Abstract-++ has a greater action potential duration effect on control conditions. To our knowledge, this is the first work that has developed mathematical models of Pb ++ effect on I CaL current to study its effect on human atrial action potential.

Particulate matter (PM) is considered the most severe environmental pollution problem due to its serious effects on human health associated with an increased risk of cardiovascular morbidity and mortality. In this work, a physicochemical characterization of PM10 from the city of Medellin was developed. The results evince that lead (Pb) is one of the most abundant elements since it is present in all analyzed samples. Therefore, Pb was chosen to perform an in-silico study to assess its effects on atrial arrhythmias generation. For this purpose, we developed a model representing the Pb2+ blocking effect on the L-type calcium channel. This formulation was incorporated in a human atrial cell mathematical model and in 2D and 3D models of human atria. The simulations showed a proarrhythmic effect at high Pb2+ concentrations, through shortening of action potential duration inducing the generation of reentrant activity and atrial flutter. The results contribute to the knowledge about the cardiac physiopathological processes, triggered by lead as one of the main PM10 metal components of air pollution, that yields the generation of arrhythmias.

Exposure to air pollutants like lead (Pb ++ ) and carbon monoxide (CO) IntroductionAir pollution is defined as the presence in the atmosphere of one or more substances in sufficient quantity to produce health alterations. Air pollution causes 4.3 million premature deaths annually [1]. In 2010, the economic cost of health impacts of air pollution in developing countries was around USD 1.7 billion [1].Lead (Pb ++ ) is a toxic agent that can exert adverse health effects in humans. According to the United States Environment Protection Agency (EPA), the Pb ++ is one of the most dangerous air pollutants, affecting multiple human body systems [2]. In general, more than 143.000 people die every year due to illnesses related to Pb ++ [3].Carbon monoxide (CO) is a toxic gas, from incomplete combustion. When people breath, the CO binds to hemoglobin and is significantly retained within the blood reducing the amount of oxygen that it can transport [4].Exposure to these air pollutants contributes to cardiovascular diseases [5]. Epidemiological studies have reported effects such as heart failure, generation of cardiac arrhythmias and decreased heart rate variability [3,[5][6][7][8][9][10][11]. Experimental studies have shown that the Pb ++ blocks the L-type calcium channels [12]. A decrease in Ltype calcium current (I CaL ) is an important mechanism that favors the generation of atrial arrhythmias [13]. Recently, it has been shown that chronic exposure to CO promotes a pathological phenotype of cardiomyocytes, where remodeling leads to an important reduction of the action potential duration (APD) in atrial myocardium increasing the risk of arrhythmias [9,10] and ischemia [14]. This study aims to assess the effects of the Pb ++ and CO at different concentrations on human atrial action potential, using computational simulation. Methods Human atrial cell modelThe Courtemanche-Ramirez-Nattel-Kneller [15,16] membrane formalism was implemented to simulate the electrical activity of human atrial cell. A 0.005 µM of acetylcholine concentration was simulated. The transmembrane voltage (V m ) is given by:where C m is the membrane capacitance (100 pF), I ion is the total membrane current, and I st is the external stimulus current. The model is considered under normal electrophysiological conditions. Model of Pb ++ and CO effects on I CaLWe developed concentration dependent equations to

Exposure to gaseous air pollutants such as carbon monoxide (CO), nitric oxide (NO) and sulfur dioxide (SO2) promotes the occurrence of cardiac diseases. Investigations have shown that CO and SO2 block the calcium channel (ICaL) of myocytes. The SO2 also increases the sodium channel (INa), the transient outward (Ito) and inward rectifying (IK1) potassium currents. The NO blocks INa and increases ICaL. We developed concentrationdependent equations to simulate the gaseous pollutants effects on the ionic currents. They were incorporated in the Courtemanche model of human atrial cell and in a 2D tissue model. A train of 10 stimuli was applied. The action potential duration (APD) was measured. S1-S2 cross-field protocol was applied to initiate a rotor. The CO and SO2 concentrations from 0 to 1000 uM and NO concentration from 0 to 500 nM were implemented. Six concentration combinations were simulated (cases 1 to 6). The gaseous air pollutants caused an APD shortening and loss of plateau phase of the action potential in a fraction that increases as the pollutant concentration increases. When the highest concentration was applied, the APD decreased by 81%. In the 2D model, from case 4 conditions it was possible to generate rotor, propagating with high stability. These results show pro-arrhythmic effects of gaseous air pollutants.