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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Microcirculatory dysfunction plays a pivotal role in the clinical development and manifestation of severe sepsis and as a marker for mortality. During this process, endothelial damage is characterized by structural and functional alterations that contribute to a great extent to tissue edema. Recent findings revealed the vagus nerve as an important transmitter of the cholinergic anti-inflammatory pathway. ⋯ On the other hand, venular wall shear rate showed no differences. In summary, by inducing the cholinergic anti-inflammatory pathway, physostigmine reduced the capillary leakage and the leukocyte-endothelial interaction. The treatment with physostigmine in endotoxemia may be of interest for clinical use, and further studies should be performed.
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We previously demonstrated that hearts from Brown Norway (BN) rats were more resistant to ischemic injury than hearts from Dahl S (SS) rats. Here we determined the susceptibility to LPS-induced cardiomyopathy in these rats and examined the involvement of inflammatory signaling. Both strains were treated with LPS (20 mg/kg) via i.p. injection for 6 h. ⋯ LPS notably up-regulated the expression of proinflammatory enzymes, iNOS and cyclooxygenase 2, in SS hearts but not in BN hearts. Interestingly, LPS did not stimulate Toll-like receptor 4 or its adaptor myeloid differentiation factor 88 expression in the hearts of either strain but did increase IkappaB and P65 phosphorylation, less prominently in BN hearts than in SS hearts. These data indicate that reduced production of proinflammatory cytokines and diminished nuclear factor kappaB activation are major mechanisms by which BN hearts are more resistant to LPS-induced myocardial dysfunction than SS hearts.
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Hemorrhage remains a major cause of preventable death following both civilian and military trauma. The goals of resuscitation in the face of hemorrhagic shock are restoring end-organ perfusion and maintaining tissue oxygenation while attempting definitive control of bleeding. However, if not performed properly, resuscitation can actually exacerbate cellular injury caused by hemorrhagic shock, and the type of fluid used for resuscitation plays an important role in this injury pattern. ⋯ The data reveal that a uniformly safe, effective, and practical resuscitation fluid when blood products are unavailable and direct hemorrhage control is delayed has been elusive. Yet, it is logical to prevent this cellular injury through wiser resuscitation strategies than attempting immunomodulation after the damage has already occurred. Thus, we describe how some novel resuscitation strategies aimed at preventing or ameliorating cellular injury may become clinically available in the future.
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Circulating angiopoietin (Ang) 1 may inhibit and Ang-2 may enhance pulmonary vascular permeability in septic and nonseptic patients with or at risk for acute lung injury or acute respiratory distress syndrome. We hypothesized that the soluble form of the Ang-binding Tie2 receptor (sTie2), whose shedding may be induced by vascular endothelial growth factor (VEGF) levels, may bind circulating Angs and thereby inhibit their effects on pulmonary vascular permeability. In 24 septic and 40 nonseptic mechanically ventilated patients, sTie2, Ang-1, Ang-2, and VEGF plasma levels were measured together with the pulmonary leak index (PLI) for (67)Gallium-labeled transferrin as a measure of pulmonary vascular permeability. ⋯ Soluble Tie2 did not affect the association between Ang-1 or Ang-2 and the PLI (beta = -0.39, P < 0.001; beta = 0.52, P < 0.001, respectively), independently of underlying disease. Although limited to correlations and associations, the clinical data support in vivo shedding of sTie2 through VEGF signaling upon pulmonary vascular injury. However, this shedding may not prevent a direct role of Angs in pulmonary vascular permeability.
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The Acute Kidney Injury Network (AKIN) group has recently proposed modifications to the risk of renal failure, injury to kidney, failure of kidney function, loss of kidney function, and end-stage renal failure (RIFLE) classification system. The few studies that have compared the two classifications have revealed no substantial differences. This study aimed to compare the AKIN and RIFLE classifications for predicting outcome in critically ill patients. ⋯ Hosmer and Lemeshow goodness-of-fit test results demonstrated good fit in both systems. The AKIN and RIFLE scoring systems displayed good areas under the receiver operating characteristic curves (0.720 + or - 0.030, P = 0.001; 0.738 + or - 0.030, P = 0.001, respectively). Compared with RIFLE criteria, this study indicated that AKIN classification does not improve the sensitivity and ability of outcome prediction in critically ill patients.