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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Our objectives were to determine the incidence of critical illness-related corticosteroid insufficiency (CIRCI) in patients with septic shock using a 1 μg corticotropin (ACTH) test and to describe their clinical outcomes. We retrospectively identified 219 consecutive patients with septic shock assessed for CIRCI with a 1 μg ACTH test. Standardized testing involved plasma cortisol measurements at baseline (T0) and at 30 min (T30) and 60 min (T60) after ACTH administration. ⋯ The incidence of CIRCI based on 1 μg ACTH was high in this septic shock cohort. The highest mortality rates were observed in patients with high baseline cortisol and in those who failed to respond appropriately to ACTH. The administration of corticosteroids was not associated with a reduction in mortality.
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We hypothesized that pretreatment with single-dose cyclosporine (CsA) prevents alterations and improves tissue oxygen and mitochondrial cytochrome oxidase redox (CytOx) state in skeletal muscle ischemia and reperfusion-reoxygenation (I/R). Latissimus dorsi muscle was prepared and mobilized in New Zealand white rabbits. Ischemia was induced for 4 h, followed by 2 h of reperfusion. ⋯ Muscle HEP levels (phosphocreatine, adenosine triphosphate) were significantly preserved in the CsA group versus the control group (P < 0.01, P < 0.05). Mitochondrial viability index and wet-to-dry ratio confirmed significantly preserved tissue and lower edema formation in the CsA group. The pretreatment with single-dose CsA prevents alterations and improves tissue oxygenation and mitochondrial oxidation in skeletal muscle I/R.
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The assessment of baroreflex function since the first appearance of endotoxemia is important because the arterial baroreflex should exert a protective role during sepsis. Nevertheless, contrasting results were previously reported. This could be due to the hemodynamic instability characterizing this condition that may per se interfere with reflex cardiovascular adjustments. ⋯ We found that blood pressure levels did not change with the infusion of LPS, whereas inflammatory cytokines increased significantly. The baroreflex sensitivity was significantly reduced 10 min after the beginning of LPS infusion, reached values about half those at baseline within 15 min after the start of infusion, and remained significantly low after the end of infusion. In conclusion, we documented that septic shock inducing LPS infusion is responsible for a very rapid impairment of the baroreflex function, independent from the level of blood pressure.
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Bacterial clearance is one of the most important beneficial consequences of the innate immune response. Chemokines are important mediators controlling leukocyte trafficking and activation, whereas reactive oxygen and nitrogen species are effectors in bacterial killing. In the present work, we used in vivo and in vitro models of infections to study the role of monocyte chemoattractant protein 1 (MCP-1)/CCL2 and nitric oxide (NO) in the bacterial clearance in sepsis. ⋯ Macrophages from CCL2 mice showed a consistent decrease in NO production when compared with wild-type controls after stimulation with LPS + interferon. Finally, we showed incubation of macrophages with E. coli, and the ERK inhibitor U0126 increased CFU numbers and decreased intracellular levels of NO. In conclusion, we demonstrated for the first time that MCP-1/CCL2 has a crucial role in the clearance of bacteria by mechanisms involving increased expression of inducible NO synthase and production of NO by ERK signaling pathways.