Pro-arrhythmic Effects of Hydrogen Sulfide in Healthy and Ischemic Cardiac Tissues: Insight From a Simulation Study

Hydrogen sulfide (H₂S), an ambient air pollutant, has been reported to increase cardiac events in patients with cardiovascular diseases, but the underlying mechanisms remain not elucidated. This study investigated the pro-arrhythmic effects of H₂S in healthy and ischemic conditions. Experimental data of H₂S effects on ionic channels (including the L-type Ca²⁺ channel and ATP-sensitive K⁺ channel) were incorporated into a virtual heart model to evaluate their integral action on cardiac arrhythmogenesis. It was shown that H₂S depressed cellular excitability, abbreviated action potential duration, and augmented tissue's transmural dispersion of repolarization, resulting in an increase in tissue susceptibility to initiation and maintenance of reentry. The observed effects of H₂S on cardiac excitation are more remarkable in the ischemic condition than in the healthy condition. This study provides mechanistic insights into the pro-arrhythmic effects of air pollution (H₂S), especially in the case with extant ischemic conditions.