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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Randomized Controlled Trial
Postinjury hyperfibrinogenemia compromises efficacy of heparin-based venous thromboembolism prophylaxis.
Venous thromboembolism (VTE) prophylaxis remains debated following trauma, and recommendations have not been established. Although hyperfibrinogenemia is a marker of proinflammatory states, it also contributes to thrombus formation. Postinjury hyperfibrinogenemia is common, but the effect of hyperfibrinogenemia on VTE prophylaxis has not been fully elucidated. Therefore, we hypothesized that heparin is less effective for VTE prophylaxis following severe injury due to hyperfibrinogenemia. ⋯ Hypercoagulability and heparin resistance are common following trauma. The preclinical and clinical relationships between fibrinogen levels and hypercoagulability implicate hyperfibrinogenemia as a potential factor in heparin resistance.
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Comparative Study
Differential changes in hepatic synthesis of albumin and fibrinogen after severe hemorrhagic shock in pigs.
Changes of plasma albumin and fibrinogen after various insults have been described as acute phase responses. This study investigated the acute changes of hepatic synthesis of albumin and fibrinogen after hemorrhage and resuscitation with lactated Ringer's (LR) solution or normal saline (NS) in pigs. ⋯ Hemorrhage and resuscitation compromised albumin synthesis, but not fibrinogen synthesis. There were no differences in hepatic synthesis of albumin or fibrinogen between LR solution and NS resuscitation.
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Hemorrhagic shock is a leading cause of trauma-related death in war and is associated with significant alterations in metabolism. Using archived serum samples from a previous study, the purpose of this work was to identify metabolic changes associated with induced hypothermia in a porcine model of hemorrhagic shock. Twelve Yorkshire pigs underwent a standardized hemorrhagic shock and resuscitation protocol to simulate battlefield injury with prolonged evacuation to definitive care in cold environments. ⋯ Using random forest analysis, a difference in metabolic response between hypothermic and normothermic animals was identified. Hypothermic resuscitation was characterized by decreased concentrations of several muscle-related metabolites including taurine, creatine, creatinine, and amino acids. This study suggests that a decrease in muscle metabolism as a result of induced hypothermia is associated with improved survival.
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The nuclear transcription factor peroxisome proliferator-activated receptor γ (PPARγ) is a key regulator of the inflammatory response to an array of biologic insults. We have previously demonstrated that PPARγ ligands reduce myocardial ischemia-reperfusion injury in rodents. In the current study, we directly determined the role of cardiomyocyte PPARγ in ischemia-reperfusion injury, using a model of conditional cardiomyocyte-specific deletion of PPARγ in vivo. ⋯ Plasma levels of the proinflammatory cytokines interleukin 1β and interleukin 6 were higher in PPARγ mice when compared with PPARγ mice. These pathological events in PPARγ mice were associated with enhanced nuclear factor κB DNA binding in the infarcted hearts. Thus, our data suggest that cardiomyocyte PPARγ is a crucial protective receptor and may prevent reperfusion injury by modulating mechanisms of inflammation.
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Hemorrhagic shock is associated with metabolic defects, including hyperglycemia and insulin resistance, but the mechanisms are unknown. We recently demonstrated that reduction of the extracellular domain of the insulin receptor by degrading proteases may lead to a reduced ability to maintain normal plasma glucose values. In shock, transfer of digestive enzymes from the lumen of the intestine into the systemic circulation after breakdown of the intestinal mucosal barrier causes inflammation and organ dysfunction. ⋯ Glucose tolerance test indicates a significant increase in plasma glucose levels 2 h after hemorrhagic shock, which are reduced to control values in the presence of protease inhibition in the lumen of the intestine. The transient reduction of the plasma glucose levels after an insulin bolus is significantly attenuated after shock but is restored when digestive enzymes in the lumen of the intestine are blocked. These results suggest that in hemorrhagic shock elevated microvascular extracellular digestive enzyme activity causes insulin receptor dysfunction, hyperglycemia, and reduced ability to regulate blood glucose values.