Comparison of the Cecum Ligation and Puncture Method and the Intraperitoneal Lipopolysaccharide Injection Method for the Construction of a New-Onset Atrial Fibrillation Model of Sepsis

Xiuwen Ling; Jun Shen; Junqing Liang; Kai Yang; Jianzhong Yang

doi:10.2147/JIR.S485142

Comparison of the Cecum Ligation and Puncture Method and the Intraperitoneal Lipopolysaccharide Injection Method for the Construction of a New-Onset Atrial Fibrillation Model of Sepsis

J Inflamm Res. 2024 Nov 19:17:9103-9117. doi: 10.2147/JIR.S485142. eCollection 2024.

Authors

Xiuwen Ling^#¹, Jun Shen^#², Junqing Liang², Kai Yang¹, Jianzhong Yang¹

Affiliations

¹ Emergency & Trauma Center, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, People's Republic of China.
² Cardiac Pacing and Electrophysiology Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People's Republic of China.

^# Contributed equally.

Abstract

Background: New-onset atrial fibrillation (AF) in sepsis significantly impacted patient morbidity and mortality, yet the optimal animal model for studying this condition remains undetermined. This study aimed to establish a stable animal model for new-onset AF in sepsis and to explore the molecular mechanisms involved.

Methods: Forty-seven Sprague-Dawley rats were utilized, with the cecal ligation and puncture (CLP) group divided into 0.6 mm and 1.0 mm needle outer diameter subgroups, and the lipopolysaccharide (LPS) group into 5 mg/kg, 10 mg/kg, 15 mg/kg, and 20 mg/kg dosage subgroups. The incidence of new-onset AF and five-day mortality rates were compared to identify the most stable modeling conditions. Selected subgroups underwent further analysis, including cardiac ultrasound, electrophysiology, and pathological examinations. Inflammation-related molecular levels in the atrium were assessed using ELISA and Western blotting (WB).

Results: The intraperitoneal injection of 10 mg/kg LPS was identified as the most stable model for new-onset AF in sepsis, with significant findings including increased left atrial area and fibrosis, left ventricular pump dysfunction, uncoordinated ventricular wall motion, and impaired electrical impulse conduction. The effective atrial refractory period was markedly shorter, and susceptibility to AF was higher in the LPS group compared to the CLP group. Molecular analysis revealed elevated levels of NOD-like receptor protein 3(NLRP3) inflammasomes, apoptosis-associated speck-like protein containing a CARD(ASC), Caspase-1 p20 Elevated levels of three inflammation-related proteins and increased activity of the Sphingosine 1-phosphate/Sphingosine 1-phosphate Receptor 2(S1P/S1P2) signaling axis.

Conclusion: Intraperitoneal injection of 10 mg/kg of LPS can successfully construct a new-onset AF model in sepsis, and NLRP3 inflammatory vesicles mediated by the S1P/S1P2 signaling axis may promote new-onset AF in sepsis.

Keywords: NLRP3 inflammasome; S1P/S1P2 signaling axis; atrial fibrillation; lipopolysaccharide; rat model; sepsis.

Grants and funding

This work was sponsored by the National Natural Science Foundation of China (grant number 82260379) and Xinjiang Uygur Autonomous Region Graduate Innovation Program (grant number XJ2024G157, XJ2024G147). No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.