Proarrhythmic effects of carbon monoxide in human ventricular tissue: insights from computational modeling

Epidemiological studies have demonstrated that ambient air pollution has been closely associated with cardiovascular diseases. Carbon monoxide (CO) is a common ambient air pollutant that can cause adverse effects on the heart. CO is known to cause tissue ischemia, resulting in ventricular arrhythmias. However, accumulating biological studies showed that CO could exert effects on multiple cardiac ionic channels under normoxic conditions, which might indicate new proarrhythmic mechanisms other than ischemia-mediated electrophysiology changes. In this work, we evaluated the functional impacts of CO on human ventricles using a multi-scale model of human ventricular tissue. Experimental data regarding the effects of CO on different ion channels were incorporated into the cell model to explore the alterations of ventricular electrophysiology. Simulation results suggested that CO significantly prolonged the duration of ventricular action potentials, enhanced the transmural dispersion of repolarization, and reduced the adaptability of ventricular tissue to fast heart rates. In addition, simulated pseudo-ECGs showed consistent manifestations with the clinical observation that CO caused an apparent QT interval prolongation and T-wave widening, indicating that CO affected the heart's abnormal ventricular repolarization.