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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Red blood cell (RBC) transfusion is associated with alterations in systemic concentrations of IL-8/CXCL8 functional homologs in a murine model. Whether RBC transfusion alters systemic neutrophil chemokine concentrations in individuals sustaining traumatic injury is not known. We conducted a retrospective, single-center study of severely injured trauma patients presenting within 12 h of injury with a base deficit greater than 6 and hypotension in the field. ⋯ Using a linear prediction model to calculate bioanalyte concentrations standardized for age, sex, Injury Severity Score, and admission SBP, we observed that CXCL8 concentrations diverged within 12 h following injury, with the transfused group showing persistently elevated CXCL8 concentrations by contrast to the decay observed in the nontransfused group. Other bioanalytes showed no differences across time. Red blood cell transfusion is associated with persistently elevated neutrophil chemokine CXCL8 concentrations following traumatic injury.
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Experimental pharmacotherapies for the acute respiratory distress syndrome (ARDS) have not met with success in the clinical realm. We hypothesized that chemically modified tetracycline 3 (CMT-3), an anti-inflammatory agent that blocks multiple proteases and cytokines, would prevent ARDS and injury in other organs in a clinically applicable, porcine model of inflammation-induced lung injury. Pigs (n = 15) were anesthetized and instrumented for monitoring. ⋯ It significantly lowered plasma concentrations of interleukin 1β (IL-1β), tumor necrosis factor α, IL-6, IL-8, and IL-10. This study presents a clinically relevant model of lung injury in which CMT-3 treatment prevented the development of ARDS due in part to reduction of multiple plasma cytokines. Treatment of sepsis patients with CMT-3 could significantly reduce progression from sepsis into ARDS.
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Lung injury from pulmonary contusion is a common traumatic injury, predominantly seen after blunt chest trauma, such as in vehicular accidents. The local and systemic inflammatory response to injury includes activation of innate immune receptors, elaboration of a variety of inflammatory mediators, and recruitment of inflammatory cells to the injured lung. Using a mouse model of pulmonary contusion, we had previously shown that innate immune Toll-like receptors 2 and 4 (TLR2 and TLR4) mediate the inflammatory response to lung injury. ⋯ We found that, in the lung, both bone marrow-derived and nonmyeloid cells contribute to TLR-dependent inflammatory responses after injury in a cell type-specific manner. We also show a novel TLR2-dependent injury mechanism that is associated with enhanced airway epithelial cell apoptosis and increased pulmonary FasL and Fas expression in the lungs from injured mice. Thus, in addition to cardiopulmonary physiological dysfunction, cell type-specific TLR and their differential response to injury may provide novel specific targets for management of patients with pulmonary contusion.
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The lymphatic circulation is an important component of the circulatory system. In preliminary studies, we found contractile activity of lymphatic vessels to be decreased during severe shock. In the present study, our aim was to observe changes in lymphatic reactivity to norepinephrine (NE) and to explore the mechanism of calcium sensitivity in rats subjected to hemorrhagic shock (HS). ⋯ Lymphatic reactivity to NE and calcium sensitivity were significantly increased in the 2-h shock group following incubation with the calcium sensitizer angiotensin II, and the lymphatic reactivity was reduced after incubation with the calcium sensitivity inhibitor insulin. In conclusion, lymphatic reactivity declines progressively during HS as a result of calcium desensitization. The results suggest that lymphatic hyporeactivity is one of the mechanisms of lymphatic hypocontraction in rats subjected to HS.
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Cirrhosis increases the risk of kidney injury and sepsis, leading to increased mortality. Elevated levels of plasma asymmetric dimethylarginine (ADMA) occur in patients critically ill with cirrhosis, renal failure, and sepsis. We used a rat model of cirrhosis with superimposed sepsis to assess the relationship of plasma and tissue ADMA profiles with acute kidney injury and survival. ⋯ Lipopolysaccharide increased hepatic AAR, decreased renal AAR, and paradoxically mediated the expression of neuronal nitric oxide synthase-β in the liver and kidneys. A novel mechanism underlies the LPS-mediated L-arginine-ADMA-nitric oxide pathway activation and exacerbation of kidney injury and mortality in our BDL model. In the presence of cirrhosis with superimposed sepsis, simultaneous lowering of ADMA levels and enhancement of L-arginine levels to restore plasma and renal AARs may be an optimal strategy for the treatment of kidney injury.