Key result
Intraperitoneal injection of 10 mg/kg of LPS successfully constructed a stable new-onset atrial fibrillation model in sepsis, characterized by increased left atrial area, fibrosis, and elevated NLRP3 inflammasomes.
Why the study?
New-onset AF in sepsis significantly impacts morbidity and mortality, but the optimal animal model for studying this condition remains undetermined.
Does intraperitoneal LPS injection or cecal ligation and puncture (CLP) better establish a stable model of new-onset atrial fibrillation in sepsis in Sprague-Dawley rats?
Does intraperitoneal LPS injection or cecal ligation and puncture (CLP) better establish a stable model of new-onset atrial fibrillation in sepsis in Sprague-Dawley rats?
Intraperitoneal injection of 10 mg/kg LPS effectively establishes a stable rat model of sepsis-induced new-onset atrial fibrillation, which appears to be mediated by the NLRP3 inflammasome and S1P/S1P2 signaling axis.
Should not yet change practice for new-onset AF in sepsis; leaves open translational value of the LPS model and S1P/S1P2-NLRP3 axis.
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.
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Shen et al. (2024) studied Sepsis-induced new-onset atrial fibrillation (n=47). Intraperitoneal lipopolysaccharide (LPS) injection vs. Cecal ligation and puncture (CLP), sham operation, and control was evaluated on Incidence of new-onset atrial fibrillation and five-day mortality rates. Intraperitoneal injection of 10 mg/kg of LPS successfully constructed a stable new-onset atrial fibrillation model in sepsis, characterized by increased left atrial area, fibrosis, and elevated NLRP3 inflammasomes.
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