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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Epidermal growth factor (EGF) is a cytoprotective protein that improves survival in preclinical models of sepsis through its beneficial effects on intestinal integrity. Alcohol use disorder worsens intestinal integrity and is associated with increased morbidity and mortality in critical illness. We sought to determine whether chronic alcohol ingestion alters the host response to systemic administration of EGF in sepsis. ⋯ EGF administration resulted in lower levels of both pro- and anti-inflammatory cytokines monocyte chemoattractant protein-1, tumor necrosis factor, and interleukin 10 in alcohol-fed mice. EGF is therefore effective at improving both intestinal integrity and mortality following sepsis in mice with chronic alcohol ingestion. However, the efficacy of EGF in sepsis is blunted in the setting of chronic alcohol ingestion, as intestinal integrity and mortality in alcohol-fed mice given EGF improves animals to levels seen in water-fed mice given vehicle but does not approach levels seen in water-fed mice given EGF.
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We have recently shown that human whole blood stored at 4°C maintains hemostatic and platelet function. In this study, we compared restoration of hemodynamic, metabolic and hemostatic function after limited resuscitation with rat fresh whole blood, rat stored whole blood, or Lactated Ringers in traumatized rats. ⋯ Hemostatic and platelet function of rat whole blood stored at 4°C is preserved for at least 7 days in vitro. Low volume resuscitation with SWB or FWB, but not LR, restores hemodynamic and metabolic function, but not the coagulopathy after severe trauma and hemorrhage.
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Pulmonary injury can be characterized by an increased need for fraction of inspired oxygen or inspired oxygen percentage (FiO2) to maintain arterial blood saturation of oxygenation (SaO2). We tested a smart oxygenation system (SOS) that uses the activity of a closed-loop control FiO2 algorithm (CLC-FiO2) to rapidly assess acute respiratory distress syndrome (ARDS) severity so that rescue ventilation (RscVent) can be initiated earlier. ⋯ Initially, sheep were spontaneously ventilating and then randomized to standard of care (SOC) (n = 6), in which RscVent began when partial pressure of oxygen (PaO2) < 90 mmHg or FiO2 < 0.6, versus SOS (n = 7), software that incorporates and displays SpO2, CLC-FiO2, and SpO2/CLC-FiO2 ratio, at which RscVent was initiated when ratio threshold < 250. RscVent was achieved using a G5 Hamilton ventilator (Bonaduz, Switzerland) with adaptive pressure ventilation and adaptive support ventilation modes for SOC and SOS, respectively.
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Red blood cell transfusions in the setting of trauma are a double-edged sword, as it is a necessary component for life-sustaining treatment in massive hemorrhagic shock, but also associated with increased risk for nosocomial infections and immune suppression. The mechanisms surrounding this immune suppression are unclear. ⋯ HMGB1 derived from the supernatant of human-stored RBCs was shown to inhibit bacterial clearance, as neutralizing antibodies to HMGB1 restored the ability of macrophages to clear bacteria. These findings demonstrate that extracellular HMGB1 within stored RBCs could be one factor leading to immune suppression following transfusion in the trauma setting.
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Renal ischemia-reperfusion (I/R) injury ranks as the primary cause of acute renal injury with severe morbidity and mortality. Side population (SP) cells have recently drawn increasing attention due to their critical role in injury repair and regeneration. Unfortunately, the underlying mechanism involved in renal I/R remains poorly elucidated. ⋯ Additionally, sonic hedgehog (SHH)-Gli 1 signaling was involved in SDF-1/CXCR4-mediated ABCG2 expression. When SP cells pretreated with AMD3100 were intravenously injected into I/R mice, SP cell-mediated decreases in blood urea nitrogen, serum creatinine, and histological score of kidney were noticeably attenuated, indicating that blocking CXCR4 pathway mitigated the therapeutic function of SP cells in renal I/R injury. Together, this research suggests that SDF-1/CXCR4 axis might act, via Shh-Gli1-ABCG2 signaling, as a positive regulator of SP cell-based therapies for renal I/R by Shh-Gli 1-ABCG2 signaling.