Fluid Resuscitation Improves Survival of Endotoxemic or Septicemic Rats: Possible Contribution of Tumor Necrosis Factor

Smith, Edward F.; Slivjak, Mark J.; Egan, John; Gagnon, R.C.; Arleth, Anthony J.; Esser, Klaus

doi:10.1159/000139053

Cited by 21 publications

(12 citation statements)

References 2 publications

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“…For instance, fluid resuscitation and broad-spectrum antibiotic therapy have been used in rodents subjected to CLP, resulting in improved survival16,17. Another intervention, intended to simulate abdominal sepsis and its treatment in humans, involves post-CLP laparotomy with excision of the necrotic cecum and peritoneal washing.…”

Section: Experimental Designmentioning

confidence: 99%

Immunodesign of experimental sepsis by cecal ligation and puncture

et al. 2008

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Sepsis remains a prevalent clinical challenge and the underlying pathophysiology is still poorly understood. To investigate the complex molecular mechanisms of sepsis, various animal models have been developed, the most frequently used being the cecal ligation and puncture (CLP) model in rodents. In this model, sepsis originates from a polymicrobial infectious focus within the abdominal cavity, followed by bacterial translocation into the blood compartment, which then triggers a systemic inflammatory response. A requirement of this model is that it is performed with high consistency to obtain reproducible results. Evidence is now emerging that the accompanying inflammatory response varies with the severity grade of sepsis, which is highly dependent on the extent of cecal ligation. In this protocol, we define standardized procedures for inducing sepsis in mice and rats by applying defined severity grades of sepsis through modulation of the position of cecal ligation. The CLP procedure can be performed in as little as 10 min for each animal by an experienced user, with additional time required for subsequent postoperative care and data collection.

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Section: Experimental Designmentioning

confidence: 99%

Immunodesign of experimental sepsis by cecal ligation and puncture

et al. 2008

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“…When challenged with intravenous endotoxin, humans also develop a hyperdynamic circulation [34]. This contrasts with the response seen in most large and small animal models, where hypodynamic shock after sepsis or endotoxemia predominates [72–74, 76–78, 82, 83]. These disparities occur from both the design characteristics of the models and the differences in human and experimental animal physiology.…”

Section: Preclinical Evidence For the Use Of Fluid Resuscitation In Smentioning

confidence: 99%

“…Activation leads to the rapid development of pulmonary hypertension and right heart dysfunction in ovine and porcine models of both sepsis and endotoxemia [82]. A similar clinical presentation of hypodynamic shock is seen in most murine models [76–78]. The dominance of hypodynamic models in the animal literature makes direct extrapolation of the effects of fluid resuscitation to human sepsis particularly problematic.…”

Section: Preclinical Evidence For the Use Of Fluid Resuscitation In Smentioning

confidence: 99%

Fluid resuscitation in human sepsis: Time to rewrite history?

Byrne

Haren

2017

Ann. Intensive Care

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Fluid resuscitation continues to be recommended as the first-line resuscitative therapy for all patients with severe sepsis and septic shock. The current acceptance of the therapy is based in part on long history and familiarity with its use in the resuscitation of other forms of shock, as well as on an incomplete and incorrect understanding of the pathophysiology of sepsis. Recently, the safety of intravenous fluids in patients with sepsis has been called into question with both prospective and observational data suggesting improved outcomes with less fluid or no fluid. The current evidence for the continued use of fluid resuscitation for sepsis remains contentious with no prospective evidence demonstrating benefit to fluid resuscitation as a therapy in isolation. This article reviews the historical and physiological rationale for the introduction of fluid resuscitation as treatment for sepsis and highlights a number of significant concerns based on current experimental and clinical evidence. The research agenda should focus on the development of hyperdynamic animal sepsis models which more closely mimic human sepsis and on experimental and clinical studies designed to evaluate minimal or no fluid strategies in the resuscitation phase of sepsis.

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“…This model has many advantages, such as controllable sepsis severity by adjusting cecal ligation length and/or number of punctures, 64,65 and, analogous to clinical scenarios, CLP mice receiving fluid resuscitation or broad-spectrum antibiotics have improved prognosis. 66,67 With clinical observations of T-cell apoptosis during sepsis reverse translated in an experimental mouse model of sepsis, researchers are able to use additional experimental techniques to perform hypothesis-driven experiments. Ultimately, validated hypotheses using mouse models will be translated to human patients to encompass a wide array of biological and pathological heterogeneity to further test these hypotheses (Fig.…”

Section: Experimental Sepsis Models Facilitate Hypothesis-drivenmentioning

confidence: 99%

Clinical and Experimental Sepsis Impairs CD8 T-Cell-Mediated Immunity

et al. 2016

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Septic patients experience chronic immunosuppression resulting in enhanced susceptibility to infections normally controlled by T cells. Clinical research on septic patients has shown increased apoptosis and reduced total numbers of CD4 and CD8 T cells, suggesting contributing mechanism driving immunosuppression. Experimental models of sepsis, including cecal ligation and puncture, reverse translated this clinical observation to facilitate hypothesis-driven research and allow the use of an array of experimental tools to probe the impact of sepsis on T-cell immunity. In addition to numerical loss, sepsis functionally impairs the antigen-driven proliferative capacity and effector functions of CD4 and CD8 T cells. Sepsis-induced impairments in both the quantity and quality of T cells results in reduced protective capacity and increased susceptibility of mice to new or previously encountered infections. Therefore, the combined efforts of clinical and experimental sepsis research have begun to elucidate the impact of sepsis on T-cell-mediated immunity and potential T-cell-intrinsic and -extrinsic mechanisms driving chronic immunosuppression. Future work will explore the impact of sepsis on the recently appreciated tissue-resident memory (TRM) T cells, which provide robust protection against localized infections, and dendritic cells, which are needed to activate T cells and promote effective T-cell responses.

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Fluid Resuscitation Improves Survival of Endotoxemic or Septicemic Rats: Possible Contribution of Tumor Necrosis Factor

Cited by 21 publications

References 2 publications

Immunodesign of experimental sepsis by cecal ligation and puncture

Immunodesign of experimental sepsis by cecal ligation and puncture

Fluid resuscitation in human sepsis: Time to rewrite history?

Clinical and Experimental Sepsis Impairs CD8 T-Cell-Mediated Immunity

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