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.
|Number of pages||8|
|Journal||Toxicology and Applied Pharmacology|
|Publication status||Published - 2012 Feb 15|
Bibliographical noteFunding Information:
We thank Changhyun Lee, Kyungmoo Ryu and Stuart P. Rosenberg for their support. This work was supported in part by a faculty research grant of Yonsei University College of Medicine [ 6-2009-0176 , 6-2010-0059 and 7-2009-0583 to B.J]; Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of education, science and technology [ 2010-0021993 to B.J]; Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of education, science and technology [ 2010-0021993 to B.J]; the Korean Healthcare Technology Research and Develop [ A085136 to B.J]; the Center for Environmentally Friendly Vehicle of the Eco-STAR project of the Ministry of Environment, Republic of Korea [ 35-1-3-09 to DC. S] and the Korean Society of Ginseng funded by Korea Ginseng Corporation [ 2010 grant to C.K].
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