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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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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The endothelial glycocalyx (GLX) is pivotal to vascular barrier function. We investigated the consequences of GLX degradation on pulmonary microvascular perfusion and, prompted by evidence that hydroxyethyl starch (HES) improves microcirculation, studied the effects of two HES preparations during GLX diminution. C57 BL/6 black mice lungs were explanted and perfused with 1-mL/min buffer solution containing autologous erythrocytes (red blood cells) at a hematocrit of 5%. ⋯ Sequelae of GLX degradation in lung include perfusion failure in microvessels, interstitial edema formation, and increase in PAP. We assume that these effects are a consequence of vascular barrier dysfunction. Beneficial effects of HES 130/0.4 are presumably a result of its lower red blood cell bridging capacity compared with HES 200/0.5.
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STAT3-mediated IL-17 production by postseptic T cells exacerbates viral immunopathology of the lung.
Survivors of severe sepsis exhibit increased morbidity and mortality in response to secondary infections. Although bacterial secondary infections have been widely studied, there remains a paucity of data concerning viral infections after sepsis. In an experimental mouse model of severe sepsis (cecal ligation and puncture [CLP]) followed by respiratory syncytial virus (RSV) infection, exacerbated immunopathology was observed in the lungs of CLP mice compared with RSV-infected sham surgery mice. ⋯ This increased IL-17 production correlated with increased STAT3 transcription factor binding to the IL-17 promoter in CD4 T cells from CLP mice. Furthermore, in vivo neutralization of IL-17 before RSV infection led to a significant reduction in virus-induced mucus production and TH2 cytokines. Taken together, these data provide evidence that postseptic CD4 T cells are primed toward IL-17 production via increased STAT3-mediated gene transcription, which may contribute to the immunopathology of a secondary viral infection.
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The continued development of nuclear weapons and the potential for thermonuclear injury necessitates the further understanding of the immune consequences after radiation combined with injury (RCI). We hypothesized that sublethal ionization radiation exposure combined with a full-thickness thermal injury would result in the production of immature myeloid cells. Mice underwent either a full-thickness contact burn of 20% total body surface area or sham procedure followed by a single whole-body dose of 5-Gy radiation. ⋯ In contrast to the T-cell-suppressive nature of myeloid-derived suppressor cells found after trauma and sepsis, myeloid cells after RCI augmented T-cell proliferation and were associated with a weak but significant increase in interferon γ and a decrease in interleukin 10. This is consistent with previous work in burn injury indicating that a myeloid-derived suppressor cell-like population increases innate immunity. Radiation combined injury results in the increase in distinct populations of Gr-1CD11b cells within the secondary lymphoid organs, and we propose these immature inflammatory myeloid cells provide innate immunity to the severely injured and immunocompromised host.
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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.