scholarly journals Experimentally Approaching the ICU: Monitoring Outcome-Based Responses in the Two-Hit Mouse Model of Posttraumatic Sepsis

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Susanne Drechsler ◽  
Katrin M. Weixelbaumer ◽  
Heinz Redl ◽  
Martijn van Griensven ◽  
Soheyl Bahrami ◽  
...  
Keyword(s):  
Mouse Model ◽  
Femur Fracture ◽  
Cecal Ligation ◽  
Blood Sampling ◽  
Cecal Ligation And Puncture ◽  
Organ Function ◽  
Daily Monitoring ◽  
Circulating Cells ◽  
Facial Vein ◽  
Insight Into

To simulate and monitor the evolution of posttraumatic sepsis in mice, we combined a two-hit model of trauma/hemorrhage (TH) followed by polymicrobial sepsis with repetitive blood sampling. Anesthetized mice underwent femur fracture/sublethal hemorrhage and cecal ligation and puncture (CLP) 48 h later. To monitor outcome-dependent changes in circulating cells/biomarkers, mice were sampled daily (facial vein) for 7 days and retrospectively divided into either dead (DIE) or surviving (SUR) by post-CLP day 7. Prior to CLP, AST was 3-fold higher in DIE, while all other post-TH changes were similar between groups. There was a significant post-CLP intergroup separation. In SUR, RBC and Hb were lower, platelets and neutrophils higher, and lymphocytes mixed compared to DIE. In DIE, all organ function markers except glucose (decrease) were few folds higher compared to SUR. In summary, the combination of daily monitoring with an adequate two-hit model simulates the ICU setting, allows insight into outcome-based responses, and can identify biomarkers indicative of death in the acute posttraumatic sepsis in mice.

scholarly journals Volatile Anesthetics Improve Survival after Cecal Ligation and Puncture

2013 ◽  
Vol 119 (4) ◽  
pp. 901-906 ◽  
Author(s):  
Inge K. Herrmann ◽  
Maricela Castellon ◽  
David E. Schwartz ◽  
Melanie Hasler ◽  
Martin Urner ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cecal Ligation ◽  
Volatile Anesthetics ◽  
Study Data ◽  
Cecal Ligation And Puncture ◽  
Immunomodulatory Effects ◽  
Organ Function ◽  
Minimal Alveolar Concentration ◽  
Sepsis Model ◽  
Sepsis Induction

Abstract Background: Sepsis remains a leading cause of death in intensive care units. There is growing evidence that volatile anesthetics have beneficial immunomodulatory effects on complex inflammation-mediated conditions. The authors investigated the effect of volatile anesthetics on the overall survival of mice in a sepsis model of cecal ligation and puncture (CLP). Methods: Mice (N = 12 per treatment group) were exposed to anesthetic concentrations of desflurane, isoflurane, and sevoflurane either during induction of sepsis or when the mice showed pronounced symptoms of inflammation. Overall survival, as well as organ function and inflammation was compared with the CLP group without intervention. Results: With desflurane and sevoflurane conditioning (1.2 minimal alveolar concentration for 2 h immediately after induction of CLP) overall survival was improved to 58% and 83%, respectively, compared with 17% in the untreated CLP group. Isoflurane did not significantly affect outcome. Application of sevoflurane 24 h after sepsis induction significantly improved overall survival to 66%. Conclusions: Administration of the volatile anesthetics desflurane and sevoflurane reduced CLP-induced mortality. Anesthesia may be a critical confounder when comparing study data where different anesthesia protocols were used.

scholarly journals Sulforaphane Suppresses Sepsis-Mediated Renal Functions in Cecal Ligation and Puncture Mouse Model

2018 ◽  
Vol 13 (6) ◽  
pp. 1934578X1801300 ◽  
Author(s):  
In-Chul Lee ◽  
Jong-Sup Bae
Keyword(s):  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Glutathione Peroxidase ◽  
Mouse Model ◽  
Plasma Levels ◽  
Renal Damage ◽  
Inflammatory Responses ◽  
Cecal Ligation ◽  
Antioxidant Defense System ◽  
Cecal Ligation And Puncture

Sulforaphane (SFN), a natural isothiocyanate present in cruciferous vegetables such as broccoli and cabbage, is effective in preventing carcinogenesis, diabetes, and inflammatory responses. This study was initiated to determine whether SFN could modulate renal functional damage in a mouse model of sepsis and to elucidate the underlying mechanisms. The potential of SFN treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured by assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity. Treatment with SFN resulted in elevated plasma levels of BUN and creatinine, and of protein in urine in mice with CLP-induced renal damage. SFN treatment also reduced the plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α),▢increased lipid peroxidation, and markedly enhanced the antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney tissues. The present results suggested that SFN protects mice against sepsis-triggered renal injury.

scholarly journals Inhibition of autophagy with 3-methyladenine is protective in a lethal model of murine endotoxemia and polymicrobial sepsis

2018 ◽  
Vol 24 (4) ◽  
pp. 231-239 ◽  
Author(s):  
Qirui Li ◽  
Lingyun Li ◽  
Xiaoyuan Fei ◽  
Yuanyue Zhang ◽  
Chang Qi ◽  
...  
Keyword(s):  
Mouse Model ◽  
Endotoxic Shock ◽  
Cecal Ligation ◽  
Shock Treatment ◽  
Mouse Bone Marrow ◽  
Cecal Ligation And Puncture ◽  
Regulatory Effect ◽  
Tnf Α ◽  
Tlr4 Signaling Pathway

Here, the regulatory role of autophagy is examined in both an LPS-induced lethal endotoxic shock mouse model and cecal ligation and puncture (CLP) mouse model. Autophagy-inhibitor 3-methyladenine (3-MA) and autophagy-enhancer rapamycin were administrated to mice challenged with LPS or CLP. Animals challenged with LPS or CLP combined with 3-MA displayed increased survival after endotoxemia, but LPS combined with rapamycin worsened the endotoxic shock of the mice. Among the different organs studied, the lungs and intestines exhibited significant differences among LPS alone, LPS combined with 3-MA and LPS combined with rapamycin. LPS combined with 3-MA attenuated the inflammatory damages of these organs as compared with LPS alone. In contrast, LPS combined with rapamycin increased damage in these organs. Consistently, serum inflammatory mediators TNF-α and IL-6 were decreased by the treatment of LPS combined with 3-MA as compared with LPS alone, while administration of LPS combined with rapamycin increased the serum TNF-α and IL-6 levels. Similar results were found in mouse bone marrow-derived macrophages exposed to LPS. Moreover, the regulatory effect of autophagy to endotoxic shock is dependent on the TLR4 signaling pathway. Our results demonstrate the central role of autophagy in the regulation of endotoxic shock and its potential modulation for endotoxic shock treatment.

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