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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β 3 -adrenergic receptor (β 3 -AR) has been proposed as a new therapy for several myocardial diseases. However, the effect of β 3 -AR activation on sepsis-induced myocardial apoptosis is unclear. Here, we investigated the effect of β 3 -AR activation on the cardiomyocyte apoptosis and cardiac dysfunction in cecal ligation and puncture (CLP)-operated rats and lipopolysaccharide (LPS)-treated cardiomyocytes. ⋯ Furthermore, administration of β 3 -AR antagonist, SR59230A (5 mg/kg), significantly decreased the maximum rate of left ventricular pressure rise (+dP/dt) in CLP-induced septic rats. SR59230A not only increased myocardial apoptosis, reduced p-Akt Ser473 and Bcl-2 contents, but also increased mitochondrial Bax, cytoplasm cytochrome c, cleaved caspase-9, and cleaved caspase-3 levels of the myocardium in septic rats. These results suggest that endogenous β 3 -AR activation alleviates sepsis-induced cardiomyocyte apoptosis via PI3K/Akt signaling pathway and maintains intrinsic myocardial systolic function in sepsis.
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The adenosine concentration and forkhead box protein (Foxp3) expression in T regulatory cells (T regs ) are increased during sepsis. However, the mechanism by which adenosine induces Foxp3 expression is incompletely understood. A cecal ligation and puncture (CLP) model was constructed using C57BL/J mice. ⋯ A2aR blockade or inhibition of CREB expression inhibited Foxp3 expression in T regs. In the CLP model, use of CREB inhibitors could inhibit Foxp3 expression and reduce the bacterial load. In summary, adenosine in sepsis promotes CREB phosphorylation via A2aR which, in turn, upregulates Foxp3 expression in T regs .
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Background: Hemolysis is a frequent complication in patients with sepsis, ARDS, or extracorporeal membrane oxygenation (ECMO). Haptoglobin (Hp) can scavenge released cell-free hemoglobin (CFH). Hemolysis and low plasma concentrations of Hp may be independently associated with mortality in critically ill patients. ⋯ Patients with initial Hp <0.66 g/L had higher risks for Hp depletion than patients with initial Hp ≥0.66 g/L. Conclusion: Patients with Hp depletion within the first week of ECMO therapy might benefit from close monitoring of hemolysis with early detection and elimination of the underlying cause. They might be potential candidates for future Hp supplementation therapy to prevent overload of the CFH-scavenger system.
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Sepsis is a life-threatening organ dysfunction caused by an unregulated host response to infection. It is an important clinical problem in acute and critical care. ⋯ Great progress has been made in the study of sepsis-associated rodent models and in vitro cellular models. However, the evidence of curcumin in the clinical management practice of sepsis is still insufficient; hence, it is very important to systematically summarize the study of curcumin and sepsis pathogenesis.