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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Increased microcirculatory flow and perfusion has been reported to improve clinical outcomes following shock. The optimal resuscitation fluid to restore the flow dynamics of the microcirculation is unknown. This review summarizes the preclinical literature to inform the direction and most important hypotheses for future clinical interventional studies. ⋯ The ideal resuscitation fluid for restoration of the microcirculation following haemorrhagic shock is likely to contain a preparation of haemoglobin, favor higher oncotic potential, and viscosity, protect and reconstitute the endothelium, and attenuate inflammation. These hypotheses that are derived from preclinical research warrant further exploration in the clinical context.
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The microbiota of critically ill patients likely undergoes dramatic changes but has not been rigorously studied with a culture-independent high-throughput approach. The aim of this study was to characterize spatial and temporal variation in the microbiota of critically ill patients. Trauma and acute surgery patients admitted to the intensive care unit (ICU) were sampled at five body sites (stool, tongue, skin, trachea, urine) every 3 to 4 days. ⋯ In several cases, clinically relevant airway infections were preceded by the appearance of the causative pathogen in tracheal microbiome profiles. These results demonstrate that the microbiome of critically ill patients undergoes a loss of diversity, loss of site specificity, and a shift toward dominant pathogens. These changes may provide opportunities to precisely modulate the microbiome and thereby improve patient outcomes.
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To explore the roles of mesenteric lymph on lung injury in heatstroke (HS), HS rat model was prepared in a prewarmed incubator. Vascular endothelium injury biomarkers (circulating endothelial cell [CEC] as well as von Willebrand factor [vWF] and thrombomodulin [TM]), proinflammatory factors (tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β], IL-6, and high mobility group box 1), and coagulant markers (activated partial thromboplastin time, prothrombin time, D-Dimer, and platelet count) were tested in HS and HS with mesenteric lymph duct ligation (LDL) rats. In addition, lung histopathology; arterial blood gas; Evans Blue dye (EBD) and protein lung permeability; intralung inflammatory parameters including bronchoalveolar lavage fluid (BALF) TNF-α, IL-1β, and IL-6 levels; myeloperoxidase (MPO) activity; and vWF immune staining were analyzed. ⋯ LDL also significantly reduced acute lung pathological injury; improved lung function indexes including arterial blood PaO2, pH, PaCO2, and lactic acid; decreased BALF TNF-α, IL-1β, and IL-6 levels and lung MPO activity; improved EBD and protein lung permeability; and inhibited lung vascular endothelium vWF expression. However, all of these parameters were not recovered to the normal states. In summary, LDL developed protection roles systemically and alleviated lung injury in HS rats which indicated that modulating mesenteric lymph flow may have some potential benefits in HS.
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Extracorporeal life support is a promising concept for selected patients in refractory cardiogenic shock and for advanced life support of persistent ventricular fibrillation cardiac arrest. Animal models of ventricular fibrillation cardiac arrest could help to investigate new treatment strategies for successful resuscitation. Associated procedural pitfalls in establishing a rat model of extracorporeal life support resuscitation need to be replaced, refined, reduced, and reported. ⋯ Establishing an extracorporeal life support model in rats has confronted us with technical challenges. Even advancements in small animal critical care management over the years delivered by an experienced team and technical modifications were not able to totally avoid such serious adverse events. Replacement, refinement, and reduction reports of serious adverse events demanding study exclusions to avoid animal resources are missing and are presented hereby.
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Sepsis is characterized by systemic activation of inflammatory and coagulation pathways in response to infection. Recently, it was demonstrated that histones released into the circulation by dying/activated cells may contribute to sepsis pathology. Although the ability of extracellular histones to modulate the procoagulant activities of several cell types has been investigated, the influence of histones on the hemostatic functions of circulating monocytes is unknown. To address this, we investigated the ability of histones to modulate the procoagulant potential of THP-1 cells and peripheral blood monocytes, and examined the effects of plasmas obtained from septic patients to induce a procoagulant phenotype on monocytic cells. ⋯ Our studies suggest that increased levels of extracellular histones found in sepsis contribute to dysregulated coagulation by increasing TF activity of monocytes. These procoagulant effects can be partially ameliorated in sepsis patients receiving UFH, thereby identifying extracellular histones as a potential therapeutic target for sepsis treatment.