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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This study's objective was to investigate the daily dynamics of fibrinogen metabolism and coagulation function for 5 days after hemorrhagic shock in pigs. Sixteen pigs were randomized into the control (C) and the hemorrhage (H) groups. On day 1, hemorrhage was induced in H by bleeding 35% of the estimated total blood volume, followed by resuscitation with lactated Ringer's solution at three times the bled volume. ⋯ Compared with day 1 control value (1.3 ± 0.1 mg/kg per hour), fibrinogen synthesis in H was increased to 3.6 ± 0.1, 5.1 ± 0.5, 2.6 ± 0.4, 2.7 ± 0.5, and 2.3 ± 0.3 mg/kg per hour on days 1 through 5 (all P < 0.05); fibrinogen breakdown in H was elevated on days 1 and 2 but returned to control values afterward. Hemorrhage caused acute decreases in fibrinogen concentration and clot strength, followed by an increase in fibrinogen concentration and recovery of clot strength. The increase in fibrinogen appeared primarily due to a sustained increase in fibrinogen synthesis.
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The plasma level of soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) has been shown to be helpful in identifying critically ill patients with infection. However, it remains unknown whether it can be used to predict prognosis in patients with severe sepsis. This study investigated whether various inflammatory mediators, including sTREM-1, could be used as reliable markers to predict the prognosis of patients receiving early goal-directed therapy (EGDT). ⋯ The only sTREM-1 level remained significantly higher in nonsurvivors until death. On multivariate regression analysis, log(sTREM-1) (P = 0.028), central venous oxygen saturation (P = 0.022), and Simplified Acute Physiology Score II (P = 0.048) values at admission were independently significant. These results suggest that plasma sTREM-1 level at admission could be used as a marker to identify patients with a poor prognosis despite complete initial resuscitation in severe sepsis.
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The cellular and biochemical mechanisms leading to acute lung injury (ALI) and subsequent multiple organ failure are only partially understood. To study the potential role of eicosanoids, particularly leukotrienes, as possible mediators of ALI, we used a murine experimental model of ALI induced by hemorrhagic shock after blood removal via cardiac puncture. Neutrophil sequestration, as shown by immunofluorescence and protein leakage into the alveolar space were measured as markers of injury. ⋯ MK886 attenuated neutrophil infiltration and protein extravasation induced by hemorrhagic shock. 5-Lipoxygenase-deficient mice showed reduced neutrophil infiltration and protein extravasation after shock treatment, indicating greatly reduced lung injury. These results support the hypothesis that 5-LO, most likely through the generation of leukotrienes, plays an important role in the pathogenesis of ALI induced by hemorrhagic shock in mice. This pathway could represent a new target for pharmacological intervention to reduce lung damage following severe primary injury.
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In clinical practice, prolonged occlusion of main arteries causes accumulation of metabolic waste and lactate. Reperfusion of blood flow is usually accompanied by circulatory shock. This study investigates the molecular mechanisms responsible for acidosis-induced hypotension and proposes therapeutic strategies for improving hemodynamic stability following ischemia-reperfusion acidosis. ⋯ Recording of electrocardiogram showed progressive development of bradyarrhythmia with ST-segment elevation in animals pretreated with PNU37883A before reperfusion. We demonstrate that acidosis-induced vasodilation is, in part, mediated by the activation of KATP channels through reduction of intracellular Ca in VSMCs. However, systemic antagonism of KATP channel significantly increases the overall mortality secondary to the development of cardiac dysrhythmia in animals with profound experimental metabolic acidosis, suggesting that activation of KATP channel is a protective response during reperfusion acidosis.
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Global cerebral ischemia and reperfusion (I/R) often result in high mortality. Free radicals have been reported to play an important role in global cerebral I/R, and therefore, reduction of these might improve the outcome. Here, we investigated the effect of hydrogen gas (H2) (a strong free radical scavenger) on the survival rate of mice following global cerebral I/R. ⋯ Histopathological analysis revealed that H2 treatment significantly attenuated neuronal injury and autophagy in the hippocampal cornu ammonis 1 sector and also brain edema, after 24 h of reperfusion. The beneficial effects of H2 treatment on brain injury were associated with significantly lower levels of oxidative stress markers (8-hydroxy-2'-deoxyguanosine and malondialdehyde) in the brain tissue. Thus, we believe that H2 may be an effective treatment for global cerebral I/R.