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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Vascular hypo-reactivity plays a critical role inducing organ injury during hemorrhagic shock. 17β-estradiol (E2) can induce vasodilation to increase blood flow in various vascular beds. This study observed whether E2 can restore vascular hypo-reactivity induced by hemorrhagic shock, and whether E2 effects are associated with RhoA-Rho kinase (ROCK)-myosin light chain kinase phosphatase (MLCP) pathway. The hemorrhagic shock model (40 ± 2 mm Hg for 1 h, resuscitation for 4 h) was established in ovary intact sham operation (OVI), ovariectomized (OVX), and OVX plus E2 supplement female mice. ⋯ In OVX plus E2 supplement mice with hemorrhagic shock, Y-27632 inhibited microvascular reactivity, which was abolished by concomitant U-46619 application. Lastly, hemorrhagic shock remarkably decreased intestinal loop blood flow, RhoA and ROCK mRNA expressions in vascular tissues in OVX females, but not in OVI females, which were reversed by E2 supplement. These results indicate that estrogen improves microvascular reactivity during hemorrhagic shock, and RhoA-ROCK signaling pathway may mediate E2 effects.
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Recent data suggests improved outcomes among cardiac intensive care unit (CICU) patients treated with norepinephrine, especially patients with severe shock. We aimed to describe the association between norepinephrine and mortality in CICU patients with severe shock, defined as those requiring high-dose vasopressors (HDV). ⋯ Mortality is high among CICU patients requiring HDV, and rises with increasing vasopressor requirements. Use of NE was associated with lower mortality among patients requiring HDV, but not among those without HDV, implying that patients with more severe shock may benefit from preferential use of NE.
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Cardiac arrest (CA) is recognized as a life-threatening disease; however, the initial resuscitation success rate has increased due to advances in clinical treatment. Levosimendan has shown potential benefits in CA patients. However, its exact function on intestinal and systemic circulation in CA or post-cardiac arrest syndrome (PCAS) remained unclear. This study preliminarily investigated the link between dynamic changes in intestine and systemic hemodynamics post-resuscitation after levosimendan administration. ⋯ Levosimendan significantly reduced the cardiac injury and corrected the metabolic status in an experimental rat model of ventricular fibrillation induced CA and cardiopulmonary resuscitation. Levosimendan may ameliorate PCAS-induced intestinal microcirculation dysfunction, partly independent of its effects on macrocirculation.
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Sepsis is the leading cause of acute kidney injury (AKI) in critical care patients. A cornerstone of sepsis-associated AKI is dysregulated inflammation driven by excessive activation of Toll-like receptor 4 (TLR4) pathway. MUC1, a membrane-bound mucin expressed in both epithelial tubular cells and renal macrophages, has been shown to be involved in the regulation of TLRs. ⋯ In human and murine primary macrophages, we showed that MUC1 is only induced in M1 type macrophages and that macrophages derived from Muc1-/- mice secreted more pro-inflammatory cytokines. Eventually, in HEK293 cells, we showed that MUC1 cytosolic domain (CT) seems necessary for the negative regulation of TLR4 by proximity ligation assay, MUC1-CT is in close relationship with TLR4 and acts as a competitive inhibitor of the recruitment of MYD88. Overall our results support that in the context of endotoxin-induced AKI, MUC1 plays a significant role in controlling disease severity by regulating negatively the TLR4-MD2 axis.
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Massive transfusion (MT) is required to resuscitate traumatically injured patients with complex derangements. Scoring systems for MT typically require laboratory values and radiological imaging that may delay the prediction of MT. ⋯ The prehospital and admission ALERT scores can accurately predict massive transfusion in trauma patients without the use of time-consuming laboratory studies, although prospective studies need to be performed to validate these findings. Early identification of patients who will require MT may allow for timely mobilization of scarce resources and could benefit patients by making blood products available for treating hemorrhagic shock.