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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Trauma remains the leading cause of death, with bleeding as the primary cause of preventable mortality. When death occurs, it happens quickly, typically within the first 6 h after injury. The principal drivers of the acute coagulopathy of trauma have been characterized, but another group of patients with early evidence of coagulopathy both physiologically and mechanistically distinct from this systemic acquired coagulopathy has been identified. ⋯ Weighted and more sophisticated systems including higher numbers of variables perform superiorly. A common limitation to all models is their retrospective nature, and prospective validations are needed. Point-of-care viscoelastic testing may be an alternative to early recognize trauma-induced coagulopathy with the risk of ongoing hemorrhage and transfusion.
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Trauma results in a persistent depression in adaptive immunity, which contributes to patient morbidity and mortality. This state of immune paralysis following trauma is characterized by a change in cell-mediated immunity, specifically a depression in T-cell function and a shift toward TH2 T-cell phenotype. Upregulation of inducible nitric oxide synthase (iNOS) is well recognized after injury and contributes to the inflammatory response and organ damage early after trauma. ⋯ This study utilized a murine model of severe peripheral tissue injury to show that iNOS is rapidly upregulated in macrophages and a (Gr-1-CD11b) myeloid-derived suppressor cell subpopulation in the spleen. Through the use of iNOS knockout mice, a specific iNOS inhibitor, and a nitric oxide (NO) scavenger, this study demonstrates that iNOS-derived NO is required for the depression in T-lymphocyte proliferation, interferon γ, and interleukin 2 production within the spleen at 48 h after trauma. These findings support the hypothesis that iNOS regulates immune suppression following trauma and suggest that targeting the sustained production of NO by iNOS may attenuate posttraumatic immune depression.
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The leading causes of death in people aged 1 to 44 years are unintentional injuries with associated hemorrhagic shock. Hemorrhagic shock followed by resuscitation (H/R) activates the nuclear factor κB (NF-κB) pathway. To further address the association between liver damage and NF-κB activation, we analyzed the H/R-induced activation of NF-κB using cis-NF-κB reporter gene mice. ⋯ Using serial liver sections, we found an association between necrotic areas, oxidative stress, and enhanced GFP-positive cells. Furthermore, enhanced GFP-positive cells surrounded areas of necrotic liver tissue, predominantly in a penumbra-like-shape pericentrally. These results elucidate spatial relationship between oxidative stress, liver necrosis, and NF-κB activation, using an in vivo approach and therefore might help to further analyze mechanisms of NF-κB activation after resuscitated blood loss.
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Hemorrhagic shock is a major cause of death in modern societies. Some patients, when treated, fail to sustain normal cardiovascular parameters, requiring fluid therapy and vasoactive drugs. Among drugs with cardiovascular profile other than catecholamine, vasopressin (VP) is emerging as an option. ⋯ The VP group also had a smaller number of adhering leukocytes and improved 72-h survival time compared with the NA one. This study suggests that, in hemorrhagic shock, treatment with low-dose VP, in combination with fluid therapy, improves tissue perfusion. This outcome is mediated mostly by V2 receptors, eliciting vasodilatation and consequently blood flow redistribution through the microcirculation.
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Reactive nitrogen species such as peroxynitrite play a significant role in burn and smoke inhalation injury. The bronchial circulation increases more than 10-fold in response to this combination injury. We hypothesized that direct delivery of low-dose WW-85, a peroxynitrite decomposition catalyst, into the bronchial artery would attenuate burn- and smoke inhalation-induced acute lung injury. ⋯ All these alterations were significantly attenuated in the WW-85 group. We demonstrated that a low dosage of WW-85 directly administered into the bronchial artery attenuated pulmonary dysfunction to the same extent as higher systemically administered doses in previous experiments. Our data strongly suggest that local airway production of peroxynitrite contributes to pulmonary dysfunction following smoke inhalation and burn injury.