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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Substantial clinical and laboratory research has revealed that major injury causes abnormalities in both the innate and adaptive immune systems. However, the relative importance of each of these systems in the immune dysfunction after injury is poorly understood and difficult to establish by clinical studies alone. Rag1 (-/-) C57BL/6 mice (Rag1), which lack an adoptive immune system, and immune-sufficient wild-type (WT) C57BL/6 mice underwent 25% total body surface area burn injury or sham injury under anesthesia and were subjected to cecal ligation and puncture (CLP) at day 10 postinjury, a time of high CLP mortality in this model. ⋯ Reconstitution of Rag1 mice with WT splenocytes at the time of injury returned cytokine production to WT levels. Intracellular cytokine expression in F4/80 macrophages was increased to a similar degree after burn, but not sham burn injury in Rag1, reconstituted Rag1 and WT animals. These studies demonstrate that the adaptive immune system is necessary for protection from polymicrobial sepsis and plays a significant role in regulating the inflammatory response to injury.
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Shock is associated with a dramatic rise in the level of inflammatory mediators found in plasma. The exact source of these mediators has remained uncertain. We recently examined a previously undescribed mechanism for production of inflammatory mediators in shock involving pancreatic digestive enzymes. ⋯ Intestinal digests with elastase, lipase, trypsin and chymotrypsin also stimulated significant cell mortality. Lipase-treated heart, liver, intestine, diaphragm, kidney, and lung stimulated cell death as well. We conclude that the intestine, as well as several other organs, may serve as a major source of inflammatory mediators during shock if exposed to digestive enzymes.
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Comparative Study
The impact of albumin on hydraulic permeability: comparison of isotonic and hypertonic solutions.
Hypertonic saline, Dextran, and albumin have been advocated for rapid restoration of intravascular volume. The goal of this study was to define how albumin impacts the effects of hypertonic saline and Dextran on hydraulic permeability. We hypothesized that albumin would decrease the hydraulic permeability (L(p)) of isotonic and hypertonic solutions containing Dextran. ⋯ All values for L(p) are x 10(-7) cm x s(-1) x cmH2O(-1). Albumin maintains low hydraulic permeability levels during perfusion with hypertonic saline. In the setting of sufficient of endothelial albumin levels, hypertonic saline and Dextran may be advantageous when used for resuscitation by decreasing trans-endothelial fluid flux and augmenting intravascular volume.
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Healthy physiological systems exhibit irregular variability whereas diseased systems display decreased signal variability or greater regularity. The objective of this article is to report a case series of critically ill adults who displayed ultra low-frequency periodic sinusoidal oscillations in cardiac output (ULF-CO) that were discovered during a clinical study testing software for continuous physiological monitoring. Data were collected from 13 critically ill surgical and trauma patients who required continuous cardiac output monitoring. ⋯ Duration of ULF-CO ranged from 4-108.1 h. ULF-CO could not be explained as a result of patterned artifact from measurement error or therapeutic intervention. ULF-CO may be a pathophysiologic marker that might serve the diagnosis, prognosis, and treatment of critical illness.
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It has been demonstrated that biopterin, an essential cofactor of nitric oxide synthase (NOS), plays an important role in the pathogenesis of endotoxin-induced shock, yet its biological significance in gram-positive sepsis remains unclear. In this study, we adopted a rat model of postburn Staphylococcus aureus sepsis to investigate the potential role of biopterin in the pathogenesis of gram-positive sepsis. Wistar rats were inflicted with a 20% total body surface area (TBSA) full-thickness scald injury followed by S. aureus challenge, and then guanosine triphosphate-cyclohydrolase I (GTP-CHI) mRNA expression and biopterin levels in liver, kidneys, lungs, and heart were determined. ⋯ Meanwhile, multiple organ dysfunction was induced by S. aureus challenge. It was shown that cardiac GTP-CHI mRNA expression and renal BH(4) levels were positively correlated with MB isoenzyme of creatine kinase (CK-MB) and creatinine (r = 0.892, P = 0.0012 and r = 0.9423, P = 0.0015, respectively). These results suggested that thermal injury combined with S. aureus challenge could induce de novo biosynthesis of biopterin, which might play a role in the development of multiple organ dysfunction syndrome secondary to postburn sepsis.