Abstract
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.
Highlights
Pro-arrhythmia risks of ambient air pollution have been long established by epidemiological evidences
Such simulated changes qualitatively matched with experimental data of Sun et al (2008), there are some quantitative discrepancies between simulation and experimental data (Figure 1C), possibly owing to a greater ICaL current density in the Pandit model as compared with the experimental data, which produced a greater action potential duration (APD) abbreviation than the experimental data of Sun et al (2008)
The effects of H2S on cardiac ion channels were based on experimental data of a H2S donor, NaHS, as NaHS is superior to the direct administration of H2S for dose control, data reproducibility, and negligible effects on the cellular Na+ concentration and pH (Zhong et al, 2003, 2010)
Summary
Pro-arrhythmia risks of ambient air pollution have been long established by epidemiological evidences. Experiments on rats have characterized the dosedependent effects of NaHS on ionic currents of the two channels, ICaL and IK,ATP (Sun et al, 2008; Zhong et al, 2010), and suggested that low doses of NaHS (i.e., 100 and 150 μmol/L) abbreviated APD by either an enhanced IK,ATP (Zhong et al, 2010) or a reduced ICaL (Sun et al, 2008). It is possible that other channel currents may be involved in their experiments owing to the use of a high concentration of intracellular ATP or channel blockers, it is unclear if the observed increase in IK,ATP or decrease in ICaL is sufficient to account for the abbreviation of the APD by NaHS
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