Toxic and Proarrhythmic Effects of Airborne Particulate Matter Exposure: In-vitro, In-vivo and In-silico Study

Exposure to particulate matter (PM) is related to an increase in cardiovascular diseases and the appearance of cardiac arrhythmias.However, the pathophysiological mechanisms have not been well established.This study aims to evaluate the toxic and proarrhythmic effects of PM, for this, PM was extracted from monitoring station filters using Soxhlet systems.Cardiomyocyte cultures of the HL-1 cell line were exposed to different PM concentrations and MTT assay was performed to assess cell viability, which decreased as the PM concentration increased.The lethal dose (LC50) obtained was adopted as the IC50 value for in-silico studies to evaluate the PM effects in 2D ventricular and atrial tissue models.As the concentration of PM increased, major pro-arrhythmic effects were observed with a shortening of the action potential duration and increasing vulnerable windows.To verify the results, we used mice with inhalation exposure to vaporized aerosols, which generate high PM levels.In-vivo programmed electrical stimulation in the exposed mice suggested a trend for a decreased ventricular effective refractory period as well as significantly increased inducible ventricular arrhythmogenesis compared to room air control animals.Overall, the results suggest cytotoxic and proarrhythmic effects of PM in a concentrationdependent manner.