Particulate air pollution induces arrhythmia via oxidative stress and calcium calmodulin kinase II activation

• Published in: Toxicology and applied pharmacology 2012-02, Vol.259 (1), p.66-73
• Main Authors: Kim, Jin-Bae, Kim, Changsoo, Choi, Eunmi, Park, Sanghoon, Park, Hyelim, Pak, Hui-Nam, Lee, Moon-Hyoung, Shin, Dong Chun, Hwang, Ki-Chul, Joung, Boyoung
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Acetylcysteine - pharmacology; Action Potentials - drug effects; Air; Air Pollutants - toxicity; AIR POLLUTION; Animals; Animals, Newborn; ANTIOXIDANTS; APOPTOSIS; Apoptosis - drug effects; Arrhythmias, Cardiac - chemically induced; Arrhythmias, Cardiac - enzymology; Arrhythmias, Cardiac - metabolism; Arrhythmias, Cardiac - prevention & control; Biological and medical sciences; BIOLOGICAL STRESS; Ca2 +/calmodulin-dependent protein kinase II; CALCIUM; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; CALMODULIN; Cardiac dysrhythmias; Cardiology. Vascular system; Cells, Cultured; Dose-Response Relationship, Drug; Environmental pollutants toxicology; Enzyme Activation; HEART; Immunoblotting; Immunohistochemistry; IN VIVO; INFUSION; Male; Medical sciences; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; OXIDATION; Oxidative stress; Oxidative Stress - drug effects; OXYGEN; Particulate matter; Particulate Matter - toxicity; RATS; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Toxicology; Vehicle Emissions - toxicity; Ventricular fibrillation; Ventricular Premature Complexes - chemically induced; Ventricular Premature Complexes - enzymology; Ventricular Premature Complexes - metabolism; Ventricular Premature Complexes - prevention & control; Ventricular tachycardia; Voltage-Sensitive Dye Imaging
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2011.12.007

Ambient particulate matter (PM) can increase the incidence of arrhythmia. However, the arrhythmogenic mechanism of PM is poorly understood. This study investigated the arrhythmogenic mechanism of PM. In Sprague–Dawley rats, QT interval was increased from 115.0±14.0 to 142.1±18.4ms (p=0.02) after endotracheal exposure of DEP (200μg/ml for 30min, n=5). Ventricular premature contractions were more frequently observed after DEP exposure (100%) than baseline (20%, p=0.04). These effects were prevented by pretreatment of N-acetylcysteine (NAC, 5mmol/L, n=3). In 12 Langendorff-perfused rat hearts, DEP infusion of 12.5μg/ml for 20min prolonged action potential duration (APD) at only left ventricular base increasing apicobasal repolarization gradients. Spontaneous early afterdepolarization (EAD) and ventricular tachycardia (VT) were observed in 8 (67%) and 6 (50%) hearts, respectively, versus no spontaneous triggered activity or VT in any hearts before DEP infusion. DEP-induced APD prolongation, EAD and VT were successfully prevented with NAC (5mmol/L, n=5), nifedipine (10μmol/L, n=5), and active Ca2+/calmodulin-dependent protein kinase II (CaMKII) blockade, KN 93 (1μmol/L, n=5), but not by thapsigargin (200nmol/L) plus ryanodine (10μmol/L, n=5) and inactive CaMKII blockade, KN 92 (1μmol/L, n=5). In neonatal rat cardiomyocytes, DEP provoked ROS generation in dose dependant manner. DEP (12.5μg/ml) induced apoptosis, and this effect was prevented by NAC and KN 93. Thus, this study shows that in vivo and vitro exposure of PM induced APD prolongation, EAD and ventricular arrhythmia. These effects might be caused by oxidative stress and CaMKII activation. ► The ambient PM consistently prolonged repolarization. ► The ambient PM induced triggered activity and ventricular arrhythmia. ► These effects were prevented by antioxidants, ICaL blockade and CaMKII blockade. ► The ambient PM can induce arrhythmia via oxidative stress and activation of CaMKII.