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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Pulmonary fibrosis is an important factor affecting the prognosis of severe septic patients with acute lung injury. The objective of this study was to explore the effect of norepinephrine (NE) and α 2 -adrenoreceptor (AR) on sepsis-associated pulmonary fibrosis and the mechanism underlying these effects. We found pulmonary fibrotic changes, and increased NE production and α 2A -AR expression in the pulmonary tissue of mice subjected to cecal ligation and puncture surgery. ⋯ Clonidine showed the opposite effect to yohimbine, which aggravated LPS-induced pulmonary fibrosis. These findings demonstrated that the sepsis-induced increase in NE promoted fibroblast differentiation via activating α 2 -AR. Blockage of α 2 -AR effectively ameliorated sepsis-associated pulmonary fibrosis by abolishing NE-induced lung fibroblast differentiation and inhibiting the PKC-p38-Smad2/3 pathway.
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Background : We explored the efficacy and main biological mechanism of geniposide intervention in sepsis. Methods : A sepsis model was established in male BALB/c mice through cecal ligation and puncture (CLP). Different doses of geniposide (20 or 40 mg/kg) were administered intravenously at 0 and/or 24 h after CLP surgery. ⋯ In addition, geniposide elevated the PPARγ level in monocytes ( P < 0.05). Conclusions : High-dose early-stage geniposide administration significantly improved the survival rate in a CLP mouse sepsis model by modulating the monocyte phenotype and regulating the cytokine network (IL-6/IL-10 levels). The pharmacological mechanism of geniposide action might be exerted primarily through PPARγ upregulation.
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Meta Analysis
Initiation timing of vasopressor in patients with septic shock: a systematic review and meta-analysis.
Background: Vasopressor plays a crucial role in septic shock. However, the time for vasopressor initiation remains controversial. We conducted a systematic review and meta-analysis to explore its initiation timing for septic shock patients. ⋯ The early group had an earlier achievement of target MAP ( P < 0.001), shorter vasopressor use duration ( P < 0.001), lower serum lactate level at 24 h ( P = 0.003), lower incidence of kidney injury ( P = 0.001), renal replacement therapy use ( P = 0.022), and longer ventilation-free days to 28 days ( P < 0.001). Conclusions: Early initiation of vasopressor (1-6 h within septic shock onset) would be more beneficial to septic shock patients. The conclusion needs to be further validated by more well-designed randomized controlled trials.
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Background: Tissue trauma and hemorrhage result in pronounced activation of the innate immune system. Given known crosstalk between inflammation and coagulation, soluble inflammatory mediators could be associated with venous thromboembolisms (VTEs) after major trauma. Objectives : This study aimed to identify plasma inflammatory mediators that are independent predictors of VTE risk in trauma patients. ⋯ We identified significant correlations between inflammation and markers of coagulation and endothelial activation. Conclusion: Sustained systemic inflammation is a key driver of VTE risk after major trauma. Therapeutics targeting innate immune activation should be considered for development of future multimodal strategies to augment current VTE prophylaxis.