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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Clinical Trial
A longer duration of polymyxin B-immobilized fiber column hemoperfusion improves pulmonary oxygenation in patients with septic shock.
Endotoxin plays an important role in the pathogenesis of septic shock. Exposure of endothelial cells to endotoxin activates endothelial cells and increases the surface expression of adhesion molecules, markers of endothelial damage in organ dysfunction. Endotoxin adsorption therapy by polymyxin B-immobilized fiber column (PMX) hemoperfusion has been used for the treatment of septic shock patients. ⋯ The norepinephrine dose and plasma concentrations of soluble endothelial leukocyte adhesion molecule 1 and soluble intercellular adhesion molecule 1 significantly (P < 0.05) decreased in the PMX greater-than-2-h (prolonged) group than in the PMX 2-h (conventional) group (-17.8 +/- 14.6 vs. -1.8 +/- 2.7 microg/min, -143.0 +/- 111.0 vs. 0 +/- 2.8 ng/mL, and -126.2 +/- 144.9 vs. 16.5 +/- 108.1 ng/mL, respectively). Changes in the PaO2-FiO2 ratio and the Sequential Organ Failure Assessment score were significantly (P < 0.05) more improved in the PMX greater-than-2-h group than in the PMX 2-h group (75.4 +/- 80.7 vs. 1.2 +/- 49.2 and -0.8 +/- 1.8 vs. 2.2 +/- 1.9 torr, respectively). We thus suggest that a longer duration of PMX treatment may improve the pulmonary oxygenation associated with decreased adhesion molecules in septic shock.
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Previously, we developed a protocol for shock resuscitation of severe trauma patients to reverse shock and regain hemodynamic stability during the first 24 intensive care unit (ICU) hours. Key hemodynamic measurements of cardiac output and preload were obtained using a pulmonary artery catheter (PAC). As an alternative, we developed a protocol that used central venous pressure (CVP) to guide decision making for interventions to regain hemodynamic stability [mean arterial pressure (MAP) >or= 65 mmHg and heart rate (HR)
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We have recently found that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, improves survival in a lethal model of hemorrhagic shock in rats. The purpose of the present study was to determine whether SAHA treatment would prevent LPS-induced septic shock and improve the survival in a murine model. C57BL/6J mice were randomly divided into two groups. ⋯ Moreover, LPS insult decreased the acetylation of histone proteins (H2A, H2B, and H3), elevated the levels of TNF-alpha in vivo (circulation) and in vitro (culture medium), increased the neutrophilic cell population in the spleen, enhanced the expression of TNF-alpha and IL-1beta genes in lung tissue, and augmented the pulmonary neutrophil infiltration. In contrast, SAHA treatment markedly attenuated all of these LPS-induced alterations. We report for the first time that administration of SAHA (50 mg/kg) significantly attenuates a variety of inflammatory markers and improves long-term survival after a lethal LPS insult.
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Prophylactic use of anticoagulants during sepsis is strongly recommended for the prevention of venous thrombosis. Moreover, recent studies suggested the positive effects of anticoagulants to the inflammation. In this study, we planned to confirm the effects of heparins on protecting against endothelial damage in endotoxemia. ⋯ The fibrinogen level was maintained at significantly better levels, and the elevation of alanine aminotransferase was significantly suppressed in enoxaparin group (P < 0.05 each). In conclusion, both UFH and enoxaparin protect against endothelial damage by preventing leukocyte adhesion. However, UFH significantly increases the bleeding area, whereas enoxaparin does not increase bleeding, and thus, it can reduce organ damages in the endotoxemic rat.