Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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This study was conducted to reveal if the mitochondrial unfolded protein response (mtUPR), a conserved mitochondrial-nuclear communication mechanism, plays a critical role in the protein quality control system to cope with damaged protein during sepsis. Sepsis was induced by cecal ligation and puncture (CLP) in Sprague-Dawley rats. The efficiency of mtUPR was evaluated by measuring the transcriptional factors (CCAAT/enhancer-binder protein homologous protein [CHOP] and CCAAT/enhancer-binder protein-β) and chaperones (heat shock protein 60 [Hsp60] and Hsp10) expression in response to hepatic mitochondrial oxidized proteins (carbonylated proteins, car-proteins) and multi-ubiquitinated proteins (ub-proteins). ⋯ Interestingly, we evaluated the ratio of mitochondrial Hsp60/Hsp10 to the ub-proteins and found that both ratios were statistically lowered at the time points of 9 and 18 h in comparison with 3 and 6 h after CLP. These ratios were also significantly negatively correlated with glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase levels, suggesting that the ratios could act as an index of mtUPR failure and be a useful tool in estimating the ability of mitochondrial-nuclear communication in sepsis. In conclusion, the results indicated that mtUPR failure occurred during sepsis, and that the index of mtUPR may be a valuable measurement in assessing the severity of organ dysfunction in the clinical setting.
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Treatment of combined traumatic brain injury and hypovolemic shock poses a particular challenge due to the possible conflicting consequences. While restoring diminished volume is the treatment goal for hypovolemia, maintaining and adequate cerebral perfusion pressure and avoidance of secondary damage remain a treatment goal for the injured brain. Various treatment modalities have been proposed, but the optimal resuscitation fluid and goals have not yet been clearly defined. ⋯ Neurological outcomes and mortality inversely correlated with the aggressiveness of resuscitation. In this study, we find that mild resuscitation with goals of restoring MAP to 80 mmHg (which is lower than baseline) provided best results when considering hemodynamic stability, survival, and neurological outcomes. An aggressive resuscitation may be detrimental, inducing processes that eventually cause a significant decrease in survival.
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Multicenter Study Comparative Study Clinical Trial
Central venous oxygen saturation under non-protocolized resuscitation is not related to survival in severe sepsis or septic shock.
Protocolized hemodynamic resuscitation in severe sepsis or septic shock is not universally applied in all emergency departments and general hospital wards around the world. It is unknown whether ScvO2 levels are associated with the clinical outcome of severe sepsis or septic shock under nonprotocolized resuscitation. In this prospective study, we enrolled 124 noncirrhotic patients who were admitted to intensive care units for severe sepsis or septic shock. ⋯ In conclusion, our results showed that mean arterial pressure and central venous pressure were still the most important hemodynamic variables in initial hemodynamic resuscitation. Low postresuscitation ScvO2 was not associated with a worse outcome. It is possible that ScvO2 less than 70% might not necessarily be associated with tissue hypoxia, and critical ScvO2 levels require to be determined by further studies.
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More than 20,000 burn injury victims suffer from smoke inhalation injury in the United States annually. In an ovine model of acute lung injury, γ-tocopherol had a beneficial effect when nebulized into the airway. We hypothesize that γ-tocopherol scavenges reactive oxygen species (ROS) and reactive nitrogen species resulting from burn and smoke inhalation injury and that these ROS/reactive nitrogen species activate the arginase pathway, leading to increased collagen deposition and decreased pulmonary function. ⋯ Arginase activity (0.15 ± 0.02 μM urea/μg protein vs. 0.24 ± 0.009, P < 0.05), ornithine aminotransferase (11,720 ± 888 vs. 13,170 ± 1,775), and collagen deposition (0.62 ± 0.12 μM hydroxyproline/μg protein vs. 1.02 ± 0.13, P < 0.05) significantly decrease with γ-tocopherol compared with injured animals without γ-tocopherol. The decreases in arginase and collagen with γ-tocopherol are associated with significantly increased diffusion capacity (P < 0.05) and decreased lung wet-to-dry ratio (P < 0.05). Smoke-induced chronic pulmonary dysfunction is mediated through the ROS/asymmetrical dimethylarginine/arginase pathway, and ROS scavengers such as γ-tocopherol may be a potential therapeutic management of burn patients with inhalation injury.
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Despite the high incidence and prognostic relevance of hemorrhagic shock and abdominal and blunt chest trauma in multiply injured patients, there are no animal models combining these injuries. Therefore, we established a new porcine multiple trauma model consisting of blunt chest trauma, penetrating abdominal trauma (two incisions in the right upper liver lobe using a four-edged scalpel and subsequent liver packing), and pressure-controlled hemorrhagic shock with a mean arterial pressure of 30 ± 5 mmHg (a maximum of 45% of the total blood volume). The combined traumatic insult led to severe signs of hemorrhagic shock and impaired pulmonary function. In conclusion, a consistent, reproducible, and clinically relevant porcine model of multisystem injury with controlled (pressure-controlled blood withdrawal) and uncontrolled components of hemorrhage (liver laceration) with the potential for rebleeding was established.