Using the Cecal Ligation and Puncture Model of Sepsis to Induce Rats to Multiple Organ Dysfunction

Cellular immunosuppression appears to be involved in sepsis and sepsis-induced multiple organ dysfunction syndrome (MODS). Recent evidence showed that parenteral vitamin C (Vit C) had the ability to attenuate sepsis and sepsis-induced MODS. Herein, we investigated the impact of parenteral Vit C on cellular immunosuppression and the therapeutic value in sepsis. Using cecal ligation and puncture (CLP), sepsis was induced in WT and Gulo−/− mice followed with 200 mg/Kg parenteral Vit C administration. The immunologic functions of CD4+CD25+ regulatory T cells (Tregs) and CD4+CD25− T cells, as well as the organ functions, were determined. Administration of parenteral Vit C per se markedly improved the outcome of sepsis and sepsis-induced MODS of WT and Gulo−/− mice. The negative immunoregulation of Tregs was inhibited, mainly including inhibiting the expression of forkhead helix transcription factor- (Foxp-) 3, cytotoxic T lymphocyte associated antigen- (CTLA-) 4, membrane associated transforming growth factor-β (TGF-βm+), and the secretion of inhibitory cytokines [including TGF-β and interleukin- (IL-) 10], as well as CD4+ T cells-mediated cellular immunosuppression which was improved by parenteral Vit C in WT and Gulo−/− septic mice. These results suggested that parenteral Vit C has the ability to improve the outcome of sepsis and sepsis-induced MODS and is associated with improvement in cellular immunosuppression.

Download Full-text

Klotho deficiency aggravates sepsis-related multiple organ dysfunction

AJP Renal Physiology ◽

10.1152/ajprenal.00625.2017 ◽

2019 ◽

Vol 316 (3) ◽

pp. F438-F448 ◽

Cited By ~ 1

Author(s):

Lectícia B. Jorge ◽

Fernanda O. Coelho ◽

Talita R. Sanches ◽

Denise M. A. C. Malheiros ◽

Leandro Ezaquiel de Souza ◽

...

Keyword(s):

Oxidative Stress ◽

Organ Dysfunction ◽

Ischemia Reperfusion Injury ◽

Blood Pressure Response ◽

Ischemia Reperfusion ◽

Antioxidant Properties ◽

Cecal Ligation ◽

Kidney Tissue ◽

Multiple Organ ◽

Multiple Organ Dysfunction

Sepsis-induced organ failure is characterized by a massive inflammatory response and oxidative stress. Acute kidney injury (AKI) occurs in approximately half of patients in septic shock, and the mortality associated with sepsis-induced AKI is unacceptably high. Klotho is a protein expressed by renal cells and has anti-senescence properties. Klotho has also been shown to protect the kidneys in ischemia-reperfusion injury and to have antioxidant properties. To analyze the role of Klotho in sepsis-related organ dysfunction and AKI, we used a cecal ligation and puncture (CLP) model of sepsis in heterozygous Klotho-haploinsufficient mice and their wild-type littermates (CLP- Kl/+ and CLP-WT mice, respectively). In comparison with the CLP-WT mice, CLP- Kl/+ mice showed lower survival, impaired renal function, impaired hepatic function, greater oxidative stress, upregulation of inflammatory pathways (at the systemic and kidney tissue levels), and increased NF-κB activation. It is noteworthy that CLP- Kl/+ mice also showed lower heart-rate variability, less sympathetic activity, impaired baroreflex sensitivity to sodium nitroprusside, and a blunted blood pressure response to phenylephrine. We also demonstrated that sepsis creates a state of acute Klotho deficiency. Given that low Klotho expression exacerbates sepsis and multiple organ dysfunction, Klotho might play a protective role in sepsis, especially in elderly individuals in whom Klotho expression is naturally reduced.

Download Full-text

Interleukin-10 Gene Transfer: Prevention of Multiple Organ Injury in a Murine Cecal Ligation and Puncture Model of Sepsis

World Journal of Surgery ◽

10.1007/s00268-006-0066-9 ◽

2006 ◽

Vol 31 (1) ◽

pp. 105-115 ◽

Cited By ~ 13

Author(s):

Burhan Kabay ◽

Cetin Kocaefe ◽

Atac Baykal ◽

Hilmi Özden ◽

Cengiz Baycu ◽

...

Keyword(s):

Gene Transfer ◽

Cecal Ligation ◽

Interleukin 10 ◽

Multiple Organ ◽

Organ Injury ◽

Cecal Ligation And Puncture ◽

Puncture Model ◽

Multiple Organ Injury

Download Full-text

Disseminated intravascular coagulation in meningococcal sepsis

Hämostaseologie ◽

10.1055/s-0037-1619581 ◽

2003 ◽

Vol 23 (03) ◽

pp. 125-130 ◽

Cited By ~ 2

Author(s):

S. Zeerleder ◽

R. Zürcher Zenklusen ◽

C. E. Hack ◽

W. A. Wuillemin

Keyword(s):

Organ Dysfunction ◽

Disseminated Intravascular Coagulation ◽

Skin Necrosis ◽

Multiple Organ ◽

Meningococcal Sepsis ◽

Multiple Organ Dysfunction ◽

Intravascular Coagulation ◽

Therapeutic Concepts ◽

New Therapeutic Concepts ◽

Coagulation And Fibrinolysis

SummaryWe report on a man (age: 49 years), who died from severe meningococcal sepsis with disseminated intravascular coagulation (DIC), multiple organ dysfunction syndrome and extended skin necrosis. We discuss in detail the pathophysiology of the activation of coagulation and fibrinolysis during sepsis. The article discusses new therapeutic concepts in the treatment of disseminated intravascular coagulation in meningococcal sepsis, too.

Download Full-text

Multiple Organ Dysfunction Syndrome of Alcoholic Origin in an 18-Year-Old Patient

The International Annals of Medicine ◽

10.24087/iam.2018.2.12.712 ◽

2018 ◽

Vol 2 (12) ◽

Author(s):

Francesco Gazia ◽

Giacomo De Luca ◽

Imbalzano Gabriele ◽

Vincenzo Pellicanò

Keyword(s):

Organ Dysfunction ◽

Multiple Organ Dysfunction Syndrome ◽

Multiple Organ ◽

Multiple Organ Dysfunction

Download Full-text

IMPACT probability of poor outcome and plasma cytokine concentrations are associated with multiple organ dysfunction syndrome following traumatic brain injury

Journal of Neurosurgery ◽

10.3171/2018.8.jns18676 ◽

2019 ◽

Vol 131 (6) ◽

pp. 1931-1937 ◽

Cited By ~ 2

Author(s):

Sungho Lee ◽

Hyunsoo Hwang ◽

Jose-Miguel Yamal ◽

J. Clay Goodman ◽

Imoigele P. Aisiku ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Organ Dysfunction ◽

Multiple Organ Dysfunction Syndrome ◽

Sofa Score ◽

Plasma Concentrations ◽

Multiple Organ ◽

Multiple Organ Dysfunction ◽

Poor Outcome ◽

Initial Plasma

OBJECTIVETraumatic brain injury (TBI) is a major cause of morbidity and mortality. Multiple organ dysfunction syndrome (MODS) occurs frequently after TBI and independently worsens outcome. The present study aimed to identify potential admission characteristics associated with post-TBI MODS.METHODSThe authors performed a secondary analysis of a recent randomized clinical trial studying the effects of erythropoietin and blood transfusion threshold on neurological recovery after TBI. Admission clinical, demographic, laboratory, and imaging parameters were used in a multivariable Cox regression analysis to identify independent risk factors for MODS following TBI, defined as maximum total Sequential Organ Failure Assessment (SOFA) score > 7 within 10 days of TBI.RESULTSTwo hundred patients were initially recruited and 166 were included in the final analysis. Respiratory dysfunction was the most common nonneurological organ system dysfunction, occurring in 62% of the patients. International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) probability of poor outcome at admission was significantly associated with MODS following TBI (odds ratio [OR] 8.88, 95% confidence interval [CI] 1.94–42.68, p < 0.05). However, more commonly used measures of TBI severity, such as the Glasgow Coma Scale, Injury Severity Scale, and Marshall classification, were not associated with post-TBI MODS. In addition, initial plasma concentrations of interleukin (IL)–6, IL-8, and IL-10 were significantly associated with the development of MODS (OR 1.47, 95% CI 1.20–1.80, p < 0.001 for IL-6; OR 1.26, 95% CI 1.01–1.58, p = 0.042 for IL-8; OR 1.77, 95% CI 1.24–2.53, p = 0.002 for IL-10) as well as individual organ dysfunction (SOFA component score ≥ 1). Finally, MODS following TBI was significantly associated with mortality (OR 5.95, 95% CI 2.18–19.14, p = 0.001), and SOFA score was significantly associated with poor outcome at 6 months (Glasgow Outcome Scale score < 4) when analyzed as a continuous variable (OR 1.21, 95% CI 1.06–1.40, p = 0.006).CONCLUSIONSAdmission IMPACT probability of poor outcome and initial plasma concentrations of IL-6, IL-8, and IL-10 were associated with MODS following TBI.

Download Full-text