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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Although hypothermia is independently associated with an increased mortality in trauma patients, it might be an effective therapeutic approach for otherwise lethal hemorrhage. The effect of hypothermia on microcirculation, however, has been poorly studied in this setting. Our goal was to characterize the effects of hypothermia on microcirculation in normal conditions and in severe hemorrhagic shock. ⋯ This is the first experimental study assessing the effect of systemic hypothermia on microcirculation in severe hemorrhagic shock. The main finding was that hypothermia did not hamper additionally the microcirculatory derangements induced by hemorrhagic shock. In addition, renal microcirculation was more susceptible to hemorrhagic shock than villi and sublingual microcirculation.
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We recently demonstrated that fibrinogen stabilizes syndecan-1 on the endothelial cell (EC) surface and contributes to EC barrier protection, though the intracellular signaling pathway remains unclear. P21 (Rac1) activated kinase 1 (PAK1) is a protein kinase involved in intracellular signaling leading to actin cytoskeleton rearrangement and plays an important role in maintaining endothelial barrier integrity. We therefore hypothesized that fibrinogen binding to syndecan-1 activated the PAK1 pathway. ⋯ We have identified a novel pathway by which fibrinogen activates PAK1 signaling to stimulate/dephosphorylate cofilin, leading to disassembly of stress fibers and reduction of endothelial permeability.
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Hepatic dysfunction frequently occurs after trauma-hemorrhage, resulting in severe pathophysiological responses that include leukocyte shifting and self-mediated mechanisms of cells, such as autophagy and apoptosis. This in vivo study aimed to characterize mitochondrial morphology, leukocyte reaction, and the processes of autophagy and apoptosis after polytrauma hemorrhage (TH) in a long-term, large animal model. Liver tissue was taken from a porcine TH model (hemorrhagic shock, blunt chest trauma, tibia fracture, and liver laceration) with an intensive care unit follow-up of 72 h. ⋯ In conclusion, the observed findings indicate that mitochondrial dysfunction might be one trigger of hepatic autophagy and apoptosis after TH. These processes occur together with the activation of anti-inflammatory leukocytes in liver tissue. Further studies are needed to elucidate the potential therapeutic effects of inhibiting mitochondrial swelling during autophagy or apoptosis.
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Interleukin-6 (IL-6) is a major cytokine released by skeletal muscle. Although IL-6 plays complex but well-known roles in host defense, the specific contribution of skeletal muscle IL-6 to innate immunity remains unknown. We tested its functional relevance by exposing inducible skeletal muscle IL-6 knockdown (skmIL-6KD) mice to a cecal slurry model of polymicrobial peritonitis and compared responses to strain-matched controls and skeletal muscle Cre-matched controls at 3, 6, and 12 h postinfection. ⋯ In both sexes at 12 h, a generalized suppression of plasma cytokines was also seen after the effects of Cre-induction with raloxifene were addressed. There were no significant effects of skmIL-6KD on mortality in either sex. Collectively, our results are consistent with skmIL-6 playing an important and previously unrecognized role in immune cell trafficking and cytokine regulation during septic shock.
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Observational Study
Evaluation of the Initiation Timing of Hydrocortisone in Adult Patients With Septic Shock.
Clinical studies evaluating the use of hydrocortisone in patients with septic shock are heterogeneous in design with conflicting results. The appropriate time in which to initiate hydrocortisone after shock onset is unknown. This study sought to compare clinical outcomes including vasopressor duration and mortality in patients with septic shock who received hydrocortisone based on timing of initiation after shock onset. ⋯ In patients in whom hydrocortisone is prescribed for vasopressor-dependent septic shock, timing is crucial and hydrocortisone should be started within the first 12 h after shock onset.