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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Nuclear factor erythroid 2-related factor (Nrf2) is a redox-sensitive transcription factor that responds to oxidative stress by activating expressions of key antioxidant and cytoprotective enzymes via the Nrf2-antioxidant response element (ARE) signaling pathway. Our objective was to characterize hyperoxia-induced acute lung injury (HALI) in Nrf2 knock-out (KO) rats to elucidate the role of this pathway in HALI. Adult Nrf2 wildtype (WT), and KO rats were exposed to room air (normoxia) or >95% O2 (hyperoxia) for 48 h, after which selected injury and functional endpoints were measured in vivo and ex vivo. ⋯ Hyperoxia had no effect on expression of Bcl-2 (anti-apoptotic protein) or peroxiredoxin-1. These results suggest that the protection offered by the Nrf2-ARE pathway against HALI is in part via its regulation of the GSH redox pathway. To the best of our knowledge, this is the first study to assess the role of the Nrf2-ARE signaling pathway in protection against HALI using a rat Nrf2 knockout model.
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Elderly patients are more susceptible to sepsis and septic shock. Early administration of broad-spectrum antibiotics is a key element of the sepsis management of bundle. Our study aimed to investigate the association between the timing of antibiotics administration and the risk of adverse outcomes in elderly patients with septic shock, and to examine the prognostic value of other bundle elements. ⋯ The timing of antibiotic administration was not associated with adverse outcomes in elderly patients with septic shock. Serum lactate level and source control implementation were independent prognostic factors in these patients.
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Excessive sympathetic outflow following trauma can lead to cardiac dysfunction, inflammation, coagulopathy, and poor outcomes. We previously reported that buprenorphine analgesia decreased survival after hemorrhagic trauma. Our aim is to examine the underlying mechanisms of mortality in a non-compressible hemorrhage rat model resuscitated with saline or adenosine, lidocaine, magnesium (ALM). ⋯ Mortality appears to be a "systems failure" associated with CNS dysregulation of cardiac function. Survival involves an increased parasympathetic dominance to support cardiac pump function with reduced myocardial inflammation. Increased cardiac α-1A adrenergic receptor in ALM survivors may be significant, as this receptor is highly protective during heart dysfunction/failure.
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Hemorrhagic shock/resuscitation (HS/R) is closely associated with overwhelming oxidative stress and systemic inflammation. As an effective activator of the nuclear factor-erythroid factor 2 related factor 2 (Nrf2) pathway, sulforaphane (SFN) exerts antioxidant and anti-inflammatory effects. We explored SFN's effects on alveolar macrophages (AMs), systemic inflammation, and pulmonary damage in an isolated murine HS/R model. ⋯ In conclusion, SFN beneficially enhances pulmonary Nrf2 activity and promotes Nrf2 accumulation in AMs' nuclei. This may exert not only local protective effects but also systemic effects via the down-regulation of pro-inflammatory cytokines. The administration of Nrf2 activator post-HS/R may represent an innovative treatment strategy.
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Observational Study
Factors Associated with Increased Mortality in Severe Abdominopelvic Injury.
Associated injuries are thought to increase mortality in patients with severe abdominopelvic trauma. This study aimed to identify clinical factors contributing to increased mortality in patients with severe abdominopelvic trauma, with the hypothesis that a greater number of concomitant injuries would result in increased mortality. ⋯ Increased number of body regions injured does not contribute to greater mortality. Uncontrolled noncompressible torso hemorrhage rather than the burden of concomitant injuries is the major contributor to the high mortality associated with severe abdominopelvic injury.