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Todd E Rasmussen - One of the best experts on this subject based on the ideXlab platform.
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the inflammatory sequelae of aortic balloon occlusion in Hemorrhagic Shock
Journal of Surgical Research, 2014Co-Authors: Jonathan J Morrison, James D Ross, Nickolay P Markov, Daniel J Scott, Jerry R Spencer, Todd E RasmussenAbstract:Abstract Background Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a hemorrhage control and resuscitative adjunct that has been demonstrated to improve central perfusion during Hemorrhagic Shock. The aim of this study was to characterize the systemic inflammatory response associated and cardiopulmonary sequelae with 30, 60, and 90 min of balloon occlusion and Shock on the release of interleukin 6 (IL-6) and tumor necrosis factor alpha. Materials and methods Anesthetized female Yorkshire swine ( Sus scrofa, weight 70–90 kg) underwent a 35% blood volume–controlled hemorrhage followed by thoracic aortic balloon occlusion of 30 (30-REBOA, n = 6), 60 (60-REBOA, n = 8), and 90 min (90-REBOA, n = 6). This was followed by resuscitation with whole blood and crystalloid over 6 h. Animals then underwent 48 h of critical care with sedation, fluid, and vasopressor support. Results All animals were successfully induced into Hemorrhagic Shock without mortality. All groups responded to aortic occlusion with a rise in blood pressure above baseline values. IL-6, as measured (picogram per milliliter) at 8 h, was significantly elevated from baseline values in the 60-REBOA and 90-REBOA groups: 289 ± 258 versus 10 ± 5; P = 0.018 and 630 ± 348; P = 0.007, respectively. There was a trend toward greater vasopressor use ( P = 0.183) and increased incidence of acute respiratory distress syndrome ( P = 0.052) across the groups. Conclusions REBOA is a useful adjunct in supporting central perfusion during Hemorrhagic Shock; however, increasing occlusion time and Shock results in a greater IL-6 release. Clinicians must anticipate inflammation-mediated organ failure in post-REBOA use patients.
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a novel fluoroscopy free resuscitative endovascular aortic balloon occlusion system in a model of Hemorrhagic Shock
Journal of Trauma-injury Infection and Critical Care, 2013Co-Authors: Daniel J Scott, Carole Y Villamaria, Robert Houston, Jonathan L Eliason, Jonathan J Morrison, Jerry R Spencer, Todd E RasmussenAbstract:Abstract : Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a potentially lifesaving maneuver in the setting of Hemorrhagic Shock. However, emergent use of REBOA is limited by existing technology, which requires large sheath arterial access and fluoroscopy- guided balloon positioning. The objectives of this study were to describe a new, fluoroscopy-free REBOA system and to compare its efficacy to existing technology. An additional objective was to characterize the survivability of 60 minutes of REBOA using these systems in a model of Hemorrhagic Shock. This study reports the feasibility and efficacy of a novel, fluoroscopy-free REBOA system in a model of Shock. Despite a significant physiologic insult, 60 minutes of REBOA is tolerated and recoverable. Development of lower profile, fluoroscopy-free endovascular balloon occlusion catheters may allow proactive aortic control in patients at risk for Hemorrhagic Shock and cardiovascular collapse.
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Hemorrhagic Shock worsens neuromuscular recovery in a porcine model of hind limb vascular injury and ischemia reperfusion
Journal of Vascular Surgery, 2011Co-Authors: Heather Hancock, Jerry R Spencer, Todd E Rasmussen, Adam Stannard, Gabriel E Burkhardt, Ken Williams, Patti Dixon, Jerry CowartAbstract:Background In order to advance beyond basic statistical limb salvage to improved functional or quality limb salvage, a better understanding of the ischemic threshold of the limb is required. To date, models of extremity ischemia and reperfusion involve small animals and few include survival with physiologic measures of nerve and muscle recovery. In addition, the effect of Hemorrhagic Shock on the ischemic threshold of the extremity is unknown. This study characterized the effect of class III Hemorrhagic Shock on the ischemic threshold of the extremity in a large-animal model of neuromuscular recovery. Methods Yorkshire/Landrace-cross swine (weight, 70-90 kg) were randomized to iliac artery repair either immediately or at 1, 3, or 6 hours after vessel loop occlusion and arteriotomy. A fifth group underwent excision of the arterial segment without repair to represent ligation. Class III Shock was created by removing 35% of total blood volume using a variable rate model. Animals were monitored for 14 days to serially collect markers of functional recovery. Results Animals with ≤1 hour ischemia (control) had clinically normal limb function by the end of the 2-week observation period, with minimal muscle and nerve changes on histology. Separate analysis of contralateral, nonexperimental limbs revealed normal histology and function. After 3 hours of ischemia, functional recovery was impaired, with moderate-to-severe degeneration of nerve and muscle noted on histology. Animals undergoing 6 hours of ischemia or ligation had minimal electromyelography response and severe systemic inflammation, which correlated with severe muscle and nerve degeneration. Concurrent class III Hemorrhagic Shock was associated with a decrement in neuromuscular recovery across all groups but was greatest in groups undergoing ≥3 hours of extremity ischemia ( P Conclusions This study demonstrates the feasibility of combined Hemorrhagic Shock and extremity ischemia-reperfusion in a large-animal survival model. The presence of Hemorrhagic Shock compounds the effect of extremity ischemia, reducing the ischemic threshold of the limb to
Achille P Caputi - One of the best experts on this subject based on the ideXlab platform.
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evidence for a role of nuclear factor κb in acute hypovolemic Hemorrhagic Shock
Surgery, 2002Co-Authors: Domenica Altavilla, Antonino Saitta, Giovanni Squadrito, Mariarosaria Galeano, Saverio F Venuti, Salvatore Guarini, Carla Bazzani, Alfio Bertolini, Achille P Caputi, Francesco SquadritoAbstract:Abstract Background. In acute hypovolemic Shock, a rapid systemic release of the inflammatory cytokine tumor necrosis factor (TNF-α) contributes to vascular failure. Nuclear factor κB (NF-κB) is an ubiquitous rapid-response transcription factor involved in inflammatory reactions and exerts its effect by expressing cytokines, chemokines, and cell adhesion molecules. The purpose of this study was to evaluate the role of NF-κB in acute hypovolemic Hemorrhagic Shock. Methods. Hemorrhagic Shock was induced in anesthetized male rats by intermittently withdrawing blood from an iliac catheter for 20 minutes (bleeding period) until mean arterial blood pressure (MAP) decreased and stabilized within the range of 20 to 30 mm Hg. Two minutes after bleeding was discontinued the rats received tacrolimus (100 μg/kg), an inhibitor of NF-κB activation, or its vehicle. We then evaluated survival rate and survival time, liver NF-κB activation by means of electrophoretic mobility shift assay, liver IκBα protein in the cytoplasm, hepatic TNF-α messenger RNA expression, plasma TNF-α, arterial blood pressure, and the contractile response of aortic rings to phenylephrine. Results. Rats that underwent Hemorrhagic Shock died 28 ± 2 minutes after bleeding was discontinued, experienced marked hypotension (MAP, 20-30 mm Hg), and had enhanced plasma levels of TNF-α (218 ± 28 pg/mL 20 minutes after bleeding was discontinued). Aortas taken 20 minutes after bleeding was discontinued in rats that underwent Hemorrhagic Shock showed marked hyporeactivity to phenylephrine (1 nmol/L-10 μmol/L) compared with aortas harvested from sham Shocked rats. Rats that underwent Hemorrhagic Shock also had increased levels of TNF-α messenger RNA in the liver. Furthermore, electrophoretic mobility shift assay showed that liver NF-κB binding activity increased in the nucleus, and Western blot analysis suggested that the levels of inhibitory IκBα protein in the cytoplasm decreased. Tacrolimus (100 μg/kg, administered 2 minutes after bleeding was discontinued) inhibited the loss of IκBα protein from the cytoplasm and prevented NF-κB binding activity in the nucleus. Moreover, tacrolimus increased survival time (118 ± 7 minutes; P Conclusions. Our results suggest that acute blood loss (50% of the estimated total blood volume during a 20-minute period) causes activation of NF-κB and that tacrolimus, by inhibiting this transcription factor, protects against acute hypovolemic Shock. (Surgery 2002;131:50-8.)
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role of tumor necrosis factor alpha in acute hypovolemic Hemorrhagic Shock in rats
American Journal of Physiology-heart and Circulatory Physiology, 1994Co-Authors: Basilia Zingarelli, Domenica Altavilla, Francesco Squadrito, Gioacchino Calapai, M Di Rosa, Achille P CaputiAbstract:Hemorrhagic Shock was induced in male anesthetized rats by intermittently withdrawing blood from an iliac catheter until mean arterial blood pressure (MAP) fell and stabilized within the range of 2...
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evidence for a role of nitric oxide in hypovolemic Hemorrhagic Shock
Journal of Cardiovascular Pharmacology, 1992Co-Authors: Basilia Zingarelli, Domenica Altavilla, Antonino Saitta, Francesco Squadrito, Gioacchino Calapai, Giuseppe M Campo, Margherita Calo, Achille P CaputiAbstract:Summary: Hypovolemic Hemorrhagic Shock was induced in rats by intermittently withdrawing blood from an iliac catheter for 20 min until mean arterial blood pressure (MAP) decreased to 30 mm Hg. Survival rate, survival time, plasma myocardial depressant factor (MDF) activity, MAP, and microscopic gastric alterations were then evaluated. NG-nitro-L-arginine methyl-ester (L-NAME), a selective inhibitor of nitric oxide (NO) production from L-arginine, was injected intravenously (i.v.) after the bleeding was discontinued. Untreated Hemorrhagic Shocked rats died in 27 ± 3.3 min, had enhanced plasma activity of MDF, and exhibited Hemorrhagic infiltrates in gastric fundus mucosa. L-NAME (5 and 10 mg/kg) significantly increased survival rate and time, blunted the increase in plasma MDF activity, and protected against the gastric lesions induced by Hemorrhagic hypovolemic Shock. All these protective effects were reversed by a bolus of L-arginine (30 mg/kg/i.v.), given 2 min after administration of L-NAME. Our findings suggest that NO production plays an important role in the pathophysiology of Hemorrhagic Shock.
Francesco Squadrito - One of the best experts on this subject based on the ideXlab platform.
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evidence for a role of nuclear factor κb in acute hypovolemic Hemorrhagic Shock
Surgery, 2002Co-Authors: Domenica Altavilla, Antonino Saitta, Giovanni Squadrito, Mariarosaria Galeano, Saverio F Venuti, Salvatore Guarini, Carla Bazzani, Alfio Bertolini, Achille P Caputi, Francesco SquadritoAbstract:Abstract Background. In acute hypovolemic Shock, a rapid systemic release of the inflammatory cytokine tumor necrosis factor (TNF-α) contributes to vascular failure. Nuclear factor κB (NF-κB) is an ubiquitous rapid-response transcription factor involved in inflammatory reactions and exerts its effect by expressing cytokines, chemokines, and cell adhesion molecules. The purpose of this study was to evaluate the role of NF-κB in acute hypovolemic Hemorrhagic Shock. Methods. Hemorrhagic Shock was induced in anesthetized male rats by intermittently withdrawing blood from an iliac catheter for 20 minutes (bleeding period) until mean arterial blood pressure (MAP) decreased and stabilized within the range of 20 to 30 mm Hg. Two minutes after bleeding was discontinued the rats received tacrolimus (100 μg/kg), an inhibitor of NF-κB activation, or its vehicle. We then evaluated survival rate and survival time, liver NF-κB activation by means of electrophoretic mobility shift assay, liver IκBα protein in the cytoplasm, hepatic TNF-α messenger RNA expression, plasma TNF-α, arterial blood pressure, and the contractile response of aortic rings to phenylephrine. Results. Rats that underwent Hemorrhagic Shock died 28 ± 2 minutes after bleeding was discontinued, experienced marked hypotension (MAP, 20-30 mm Hg), and had enhanced plasma levels of TNF-α (218 ± 28 pg/mL 20 minutes after bleeding was discontinued). Aortas taken 20 minutes after bleeding was discontinued in rats that underwent Hemorrhagic Shock showed marked hyporeactivity to phenylephrine (1 nmol/L-10 μmol/L) compared with aortas harvested from sham Shocked rats. Rats that underwent Hemorrhagic Shock also had increased levels of TNF-α messenger RNA in the liver. Furthermore, electrophoretic mobility shift assay showed that liver NF-κB binding activity increased in the nucleus, and Western blot analysis suggested that the levels of inhibitory IκBα protein in the cytoplasm decreased. Tacrolimus (100 μg/kg, administered 2 minutes after bleeding was discontinued) inhibited the loss of IκBα protein from the cytoplasm and prevented NF-κB binding activity in the nucleus. Moreover, tacrolimus increased survival time (118 ± 7 minutes; P Conclusions. Our results suggest that acute blood loss (50% of the estimated total blood volume during a 20-minute period) causes activation of NF-κB and that tacrolimus, by inhibiting this transcription factor, protects against acute hypovolemic Shock. (Surgery 2002;131:50-8.)
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role of tumor necrosis factor alpha in acute hypovolemic Hemorrhagic Shock in rats
American Journal of Physiology-heart and Circulatory Physiology, 1994Co-Authors: Basilia Zingarelli, Domenica Altavilla, Francesco Squadrito, Gioacchino Calapai, M Di Rosa, Achille P CaputiAbstract:Hemorrhagic Shock was induced in male anesthetized rats by intermittently withdrawing blood from an iliac catheter until mean arterial blood pressure (MAP) fell and stabilized within the range of 2...
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evidence for a role of nitric oxide in hypovolemic Hemorrhagic Shock
Journal of Cardiovascular Pharmacology, 1992Co-Authors: Basilia Zingarelli, Domenica Altavilla, Antonino Saitta, Francesco Squadrito, Gioacchino Calapai, Giuseppe M Campo, Margherita Calo, Achille P CaputiAbstract:Summary: Hypovolemic Hemorrhagic Shock was induced in rats by intermittently withdrawing blood from an iliac catheter for 20 min until mean arterial blood pressure (MAP) decreased to 30 mm Hg. Survival rate, survival time, plasma myocardial depressant factor (MDF) activity, MAP, and microscopic gastric alterations were then evaluated. NG-nitro-L-arginine methyl-ester (L-NAME), a selective inhibitor of nitric oxide (NO) production from L-arginine, was injected intravenously (i.v.) after the bleeding was discontinued. Untreated Hemorrhagic Shocked rats died in 27 ± 3.3 min, had enhanced plasma activity of MDF, and exhibited Hemorrhagic infiltrates in gastric fundus mucosa. L-NAME (5 and 10 mg/kg) significantly increased survival rate and time, blunted the increase in plasma MDF activity, and protected against the gastric lesions induced by Hemorrhagic hypovolemic Shock. All these protective effects were reversed by a bolus of L-arginine (30 mg/kg/i.v.), given 2 min after administration of L-NAME. Our findings suggest that NO production plays an important role in the pathophysiology of Hemorrhagic Shock.
Rosemary A Kozar - One of the best experts on this subject based on the ideXlab platform.
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lyophilized plasma attenuates vascular permeability inflammation and lung injury in Hemorrhagic Shock
PLOS ONE, 2018Co-Authors: Shibani Pati, Zhanglong Peng, Katherine Wataha, Byron Miyazawa, Daniel R Potter, Rosemary A KozarAbstract: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.
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loss of syndecan 1 abrogates the pulmonary protective phenotype induced by plasma after Hemorrhagic Shock
Shock, 2017Co-Authors: Zhanglong Peng, Pyong Woo Park, Rosemary A KozarAbstract:Syndecan-1 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 (WT) and syndecan-1−/− mice were subjected to Hemorrhagic Shock followed by resuscitation with lactated ringers (LR) or FFP and compared to Shock alone and shams. Lungs were harvested after 3 hours 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 lead 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.
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syndecan 1 restitution by plasma after Hemorrhagic Shock
Journal of Trauma-injury Infection and Critical Care, 2015Co-Authors: Rosemary A Kozar, Shibani PatiAbstract:Over the past seven years, there have been a number of retrospective studies demonstrating that the early and empiric use of fresh frozen plasma to patients in Hemorrhagic Shock and receiving a massive transfusion is beneficial.1–3 More recently a prospective observational multicenter massive transfusion study (PROMMTT), confirmed that increased ratios of plasma to red blood cells and platelets to red blood cells decreased early mortality from hemorrhage.4 A prospective randomized optimum platelet and plasma ratios (PROP:P:R) study was recently completed and currently under analysis. Results of these studies have dramatically changed the manner in which bleeding trauma patients are resuscitated5, though the mechanism of protection remains unclear. We hypothesized that central to plasma’s protection is the endothelium. The important role of the endothelium to the pathophysiology of Hemorrhagic Shock has been coined the endotheliopathy of trauma.6 Injury to the endothelium from trauma and hemorrhage results in alterations in coagulation, inflammation, vasoregulation, and organ-specific barrier integrity. This review will focus on the endothelium as a therapeutic target to mechanistically explain the protection provided by plasma to the endothelium.
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modulation of syndecan 1 shedding after Hemorrhagic Shock and resuscitation
PLOS ONE, 2011Co-Authors: Ricky J L Haywoodwatson, Pyong Woo Park, John B. Holcomb, Ernest A Gonzalez, Zhanglong Peng, Shibani Pati, Weiwei Wang, Ana Maria Zaske, Tyler Menge, Rosemary A KozarAbstract:The early use of fresh frozen plasma as a resuscitative agent after Hemorrhagic Shock has been associated with improved survival, but the mechanism of protection is unknown. Hemorrhagic Shock causes endothelial cell dysfunction and we hypothesized that fresh frozen plasma would restore endothelial integrity and reduce syndecan-1 shedding after Hemorrhagic Shock. A prospective, observational study in severely injured patients in Hemorrhagic Shock demonstrated significantly elevated levels of syndecan-1 (554±93 ng/ml) after injury, which decreased with resuscitation (187±36 ng/ml) but was elevated compared to normal donors (27±1 ng/ml). Three pro-inflammatory cytokines, interferon-γ, fractalkine, and interleukin-1β, negatively correlated while one anti-inflammatory cytokine, IL-10, positively correlated with shed syndecan-1. These cytokines all play an important role in maintaining endothelial integrity. An in vitro model of endothelial injury then specifically examined endothelial permeability after treatment with fresh frozen plasma orlactated Ringers. Shock or endothelial injury disrupted junctional integrity and increased permeability, which was improved with fresh frozen plasma, but not lactated Ringers. Changes in endothelial cell permeability correlated with syndecan-1 shedding. These data suggest that plasma based resuscitation preserved endothelial syndecan-1 and maintained endothelial integrity, and may help to explain the protective effects of fresh frozen plasma after Hemorrhagic Shock.
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plasma restoration of endothelial glycocalyx in a rodent model of Hemorrhagic Shock
Anesthesia & Analgesia, 2011Co-Authors: Rosemary A Kozar, Pyong Woo Park, John B. Holcomb, Zhanglong Peng, Shibani Pati, Rongzhen Zhang, Angel ParedesAbstract:BACKGROUND The use of plasma-based resuscitation for trauma patients in Hemorrhagic Shock has been associated with a decrease in mortality. While some have proposed a beneficial effect through replacement of coagulation proteins, the putative mechanisms of protection afforded by plasma are unknown. We have previously shown in a cell culture model that plasma decreases endothelial cell permeability compared to crystalloid. The endothelial glycocalyx consists of proteoglycans and glycoproteins attached to a syndecan backbone, which together protect the underlying endothelium. We hypothesize that endothelial cell protection by plasma is due, in part, to its restoration of the endothelial glycocalyx and preservation of syndecan-1 after Hemorrhagic Shock.
Domenica Altavilla - One of the best experts on this subject based on the ideXlab platform.
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evidence for a role of nuclear factor κb in acute hypovolemic Hemorrhagic Shock
Surgery, 2002Co-Authors: Domenica Altavilla, Antonino Saitta, Giovanni Squadrito, Mariarosaria Galeano, Saverio F Venuti, Salvatore Guarini, Carla Bazzani, Alfio Bertolini, Achille P Caputi, Francesco SquadritoAbstract:Abstract Background. In acute hypovolemic Shock, a rapid systemic release of the inflammatory cytokine tumor necrosis factor (TNF-α) contributes to vascular failure. Nuclear factor κB (NF-κB) is an ubiquitous rapid-response transcription factor involved in inflammatory reactions and exerts its effect by expressing cytokines, chemokines, and cell adhesion molecules. The purpose of this study was to evaluate the role of NF-κB in acute hypovolemic Hemorrhagic Shock. Methods. Hemorrhagic Shock was induced in anesthetized male rats by intermittently withdrawing blood from an iliac catheter for 20 minutes (bleeding period) until mean arterial blood pressure (MAP) decreased and stabilized within the range of 20 to 30 mm Hg. Two minutes after bleeding was discontinued the rats received tacrolimus (100 μg/kg), an inhibitor of NF-κB activation, or its vehicle. We then evaluated survival rate and survival time, liver NF-κB activation by means of electrophoretic mobility shift assay, liver IκBα protein in the cytoplasm, hepatic TNF-α messenger RNA expression, plasma TNF-α, arterial blood pressure, and the contractile response of aortic rings to phenylephrine. Results. Rats that underwent Hemorrhagic Shock died 28 ± 2 minutes after bleeding was discontinued, experienced marked hypotension (MAP, 20-30 mm Hg), and had enhanced plasma levels of TNF-α (218 ± 28 pg/mL 20 minutes after bleeding was discontinued). Aortas taken 20 minutes after bleeding was discontinued in rats that underwent Hemorrhagic Shock showed marked hyporeactivity to phenylephrine (1 nmol/L-10 μmol/L) compared with aortas harvested from sham Shocked rats. Rats that underwent Hemorrhagic Shock also had increased levels of TNF-α messenger RNA in the liver. Furthermore, electrophoretic mobility shift assay showed that liver NF-κB binding activity increased in the nucleus, and Western blot analysis suggested that the levels of inhibitory IκBα protein in the cytoplasm decreased. Tacrolimus (100 μg/kg, administered 2 minutes after bleeding was discontinued) inhibited the loss of IκBα protein from the cytoplasm and prevented NF-κB binding activity in the nucleus. Moreover, tacrolimus increased survival time (118 ± 7 minutes; P Conclusions. Our results suggest that acute blood loss (50% of the estimated total blood volume during a 20-minute period) causes activation of NF-κB and that tacrolimus, by inhibiting this transcription factor, protects against acute hypovolemic Shock. (Surgery 2002;131:50-8.)
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role of tumor necrosis factor alpha in acute hypovolemic Hemorrhagic Shock in rats
American Journal of Physiology-heart and Circulatory Physiology, 1994Co-Authors: Basilia Zingarelli, Domenica Altavilla, Francesco Squadrito, Gioacchino Calapai, M Di Rosa, Achille P CaputiAbstract:Hemorrhagic Shock was induced in male anesthetized rats by intermittently withdrawing blood from an iliac catheter until mean arterial blood pressure (MAP) fell and stabilized within the range of 2...
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evidence for a role of nitric oxide in hypovolemic Hemorrhagic Shock
Journal of Cardiovascular Pharmacology, 1992Co-Authors: Basilia Zingarelli, Domenica Altavilla, Antonino Saitta, Francesco Squadrito, Gioacchino Calapai, Giuseppe M Campo, Margherita Calo, Achille P CaputiAbstract:Summary: Hypovolemic Hemorrhagic Shock was induced in rats by intermittently withdrawing blood from an iliac catheter for 20 min until mean arterial blood pressure (MAP) decreased to 30 mm Hg. Survival rate, survival time, plasma myocardial depressant factor (MDF) activity, MAP, and microscopic gastric alterations were then evaluated. NG-nitro-L-arginine methyl-ester (L-NAME), a selective inhibitor of nitric oxide (NO) production from L-arginine, was injected intravenously (i.v.) after the bleeding was discontinued. Untreated Hemorrhagic Shocked rats died in 27 ± 3.3 min, had enhanced plasma activity of MDF, and exhibited Hemorrhagic infiltrates in gastric fundus mucosa. L-NAME (5 and 10 mg/kg) significantly increased survival rate and time, blunted the increase in plasma MDF activity, and protected against the gastric lesions induced by Hemorrhagic hypovolemic Shock. All these protective effects were reversed by a bolus of L-arginine (30 mg/kg/i.v.), given 2 min after administration of L-NAME. Our findings suggest that NO production plays an important role in the pathophysiology of Hemorrhagic Shock.
