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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Graded lower-body negative pressure was used to create a hemodynamic response similar to hemorrhage. Echocardiogram measurements showed a maximal reduction of 32.4% in stroke volume. ⋯ In particular, the LVET and pre-ejection period/LVET features, extracted from SCG, were significantly different between, and correlated with, the different stages of lower-body negative pressure (r = 0.9 and 0.88, P < 0.05), for 32 subjects. These results suggest a portable, cost-effective solution for identification of mild or moderate hemorrhage using accelerometers.
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Acute myocardial infarction is a leading cause of mortality and morbidity worldwide. Although essential for successful recovery, myocardium reperfusion is associated with reperfusion injury. Two major cell survival signaling cascades are known to be protective against ischemia-reperfusion (I/R) injury: the reperfusion injury salvage kinase, including Akt, extracellular signal-regulated kinase 1/2, and the downstream target GSK-3β, and the survivor activating factor enhancement, which involves STAT-3. ⋯ On the contrary, FDX did not have an effect on infarct size or hemodynamic parameters in the isolated-heart model. Fondaparinux decreased I/R injury in vivo, but not in a crystalloid-perfused isolated heart. Under our experimental conditions, FDX required whole blood to be protective, and this beneficial effect was mediated through STAT-3 phosphorylation.
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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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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.