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Updated: Jun 23, 2025
Evaluation of a Reliable Biomarker in a Cecal Ligation and Puncture-Induced Mouse Model of Sepsis
Published on: December 9, 2022
CECAL SLURRY AS AN ALTERNATIVE MODEL TO CECAL LIGATION AND PUNCTURE FOR THE STUDY OF SEPSIS-INDUCED CARDIOVASCULAR
Gabrielle Delfrate1, Lucas Braga Albino, Jamil Assreuy
1Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Insights
The cecal slurry (CS) model for sepsis research in rats is standardized and replicates key cardiovascular dysfunction. This less invasive, more homogeneous model offers an alternative to the cecal ligation and puncture (CLP) method.
Area of Science:
- Biomedical Research
- Animal Models of Disease
- Sepsis Pathophysiology
Background:
- Sepsis is a critical condition often studied using animal models.
- The cecal ligation and puncture (CLP) model is standard but invasive and variable.
- The cecal slurry (CS) model is less invasive but lacks standardization and its cardiovascular effects are understudied.
Purpose of the Study:
- To standardize the cecal slurry (CS) model in Wistar rats.
- To evaluate sepsis-induced cardiovascular dysfunction using the standardized CS model.
- To compare the CS model with the established cecal ligation and puncture (CLP) model.
Main Methods:
- Standardization of the cecal slurry (CS) preparation and administration in Wistar rats.
- In vivo and ex vivo assessment of cardiovascular parameters, including blood pressure, heart rate, and vascular reactivity.
- Biochemical analysis to assess organ dysfunction and measurement of nitric oxide metabolites.
Main Results:
- The standardized CS model induced hypotension, tachycardia, and reduced contractile responses to vasoconstrictors.
- Organ dysfunction was indicated by elevated lactate, AST, ALT, creatinine, and urea levels.
- The CS model demonstrated increased nitric oxide metabolite production, bacterial spread, and greater homogeneity compared to CLP.
Conclusions:
- The standardized CS model effectively replicates sepsis-induced cardiovascular dysfunction in rats.
- The CS model is less invasive, causes less animal suffering, and offers better homogeneity than the CLP model.
- The CS model is a viable and potentially superior alternative for sepsis research.
Abstract:
Sepsis is a life-threatening condition widely studied by animal models. Cecal ligation and puncture (CLP) is still regarded as the gold standard model for sepsis. However, CLP has limitations due to its invasiveness and variability. Cecal slurry (CS) model is a nonsurgical and thus less invasive alternative. However, the lack of standardization of the CS model in the literature limits its practical application. Additionally, it is not well studied whether CS model reproduces septic cardiovascular dysfunction in rats, which is a crucial issue in septic patients. Thus, this study aimed to standardize the CS model in Wistar rats and evaluate sepsis-induced cardiovascular dysfunction compared to CLP. Our results showed that CS model induced important features of sepsis cardiovascular dysfunction 24 h after its onset, such as hypotension, tachycardia, and decreased contractile response to vasoconstrictors both in vivo and ex vivo as well changes in renal blood flow. Increases in blood lactate, AST, ALT, creatinine, and urea indicated organ dysfunction. CS model also induced increased production of nitric oxide metabolites and bacterial spread to tissues. CS model causes less animal suffering, it is a nonsurgical model, and, more importantly, it replicates the cardiovascular dysfunction induced by sepsis with better homogeneity than CLP. Therefore, CS model serves as an alternative and possibly as a better model for sepsis research.
