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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Cardiac cycle is regulated by a complex interplay between autonomic nervous system and cardiac pacemaker cells. Decreased heart rate variability (HRV) and increased cardiac rhythm regularity are associated with poor prognosis in patients with systemic inflammation (e.g., sepsis). However, the underlying mechanism of decreased HRV in systemic inflammation is not understood. ⋯ The chronotropic responsiveness to adrenergic stimulation was identical in controls and endotoxin-treated rats. These data propose that systemic inflammation is linked to reduced cardiac responsiveness to cholinergic stimulation. This may lead to partial uncoupling of cardiac pacemaker cells from autonomic neural control and can explain decreased HRV during systemic inflammation.
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The objective of the study was to investigate the mechanisms of insufficient interferon-γ (IFN-γ) response to interleukin 18 (IL-18) and the treatment for the insufficient response in septic mice. Interleukin 18 stimulation does not restore IFN-γ production by blood mononuclear cells in septic patients but does restore its production in postoperative patients. Although sepsis impairs the IFN-γ response to IL-18, little is known about why the IL-18/IFN-γ-mediated immune response is ineffective in patients with sepsis. ⋯ Neutralization of IL-10 restored the IL-18R expression on liver NK cells and restored the IFN-γ response in the septic mice, improving their survival. Sepsis might impair IL-18R expression on liver and spleen NK cells and impair the IL-18-mediated IFN-γ response. Neutralization of IL-10 may restore this response in septic hosts, thereby improving survival.
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Hypothermia is considered an independent predictor of death after trauma. The aim of this study was to assess these premises based on data from the TraumaRegistry DGU® (TR-DGU) using its outcome predication tool, the Revised Injury Severity Classification (RISC) score, in comparison with three previously published regression models by Shafi, Martin, and Wang. We hypothesized that body temperature on admission would improve accuracy of the RISC score. ⋯ Comparison of the above models revealed hypothermia as an independent risk factor (Martin: OR, 1.43 [95% CI, 2.21-1.42*]; and Wang: OR, 1.77 [95% CI, 2.21-1.42*]) only, although it would drop out from the model (RISC: OR, 1.12 [95% CI, 1.41-0.89; P = 0.33] and Shafi: OR, 1,.21 [95% CI, 1.60-0.92; P = 0.17]) as long as parameters to indicate hemorrhage and/or coagulopathy were included in sufficient number, a finding confirmed by a subsequent sensitivity analysis. We conclude that hypothermia is a result of injury severity and therefore unlikely to be an independent predictor of mortality. Our data suggest that hypothermia belongs closely to the hemorrhage/coagulopathy group of predictors.
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The investigation of the trauma-induced innate immune responses is hampered by the wide variability in patients, type of trauma, and environmental factors. To circumvent this heterogeneity, we examined whether the systemic innate immune response toward human experimental endotoxemia is similar to the response during systemic inflammatory response syndrome after trauma. We tested the hypothesis that the innate immune response to pathogen-associated molecular pattern (e.g., lipopolysaccharides [LPSs]) and danger-associated molecular pattern (as induced by injury) leads to a comparable in vivo activation of human neutrophils. ⋯ A significant difference between both conditions was seen in CD66b expression and for endotoxin resulted in an increased CD66b expression, whereas injury did not. Neutrophil activation was present 3 h after onset of inflammation, both during experimental endotoxemia as well as in trauma patients. Endotoxin and trauma appear to induce a similar neutrophil activation phenotype.
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The aim of this study was to investigate the effect of 17β-estradiol (E2) on hepatocyte apoptosis after reduced-size hepatic ischemia/reperfusion (I/R) injury and its mechanism. A rat model of reduced-size hepatic I/R injury was established. Sprague-Dawley rats were randomly allocated into sham, I/R, and E2 + I/R group. 17β-Estradiol (4 mg/kg) or the vehicle was administered i.p. 1 h before ischemia and immediately after operation. ⋯ Furthermore, E2 inhibited hepatocellular apoptosis by upregulating the ratio of Bcl-2 and Bax expression, reduced cytosolic cytochrome c level, and decreased caspase 9 and caspase 3 activities. The 7-day survival rate was significantly higher in the E2 + I/R group than in the I/R group. These results indicated that E2 protects liver tissues from reduced-size hepatic I/R injury by suppressing mitochondrial apoptotic pathways.