Xiuwen Ling,1,* Jun Shen,2,* Junqing Liang,2 Kai Yang,1 Jianzhong Yang1 

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

*These authors contributed equally to this work

Correspondence: Jianzhong Yang, Emergency & Trauma Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China, Tel/Fax +86 18040399020, Email 18040399020@163.com

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: sepsis, atrial fibrillation, rat model, lipopolysaccharide, NLRP3 inflammasome, S1P/S1P2 signaling axis