a swine model using platelet contractile force and clot elastic modulus.

PubMed

White, Nathan J; Martin, Erika J; Brophy, Donald F; Ward, Kevin R

2011-07-01

A significant proportion of severely injured patients develop early coagulopathy, characterized by abnormal clot formation, which impairs resuscitation and increases mortality. We have previously demonstrated an isolated decrease in clot strength by thrombelastography in a swine model of nonresuscitated traumatic shock. In order to more closely examine platelet-fibrin interactions in this setting, we define the observed decrease in clot strength in terms of platelet-induced clot contraction and clot elastic modulus using the Hemostasis Analysis System (HAS) (Hemodyne Inc., Richmond, Virginia, USA). Whole blood was sampled for HAS measurements, metabolic measurements, cell counts, and fibrinogen concentration at baseline prior to injury and again at a predetermined level of traumatic shock defined by oxygen debt. Male swine (N=17) received femur fracture and controlled arterial hemorrhage to achieve an oxygen debt of 80 ml/kg. Platelet counts were unchanged, but fibrinogen concentration was reduced significantly during shock (167.6 vs. 66.7 mg/dl, P=0.0007). Platelet contractile force generated during clot formation did not change during shock (11.7 vs. 10.4 kdynes, P=0.41), but clot elastic modulus was dynamically altered, resulting in a lower final value (22.9 vs. 17.3 kdynes/cm, P<0.0001). In this model of traumatic shock, platelet function was preserved, whereas terminal clot elastic modulus was reduced during shock in a manner most consistent with early changes in the mechanical properties of the developing fibrin fiber network.

The gene expression of cytokines and chemokines induced by tourniquet shock in mice.

PubMed

Tanaka, Jin; Ishida, Yuko; Ohshima, Tohru; Kondo, Toshikazu

2003-09-01

Traumatic shock is one of the major fields in forensic pathology, but its mechanism remains elusive from the pathophysiological aspects. Tourniquet shock has been established as one of the animal models of traumatic shock, and we examined the gene expression of cytokines and chemokines in the lung and liver in tourniquet shock using mice. Tourniquet was conducted by the application of elastic bands with five turns at both the thighs as high as possible for 2 h, followed by reperfusion. In this procedure, more than 90% mice died within 48 h after reperfusion. Serum hepatic transaminase and hematocrit values significantly increased at 2 h after reperfusion, and their elevation was still evident after 10 h. Histopathologically, hemorrhages, congestion and leukocyte recruitment were observed in the lung and liver specimens after 6 h of reperfusion. Immunohistochemical analysis with anti-myeloperoxidase antibody demonstrated a massive neutrophil infiltration in the lung and liver at 2 h or more after reperfusion. RT-PCR analyses demonstrated that the gene expression of interleukin-1beta, tumor necrosis factor-alpha, monocytes chemoattractant protein-1, macrophage inflammatory protein (MIP)-1alpha, MIP-2, KC and vascular endothelial adhesion molecule-1 was most enhanced in the lung and liver at 2 h after reperfusion. Thus, the gene expression of cytokines and chemokines is presumed to be closely related with the onset of tourniquet shock. From the forensic aspects, these cytokines and chemokines are considered to be useful markers for the early diagnosis of tourniquet shock.

An unusual complication of combined gonioscopy-assisted transluminal trabeculotomy and phacoemulsification: vision loss due to intracapsular hematoma.

PubMed

Yalinbas, Duygu; Aktas, Zeynep; Hepsen, İbrahim; Dilekmen, Nilay

2017-09-23

To report two cases with an acute vision loss due to intracapsular hemorrhage (hematoma) after an uncomplicated gonioscopy-assisted transluminal trabeculotomy (GATT) combined with phacoemulsification surgery. Case report. Seventy-six-year-old male and 75-year-old female patients with cataract and pseudoexfoliative glaucoma (XFG) uncontrolled with maximum medical therapy both underwent GATT combined with phacoemulsification. Shortly after the surgery, intracapsular hematoma behind the intraocular lens (IOL) were noted in both patients. Hematoma cleared in both of them via IOL extraction-anterior vitrectomy and YAG-laser capsulotomy, respectively. Hematoma cleared in both patients without any surgical complications. Vision loss due to unclearing intracapsular hematoma might be an early complication of combined GATT and phacoemulsification surgery.

Early plasma transfusion is associated with improved survival after isolated traumatic brain injury in patients with multifocal intracranial hemorrhage.

PubMed

Chang, Ronald; Folkerson, Lindley E; Sloan, Duncan; Tomasek, Jeffrey S; Kitagawa, Ryan S; Choi, H Alex; Wade, Charles E; Holcomb, John B

2017-02-01

Plasma-based resuscitation improves outcomes in trauma patients with hemorrhagic shock, while large-animal and limited clinical data suggest that it also improves outcomes and is neuroprotective in the setting of combined hemorrhage and traumatic brain injury. However, the choice of initial resuscitation fluid, including the role of plasma, is unclear for patients after isolated traumatic brain injury. We reviewed adult trauma patients admitted from January 2011 to July 2015 with isolated traumatic brain injury. "Early plasma" was defined as transfusion of plasma within 4 hours. Purposeful multiple logistic regression modeling was performed to analyze the relationship of early plasma and inhospital survival. After testing for interaction, subgroup analysis was performed based on the pattern of brain injury on initial head computed tomography: epidural hematoma, intraparenchymal contusion, subarachnoid hemorrhage, subdural hematoma, or multifocal intracranial hemorrhage. Of the 633 isolated traumatic brain injury patients included, 178 (28%) who received early plasma were injured more severely coagulopathic, hypoperfused, and hypotensive on admission. Survival was similar in the early plasma versus no early plasma groups (78% vs 84%, P = .08). After adjustment for covariates, early plasma was not associated with improved survival (odds ratio 1.18, 95% confidence interval 0.71-1.96). On subgroup analysis, multifocal intracranial hemorrhage was the largest subgroup with 242 patients. Of these, 61 (25%) received plasma within 4 hours. Within-group logistic regression analysis with adjustment for covariates found that early plasma was associated with improved survival (odds ratio 3.34, 95% confidence interval 1.20-9.35). Although early plasma transfusion was not associated with improved in-hospital survival for all isolated traumatic brain injury patients, early plasma was associated with increased in-hospital survival in those with multifocal intracranial hemorrhage. Copyright © 2016 Elsevier Inc. All rights reserved.

Osthol attenuates neutrophilic oxidative stress and hemorrhagic shock-induced lung injury via inhibition of phosphodiesterase 4.

PubMed

Tsai, Yung-Fong; Yu, Huang-Ping; Chung, Pei-Jen; Leu, Yann-Lii; Kuo, Liang-Mou; Chen, Chun-Yu; Hwang, Tsong-Long

2015-12-01

Oxidative stress caused by neutrophils is an important pathogenic factor in trauma/hemorrhagic (T/H)-induced acute lung injury (ALI). Osthol, a natural coumarin found in traditional medicinal plants, has therapeutic potential in various diseases. However, the pharmacological effects of osthol in human neutrophils and its molecular mechanism of action remain elusive. In this study, our data showed that osthol potently inhibited the production of superoxide anion (O2(•-)) and reactive oxidants derived therefrom as well as expression of CD11b in N-formylmethionylleucylphenylalanine (FMLP)-activated human neutrophils. However, osthol inhibited neutrophil degranulation only slightly and it failed to inhibit the activity of subcellular NADPH oxidase. FMLP-induced phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) was inhibited by osthol. Notably, osthol increased the cAMP concentration and protein kinase A (PKA) activity in activated neutrophils. PKA inhibitors reversed the inhibitory effects of osthol, suggesting that these are mediated through cAMP/PKA-dependent inhibition of ERK and Akt activation. Furthermore, the activity of cAMP-specific phosphodiesterase (PDE) 4, but not PDE3 or PDE7, was significantly reduced by osthol. In addition, osthol reduced myeloperoxidase activity and pulmonary edema in rats subjected to T/H shock. In conclusion, our data suggest that osthol has effective anti-inflammatory activity in human neutrophils through the suppression of PDE4 and protects significantly against T/H shock-induced ALI in rats. Osthol may have potential for future clinical application as a novel adjunct therapy to treat lung inflammation caused by adverse circulatory conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

Beta-blockade prevents hematopoietic progenitor cell suppression after hemorrhagic shock.

PubMed

Elhassan, Ihab O; Hannoush, Edward J; Sifri, Ziad C; Jones, Eyone; Alzate, Walter D; Rameshwar, Pranela; Livingston, David H; Mohr, Alicia M

2011-08-01

Severe injury is accompanied by sympathetic stimulation that induces bone marrow (BM) dysfunction by both suppression of hematopoietic progenitor cell (HPC) growth and loss of cells via HPC mobilization to the peripheral circulation and sites of injury. Previous work demonstrated that beta-blockade (BB) given prior to tissue injury both reduces HPC mobilization and restores HPC colony growth within the BM. This study examined the effect and timing of BB on BM function in a hemorrhagic shock (HS) model. Male Sprague-Dawley rats underwent HS via blood withdrawal, maintaining the mean arterial blood pressure at 30-40 mm Hg for 45 min, after which the extracted blood was reinfused. Propranolol (10 mg/kg) was given either prior to or immediately after HS. Blood pressure, heart rate, BM cellularity, and death were recorded. Bone marrow HPC growth was assessed by counting colony-forming unit-granulocyte-, erythrocyte-, monocyte-, megakaryocyte (CFU-GEMM), burst-forming unit-erythroid (BFU-E), and colony-forming unit-erythroid (CFU-E) cells. Administration of BB prior to injury restored HPC growth to that of naïve animals (CFU-GEMM 59 ± 11 vs. 61 ± 4, BFU-E 68 ± 9 vs. 73 ± 3, and CFU-E 81 ± 35 vs. 78 ± 14 colonies/plate). Beta-blockade given after HS increased the growth of CFU-GEMM, BFU-E, and CFU-E significantly and improved BM cellularity compared with HS alone. The mortality rate was not increased in the groups receiving BB. Administration of propranolol either prior to injury or immediately after resuscitation significantly reduced post-shock BM suppression. After HS, BB may improve BM cellularity by decreasing HPC mobilization. Therefore, the early use of BB post-injury may play an important role in attenuating the BM dysfunction accompanying HS.

THE STATE OF THE VESSELS OF THE MESENTERY IN SHOCK PRODUCED BY CONSTRICTING THE LIMBS AND THE BEHAVIOR OF THE VESSELS FOLLOWING HEMORRHAGE

PubMed Central

Page, Irvine H.; Abell, Richard G.

1943-01-01

1. Direct observations of the arteries, arterioles, capillaries, veins, and lymphatics in the mesentery of anesthetized cats put into shock by incomplete occlusion of the circulation of the limbs showed that: (a) Marked constriction of the arteries and arterioles, produced by muscular contraction, occurred usually within an hour after incomplete occlusion of the limbs, lasted several hours, and finally gave way in most instances to relaxation an hour or more before death. The constriction reduced the blood supply to the mesentery and intestine and the venous return from them. It did not, however, interrupt the blood flow. No pooling or stagnation of blood was seen even as a terminal phenomenon. (b) The veins of the mesentery also became constricted but showed less tendency to dilate as death approached. The lymphatics likewise became somewhat narrowed. Even during the terminal stage the leukocytes moved along without change in shape or sticking to the walls of the capillaries or venules. (c) Hematocrit determinations showed progressive hemoconcentration of moderate degree. (d) Autopsy usually showed the presence of small hemorrhages in many parts of the body, especially the heart, liver, spleen, and lungs. (e) Bilateral nephrectomy, suprarenalectomy, and pancreatectomy did not significantly alter the morphological picture elicited by shock induced by restriction of the circulation to the limbs. 2. Removal of large amounts of blood was always followed within a short time by constriction of arteries, arterioles, veins, and lymphatics of the mesentery. 3. Fall in arterial pressure produced by pithing was not accompanied by change in diameter of the arteries, arterioles, veins, or lymphatics, or by blanching of the mesentery or gut. PMID:19871278

The Air Force Critical Care Air Transport Team (CCATT): Using the Estimating Supplies Program (ESP) to Validate Clinical Requirements

DTIC Science & Technology

2005-04-05

categories are postsurgical cases, and represent thoracic, staged exploratory laparotomy, vascular/amputation, and craniotomy PCs for which surgical...Post Surgical Craniotomy J – Environmental Emergency E – Burns > 20% BSA K – Medical, Anaphylaxis/Asthma F – Class III and IV Hemorrhagic Shock...Amputation G – Crush/Blunt Injury K – Med, Anaphylaxis Asthma D – Post Surgical Craniotomy H – Head Injury

Hemodynamics Associated with Breathing Through an Inspiratory Impedance Threshold Device in Human Volunteers

DTIC Science & Technology

2004-01-01

nerve stimulation combined with an inspiratory impedance threshold in a pig model of hemorrhagic shock. Crit Care Med 2003; 31:1197–1202 16. Coast JR...training. Because of the po- tential effects on cardiovascular function, sub- jects refrained from exercise and stimulants such as caffeine and other...controlled trial. Setting: Laboratory. Subjects: Ten women and ten men. Interventions: We measured hemodynamic and respiratory re- sponses during two

Injury Pattern and Mortality of Noncompressible Torso Hemorrhage in UK Combat Casualties

DTIC Science & Technology

2013-08-01

body disruption (5.1%), and multiple-organ failure (4.0%). On multivariate analysis, major arterial and pulmonary hilar injury are most lethal with odds...death. Major arterial and pulmonary hilar injuries are independent predictors of mortality. (J Trauma Acute Care Surg. 2013;75: S263YS268. Copyright...physiologic or procedural indices of shock.8 Anatomic refers to those injuries to a named torso vessel, pulmonary injury (massive hemothorax or hilar

Pyruvate-Enhanced Resuscitation for Hemorrhagic Shock and Hindlimb Ischemia

DTIC Science & Technology

2015-06-06

Albert Yurvati Albert H Olivencia-Yurvati 611102 c . THIS PAGE The public reporting burden for this collection of information is estimated to average 1...journals (N/A for none) ( c ) Presentations Received Paper TOTAL: Received Paper TOTAL: Number of Non Peer-Reviewed Conference Proceeding publications (other...Mallet . “Surgical management of the goat.” , Lab Animal (06 2011) Devin C . Flaherty, DO, PhD, Besim Hoxha, MD, Shirley Nelson, RLAT, Jie Sun, BS

Evaluation of Wireless Vital Signs Monitor in Trauma Patients

DTIC Science & Technology

2014-06-01

p=NS These data show that the R wave detection and pulse oximeter in the MWVSM finger probe are more accurate and follow changes better than those... oximeter signal failed to register with the thready pulse characteristic of hemorrhagic shock. This observation suggests that using a forehead and...would be more useful to measure from the forehead (e.g. near infrared spectroscopy (NIRS) or Bispectral EEG (BIS)) or extremity? 2) Does pulse

Assessment of Aeromedical Evacuation Transport Patient Outcomes With and Without Cabin Altitude Restriction

DTIC Science & Technology

2017-08-24

reaction to stress (physical restraints) Other • Acute post-hemorrhagic anemia • Post-operative infection • Traumatic shock • Fat embolism ...decompression sickness/air gas embolism , and severe pulmonary disease [9]. The goal of this retrospective matched case-control study was to determine whether...patients who have cardiopulmonary concerns, free air in any closed cavity (e.g., skull, peritoneal cavity, injury, embolism ), or evolved gas (e.g

Evaluation of Resuscitation Fluids on Endothelial Glycocalyx, Venular Blood Flow, and Coagulation Function After Hemorrhagic Shock in Rats

DTIC Science & Technology

2013-10-01

thrombin inhibition, leading to coagulopathy. Using intravital microscopy, we have obtained direct in vivo data showing glycocalyx thickness reduction...collected in 3.2% citrate for coagulation assays (ROTEM, TEM Innovations GmbH, Munich, Germany). Intravital Microscopy The system described in detail...microscopic fields containing venules were randomly selected. The first dye (TR-Dx70) was injected 5 min before baseline. Image sequences of

Educating the Educator: Use of Advanced Bleeding Control Mechanisms in Athletic Training: A Shift in the Thought Process of Prehospital Care. Part 2: Hemostatic Agents

ERIC Educational Resources Information Center

Payne, Ellen K.; Berry, David C.; Seitz, S. Robert

2014-01-01

In Part 1 of this series [see: EJ1044392], the concepts of hemorrhaging, shock, and controlling bleeding as they relate to athletic training and prehospital emergency care along with the use of tourniquets were presented for athletic training educators (ATEs) to teach the skill in the classroom. This article, Part 2 of advanced bleeding control,…

Early Whole Blood for Patients Requiring Massive Transfusion after Major Trauma

DTIC Science & Technology

2013-03-01

Inflammation and Adiposity after Hemorrhagic Shock and Resuscitation (PI Kozar) Evaluate sarcopenia based on admission CT and compare to BMI and...our collaborator, Dr. Mourtzakis, for calculation of sarcopenia based on muscle mass at the third lumbar vertebrae. There were 58 patients admitted...We are in the process of determining which of the 45 patients had an abdominal CT. We have just completed a retrospective review of elderly trauma

Exercise-induced stress resistance is independent of exercise controllability and the medial prefrontal cortex

PubMed Central

Greenwood, Benjamin N.; Spence, Katie G.; Crevling, Danielle M.; Clark, Peter J.; Craig, Wendy C.; Fleshner, Monika

2014-01-01

Exercise increases resistance against stress-related disorders such as anxiety and depression. Similarly, the perception of control is a powerful predictor of neurochemical and behavioral responses to stress, but whether the experience of choosing to exercise, and exerting control over that exercise, is a critical factor in producing exercise-induced stress resistance is unknown. The current studies investigated whether the protective effects of exercise against the anxiety- and depression-like consequences of stress are dependent on exercise controllability and a brain region implicated in the protective effects of controllable experiences, the medial prefrontal cortex. Adult male Fischer 344 rats remained sedentary, were forced to run on treadmills or motorised running wheels, or had voluntary access to wheels for 6 weeks. Three weeks after exercise onset, rats received sham surgery or excitotoxic lesions of the medial prefrontal cortex. Rats were exposed to home cage or uncontrollable tail shock treatment three weeks later. Shock-elicited fear conditioning and shuttle box escape testing occurred the next day. Both forced and voluntary wheel running, but not treadmill training, prevented the exaggerated fear conditioning and interference with escape learning produced by uncontrollable stress. Lesions of the medial prefrontal cortex failed to eliminate the protective effects of forced or voluntary wheel running. These data suggest that exercise controllability and the medial prefrontal cortex are not critical factors in conferring the protective effects of exercise against the affective consequences of stressor exposure, and imply that exercise perceived as forced may still benefit affect and mental health. PMID:23121339

How to deal with penile carcinoma inguinal metastases invading femoral vessels.

PubMed

Fodor, Marius; Petrut, Bogdan; Fodor, Lucian

2017-01-01

Penile cancer accounts for 1-10% of men neoplastic diseases and 30-60% of patients have inguinal metastases at the time of diagnosis. Inguinal metastases of penile cancer with femoral vessel involvement could lead to vascular fistula and hemorrhagic shock. We present 3 consecutive patients with inguinal metastases of penile cancer complicated by infection and hemorrhage from femoral vessels invaded by the tumor. Simultaneous extra-anatomical axillo-femoral bypass graft, wide excision of tumor and groin defect reconstruction was used to achieve "tumor-free" oncologic aim and to save the lower limb. We consider the extra-anatomic axillo-femoral bypass associated with wide inguinal tumor excision and defect covering a feasible surgical solution for improving the life quality and extend life expectancy in patients with lymph node metastasis of penile cancer complicated by necrosis, infection and femoral vessel involvement.

A Case Report of Gastrointestinal Hemorrhage and Perforation During Apatinib Treatment of Gastric Cancer.

PubMed

Li, Xiao-Fen; Tan, Yi-Nuo; Cao, Ying; Xu, Jing-Hong; Zheng, Shu; Yuan, Ying

2015-09-01

Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which shows good efficacy and safety in clinical trials for chemotherapy-refractory gastric cancer patients. Till now, there is no case report after apatinib came in the market. We presented a 55-year-old Chinese woman with advanced gastric cancer, who received apatinib after failure of second-line chemotherapy. On the 19th day of apatinib administration, she suffered from gastrointestinal hemorrhage. Then, her condition rapidly deteriorated to gastrointestinal perforation. Although the patient received timely medical and surgical treatment, she finally died of septic shock. Although apatinib shows exciting efficacy and good tolerance in phase II and III clinical trials, this novel targeted drug should be prescribed carefully and close clinical monitoring is needed when using it.

A Case Report of Gastrointestinal Hemorrhage and Perforation During Apatinib Treatment of Gastric Cancer

PubMed Central

Li, Xiao-Fen; Tan, Yi-Nuo; Cao, Ying; Xu, Jing-Hong; Zheng, Shu; Yuan, Ying

2015-01-01

Abstract Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which shows good efficacy and safety in clinical trials for chemotherapy-refractory gastric cancer patients. Till now, there is no case report after apatinib came in the market. We presented a 55-year-old Chinese woman with advanced gastric cancer, who received apatinib after failure of second-line chemotherapy. On the 19th day of apatinib administration, she suffered from gastrointestinal hemorrhage. Then, her condition rapidly deteriorated to gastrointestinal perforation. Although the patient received timely medical and surgical treatment, she finally died of septic shock. Although apatinib shows exciting efficacy and good tolerance in phase II and III clinical trials, this novel targeted drug should be prescribed carefully and close clinical monitoring is needed when using it. PMID:26426663

Fluoroscopy-free Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for controlling life threatening postpartum hemorrhage

PubMed Central

Stensaeth, Knut Haakon; Sovik, Edmund; Haig, Ingrid Natasha Ylva; Skomedal, Erna; Jorgensen, Arve

2017-01-01

Background Severe postpartum hemorrhage occurs in 1/1000 women giving birth. This condition is often dramatic and may be life threatening. Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) has in recent years been introduced as a novel treatment for hemorrhagic shock. We present a series of fluoroscopy-free REBOA for controlling life threatening postpartum hemorrhage. Methods In 2008 an ‘aortic occlusion kit’ was assembled and used in three Norwegian university hospitals. The on-call interventional radiologist (IR) was to be contacted with a response time < 30 minutes in case of life threatening PPH. Demographics and characteristics were noted from the medical records. Results This retrospective study includes 36 patients treated with fluoroscopy-free REBOA for controlling severe postpartum hemorrhage in the years 2008–2015. The REBOA success rate was 100% and no patients died from REBOA related complications. Uterine artery embolization was performed in 17 (47%) patients and a hysterectomy in 16 (44%) patients. A short (11cm) introducer length was strongly associated with iliac artery thrombus formation (ρ = 0.50, P = 0.002). In addition, there was a strong negative correlation between uterine artery embolization and hysterectomy (ρ = -0.50, P = 0.002). Conclusions Our Norwegian experience indicates the clinical safety and feasibility of REBOA in life threatening PPH. Also, REBOA can be used in an emergency situation without the use of fluoroscopy with a high degree of technical success. It is important that safety implementation of REBOA is established, especially through limited aortic balloon occlusion time and a thorough balloon deflation regime. PMID:28355242

Testosterone receptor blockade after trauma-hemorrhage improves cardiac and hepatic functions in males.

PubMed

Remmers, D E; Wang, P; Cioffi, W G; Bland, K I; Chaudry, I H

1997-12-01

Although studies have shown that testosterone receptor blockade with flutamide after hemorrhage restores the depressed immune function, it remains unknown whether administration of flutamide following trauma and hemorrhage and resuscitation has any salutary effects on the depressed cardiovascular and hepatocellular functions. To study this, male rats underwent a laparotomy (representing trauma) and were then bled and maintained at a mean arterial pressure (MAP) of 40 mmHg until the animals could not maintain this pressure. Ringer lactate was given to maintain a MAP of 40 mmHg until 40% of the maximal shed blood volume was returned in the form of Ringer lactate. The rats were then resuscitated with four times the shed blood volume in the form of Ringer lactate over 60 min. Flutamide (25 mg/kg) or an equal volume of the vehicle propanediol was injected subcutaneously 15 min before the end of resuscitation. Various in vivo heart performance parameters (e.g., maximal rate of the pressure increase or decrease), cardiac output, and hepatocellular function (i.e., the maximum velocity and the overall efficiency of indocyanine green clearance) were determined at 20 h after resuscitation. Additionally, hepatic microvascular blood flow (HMBF) was determined using a laser Doppler flowmeter. The results indicate that left ventricular performance, cardiac output, HMBF, and hepatocellular function decreased significantly at 20 h after the completion of trauma, hemorrhage, and resuscitation. Administration of the testosterone receptor blocker flutamide, however, significantly improved cardiac performance, HMBF, and hepatocellular function. Thus flutamide appears to be a novel and useful adjunct for improving cardiovascular and hepatocellular functions in males following trauma and hemorrhagic shock.

Clinical features and patient management of Lujo hemorrhagic fever.

PubMed

Sewlall, Nivesh H; Richards, Guy; Duse, Adriano; Swanepoel, Robert; Paweska, Janusz; Blumberg, Lucille; Dinh, Thu Ha; Bausch, Daniel

2014-01-01

In 2008 a nosocomial outbreak of five cases of viral hemorrhagic fever due to a novel arenavirus, Lujo virus, occurred in Johannesburg, South Africa. Lujo virus is only the second pathogenic arenavirus, after Lassa virus, to be recognized in Africa and the first in over 40 years. Because of the remote, resource-poor, and often politically unstable regions where Lassa fever and other viral hemorrhagic fevers typically occur, there have been few opportunities to undertake in-depth study of their clinical manifestations, transmission dynamics, pathogenesis, or response to treatment options typically available in industrialized countries. We describe the clinical features of five cases of Lujo hemorrhagic fever and summarize their clinical management, as well as providing additional epidemiologic detail regarding the 2008 outbreak. Illness typically began with the abrupt onset of fever, malaise, headache, and myalgias followed successively by sore throat, chest pain, gastrointestinal symptoms, rash, minor hemorrhage, subconjunctival injection, and neck and facial swelling over the first week of illness. No major hemorrhage was noted. Neurological signs were sometimes seen in the late stages. Shock and multi-organ system failure, often with evidence of disseminated intravascular coagulopathy, ensued in the second week, with death in four of the five cases. Distinctive treatment components of the one surviving patient included rapid commencement of the antiviral drug ribavirin and administration of HMG-CoA reductase inhibitors (statins), N-acetylcysteine, and recombinant factor VIIa. Lujo virus causes a clinical syndrome remarkably similar to Lassa fever. Considering the high case-fatality and significant logistical impediments to controlled treatment efficacy trials for viral hemorrhagic fever, it is both logical and ethical to explore the use of the various compounds used in the treatment of the surviving case reported here in future outbreaks. Clinical observations should be systematically recorded to facilitate objective evaluation of treatment efficacy. Due to the risk of secondary transmission, viral hemorrhagic fever precautions should be implemented for all cases of Lujo virus infection, with specialized precautions to protect against aerosols when performing enhanced-risk procedures such as endotracheal intubation.

Percutaneous transsplenic portal vein catheterization: technical procedures, safety, and clinical applications.

PubMed

Zhu, Kangshun; Meng, Xiaochun; Zhou, Bin; Qian, Jiesheng; Huang, Wensou; Deng, Meihai; Shan, Hong

2013-04-01

To evaluate the safety and feasibility of percutaneous transsplenic portal vein catheterization (PTSPC) by retrospective review of its use in patients with portal vein (PV) occlusion. From July 2004 to December 2010, 46 patients with a history of uncontrolled gastroesophageal variceal bleeding secondary to portal hypertension underwent endovascular PV interventions via a percutaneous transsplenic approach. All patients had occlusion of the main PV or central intrahepatic PV branches, which prevented the performance of a transhepatic approach. A vein within the splenic parenchyma was punctured under fluoroscopic guidance by referencing preoperative computed tomography images. PTSPC-related complications and clinical applications were analyzed. PTSPC was successfully performed in 44 of 46 patients (96%); two failures were caused by inaccessible small intrasplenic veins. PTSPC-related major bleeding complications occurred in three patients (6.5%), including large intraperitoneal hemorrhage in one patient and large splenic subcapsular hemorrhage in two patients. Two of the three patients developed hypotension, and one developed severe anemia. All three of the patients required blood transfusions. PTSPC-related minor bleeding complications occurred in six patients (13%) as a result of a small splenic subcapsular hemorrhage. In addition, three patients exhibited mild left pleural effusion, which subsided spontaneously 1 week later. All 44 patients successfully treated via PTSPC received gastroesophageal variceal embolization. Eight patients received PV stents, five for treatment of PV occlusion and three during transjugular intrahepatic portosystemic shunt placement. PTSPC is a safe and effective access for endovascular PV interventions in patients without a transhepatic window. Copyright © 2013 SIR. Published by Elsevier Inc. All rights reserved.

Fresh Whole Blood Use for Hemorrhagic Shock: Preserving Benefit While Avoiding Complications

DTIC Science & Technology

2012-10-01

coagulation factor deficiency), and improved blood bank economics.1–3 However, component usage in austere settings (developing world and combat) is often...limited by storage requirements for blood products (refrig- eration for red blood cells [RBCs], room temperature with agitation for platelets [PLTs...red blood cell (RBC) or plasma product inven- tory” (Ref. 1 in Table 1). Most civilian institutions define it as fresh if it is stored for 48 hours

Potential Resuscitation Strategies for Treatment of Hemorrhagic Shock

DTIC Science & Technology

2004-09-01

thrombus (the “pop-clot” pressure); 2) an injectable clot stabilizer (“fix-a-leak”) that is a naturally occurring factor in the clotting cascade (human...recombinant Factor VIIa); and 3) the maximum time up to 24 hours for hypotensive resuscitation below the “pop-the-clot” pressure (“how low for how long...To prevent this blood products are given as soon as possible in the emergency department. Only crystalloids and colloids are currently available on

Cullin 5 Expression in the Rat: Cellular and Tissue Distribution, and Changes in Response to Water Deprivation and Hemorrhagic Shock

DTIC Science & Technology

2003-02-28

of Health p53 tumor suppressor PBS phosphate buffered saline PCO2 partial pressure of carbon dioxide PO2 partial pressure of oxygen PCR...buffered saline TTBS tween-20 tris buffered saline TonEBP tonicity-response enhancer binding protein TSNRP TriService Nursing Research Program...growth and metabolism (Hochstrasser, 1995; Deshaies, 1999). Although traditionally seen as no more than a means of eliminating no longer needed

Interventional Vitamin C A Strategy for Attenuation of Coagulopathy and Inflammation in Hemorrhagic Trauma and Shock

DTIC Science & Technology

2016-10-01

evident in liver and kidney sections. Treatment with VitC (200mg/kg) was associated with a lower degree of histological tissue injury and a...significantly reduced ALI score. Treatment with VitC also reduced the expression of pro-inflammatory mediators in lungs, liver and kidneys . In addition, VitC...Euthasol IV  Tissue samples (lung, liver and kidney ) obtained for histology and molecular characterization Definitive trial conducted: Eight (8

The Ratio of Blood Products Transfused Affects Mortality in Patients Receiving Massive Transfusions at a Combat Support Hospital

DTIC Science & Technology

2007-10-01

therapy resuscitation, and exacer- bated by hemorrhagic shock, metabolic acidosis, hypother- mia, hyperfibrinolysis, hypocalcemia , and anemia.11,14–19...outcome studies examining the effect of blood product transfusion ratios for trauma patients requiring massive transfusion. Most deaths (80% to 85%) that...calculation of apheresis platelet units transfused, though FWB has previously been shown to be as effective as 10 units of platelet concentrate.33 The

Closed-Loop Resuscitation of Hemorrhagic Shock: Novel Solutions Infused to Hypotensive and Normotensive Endpoints

DTIC Science & Technology

2007-06-29

Anesthesia & Analgesia 98(4S):SCA 85, 2004. 5. Kramer GC, Brown TLH, Michell MW, Oliveira H, Herndon DN, Muller M, Baker RD: Enteral Resuscitation...Honolulu, Hawaii; Anesth Analg 98(4S):SCA 85, 2004. 10. Bruttig, SPGC, Kramer, GC: Clinical record of emergency vascular access using adult intraosseous ...supplement 1): abstracts 49, 2007. NATO Reports: 1. Bruttig SP, Kramer GC: Clinical record of emergency vascular access using adult intraosseous (10

The Role of Endorphins in the Pathophysiology of Hemorrhagic and Endotoxic Shock in the Subhuman Primate.

DTIC Science & Technology

1982-09-01

beneficial effects are dose -dependent,2 independent of blood reinfusion,4 and reproducible by other opiate receptor antagonists. 5 Before embarking on...clinical studies we decided to investigate the mechanisms of action, doses required, and efficacy in a species closer to man. We also thought this was...2 _met 5-enkephalinamide into the third cerebral ventricle of three monkeys produced bradycardia and hypotension which were dose -dependent and

Life or death? A Physiogenomic Approach to Understand Individual Variation in Responses to Hemorrhagic Shock

DTIC Science & Technology

2011-01-01

Olaomi, O.; Olldashi, F.; Perel, P.; Peto, R.; Ramana, P. V.; Ravi, R. R.; Yutthakasemsunt, S. Effects of tranexamic acid on death, vascular...Glutamine [197-199] Yes Histone deacetylase inhibitors (e.g., valproic acid ) [168-169, 200-201] No Naloxone [202] Yes 430 Current Genomics, 2011, Vol...regulation and dynamics of ribonucleic Acid . Endocrinology, 2010, 151, 1391-1397. [44] Spriggs, K. A.; Bushell, M.; Willis, A. E. Translational regulation

Resuscitative therapy with erythropoietin reduces oxidative stress and inflammatory responses of vital organs in a rat severe fixed-volume hemorrhagic shock model.

PubMed

Ranjbaran, Mina; Kadkhodaee, Mehri; Seifi, Behjat; Mirzaei, Reza; Ahghari, Parisa

2018-01-01

Hemorrhagic shock (HS) still has a high mortality rate and none of the known resuscitative regimens completely reverse its adverse outcomes. This study investigated the effects of different models of resuscitative therapy on the healing of organ damage in a HS model. Male Wistar rats were randomized into six groups: Sham, without HS induction; HS, without resuscitation; HS+Blood, resuscitation with the shed blood; HS+Blood+NS, resuscitation with blood and normal saline; HS+Blood+RL, resuscitation with blood and Ringer's lactate; EPO, erythropoietin was added to the blood and RL. Blood and urine samples were obtained 3 h after resuscitation. Kidney, liver and brain tissue samples were harvested for multiple organ failure evaluation. Survival rate was the highest in the Sham, EPO and HS+Blood+RL groups compared to others. Plasma creatinine concentration, ALT, AST, urinary NAG activity and renal NGAL mRNA expression significantly increased in the HS+Blood+RL group compared to the Sham group. There was a significant increase in tissue oxidative stress markers and pro-inflammatory cytokines in HS+Blood+RL group compared to the Sham rats. EPO had more protective effects on multiple organ failure compared to the HS+Blood+RL group. EPO, as a resuscitative treatment, attenuated HS-induced organ damage. It seems that it has a potential to be attractive for clinical trials.

Dimethyl Sulfoxide Attenuates Acute Lung Injury Induced by Hemorrhagic Shock/Resuscitation in Rats.

PubMed

Tsung, Yu-Chi; Chung, Chih-Yang; Wan, Hung-Chieh; Chang, Ya-Ying; Shih, Ping-Cheng; Hsu, Han-Shui; Kao, Ming-Chang; Huang, Chun-Jen

2017-04-01

Inflammation following hemorrhagic shock/resuscitation (HS/RES) induces acute lung injury (ALI). Dimethyl sulfoxide (DMSO) possesses anti-inflammatory and antioxidative capacities. We sought to clarify whether DMSO could attenuate ALI induced by HS/RES. Male Sprague-Dawley rats were allocated to receive either a sham operation, sham plus DMSO, HS/RES, or HS/RES plus DMSO, and these were denoted as the Sham, Sham + DMSO, HS/RES, or HS/RES + DMSO group, respectively (n = 12 in each group). HS/RES was achieved by drawing blood to lower mean arterial pressure (40-45 mmHg for 60 min) followed by reinfusion with shed blood/saline mixtures. All rats received an intravenous injection of normal saline or DMSO immediately before resuscitation or at matching points relative to the sham groups. Arterial blood gas and histological assays (including histopathology, neutrophil infiltration, and lung water content) confirmed that HS/RES induced ALI. Significant increases in pulmonary expression of tumor necrosis factor-α (TNF-α), malondialdehyde, nuclear factor-kappa B (NF-κB), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2) confirmed that HS/RES induced pulmonary inflammation and oxidative stress. DMSO significantly attenuated the pulmonary inflammation and ALI induced by HS/RES. The mechanisms for this may involve reducing inflammation and oxidative stress through inhibition of pulmonary NF-κB, TNF-α, iNOS, and COX-2 expression.

Vitamin D serostatus and dengue fever progression to dengue hemorrhagic fever/dengue shock syndrome.

PubMed

Villamor, E; Villar, L A; Lozano, A; Herrera, V M; Herrán, O F

2017-10-01

Vitamin D could modulate pathways leading to dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). We examined the associations of serum total 25-hydroxy vitamin D [25(OH)D] and vitamin D binding protein (VDBP) concentrations in patients with uncomplicated dengue fever (DF) with risk of progression to DHF/DSS. In a case-control study nested in a cohort of DF patients who were followed during the acute episode in Bucaramanga, Colombia, we compared 25(OH)D and VDBP at onset of fever between 110 cases who progressed to DHF/DSS and 235 DF controls who did not progress. 25(OH)D concentrations were also compared between the acute sample and a sample collected >1 year post-convalescence in a subgroup. Compared with 25(OH)D ⩾75 nmol/l, adjusted odds ratios (95% CI) for progression were 0·44 (0·22-0·88) and 0·13 (0·02-1·05) for 50 to 75 nmol/l (vitamin D insufficiency) and <50 nmol/l (vitamin D deficiency), respectively (P, trend = 0·003). Mean 25(OH)D concentrations were much lower post-convalescence compared with the acute episode, regardless of case status. Compared with controls, mean VDBP was non-significantly lower in cases. We conclude that low serum 25(OH)D concentrations in DF patients predict decreased odds of progression to DHF/DSS.

Effect of tranexamic acid on intra- and postoperative haemorrhage in dogs with surgically treated hemoperitoneum.

PubMed

Sigrist, N; Olgiati, L; Jud Schefer, R S

2018-05-01

Tranexamic acid (TXA) is an antifibrinolytic drug that is used for uncontrolled bleeding of various origin. This retrospective study investigated the effect of tranexamic acid administration on bleeding tendency in dogs with surgically managed hemoperitoneum. Thirty dogs were treated with (TXA group) and 25 dogs without (CTR group) tranexamic acid prior to surgery. Various parameters (decrease in haematocrit, number of transfusions, shock index and changes in abdominal fluid accumulation) were used for characterization of bleeding tendency and compared between groups. Groups were similar at presentation and prior to surgery. None of the dogs undergoing rotational thromboelastography analysis showed hyperfibrinolysis prior to surgery. Overall transfusion and erythrocyte transfusion requirements as well as bleeding tendency, hospitalisation time and hospital discharge rate were similar between groups. Dogs of the TXA group received significantly more intraoperative plasma transfusions (P=0.013) and showed a higher systolic and mean arterial blood pressure (P=0.002 and 0.050) and lower shock index (P=0.028) with less dogs being in shock (P=0.012) at 24h. In summary, in this study population of dogs with surgically managed spontaneous hemoperitoneum dogs treated with tranexamic acid received more plasma transfusions intraoperatively and showed a lower shock index 24h after presentation. In dogs with surgically treated hemoabdomen tranexamic acid administration prior to surgery does not reduce red blood cell transfusion requirements or postoperative bleeding tendency.

Could implantable cardioverter defibrillators provide a human model supporting the learned helplessness theory of depression?

PubMed

Goodman, M; Hess, B

1999-01-01

Affective symptoms were examined retrospectively in 25 patients following placement of implantable cardioverter defibrillators (ICD) which can produce intermittent shocks without warning in response to cardiac ventricular arrhythmias. The number of ICD random, uncontrollable discharge shocks and pre-ICD history of psychological distress (i.e., depression and/or anxiety) were documented in all patients using a demographics questionnaire and a standardized behavioral/psychological symptoms questionnaire (i.e., Symptom Checklist-90 Revised). ICD patients were dichotomized into two groups: those without a history of psychological distress prior to ICD (n = 18) and those with a history of psychological distress prior to ICD (n = 7). In ICD patients without a prior history, results indicated that quantity of ICD discharge shocks was significantly predictive of current reported depression (r = 0.45, p = 0.03) and current reported anxiety (r = 0.51, p = 0.02). Conversely, in patients with a reported history of psychological distress, there was no significant relationship found between quantity of discharge shocks and current reported depression or anxiety. This study may provide evidence in support of a human model of learned helplessness in that it supports the notion that exposure to an unavoidable and inescapable aversive stimulus was found to be related to patients' reported depression. Further studies may wish to prospectively consider a larger sample as well as a more comprehensive assessment of premorbid psychological symptoms.

Immunotherapy in the management of sepsis.

PubMed Central

Fagan, E. A.; Singer, M.

1995-01-01

The pathophysiological effects of severe sepsis, septic shock and related syndromes result from tissues damaged by the uncontrolled production of the mediators of inflammation. Early deaths are related primarily to the acute effects of the systemic inflammatory response. Later deaths are related more closely to the consequences of multiple organ dysfunction. Monoclonal antibodies and other immunotherapies have been developed against bacterial products, cytokines and other mediators involved in this systemic inflammatory response. Immunotherapies may improve outcome in the critically ill with sepsis if used early and as part of the therapeutic regimen of antimicrobial agents and intensive care support. PMID:7724438

A Term Infant of Neonatal Toxic Shock Syndrome-Like Exanthematous Disease Complicated with Hemophagocytic Syndrome.

PubMed

Kaga, Akimune; Watanabe, Hiroshi; Miyabayashi, Hiroki; Metoki, Takaya; Kitaoka, Setsuko; Kumaki, Satoru

2016-10-01

Neonatal toxic shock syndrome-like exanthematous disease (NTED) is a newly recognized neonatal infectious disease, caused by the superantigen toxic shock syndrome toxin-1 (TSST-1). TSST-1 is mainly produced by methicillin-resistant Staphylococcus aureus, and the immune responses to TSST-1 are known to cause toxic shock syndrome, a life-threatening infectious disease. The clinical symptoms of NTED are skin rash, fever, and thrombocytopenia, but severe thrombocytopenia is rare in term infants with NTED. Although the cause of NTED is the same as that of toxic shock syndrome, the clinical symptoms of NTED are milder than toxic shock syndrome. The mild phenotype of NTED has been explained by selectively elevated serum levels of anti-inflammatory cytokine interleukin (IL)-10, which suppress immune responses to TSST-1. In the present study, we report a term female infant of NTED complicated with hemophagocytic syndrome (HPS). HPS is characterized by systemic inflammation and hemophagocytosis, caused by uncontrolled activation of T cells and macrophages. The serum IL-10 level of the patient at 4 days of age was relatively low (67 pg/mL) for NTED but still higher than normal controls (< 2.0 pg/mL). The patient also showed severe thrombocytopenia. We speculate that the serum IL-10 level of the patient was enough to supress immune responses to TSST-1, thereby resulting in NTED, but not enough to suppress the onset of HPS. This is the first reported case of NTED complicated with HPS. If a physician encounters an NTED patient with severe cytopenia, microscopic examination of peripheral blood smear should be carried out to exclude HPS.

Walter B. Cannon's World War I experience: treatment of traumatic shock then and now.

PubMed

Ryan, Kathy L

2018-06-01

Walter B. Cannon (1871-1945), perhaps America's preeminent physiologist, volunteered for service with the Army Expeditionary Force (AEF) during World War I. He initially served with Base Hospital No. 5, a unit made up of Harvard clinicians, before moving forward to the front lines to serve at a casualty clearing station run by the British. During his time there, he performed research on wounded soldiers to understand the nature and causes of traumatic shock. Subsequently, Cannon performed animal experimentation on the causes of traumatic shock in the London laboratory of Dr. William Bayliss before being assigned to the AEF Central Medical Laboratory in Dijon, France, where he continued his experimental studies. During this time, he also developed and taught a curriculum on resuscitation of wounded soldiers to medical providers. Although primarily a researcher and teacher, Cannon also performed clinical duties throughout the war, serving with distinction under fire. After the war, Cannon wrote a monograph entitled Traumatic Shock (New York: Appleton, 1923), which encapsulated the knowledge that had been gained during the war, both from direct observation of wounded soldiers, as well as laboratory experimentation on the causes and treatment of traumatic shock. In his monograph, Cannon elucidates a number of principles concerning hemorrhagic shock that were later forgotten, only to be "rediscovered" during the current conflicts in Iraq and Afghanistan. This paper summarizes Cannon's wartime experiences and the knowledge gained concerning traumatic shock during World War I, with a comparison of current combat casualty care practices and knowledge to that which Cannon and his colleagues understood a century ago.

Activation of MDL-1 (CLEC5A) on immature myeloid cells triggers lethal shock in mice

PubMed Central

Cheung, Ricky; Shen, Fran; Phillips, Joseph H.; McGeachy, Mandy J.; Cua, Daniel J.; Heyworth, Paul G.; Pierce, Robert H.

2011-01-01

Systemic inflammatory response syndrome (SIRS) is a potentially lethal condition, as it can progress to shock, multi-organ failure, and death. It can be triggered by infection, tissue damage, or hemorrhage. The role of tissue injury in the progression from SIRS to shock is incompletely understood. Here, we show that treatment of mice with concanavalin A (ConA) to induce liver injury triggered a G-CSF–dependent hepatic infiltration of CD11b+Gr-1+Ly6G+Ly6C+ immature myeloid cells that expressed the orphan receptor myeloid DAP12–associated lectin–1 (MDL-1; also known as CLEC5A). Activation of MDL-1 using dengue virus or an agonist MDL-1–specific antibody in the ConA-treated mice resulted in shock. The MDL-1+ cells were pathogenic, and in vivo depletion of MDL-1+ cells provided protection. Triggering MDL-1 on these cells induced production of NO and TNF-α, which were found to be elevated in the serum of treated mice and required for MDL-1–induced shock. Surprisingly, MDL-1–induced NO and TNF-α production required eNOS but not iNOS. Activation of DAP12, DAP10, Syk, PI3K, and Akt was critical for MDL-1–induced shock. In addition, Akt physically interacted with and activated eNOS. Therefore, triggering of MDL-1 on immature myeloid cells and production of NO and TNF-α may play a critical role in the pathogenesis of shock. Targeting the MDL-1/Syk/PI3K/Akt/eNOS pathway represents a potential new therapeutic strategy to prevent the progression of SIRS to shock. PMID:22005300

Dengue Hemorrhagic Fever: A State-of-the-Art Review Focused in Pulmonary Involvement.

PubMed

de Almeida, Renata Rocha; Paim, Bernardo; de Oliveira, Solange Artimos; Souza, Arthur Soares; Gomes, Antônio Carlos Portugal; Escuissato, Dante Luiz; Zanetti, Gláucia; Marchiori, Edson

2017-08-01

Dengue fever is an arboviral disease transmitted to humans through the bites of infected female Aedes mosquitoes. Dengue virus is a member of the Flaviviridae family, and human infection can be caused by any of the four antigenically distinct serotypes (DENV 1-4). The infection has become recognized as the most important and prevalent arboviral disease in humans, endemic in almost 100 countries worldwide. Nearly 3 billion people live in areas with transmission risk. Autochthonous transmission of the virus in previously disease-free areas, increased incidence in endemic areas, and epidemic resurgence in controlled regions could increase the risk of contracting more severe forms of the disease, such as dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS). Symptomatic dengue virus infection can present with a wide range of clinical manifestations, from mild fever to life-threatening DSS. Thoracic complications may manifest as pleural effusion, pneumonitis, non-cardiogenic pulmonary edema, and hemorrhage/hemoptysis. No vaccine is currently available and no specific treatment for dengue fever exists, but prevention and prompt management of complications in patients with DHF can help reduce mortality. This review describes the main clinical, pathological, and imaging findings of thoracic involvement in DHF.

An expanded dengue syndrome patient with manifestation myocarditis: case report

NASA Astrophysics Data System (ADS)

Arifijanto, M. V.; Luqmana, H. P.; Rusli, M.; Bramantono

2018-03-01

Dengue infection may manifest asymptomatic, dengue fever, dengue hemorrhagic fever, dengue shock syndrome. However, atypical manifestations in other organs have been increasingly reported and called expanded dengue syndrome. One of the cardiac complications in dengue is myocarditis. An 18-year-old woman complains of high fever since 3 days, epistaxis, chest pain, dyspnea, and vomiting. Laboratory examination obtained thrombocytopenia, hemoconcentration, NS1, IgG-IgM dengue positive, CKMB and Troponin- I increase. Electrocardiogram result ischemic anterior-posterior. Echocardiography results hyperechogenic on myocardial suspicious a myocarditis. The patient was diagnosed with acute myocarditis and dengue hemorrhagic fever. Condition improved after five days of treatment. Cardiac complications in dengue are now increasingly observed with the most common case is myocarditis. The main mechanism of dengue myocarditis is still unknown though both direct viral infection and immune mediated damage have been suggested to be the cause of myocardial damage. The low incidence of dengue myocarditis is because it’s asymptomatic and diagnosis is easily missed. Almost all cases of dengue myocarditis are self-limiting and severe myocarditis leading to dilated cardiomyopathy is extremely rare. There have been reported a patient with dengue hemorrhagic fever with manifestation myocarditis. Condition improve with supportive management.

Obscured hemorrhagic pancreatitis after orthotopic heart transplantation complicated with acute right heart failure and hepatic dysfunction: a case report.

PubMed

Lin, Ting-Wei; Tsai, Meng-Ta; Roan, Jun-Neng; Liu, Yi-Sheng; Tsai, Hong-Ming; Luo, Chwan-Yau

2016-12-01

Pancreatitis is a serious complication after cardiac surgery and can lead to significant morbidities and mortality. The incidence of pancreatitis is even higher in patients undergoing heart transplantation than in those undergoing other cardiac surgeries. Nevertheless, the clinical presentations of pancreatitis are frequently atypical in these patients. We report a heart recipient who was complicated with acute right heart failure initially after orthotopic heart transplantation and developed devastating unanticipated hemorrhagic pancreatitis 1 month after the transplantation. This crypto-symptomatic pancreatitis was not diagnosed until massive internal bleeding and hemorrhagic shock occurred, because the typical presentations of acute pancreatitis were masked by the intra-abdominal manifestations caused by right heart failure and congestive liver dysfunction. The patient underwent a successful transarterial embolization. The causes of pancreatitis after heart transplantation include low cardiac output, immunosuppressant use and cytomegalovirus infection. The typical symptoms of pancreatitis might be not apparent in patients after heart transplantation because of their immunosuppressive status. Furthermore, in patients complicated with right heart failure after transplantation, the manifestation of pancreatitis could be even more obscure. The prompt diagnosis is highly depended on the clinician's astuteness.

How to deal with penile carcinoma inguinal metastases invading femoral vessels

PubMed Central

FODOR, MARIUS; PETRUT, BOGDAN; FODOR, LUCIAN

2017-01-01

Penile cancer accounts for 1–10% of men neoplastic diseases and 30–60% of patients have inguinal metastases at the time of diagnosis. Inguinal metastases of penile cancer with femoral vessel involvement could lead to vascular fistula and hemorrhagic shock. We present 3 consecutive patients with inguinal metastases of penile cancer complicated by infection and hemorrhage from femoral vessels invaded by the tumor. Simultaneous extra-anatomical axillo-femoral bypass graft, wide excision of tumor and groin defect reconstruction was used to achieve “tumor-free” oncologic aim and to save the lower limb. We consider the extra-anatomic axillo-femoral bypass associated with wide inguinal tumor excision and defect covering a feasible surgical solution for improving the life quality and extend life expectancy in patients with lymph node metastasis of penile cancer complicated by necrosis, infection and femoral vessel involvement. PMID:29151798

Deciphering the complexity of acute inflammation using mathematical models.

PubMed

Vodovotz, Yoram

2006-01-01

Various stresses elicit an acute, complex inflammatory response, leading to healing but sometimes also to organ dysfunction and death. We constructed both equation-based models (EBM) and agent-based models (ABM) of various degrees of granularity--which encompass the dynamics of relevant cells, cytokines, and the resulting global tissue dysfunction--in order to begin to unravel these inflammatory interactions. The EBMs describe and predict various features of septic shock and trauma/hemorrhage (including the response to anthrax, preconditioning phenomena, and irreversible hemorrhage) and were used to simulate anti-inflammatory strategies in clinical trials. The ABMs that describe the interrelationship between inflammation and wound healing yielded insights into intestinal healing in necrotizing enterocolitis, vocal fold healing during phonotrauma, and skin healing in the setting of diabetic foot ulcers. Modeling may help in understanding the complex interactions among the components of inflammation and response to stress, and therefore aid in the development of novel therapies and diagnostics.

Cola-colored dialysate as a gastrointestinal sequelae of cardiac surgery in a patient who underwent peritoneal dialysis.

PubMed

Ling, Eng-Kian; Lin, Bing-Shi; Chiang, Shou-Shan; Tsai, Ming-Hsien

2012-01-01

The discoloration of effluent peritoneal dialysate, which is transparent in origin, is seen in some particular conditions including chyloperitoneum, calcium channel blocker usage, hemoperitoneum, perforated cholecystitis, iron administration, and hemorrhagic pancreatitis. We report a case of a 60-year-old woman who underwent peritoneal dialysis for 3 years and presented with conspicuous cola-colored (brownish-black) dialysate after a cardiac surgery. The findings of the dialysate analysis and the abdominal computed tomography showed that this discoloration could be due to the presence of methemalbumin caused by pancreatitis (not hemorrhagic) combined with intra-abdominal bleeding-both of which are rare gastrointestinal complications of cardiac surgery. She eventually died of pulseless electrical activity due to severe sepsis with profound shock. Therefore, the rare event of cola-colored peritoneal dialysate could present as severe gastrointestinal sequelae of cardiac surgery and may indicate a poor prognosis.

The Subjective Experience of Patients Diagnosed with Hereditary Hemorrhagic Telangiectasia: a Qualitative Study.

PubMed

Geerts, Laura; Fantini-Hauwel, Carole; Brugallé, Elodie; Boute, Odile; Frénois, Frédéric; Defrance, Lydie; Manouvrier-Hanu, Sylvie; Petit, Florence; Antoine, Pascal

2017-06-01

The aim of the present study was to understand the context and psychological impact for patients diagnosed with hereditary hemorrhagic telangiectasia (HHT). Semi-structured interviews were conducted with 9 patients affected by HHT, and the transcripts were analyzed using interpretative phenomenological analysis. The results of this study allowed us to propose a new hypothesis to explain the delay in diagnosis: the trivialization of symptoms associated with HHT. Moreover, the results showed that a genetic diagnosis of HHT results in emotional shock, uncertainty about the future, and worry about one's children in parents who are confronted with the dilemma of facing the reality of the diagnosis or delaying dealing with the diagnosis until disease onset. Family and personal perceptions of the disease influenced not only the delay in diagnosis but also the emotional and behavioral reactions of patients following a genetic diagnosis.

Females do not express learned helplessness like males do.

PubMed

Dalla, Christina; Edgecomb, Carol; Whetstone, Abigail S; Shors, Tracey J

2008-06-01

Women are more likely than men to suffer from stress-related mental disorders, such as depression. In the present experiments, we identified sex differences in one of the most common animal models of depression, that of learned helplessness. Male and female rats were trained to escape a mild footshock each day for 7 days (controllable stress). Each rat was yoked to another rat that could not escape (uncontrollable stress), but was exposed to the same amount of shock. One day later, all stressed rats and unstressed controls were tested on a more difficult escape task in a different context. Most males exposed to uncontrollable stress did not learn to escape and were therefore helpless. In contrast, most females did learn to escape on the more difficult escape task, irrespective of whether they had been exposed to controllable or uncontrollable stress. The sex differences in helplessness behavior were not dependent on the presence of sex hormones in adulthood, because neither ovariectomy of females nor castration of males abolished them. The absence of helplessness in females was neither dependent on organizational effects of testosterone during the day of birth, because masculinized females did not express helplessness as adults. Thus, sex differences in helplessness behavior are independent of gonadal hormones in adulthood and testosterone exposure during perinatal development. Learned helplessness may not constitute a valid model for depressive behavior in women, at least as reflected by the response of female rats to operant conditioning procedures after stressful experience.

Administration of progesterone after trauma and hemorrhagic shock prevents hepatocellular injury.

PubMed

Kuebler, Joachim F; Yokoyama, Yukihiro; Jarrar, Doraid; Toth, Balazs; Rue, Loring W; Bland, Kirby I; Wang, Ping; Chaudry, Irshad H

2003-07-01

Administration of a single dose of progesterone following trauma and hemorrhage in progesterone-deficient rats would ameliorate the inflammatory response and hepatocellular damage. A university laboratory. Ovariectomized female Sprague-Dawley rats (250-350 g; Charles River Laboratories, Wilmington, Mass) underwent a 5-cm midline laparotomy (ie, induction of soft tissue trauma), were bled to a mean arterial blood pressure of 35 mm Hg for about 90 minutes, and then were resuscitated using Ringer lactate solution. Progesterone (25 mg/kg of body weight) or vehicle was administered subcutaneously at the end of resuscitation. In additional animals, Kupffer cells were isolated following trauma, hemorrhage, and resuscitation and treated in vitro with progesterone, lipopolysaccharide, or both. Six hours following resuscitation, plasma tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) levels and liver myeloperoxidase activity were determined. Hepatocellular function (maximum velocity of indocyanine green clearance [Vmax] and the efficiency of the active transport or Michaelis-Menten constant [Km]) and plasma levels of transaminases were measured 20 hours after resuscitation. Kupffer cell IL-6 and TNF-alpha production were assessed. Plasma levels of TNF-alpha, IL-6, aspartate aminotransferase, and alanine aminotransferase, as well as hepatic myeloperoxidase activity were increased, whereas indocyanine green clearance was depressed in vehicle-treated rats following trauma-hemorrhage. Animals treated with progesterone showed significantly reduced levels of the TNF-alpha, IL-6, and transaminases as well as reduced myeloperoxidase activity in the liver. Progesterone-treated animals showed increased Vmax and Kmax values for indocyanine green. In vitro treatment of Kupffer cells with progesterone decreased TNF-alpha production but did not affect the production of IL-6. Progesterone administration following trauma-hemorrhage ameliorates the proinflammatory response and, subsequently, the hepatocellular injury via direct action on immunocompetent cells.

A fresh frozen plasma to red blood cell transfusion ratio of 1:1 mitigates lung injury in a rat model of damage control resuscitation for hemorrhagic shock.

PubMed

Zhao, Jingxiang; Pan, Guocheng; Wang, Bo; Zhang, Yuhua; You, Guoxing; Wang, Ying; Gao, Dawei; Zhou, Hong; Zhao, Lian

2015-06-01

We aimed to evaluate the effects of resuscitation with different ratios of fresh frozen plasma (FFP) to red blood cells (RBCs) on pulmonary inflammatory injury and to illuminate the beneficial effects of FFP on lung protection compared with lactated ringers (LR) using a rat model of hemorrhagic shock. Rats underwent pressure-controlled hemorrhage for 60 minutes and were then transfused with LR for initial resuscitation. Thereafter, the rats were transfused with varying ratios of FFP:RBC (1:4, 1:2, 1:1, and 2:1) or LR:RBC (1:1) to hold their mean arterial pressure (MAP) at 100 ± 3 mm Hg for 30 minutes. After 4 hours of observation, lung tissue was harvested to determine the wet/dry weight, myeloperoxidase levels, tumor necrosis factor α levels, macrophage inflammatory protein 2 (MIP-2) levels, inducible nitric oxide synthase activity, and the nuclear factor κB p65 DNA-binding activity. With an increase in the FFP:RBC ratio, the volume of required RBC to maintain the target MAP decreased. The MAP value in each group was not significantly different during the whole experiment period. The values of the wet/dry weights and MIP-2 were significantly lower in the FFP:RBC = 1:1 group than the other groups (P < .05). All parameters detected above were predominantly lower in the FFP:RBC = 1:1 group than the FFP:RBC = 1:2 group and the LR:RBC = 1:1 group (P < .05). In addition, all parameter values were lower in the FFP:RBC = 1:1 group than in the FFP:RBC = 2:1 group, but only the wet/dry weight, myeloperoxidase, and MIP-2 values were significantly different (P < .05). Resuscitation with a 1:1 ratio of FFP to RBC results in decreased lung inflammation. Compared with LR, FFP could further mitigate lung inflammatory injury. Copyright © 2015. Published by Elsevier Inc.

Initial Clinical Experience with Ahmed Valve Implantation in Refractory Pediatric Glaucoma

PubMed

Novak-Lauš, Katia; Škunca Herman, Jelena; Šimić Prskalo, Marija; Jurišić, Darija; Mandić, Zdravko

2016-12-01

The purpose is to report on the safety and efficacy of Ahmed Glaucoma Valve (AGV, New World Medical, Inc., Rancho Cucamonga, CA, USA) implantation for the management of refractory pediatric glaucoma observed during one-year follow up period. A retrospective chart review was conducted on 10 eyes, all younger than 11 years, with pediatric glaucoma that underwent AGV implantation for medicamentously uncontrolled intraocular pressure (IOP) between 2010 and 2014. Outcome measures were control of IOP below 23 mm Hg (with or without antiglaucoma medications) and changes in visual acuity. Complications were recorded. After AGV implantation, IOP values ranged from 18 mm Hg to 23 mm Hg (except for one eye with postoperative hypotonia due to suprachoroid hemorrhage, where the postoperative IOP value was 4 mm Hg). The number of antiglaucoma medications was reduced, i.e. four patients had two medications, one patient had one medication, and the others did not need antiglaucoma medication on the last follow-up visit. One eye had suprachoroid hemorrhage, one eye had long-term persistent uveitic membrane, and two eyes had tube-cornea touch. In conclusion, AGV implantation appears to be a viable option for the management of refractory pediatric glaucoma and shows success in IOP control. However, there was a relatively high complication rate limiting the overall success rate.

A Single-Center Review of Facial Fractures as the Result of High-Speed Projectile Injuries

PubMed Central

Liu, Farrah C.; Halsey, Jordan N.; Hoppe, Ian C.; Ciminello, Frank S.; Lee, Edward S.; Granick, Mark S.

2018-01-01

Purpose: Gunshot injuries to the face that result in fractures of the underlying skeleton present a challenge in management. The goal of this study was to evaluate patterns of facial fractures as a result of gunshot injuries and strategies for management. Methods: A retrospective review of facial fractures resulting from gunshot injuries in a level 1 trauma center was performed for the years 2000 to 2012. Data were collected for patient demographics, fracture distribution, concomitant injuries, and surgical management strategies. Results: A total of 190 patients sustained facial fractures from a gunshot injury. The average age was 29.9 years, and 90% were male. Sixteen injuries were self-inflicted. The most common fractures were of the mandible and the orbit. Uncontrolled hemorrhage was noted on presentation in 68 patients; 100 patients were intubated on arrival. The average Glasgow Coma Scale score on arrival was 11.9. Concomitant injuries included skull fracture, intracranial hemorrhage, and intrathoracic injury. Surgical management was required in 89 patients. Nine patients required soft-tissue coverage. Thirty patients expired. Conclusion: Gunshot injuries to the face resulting in fractures of the underlying skeleton have high instances of morbidity and mortality. Life-threatening concomitant injuries can complicate management of facial fractures in this population. PMID:29713397

A low-cost uterine balloon tamponade for management of postpartum hemorrhage: modeling the potential impact on maternal mortality and morbidity in sub-Saharan Africa.

PubMed

Herrick, Tara; Mvundura, Mercy; Burke, Thomas F; Abu-Haydar, Elizabeth

2017-11-13

Postpartum hemorrhage (PPH) is the leading cause of maternal deaths worldwide. This study sought to quantify the potential health impact (morbidity and mortality reductions) that a low-cost uterine balloon tamponade (UBT) could have on women suffering from uncontrolled PPH due to uterine atony in sub-Saharan Africa. The Maternal and Neonatal Directed Assessment of Technology (MANDATE) model was used to estimate maternal deaths, surgeries averted, and cases of severe anemia prevented through UBT use among women with PPH who receive a uterotonic drug but fail this therapy in a health facility. Estimates were generated for the year 2018. The main outcome measures were lives saved, surgeries averted, and severe anemia prevented. The base case model estimated that widespread use of a low-cost UBT in clinics and hospitals could save 6547 lives (an 11% reduction in maternal deaths), avert 10,823 surgeries, and prevent 634 severe anemia cases in sub-Saharan Africa annually. A low-cost UBT has a strong potential to save lives and reduce morbidity. It can also potentially reduce costly downstream interventions for women who give birth in a health care facility. This technology may be especially useful for meeting global targets for reducing maternal mortality as identified in Sustainable Development Goal 3.

Ebola haemorrhagic fever virus: pathogenesis, immune responses, potential prevention.

PubMed

Marcinkiewicz, Janusz; Bryniarski, Krzysztof; Nazimek, Katarzyna

2014-01-01

Ebola zoonotic RNA filovirus represents human most virulent and lethal pathogens, which induces acute hemorrhagic fever and death within few days in a range of 60-90% of symptomatic individuals. Last outbreak in 2014 in West Africa caused panic that Ebola epidemic can be spread to other continents. Number of deaths in late December reached almost 8,000 individuals out of more than 20,000 symptomatic patients. It seems that only a coordinated international response could counteract the further spread of Ebola. Major innate immunity mechanisms against Ebola are associated with the production of interferons, that are inhibited by viral proteins. Activation of host NK cells was recognized as a leading immune function responsible for recovery of infected people. Uncontrolled cell infection by Ebola leads to an impairment of immunity with cytokine storm, coagulopathy, systemic bleeding, multi-organ failure and death. Tested prevention strategies to induce antiviral immunity include: i. recombinant virus formulations (vaccines); ii. cocktail of monoclonal antibodies (serotherapy); iii. alternative RNA-interference-based antiviral methods. Maintaining the highest standards of aseptic and antiseptic precautions is equally important. Present brief review summarizes a current knowledge concerning pathogenesis of Ebola hemorrhagic disease and the virus interaction with the immune system and discusses recent advances in prevention of Ebola infection by vaccination and serotherapy.

The focused abdominal sonography for trauma examination can reliably identify patients with significant intra-abdominal hemorrhage in life-threatening pelvic fractures.

PubMed

Christian, Nicole Townsend; Burlew, Clay Cothren; Moore, Ernest E; Geddes, Andrea E; Wagenaar, Amy E; Fox, Charles J; Pieracci, Fredric M

2018-06-01

The focused abdominal sonography for trauma (FAST) examination has been reported to be unreliable in pelvic fracture patients. Additionally, given the advent of new therapeutic interventions, such as resuscitative endovascular balloon occlusion of the aorta (REBOA), rapid identification of intra-abdominal hemorrhage compared with Zone III hemorrhage may guide different therapeutic strategies. We hypothesized that FAST is reliable for detecting clinically significant intra-abdominal hemorrhage in the face of complex pelvic fractures. Our pelvic fracture database of all hemodynamically unstable patients requiring intervention from January 1, 2005, to July 1, 2015, was reviewed. The FAST examination was compared with operative and computed tomography (CT) scan findings. Confirmatory evaluation for FAST(-) patients was considered positive if therapeutic intervention was required. During the study period, 81 patients in refractory shock with FAST imaging in our emergency department (ED) underwent pelvic packing. Mean age was 45 ± 2 years and Injury Severity Score was 50 ± 1.5. The FAST examination was negative in 53 patients; 52 patients did not require operative intervention for abdominal bleeding while one patient required splenectomy. The FAST examination was positive in 28 patients; 26 had findings confirmed by CT or laparotomy while two patients did not have intra-abdominal hemorrhage on further evaluation. The sensitivity and specificity for FAST in this population was 96% and 96%, respectively, positive predictive value was 93%, and negative predictive value was 98%. The false-negative and -positive rates for FAST were 2% and 7%. Focused abdominal sonography for trauma examination reliably identifies clinically significant hemoperitoneum in life-threatening, pelvic fracture related hemorrhage. The incidence of a false-negative FAST in this unstable pelvic fracture population was 2%. FAST results may be used when determining the role of REBOA in these multisystem trauma patients and requires further study. REBOA placement should be considered in hemodynamically unstable pelvic fracture patients who are FAST(-), while laparotomy should be used in FAST(+) patients. Therapeutic, level IV.

Non-traumatic hemorrhage is controlled with REBOA in acute phase then mortality increases gradually by non-hemorrhagic causes: DIRECT-IABO registry in Japan.

PubMed

Matsumura, Y; Matsumoto, J; Idoguchi, K; Kondo, H; Ishida, T; Kon, Y; Tomita, K; Ishida, K; Hirose, T; Umakoshi, K; Funabiki, T

2017-08-22

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is now a feasible and less invasive resuscitation procedure. This study aimed to compare the clinical course of trauma and non-trauma patients undergoing REBOA. Patient demographics, etiology, bleeding sites, hemodynamic response, length of critical care, and cause of death were recorded. Characteristics and outcomes were compared between non-trauma and trauma patients. Kaplan-Meier survival analysis was then conducted. Between August 2011 and December 2015, 142 (36 non-trauma; 106 trauma) cases were analyzed. Non-traumatic etiologies included gastrointestinal bleeding, obstetrics and gynecology-derived events, visceral aneurysm, abdominal aortic aneurysm, and post-abdominal surgery. The abdomen was a common bleeding site (69%), followed by the pelvis or extra-pelvic retroperitoneum. None of the non-trauma patients had multiple bleeding sites, whereas 45% of trauma patients did (P < 0.001). No non-trauma patients required resuscitative thoracotomy compared with 28% of the trauma patients (P < 0.001). Non-trauma patients presented a lower 24-h mortality than trauma patients (19 vs. 51%, P = 0.001). The non-trauma cases demonstrated a gradual but prolonged increased mortality, whereas survival in trauma cases rapidly declined (P = 0.009) with similar hospital mortality (68 vs. 64%). Non-trauma patients who survived for 24 h had 0 ventilator-free days and 0 ICU-free days vs. a median of 19 and 12, respectively, for trauma patients (P = 0.33 and 0.39, respectively). Non-hemorrhagic death was more common in non-trauma vs. trauma patients (83 vs. 33%, P < 0.001). Non-traumatic hemorrhagic shock often resulted from a single bleeding site, and resulted in better 24-h survival than traumatic hemorrhage among Japanese patients who underwent REBOA. However, hospital mortality increased steadily in non-trauma patients affected by non-hemorrhagic causes after a longer period of critical care.

Acidosis and Correction of Acidosis Does Not Affect rFVIIa Function in Swine

DTIC Science & Technology

2012-12-15

and its correction (or normalization of pH) has been suggested before clinical use of rFVIIa [21, 22]. FVII is one of the many coagulation factors ...A or B (deficient in Factor VIII and Factor IX). Mice lacking FVII die in-utero or soon after birth due to vascular and hemostatic defects [23...the activity of recombinant activated Factor VII (rFVIIa) in vitro. However, it is not known if acidosis induced by hemorrhagic shock or infusion of

Development of Liposome Encapsulated Hemoglobin (LEH) and Studies of Hemorrhagic Shock by Use of Imaging Studies with Oxygen-15 and Other Radiotracers

DTIC Science & Technology

2004-09-01

hemoglobin in the oxy-hemoglobin state [Stratton 1988; Takeoka 1997]. 3) Decreased Vasoactivity. Because LEH has physical properties closer to red cells...in rabbit arterial segments. J Appl Physiol 82:1826-1835. [21] Sakai H, Horinouchi H, Masada Y, Takeoka S, Ikeda E, Takaori M, Kobayashi K and...4317-4325. [22] Sakai H, Horinouchi H, Tomiyama K, Ikeda E, Takeoka S, Kobayashi K and Tsuchida E (2001) Hemoglobin-vesicles as oxygen carriers

Clinical Study of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) for Severe Pelvic Fracture and Intra Abdominal Hemorrhagic Shock using Continuous Vital Signs

DTIC Science & Technology

2017-11-01

University of Maryland Baltimore, MD 21202 DATE OF REPORT: November 2017 TYPE OF REPORT: Final PREPARED FOR: U.S. Army Medical Research and Materiel...ES) 10. SPONSOR/MONITOR’S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5014 11. SPONSOR/MONITOR’S REPORT...Prytime Medical , Boerne, TX )) in October 2015, we incorporated this catheter into our practice in February 2016. Our REBOA training course (Basic

Studies of the Effects of Perfluorocarbon Emulsions on Platelet Number and Function in Models of Critical Battlefield Injury

DTIC Science & Technology

2016-01-01

TBI), hemorrhagic shock and burns by enhanced delivery of oxygen . A class-based side effect of PFC (day 2-5 after infusion in 30-50%) may be...anesthesia level assessment. Animals were transported to the laboratory. Then, the animals were intubated and ventilated with 70% nitrogen/30% oxygen ...intubated with an endotracheal tube (ID= 9~10 mm with cuff), an orogastric tube placed to expel vomit, and ventilated with mixed nitrogen/ oxygen (80:20

Prevention of Trauma/Hemorrhagic Shock-Induced Mortality, Apoptosis, Inflammation and Mitochondrial Dysfunction

DTIC Science & Technology

2015-02-01

strongly suggesting a contribution to prevention of pulmonary cell apoptosis (Table 1).Discussion To investigate the impact of T/HS on the innate host...we hypothesized that loss of these cells may contribute to impaired innate host defense of the lung following T/HS. We began to address the role of the...intervention involves restoration of impaired innate epithelial cell immunity within the lung. Within the first category is the use of IL-6 as a resus

Studies of the Effects of Perfluorocarbon Emulsions on Platelet Number and Function in Models of Critical Battlefield Injury

DTIC Science & Technology

2015-01-01

Year three: Using the ovine polytrauma model of combined hemorrhagic shock and blast TBI to test the effect of PFC intravenous infusion on platelet...could not be reassembled until late October. The schedule for testing and developing a sheep polytrauma model which combines blast injury with...This research project going forward is to assess PFC’s effect on platelet number and function in sheep 9 10 polytrauma model which combined blast

Application of Combined Cardioprotective Agents to Preserve Organ Function and Improve Survival during Experimental Hemorrhagic Shock

DTIC Science & Technology

2017-09-01

performed the studies on 15 rats (8 rats in preconditioning group and 7 rats in control group ), and observed that only 1 rat in the female preconditioning...This first set of data suggested that the goals of approximately 33% or more rats surviving over 3 days in the control group could not be reached... control group . The findings with isoflurane were unexpected but may be some of the most important findings to date. If it is protective then this

Geldanamycin Treatment Inhibits Hemorrhage-induced Increases in KLF6 and iNOS Expression in Unresuscitated Mouse Organs: Role of Inducible HSP70

DTIC Science & Technology

2004-08-01

stress-related proteins and whether changes can be inhibited by drugs reported to provide protection from ischemia and reperfusion injury . Male Swiss...stimulated by heat stress limit injury to tissues caused by ischemia and reperfusion (34). Likewise, inhibition of nitric oxide production results in...transfer of heat shock protein 70 protects lung grafts from ischemia - reperfusion injury . Ann Thorac Surg 67: 1421–1427, 1999. 13. Kiang JG, Carr FE, Burns

Modulation of Acetylation: Creating a Pro-survival and Anti-Inflammatory Phenotype in Lethal Hemorrhagic and Septic Shock

DTIC Science & Technology

2011-01-01

myocardial ischemia - reperfusion injury in mice,” The FASEB Journal, vol. 22, no. 10, pp. 3549– 3560, 2008. [49] A. Krivoruchko and K. B. Storey...H3/4 in vitro and in vivo [48]. Using standard murine model of heart ischemia - reperfusion , Granger. demonstrated that HDACI significantly reduce...phosphorylation of Akt and decreases the expression of proapoptotic BAD ( Bcl -xl/ Bcl - 2 associated death promoter) 4 Journal of Biomedicine and

Prevention of Trauma/Hemorrhagic Shock-Induced Mortality, Apoptosis, Inflammation and Mitochondrial Dysfunction Using IL-6 as a Resuscitation Adjuvant

DTIC Science & Technology

2011-12-01

infiltrating PMNs is not merely limited to organs that have been directly injured from trauma. Ischemia - reperfusion injury (which occurs after... injury by facilitating inflammatory cell adhesion in an animal model of myocardial ischemia - reperfusion [61,62]. Fabp2 and Fabp5 have been implicated in...Bauer A, Tweardy DJ (1998) Activation of STAT proteins following ischemia reperfusion injury demonstrates a distinct IL- 6 and G-CSF mediated profile

Prevention of Trauma/Hemorrhagic Shock-Induced Mortality, Apoptosis, Inflammation and Mitochondrial Dysfunction

DTIC Science & Technology

2012-12-01

injury, which they wanted to use to establish if kidney injury occurred in our standard rat T/HS model and to determine whether kidney injury could be...prevented by use of IL-6 as a resuscitation adjuvant. In this experiment, we subjected 6 rats each to either our sham protocol or our standard T/HS...time of accumulation in our standard T/HS protocol. Our results demonstrated that shred blood accumulated sIL-6R over time to concentrations (100 ng

A Novel Method for Inducing Therapeutic Hypothermia in a Swine Model of Blast-Induced Traumatic Brain Injury with Associated Hemorrhagic Shock

DTIC Science & Technology

2012-05-01

injury (TBI) remains a significant cause of mortality and morbidity in military and civilian life . The use of therapeutic hypothermia in the...of hypothermia using the lungs as a heat exchanger. Using an inhalant of perfluorocarbon (PFC) mist and heliox, evaporative cooling is achieved...animals has been built and bench tested. The device consists of a ventilator capable of delivering cooled respiratory gases and aerosol PFC into the

Hypertonic 15% sodium pyruvate offers no initial resuscitation advantage compared with 8% hypertonic NACl in sheep with multiple hemorrhages.

PubMed

do Nascimento, Paulo; Vaid, Sumreen U; Hoskins, Stephen L; Espana, Jonathan M; Kinsky, Michael P; Kramer, George C

2007-05-01

Initial fluid resuscitation of hemorrhagic shock might be enhanced by the infusion of monocarboxylate-energy substrates. We evaluated hemodynamics, metabolism, and fluid dynamics for initial resuscitation of hemorrhage using small volume 15% sodium pyruvate solution (HPY) compared with osmotically matched 8% hypertonic saline (HS). Instrumented conscious sheep were hemorrhaged 25 mL/kg at time zero through 15 min (T0-T15) and 5 mL/kg for 5 min at T50 to T55 and T70 to T75. Fluid resuscitation from T30 to T180 was performed by a computer-controlled closed-loop system, which titrated infusion rate to a mean arterial pressure of 90 mmHg. Initial infusion was 4 mL/kg of either HPY or HS, followed by the administration of lactated Ringer. Both HPY and HS restored cardiac index similarly. The lactate/pyruvate ratio was used to assess metabolic debt and was significantly higher (T180), whereas oxygen delivery was significantly lower (T120) with HPY versus HS. Total fluid administered was similar, with 43.7 +/- 6.2 mL/kg for HPY and 39.4 +/- 6.8 mL/kg for HS. Plasma volume was similarly increased and approached baseline values for both groups. Initial resuscitation with small volume HPY offered no hemodynamic or metabolic advantage compared with small volume HS when the fluids were infused to an end point pressure.

Postpartum Hemorrhage.

PubMed

Newsome, Janice; Martin, Jonathan G; Bercu, Zachary; Shah, Jay; Shekhani, Haris; Peters, Gail

2017-12-01

Interventional radiologists are often called for emergent control of abnormal uterine bleeding. Bleeding, even heavy bleeding as a result of uterine fibroids is not a common emergent procedure; instead, pregnancy and pregnancy related conditions, trauma and malignancy associated with bleeding can be the source of many interventional radiology on call events or procedures. Postpartum hemorrhage (PPH) is the most common cause, and is defined as blood loss of 500mL after vaginal delivery or 1000mL after cesarean section. Several authors have suggested a simpler definition of any amount of blood loss that creates hemodynamic instability in the mother. Regardless, PPH can be a life-threatening emergency and is a leading cause of maternal mortality requiring prompt action. Primary PPH is bleeding within the first 24 hour of delivery and secondary PPH is hemorrhage that occurs more than 24 hour after delivery. In addition to death, other serious morbidity resulting from postpartum bleeding includes shock, adult respiratory distress syndrome, coagulopathy, and loss of fertility due to hysterectomy. Transcatheter uterine artery embolization was first introduced as a treatment for PPH in 1979. It is a nonsurgical, minimally invasive, extremely safe and effective treatment for controlling excessive bleeding of the female reproductive track usually after conservative measures have failed, yet somewhat underused. Referring providers have limited awareness of the procedure. In hospitals where interventional radiologists have the experience and technical expertise to perform pelvic arteriography and embolization, this therapeutic option can play a pivotal role in the management of emergent obstetric hemorrhage. Copyright © 2017 Elsevier Inc. All rights reserved.