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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Gram-negative sepsis is a potentially fatal clinical syndrome characterized by a proinflammatory response (tumor necrosis factor-alpha) to bacterial (endo)toxins and gut barrier function loss. Recently, we found that high-fat enteral nutrition protects against late bacterial translocation in a model of hemorrhagic shock in rats. However, the basis for this protection is unknown. ⋯ In parallel, intestinal barrier function was preserved in HS-HF rats, evidenced by a reduced permeability to horseradish peroxidase (P < 0.05), less bacterial invasion, and a 10-fold reduction of bacterial translocation early after hemorrhagic shock. This report describes a new strategy to nutritionally prevent endotoxemia, the subsequent inflammatory response and gut barrier failure following hemorrhagic shock. High-fat enteral nutrition requires further evaluation as an intervention to prevent a potentially fatal systemic inflammatory response in patients at risk for sepsis.
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C5a-C5aR signaling plays an essential role in innate immunity of neutrophils. However, excessive interaction of C5a-C5aR results in harmful effects in these cells. In sepsis, robust generation of C5a occurs; blockade of either C5a or C5aR greatly improves survival in experimental sepsis following cecal ligation and puncture (CLP). ⋯ Following CLP, there is a positive correlation between C5aR content on blood neutrophils and survival of individual animals; high levels of C5aR on neutrophils are associated with survival, whereas low levels of C5aR on neutrophils predict mortality. These data suggest that in sepsis C5a-C5aR signaling is excessive, resulting in paralysis of neutrophil function. Interception of either C5a or C5aR dramatically improves survival during experimental sepsis.
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The defect in energy production in an organism during shock states may be related to the impairment of mitochondrial respiration early in shock. The aim of this study was to investigate the timing and degree of cellular energetic changes during hemorrhagic shock in real time. Instrumented, splenectomized swine were randomized to undergo hemorrhagic shock, induced by a 35% blood volume bleed, for 90 min with (n = 10) or without (n = 9) subsequent resuscitation. ⋯ StO2 in skeletal muscle, stomach, and liver correlated with whole organism oxygen delivery (r2 = 0.356, 0.368, and 0.432, respectively). We conclude that hemorrhagic shock induces early elevation of phosphomonoesters in skeletal muscle, which correlates with the severity of shock. This implies an early transition to anaerobic glycolysis during hemorrhagic shock, which may be indicative of early mitochondrial dysfunction.
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It has been suggested that hyperdynamic (HD) resuscitation improves outcomes. We hypothesized that initial HD resuscitation of burn injury using fluid and inotropes would improve metabolic function as indicated by base excess. We used an anesthetized ovine model of 60% TBSA full-thickness flame burn with delayed resuscitation started at 90 min after burn and continued for 8 h. ⋯ The mean postburn urinary outputs were similar in both Parkland and HD-Drug groups, e.g., Parkland (0.9 +/- 0.08 mL/kg/h), HD-Drug (1.0 +/- 0.2 mL/kg/h) and increased in HD-Fluid (3.7 +/- 1.0 mL/kg/h; P = 0.0005). Base excess remained positive in both HD-Drug (+2.5 +/- 1 mmol/L) and Parkland (+1.5 +/- 1.7 mmol/L), and declined to -4.0 +/- 3.6 mmol/L in HD-Fluid group (P = 0.036). We conclude that there may be no benefit to using hyperdynamic regimens for the initial resuscitation of burn injury.