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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Extensively burned patients often suffer from sepsis (especially caused by Pseudomonas aeruginosa), which may prolong metabolic derangement, contribute to multiple organ failure, and increase mortality. The molecular and cellular mechanisms of such infection-related metabolic derangement and organ dysfunction are unclear. We have previously shown that severely burned patients have significant and persisting hepatic endoplasmic reticulum (ER) stress. ⋯ Our results showed that burn injury and LPS injection induced inflammasome activation in liver and augmented hepatic ER stress and liver damage. Although there was an increased metabolic demand after burn, hepatic NLRP3 inflammasome activation corresponded to inhibition of PGC-1α (peroxisome proliferator-activated receptor γ-coactivator 1α) and its upstream regulators protein kinase A catalyst unit, AMP-activated protein kinase α, and sirtuin-1 may provide a mechanism for the enhanced metabolic derangement after major burn injury plus sepsis. In conclusion, burn + LPS augments inflammasome activation and ER stress in liver, which in turn contribute to postburn metabolic derangement.
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Hemorrhagic shock (HS) can initiate an exaggerated systemic inflammatory response and multiple organ failure, especially if followed by a subsequent inflammatory insult ("second hit"). We have recently shown that histone deacetylase inhibitors can improve survival in rodent models of HS or septic shock, individually. In the present study, we examined whether valproic acid (VPA), a histone deacetylase inhibitor, could prolong survival in a rodent "two-hit" model: HS followed by septic shock from cecal ligation and puncture (CLP). ⋯ We have demonstrated that VPA treatment improves survival and attenuates inflammation in a rodent two-hit model.
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Comparative Study
Midterm effects of fluid resuscitation strategies in an experimental model of lung contusion and hemorrhagic shock.
This study compared three different fluid resuscitation strategies in terms of respiratory tolerance and hemodynamic efficacy in a pig model of blunt chest trauma with lung contusion and controlled hemorrhagic shock. We hypothesized that the choice of fluid resuscitation strategy (type and amount of fluids) may impact differently contused lungs in terms of extravascular lung water (EVLW) 20 h after trauma. ⋯ This study demonstrated the impact of fluid resuscitation on contused lungs. Twenty hours after the trauma, all three resuscitation approaches showed modest clinical consequences, with moderate lung edema and reduced compliance in response to the infused volume.
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Gender-oriented studies in shock, trauma, and/or sepsis require accurate monitoring of hormonal fluctuations as estrogens may influence various end points. Yet, monitoring is challenging in small laboratory animals: e.g., despite its subjectivity, vaginal smears are the major method for determination of estrus cycle phases in mice. Using female mice of different age, we aimed to (a) characterize general age-related changes in systemic estrogens and (b) examine the utility of determination of the estrus cycle by vaginal smears and/or impedance simultaneously comparing them with oscillation of systemic estrogens. ⋯ In conclusion, while the fecal estrogens oscillation and frequency of estrus phase were affected by age, the systemic hormone release persisted. In mice, vaginal cytology did not reflect changes of systemic (fecal) estrogens, whereas impedance accurately identified estrus. The flaws and advantages of the examined monitoring methods should be considered in the design of future shock studies.
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Noncompressible torso hemorrhage is a leading cause of death in trauma, with many patients dying before definitive hemorrhage control. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an adjunct than can be used to expand the window of salvage in patients with end-stage hemorrhagic shock. The aim of this study was to evaluate the effect of continuous and intermittent REBOA (iREBOA) on mortality using a highly lethal porcine model of noncompressible torso hemorrhage. ⋯ Overall mortality for the cREBOA, iREBOA, and nREBOA groups was 25.0%, 37.5%, and 100.0% (P = 0.001). Resuscitative endovascular balloon occlusion of the aorta can temporize exsanguinating hemorrhage and restore life-sustaining perfusion, bridging critical physiology to definitive hemorrhage control. Prospective observational studies of REBOA as a hemorrhage control adjunct should be undertaken in appropriate groups of human trauma patients.