Autonomic- Immunoinflammatory-Cardiac Interplay during Lipopolysaccharide-Induced Systemic Inflammation

Background: Lipopolysaccharide (LPS) triggers complex autonomic-immunoinflammatory- cardiac interplay that underscores the need for temporal dynamics, cytokine pleiotropy, and methodological nuances. Therefore, the study aimed to evaluate autonomic alterations, cardiac electrical alterations, Vagal Neuro-Immunomodulation Index (VNIM), and assess systemic and cardiac inflammatory markers following LPS-induced endotoxemia in a preclinical rat model. Methods: Male Wistar rats were divided into two groups: control and LPS-treated (n = 5 per group). Endotoxemia was induced by intraperitoneal administration of LPS (3 mg/kg), and lead-II electrocardiogram (ECG) signals were recorded after 24 hours for heart rate variability (HRV) analysis and ventricular repolarization/morphological analysis (QT, JT, Tpeak–Tend, ST segment, and Q waves). Biochemical analysis, including inflammatory markers, was quantified in plasma and cardiac tissue. The VNIM was obtained as the ratio of vagal activity to the inflammatory markers. Results: LPS administration resulted in a significant increase in core temperature, tachycardia, and marked reductions in HRV indices, indicating impaired autonomic regulation. LPS-treated rats exhibited significantly higher levels of plasma C-reactive protein (CRP), heart IL-6, and leukocyte counts. ECG analysis demonstrated prolonged QT, JT, and Tpeak–Tend intervals, alongside ST segment depression and Q-wave inversion, indicative of electrical remodelling and myocardial damage. The VNIM index was significantly reduced across all inflammatory markers, demonstrating a breakdown of parasympathetic regulation over immune activation. Correlation analyses revealed significant associations among autonomic, immunoinflammatory, and cardiac parameters. Conclusion: LPS-induced endotoxemia in rats leads to pronounced autonomic and inflammatory dysregulation, accompanied by distinct ECG abnormalities and reduced VNIM. The integration of HRV, cytokine, and ECG profiling provides valuable insight into the autonomic-inflammatory-cardiac interplay during systemic inflammation, supporting their utility in early diagnosis and monitoring of sepsis and related conditions.