期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 259, 期 1, 页码 66-73出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2011.12.007
关键词
Particulate matter; Oxidative stress; Ca2+/calmodulin-dependent protein kinase II; Ventricular tachycardia; Ventricular fibrillation
资金
- Yonsei University College of Medicine [6-2009-0176, 6-2010-0059, 7-2009-0583]
- National Research Foundation of Korea
- Ministry of education, science and technology [2010-0021993]
- Korean Healthcare Technology Research and Develop [A085136]
- Ministry of Environment, Republic of Korea [35-1-3-09]
- Korea Ginseng Corporation
- Korean Society of Ginseng
- Korea Environmental Industry & Technology Institute (KEITI) [35-1-3-09] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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 +/- 18.4 ms (p = 0.02) after endotracheal exposure of DEP (200 mu g/ml for 30 min, 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, 5 mmol/L, n = 3). In 12 Langendorff-perfused rat hearts, DEP infusion of 12.5 mu g/ml for 20 min 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 (5 mmol/L, n = 5), nifedipine (10 mu mol/L, n = 5), and active Ca2+/calmodulin-dependent protein kinase II (CaMKII) blockade, KN 93 (1 mu mol/L, n = 5), but not by thapsigargin (200 nmol/L) plus ryanodine (10 mu mol/L, n = 5) and inactive CaMKII blockade, KN 92 (1 mu mol/L, n = 5). In neonatal rat cardiomyocytes, DEP provoked ROS generation in dose dependant manner. DEP (12.5 mu g/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. (C) 2012 Elsevier Inc. All rights reserved.
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