Abstract
BACKGROUND AND OBJECTIVES: Ambient particulate matter (PM) in real urban air pollution (RUA) is an environmental health risk factor associated with increased cardiac events. This study investigated the threshold level to induce arrhythmia, as well as arrhythmogenic mechanism of RUA that mainly consisted of PM <2.5 μm in aerodynamic diameter close to ultrafine particles. METHODS: RUA was artificially produced by a lately developed pyrolysis based RUA generator. C57BL/6 mice were divided into 4 groups: a control group (control, n=12) and three groups with exposure to RUA with the concentration of 200 μg/m³ (n=12), 400 μg/m³ (n=12), and 800 μg/m³ (n=12). Mice were exposed to RUA at each concentration for 8 hr/day and 5 day/week to mimic ordinary human activity during 3 weeks. RESULTS: The QRS and QTc intervals, as well as intracellular Ca(2+) duration, apicobasal action potential duration (APD) gradient, fibrosis, and inflammation of left ventricle of mouse hearts were increased dose-dependently with the increase of RUA concentration, and significantly increased at RUA concentration of 400 μg/m³ compared to control (all p<0.001). In mice exposed to RUA concentration of 800 μg/m³, spontaneous ventricular arrhythmia was observed in 42%, with significant increase of inflammatory markers, phosphorylated Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), and phospholamban (PLB) compared to control. CONCLUSIONS: RUA could induce electrophysiological changes such as APD and QT prolongation, fibrosis, and inflammation dose-dependently, with significant increase of ventricular arrhythmia at the concentration of 400 μg/m³. RUA concentration of 800 μg/m³ increased phosphorylation of CaMKII and PLB.