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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Clinical Trial
Cardiac Variation of Internal Jugular Vein as a Marker of Volume Change in Hemorrhagic Shock.
Fluid resuscitation, which is critical to counter acute hemorrhagic shock, requires prompt and accurate intravascular volume estimation for optimal fluid administration. This study aimed to evaluate whether cardiac variation of internal jugular vein (IJV), evaluated by ultrasonography, could detect hypovolemic status and predict response to fluid resuscitation. ⋯ Cardiac variation of IJV may be a reliable indicator of intravascular volume loss and response to fluid administration in hemorrhagic shock.
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The purpose of this study was to reveal possible consequences of long-bone fracture on cardiac tissue and to analyze the role of systemically elevated danger associated molecular patterns, complement anaphylatoxins and cytokines. Blood samples of mice, pigs, and humans after a fracture were analyzed by ELISAs for complement component 5a (C5a), tumor necrosis factor (TNF), and extracellular histones. In vivo results were completed by in vitro experiments with human cardiomyocytes treated with TNF and extracellular histones. ⋯ Further, the presence of TNF leads to elevation of reactive oxygen species, troponin I release, and histone appearance in supernatant of human cardiomyocytes. Incubation of human PMNs with histones and plasma of patients after fracture lead to formation of neutrophil extracellular traps. Present results suggest that structural alterations in the heart might be consequences of the complement activation, the release of extracellular histones, and the systemic TNF elevation in the context of a long bone fracture.
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Comparative Study
Superior Effects of Nebulized Epinephrine to Nebulized Albuterol and Phenylephrine in Burn and Smoke Inhalation-Induced Acute Lung Injury.
The severity of burn and smoke inhalation-induced acute lung injury (BSI-ALI) is associated with alveolar and interstitial edema, bronchospasm, and airway mucosal hyperemia. Previously, we have reported beneficial effects of epinephrine nebulization on BSI-ALI. However, the underlying mechanisms of salutary effects of nebulized epinephrine remain unclear. ⋯ Epinephrine and phenylephrine groups significantly reduced trachea wet-to-dry weight ratio and lung vascular endothelial growth factor-A level compared with control group. Histopathologically, epinephrine group significantly reduced lung severity scores and preserved vascular endothelial-cadherin level in pulmonary arteries. In conclusion, the results of our studies suggest that nebulized epinephrine more effectively ameliorated the severity of BSI-ALI than albuterol or phenylephrine, possibly by its combined α1- and β2-agonist properties.
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Adrenomedullin is a vasoactive peptide that improves endothelial barrier function in sepsis, but may also cause hypotension and organ failure. Treatment with a non-neutralizing monoclonal anti-adrenomedullin antibody showed improvement in murine sepsis models. We tested the effects of the humanized monoclonal anti-adrenomedullin antibody Adrecizumab in a porcine two-hit model of hemorrhagic and septic shock. ⋯ After induction of sepsis, plasma adrenomedullin increased immediately in both the groups, but increased quicker and more pronounced in the antibody group. In this two-hit shock model, treatment with an anti-adrenomedullin antibody significantly increased plasma adrenomedullin levels, while significantly less animals developed septic shock and renal granulocyte extravasation was significantly reduced. Thus, therapy with Adrecizumab may provide benefit in sepsis, and clinical investigation of this drug candidate is warranted.
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Macrophages play a key role in the development of sepsis-induced acute respiratory distress syndrome (ARDS). Recent evidence has proved that glycolysis plays an important role in regulating macrophage polarization through metabolic reprogramming. Bone marrow mesenchymal stem cells (BMSCs) can alleviate sepsis-induced lung injury and possess potent immunomodulatory and immunosuppressive properties via secreting exosomes. ⋯ Finally, a model of LPS-induced ARDS in mice was established, we found that BMSCs-derived exosomes ameliorated the LPS-induced inflammation and lung pathological damage. Meanwhile, we found that intratracheal delivery of BMSCs-derived exosomes effectively down-regulated LPS-induced glycolysis in mice lung tissue. These findings reveal new mechanisms of BMSCs-derived exosomes in regulating macrophage polarization which may provide novel strategies for the prevention and treatment of LPS-induced ARDS.