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other·preclinical research, biomedical research, critical care, immunology·PMC10082063

A MODIFIED SURGICAL SEPSIS MODEL SATISFYING SEPSIS-3 AND HAVING HIGH CONSISTENCY OF MORTALITY

Shock (Augusta, Ga.) · 6 authors, 3 centres

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TL;DR

A modified cecal ligation and perforation (M-CLP) procedure in rats was developed to improve clinical relevance and reproducibility over traditional CLP. More rats in the M-CLP group met Sepsis-3 criteria and demonstrated more consistent survival rates across independent experiments.

Full summary

548 CHARS

M-CLP involved four 3-mm cecal punctures, wrapping the ligated cecum in a glove finger with seven zigzag incisions, standardized fecal content volume, and 5% glucose resuscitation at 12 hours. At 24 hours postoperatively, organ function was assessed via blood pressure, histopathology, blood tests, and behavioral testing; cytokines were measured by ELISA; and T-cell suppression was evaluated by flow cytometry. Survival was monitored over 14 days across three independent experiments. M-CLP survival rates were more consistent across experiments.

STUDY TYPE

other

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preclinical research

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AI pipeline

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100% · A

ORIGINAL PAPER

PMC10082063

A MODIFIED SURGICAL SEPSIS MODEL SATISFYING SEPSIS-3 AND HAVING HIGH CONSISTENCY OF MORTALITY

Shock (Augusta, Ga.)

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ABSTRACT

ABSTRACT Background : Cecal ligation and perforation (CLP) is currently considered the criterion standard model of sepsis; however, there are some deficiencies, such as low clinical relevance, inconsistency in severity grading, and an unknown proportion of CLP animals meeting the requirements of sepsis-3. Methods : Adult rats were randomly divided into the following three groups: modified CLP (M-CLP) group, CLP group, and sham group. The vital organ function of rats was evaluated 24 hours postoperatively by blood pressure, behavioral testing, histopathology, and blood test. Cytokine levels were determined by enzyme-linked immunosorbent assay, and T-cell suppression was assessed by flow cytometry. The stability of the model was evaluated by comparing the survival rates of repeated experiments in all groups from day 1 to day 14. Results : More rats in the M-CLP group met Sepsis-3 criteria than those in the CLP group 24 hours postoperatively (53.1% vs. 21.9%, P = 0.01). Rats in the M-CLP group developed more serious hepatic, pulmonary, and renal dysfunction. Similar to human sepsis, rats in the M-CLP group demonstrated more serious immunosuppression and systemic inflammation compared with the CLP group. In addition, disease development and severity, which was indicated by the stable survival rates of model animals, were more stable in the M-CLP group. Conclusions : More rats could meet Sepsis-3 criteria with this novel surgical procedure, which may reduce the number of animals needed in preclinical sepsis experiments. This stable M-CLP model may contribute to the development of new therapies.

CITATION EXPORT

Jiebo Wang, Lianming Liao, Ying Chen et al.. A MODIFIED SURGICAL SEPSIS MODEL SATISFYING SEPSIS-3 AND HAVING HIGH CONSISTENCY OF MORTALITY. Shock (Augusta, Ga.). (2023). https://doi.org/10.1097/SHK.0000000000002096

AUTHORS

6 · 3 CENTRES

Jiebo Wang, Lianming Liao, Ying Chen, Liji Chen, Zhongmeng Lai, Liangcheng Zhang

∗Department of Anesthesiology, Fujian Medical University Union Hospital, Fuzhou, China
†Center of Laboratory Medicine, Union Hospital of Fujian Medical University, Fuzhou, China
‡Department of Anesthesiology, Longyan First Affiliated Hospital of Fujian Medical University, Longyan City, China