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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Leukocyte-platelet aggregates (LPA) are associated with atherosclerosis, SIRS and sepsis. Severely injured patients often develop granulocytosis and present with coagulopathy with prolonged clotting times, impaired clot stability and fibrinolytic activation. Following major trauma, 'capture' of functional platelets on activated granulocytes might exacerbate trauma-induced coagulopathy. This study investigated whether the prevalence of activated granulocytes and/or platelets could impair the functional clot firmness in a viscoelastic test (ROTEM). ⋯ Our data obtained in an ex vivo assay indicate that the formation of LPA is associated with a diminished platelet count and a consecutive reduction in MCF.
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Circulatory shock is a frequent cause of death and a most important unresolved medical problem. Reduction of blood supply to the intestine during ischemia disrupts the mucosal epithelial barrier allowing inflammatory materials in the lumen of the intestine, including digestive enzymes, to cross the intestinal wall (Fig. 1). The transport of digestive enzymes leads to uncontrolled digestive enzyme activity in the circulation, which generates cell/tissue damage and a strong inflammatory reaction. Recent studies have demonstrated that the uncontrolled proteolytic activity causes cleavage of important membrane receptors on the endothelial cells (e.g., insulin receptor, VEGFR-2 and E-cadherin) and loss of the associated cell functions. So, understanding the contribution of degrading proteases to circulatory shock serves to elucidate the mechanisms leading to multi-organ failure and to detect potential biomarkers and/or therapeutic targets.(Figure is included in full-text article.) ⋯ : Our preliminary results suggest that there is an increase in protease activity into the systemic circulation following hemorrhagic shock leading to generation of peptide fragments in plasma.
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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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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.
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The mini-fluid challenge may predict fluid responsiveness with minimum risk of fluid overloading. However, the amount of fluid, as well as the best manner to evaluate the effect are unclear. In this prospective observational pilot study, the value of changes in pulse contour cardiac output (CO) measurements during mini-fluid challenges is investigated. ⋯ The use of less invasive Modelflow pulse contour cardiac output measurements in a mini- fluid challenge of only 150 mL can predict fluid responsiveness and may reduce unnecessary fluid loading. It seems to perform better than PulseCO in this respect.