title: Particulate air pollution induces arrhythmia via oxidative stress and calcium calmodulin kinase II activation.
abstract: 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 Ca(2+)/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.
authors.affiliation: The Division of Cardiology, Kyung Hee University College of Medicine, 1 Hoegi-dong, Dongdaemun-Gu, Seoul, Republic of Korea.
authors.forename: Jin-Bae
authors.initials: JB
authors.lastname: Kim
authors.forename: Changsoo
authors.initials: C
authors.lastname: Kim
authors.forename: Eunmi
authors.initials: E
authors.lastname: Choi
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Park
authors.forename: Hyelim
authors.initials: H
authors.lastname: Park
authors.forename: Hui-Nam
authors.initials: HN
authors.lastname: Pak
authors.forename: Moon-Hyoung
authors.initials: MH
authors.lastname: Lee
authors.forename: Dong Chun
authors.initials: DC
authors.lastname: Shin
authors.forename: Ki-Chul
authors.initials: KC
authors.lastname: Hwang
authors.forename: Boyoung
authors.initials: B
authors.lastname: Joung
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*; D018879:Ventricular Premature Complexes / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D001335:Vehicle Emissions; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D000111:Acetylcysteine