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 studies indicate potential differences in the efficacy of immunoglobulin (Ig) preparations in patients with sepsis. A recent meta-analysis showed improved survival rates with IgM-enriched Igs. It was the objective of the present study to characterize microcirculatory actions of different clinically used Ig preparations in a rodent endotoxin model by intravital microscopy. ⋯ This was associated with normalization of capillary perfusion at 24 h of endotoxemia, whereas intravenous IgG could not prevent LPS-mediated microvascular perfusion failure. We demonstrate that IgM-enriched Igs are superior to IgG alone in attenuating LPS-induced leukocytic inflammation and microcirculatory dysfunction. Our findings can explain better efficacy of IgM-enriched Igs in patients with severe sepsis.
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Central and mixed venous oxygen saturations have been used to guide resuscitation in circulatory failure, but the impact of arterial oxygen tension on venous oxygen saturation has not been thoroughly evaluated. This observational study investigated the impact of arterial oxygen tension on venous oxygen saturation in circulatory failure. Twenty critically ill patients with circulatory failure requiring mechanical ventilation and a pulmonary artery catheter in an intensive care unit in a tertiary hospital in Western Australia were recruited. ⋯ An increase in inspired oxygen concentration significantly increased the arterial oxygen tension from 12.5 to 38.4 kPa (93.8-288 mmHg) (mean difference, 25.9 kPa; 95% confidence interval [CI], 7.5-31.9 kPa; P < 0.001) and the venous oxygen saturation from 69.9% to 76.5% (mean difference, 6.6%; 95% CI, 5.3% - 7.9%; P < 0.001). The effect of arterial oxygen tension on venous oxygen saturation was more significant than the effect associated with changes in cardiac index (mean difference, 2.8%; 95% CI, -0.2% to 5.8%; P = 0.063). In conclusion, arterial oxygen tension has a significant effect on venous oxygen saturation, and this effect is more significant and consistent than the effect associated with changes in cardiac index.
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The inflammatory response after severe blunt chest trauma often leads to acute lung injury and acute respiratory distress syndrome which are associated with high mortality rates. Whereas the role of innate immunity in acute lung injury has been broadly investigated, the immune response after blunt chest trauma is still poorly understood. Therefore, the role of complement and neutrophils was determined in bilateral lung injury induced by a single blast wave. ⋯ Furthermore, blockade of C5a ameliorated the buildup of the proinflammatory cytokine TNF-alpha, diminished the increase of cytokine-induced neutrophil chemoattractant 1, and altered the levels of the anti-inflammatory cytokine IL-10. These data suggest that blunt chest trauma leads to systemic activation of complement and robust C5a generation, which causes perturbations in defensive functions of neutrophils. Thus, C5a might represent a potential target for therapeutic immunomodulation to prevent immune dysfunctions post-trauma and thereby, perhaps, the progression to acute respiratory distress syndrome.
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Deltorphin E was investigated as a pharmaceutical intervention in the ischemic hemorrhagic model. To monitor the hemodynamic biomarkers mean arterial pressure (MAP) and heart rate (HR) and to facilitate i.v. injections, rats were surgically fitted with femoral artery and vein catheters under anesthesia. After removal of 48% of total blood volume (range, 12-15 mL), posthemorrhage i.v. injections of 5.5-mg/kg deltorphin E were found to significantly (P < 0.05) increase maximum MAP, pulse pressure, and survival after hemorrhage, whereas lactic acid concentration was decreased when compared with saline injections. ⋯ Only the antagonists tested, known to affect delta(2)-opioid receptors, interfered with the deltorphin E survival benefit after hemorrhage. As a conclusion, deltorphin E is an effective pharmaceutical intervention in severe hemorrhagic shock and, perhaps, in other ischemic shock scenarios when administered after the onset of stress. Therefore, deltorphin E may have clinical potential.