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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Myeloid differentiation 2 (MD-2) plays a critical role in orchestrating the innate immune response and the development of sepsis and subsequent organ dysfunction after trauma. The objectives of this prospective study were to identify haplotype tag single-nucleotide polymorphisms (htSNPs) within the entire MD-2 gene and to investigate their clinical relevance in patients with major trauma. A total of 726 patients with major trauma were prospectively recruited and composed of two different geographic populations (Chongqing in southwestern China and Zhejiang in eastern China). ⋯ However, only the rs11465996 polymorphism was shown to be significantly associated with higher sepsis morbidity rate and MOD scores in patients with major trauma in both Chongqing and Zhejiang districts. In addition, the rs11465996 polymorphism was significantly associated with tumor necrosis factor α production by peripheral blood leukocytes in response to bacterial lipoprotein stimulation. Among the three htSNPs of the entire MD-2 gene, only the rs11465996 might be used as relevant risk estimate for the development of sepsis and MOD syndrome in patients with major trauma.
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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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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.
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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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Trauma patients are often transfused allogeneic red blood cells (RBCs) in an effort to augment tissue oxygen delivery. However, the effect of RBC transfusion on microvascular perfusion in this patient population is not well understood. To this end, we investigated the effect of RBC transfusion on sublingual microvascular perfusion in trauma patients. ⋯ Pretransfusion PPC may be selectively deranged in otherwise stable trauma patients. Patients with relatively altered baseline PPC tend to demonstrate improvement in perfusion following transfusion, whereas those with relatively normal perfusion at baseline tend to demonstrate either no change or, in fact, a decline in PPC. Bedside sublingual imaging may have the potential to detect subtle perfusion defects and ultimately inform clinical decision making with respect to transfusion.