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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In addition to standard management of hemorrhagic shock (HS) hyperoxia (mechanical ventilation at FiO2=1.0) and hypothermia can be used to increase O2 supply and to reduce O2 demand. However, hypothermia and hyperoxia can aggravate oxidative stress and metabolic acidosis. Since the latter is linked to deranged glucose metabolism, we investigated their effects on glucose metabolism during hemorrhage and resuscitation. ⋯ Supported by the Federal German Department of Defence (AZ E/U2AD/CF523/DF556).
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Venous thromboembolic events (VTE) occur in up to 20% of trauma patients and of these, pulmonary embolus is fatal in up to 50%. It is unknown whether fibrinolytic activation and consumption of precursors may subsequently render patients hypercoagulable. We hypothesised that an early hyperfibrinolytic state would lead to a propensity for developing VTE. ⋯ Patients developing VTE demonstrate early hyperfibrinolysis following injury. Hyperfibrinolysis depletes plasminogen and may induce a procoagulant state increasing susceptibility to VTE. Fibrinolytic profiling may improve risk stratification and enable targeted prophylaxis.
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Hemorrhagic shock (HS) is a common cause of death in severely injured patients and is associated with impairment of organ perfusion, systemic inflammatory response and multiple organ failure. The aim of the present study was to evaluate the effects of artesunate, the drug of choice for the treatment of falciparum malaria, on organ injury and dysfunction associated with HS in the rat. ⋯ A single-centre placebo-controlled randomized phase II clinical trial will be conducted at Barts Health NHS Trust (TOP-ART) in late 2015 to evaluate the effects of GMP-artesunate in patients with severe hemorrhage following trauma.
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The mortality rate of acute respiratory distress syndrome (ARDS) remains unacceptably high despite that lung protective ventilatory strategies have been widely used. Pharmacological therapy is required to further reduce ARDS mortality. Mechanical ventilation is associated with oxidative stress and lung fibrosis, which may contribute to increased mortality and poor quality of life in ARDS. We hypothesized that the cytokine, midkine (MK), that can be upregulated during oxidative stress, facilitates the development of ARDS- associated lung fibrosis. ⋯ MK may serves as a biomarker for ARDS, as well as acting as an effector activating MK- Notch2-ACE signaling pathway, contributing to lung remodeling. The MK appears to be a potential therapeutic target in the context of ARDS associated lung fibrosis.
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In sepsis myocardial dysfunction is correlated with high mortality rates. Damage associated molecular patterns are released from cells during sepsis. Furthermore, the complement activation product C5a resulted in murine cardiomyocyte in defective contractility and relaxation, suggesting that interaction of C5a with its receptors is involved in the development of septic cardiomyopathy. We hypothesized that during sepsis interaction of C5a with its receptors contribute to cardiac dysfunction. ⋯ The current studies indicate that addition of C5a or extracellular histones to CMs are associated with buildup of [Ca2+]i and ROS. Cardiac dysfunction during sepsis was correlated with presence of both C5a receptors and extracellular histones. Collectively, these alterations may explain at least in part, the cardiomyopathy in sepsis.