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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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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Oxidative stress is believed to accompany reperfusion and to mediate dysfunction of the liver after traumatic-hemorrhagic shock (THS). Recently, endoplasmic reticulum (ER) stress has been suggested as an additional factor. This study investigated whether reperfusion after THS leads to increased oxidative and/or ER stress in the liver. ⋯ Incidence for sustained ER stress and subsequent apoptosis induction were found at 18 h after shock. Thus, THS or reperfusion induces early and persistent ER stress of the liver, independent of oxidative or nitrosylative stress. Although ER stress was not associated with depressed hepatocyte function, it may act as an early trigger of protracted cell death, thereby contributing to delayed organ failure after THS.
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In the intensive care unit (ICU) of our tertiary care university medical center, central venous pressure (CVP) measurements derived from bedside monitors differ considerably from measurements by trained intensivists using paper tracings. To quantify these differences, printed CVP tracings and concurrent respiratory waveforms were collected from 100 consecutive critically ill patients along with the corresponding monitor-displayed CVP. Four blinded intensivists interpreted the tracings. ⋯ To determine the potential clinical impact of these differences, we used the original Surviving Sepsis Campaign Guidelines for fluid administration based upon the measurement of CVP. For individual physicians, protocol-driven fluid management strategy would have differed in 19.2% to 25.3% of cases, dependent upon which measured value was chosen. Although protocol-driven strategies to direct fluid infusion therapy may improve outcomes, these interventions in a specific patient are dependent upon the method by which the CVP is measured.
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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.