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

Abstract

Hydrogen sulfide (H 2 S), 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 H 2 S in healthy and ischemic conditions. Experimental data of H 2 S effects on ionic channels (including the L-type Ca 2+ 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 H 2 S 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 H 2 S 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 (H 2 S), especially in the case with extant ischemic conditions.

Mechanistic Insights Into Inflammation-Induced Arrhythmias: A Simulation Study

“…Although the effects of inflammatory cytokines on individual ion channels have been investigated in these studies, its integral effect on ventricular cellular action potential (AP) and its conduction properties remain unclear. In recent years, emerging cardiac simulations have provided powerful tools for exploring the pathogenesis of cardiovascular diseases ( Xie et al, 2004 ; Arevalo et al, 2016 ; Zhang et al, 2019 , 2020 ). In our recent work, we constructed a multiscale ventricle model that is able to reproduce both physiological and pathological phenomena on different scales ( Bi et al, 2021 ).…”

Air Pollution and Cardiac Arrhythmias: From Epidemiological and Clinical Evidences to Cellular Electrophysiological Mechanisms

“…Systemic inflammation is known to contribute to the progression of atherosclerosis (41), resulting in chronic and acute ischemia. Ischemic heart disease leads to ion channel remodeling, augments spatial dispersion of depolarization, thereby providing substrates for cardiac arrhythmias (42,43). Second, in some severe inflammatory states such as sepsis and septic shock, the increased cytokine levels cause myocardial dysfunction that might contribute to the occurrence of various types of arrhythmias.…”

“…H 2 S was also reported to inhibit the I CaL in a concentration-dependent manner (142,143), and the involvement of I CaL was further evidenced by the observation that blockage of I KATP did not completely eliminate the effect of H 2 S (144). In our previous simulation study, we investigated the proarrhythmic effects of H 2 S using a multi-scale virtual heart (43). Briefly, the effects of H 2 S on ionic currents were incorporated into a mathematical myocyte model, and were further expanded to tissue levels.…”

“…These actions together lead to increased tissue susceptibility for initiation and maintenance of reentry arrhythmia. In addition, the vulnerability to reentry arrhythmia could be further exacerbated in mild ischemia due to the involvement of I KATP (43).…”

A case of syncope in a villager with hypertrophic cardiomyopathy after hydrogen sulfide exposure by an unauthorized discharge of wastewater

“…In an experimental study conducted based on this, hydrogen sulfide inhibits cell excitability, shortens the duration of action potentials, increases transmural dispersion of tissue repolarization, increases the sensitivity to tissue reentry initiation and maintenance, and causes pro-arrhythmic effects. 9 Cases of hydrogen sulfide poisoning in existing industrial sites and unmanaged toilets have been frequently described, but there have been no cases reported of poisoning of the public due to an illegal discharge of wastewater. Therefore, we would like to communicate such a case report.…”