Mechanistic Insights Into Inflammation-Induced Arrhythmias: A Simulation Study

Area of Science:

• Cardiovascular Physiology
• Computational Biology
• Immunology

Background:

• Cardiovascular diseases are a leading cause of death, with ventricular arrhythmias being a primary cause.
• Inflammation is implicated in the development of ventricular fibrillation (VF).
• Inflammatory cytokines affect cardiomyocyte ion channels, prolonging action potential duration (APD), but mechanisms remain unclear.

Purpose of the Study:

• To investigate the impact of systemic inflammation on ventricular electrophysiology using multiscale virtual heart models.
• To elucidate the mechanistic links between inflammatory cytokines and ventricular arrhythmias.

Main Methods:

• Incorporated experimental data for tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1β), and interleukin-6 (IL-6) into a cardiomyocyte cell model.
• Evaluated individual and combined cytokine effects on action potential (AP) and excitation wave conduction in a tissue model.
• Utilized multiscale virtual heart models to simulate electrophysiological changes.

Main Results:

• Simulations showed inflammatory cytokines significantly prolonged APD.
• Enhanced transmural and regional repolarization heterogeneities, predisposing to arrhythmias.
• Reduced ventricular tissue adaptability to rapid heart rates and simulated prolonged QT intervals on pseudo-ECGs.

Conclusions:

• Inflammatory cytokines critically alter ventricular electrophysiology, increasing arrhythmia susceptibility.
• Virtual heart models provide mechanistic insights into inflammation-driven ventricular arrhythmias.
• Findings correlate with clinical observations of prolonged QT intervals in inflammatory states.