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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 ± 18.4 ms (p = 0.02) after endotracheal exposure of DEP (200 μg/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 μg/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 μmol/L, n = 5), and active Ca{sup 2+}/calmodulin-dependent protein kinase II (CaMKII) blockade, KN 93 (1 μmol/L, n = 5), but not by thapsigargin (200 nmol/L) plus ryanodine (10 μmol/L, n = 5) andmore » inactive CaMKII blockade, KN 92 (1 μmol/L, n = 5). In neonatal rat cardiomyocytes, DEP provoked ROS generation in dose dependant manner. DEP (12.5 μg/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. -- Highlights: ► The ambient PM consistently prolonged repolarization. ► The ambient PM induced triggered activity and ventricular arrhythmia. ► These effects were prevented by antioxidants, I{sub CaL} blockade and CaMKII blockade. ► The ambient PM can induce arrhythmia via oxidative stress and activation of CaMKII.« less

Authors:
 [1];  [2];  [3]; ; ; ;  [4];  [2];  [3];  [5];  [5];  [4]
  1. The Division of Cardiology, Kyung Hee University College of Medicine, 1 Hoegi-dong, Dongdaemun-Gu, Seoul (Korea, Republic of)
  2. The Department of Preventive Medicine, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of)
  3. Cardiovascular Research Institute and Severance Biomedical Science Institute, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of)
  4. The Division of Cardiology, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul (Korea, Republic of)
  5. (Korea, Republic of)
Publication Date:
OSTI Identifier:
22215241
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 259; Journal Issue: 1; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AIR POLLUTION; ANTIOXIDANTS; APOPTOSIS; BIOLOGICAL STRESS; CALCIUM; CALMODULIN; HEART; IN VIVO; INFUSION; OXIDATION; OXYGEN; RATS

Citation Formats

Kim, Jin-Bae, Kim, Changsoo, Choi, Eunmi, Park, Sanghoon, Park, Hyelim, Pak, Hui-Nam, Lee, Moon-Hyoung, Shin, Dong Chun, Hwang, Ki-Chul, The Division of Cardiology, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul, and Joung, Boyoung, E-mail: cby6908@yuhs.ac. Particulate air pollution induces arrhythmia via oxidative stress and calcium calmodulin kinase II activation. United States: N. p., 2012. Web. doi:10.1016/J.TAAP.2011.12.007.
Kim, Jin-Bae, Kim, Changsoo, Choi, Eunmi, Park, Sanghoon, Park, Hyelim, Pak, Hui-Nam, Lee, Moon-Hyoung, Shin, Dong Chun, Hwang, Ki-Chul, The Division of Cardiology, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul, & Joung, Boyoung, E-mail: cby6908@yuhs.ac. Particulate air pollution induces arrhythmia via oxidative stress and calcium calmodulin kinase II activation. United States. doi:10.1016/J.TAAP.2011.12.007.
Kim, Jin-Bae, Kim, Changsoo, Choi, Eunmi, Park, Sanghoon, Park, Hyelim, Pak, Hui-Nam, Lee, Moon-Hyoung, Shin, Dong Chun, Hwang, Ki-Chul, The Division of Cardiology, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul, and Joung, Boyoung, E-mail: cby6908@yuhs.ac. Wed . "Particulate air pollution induces arrhythmia via oxidative stress and calcium calmodulin kinase II activation". United States. doi:10.1016/J.TAAP.2011.12.007.
@article{osti_22215241,
title = {Particulate air pollution induces arrhythmia via oxidative stress and calcium calmodulin kinase II activation},
author = {Kim, Jin-Bae and Kim, Changsoo and Choi, Eunmi and Park, Sanghoon and Park, Hyelim and Pak, Hui-Nam and Lee, Moon-Hyoung and Shin, Dong Chun and Hwang, Ki-Chul and The Division of Cardiology, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul and Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, 250 Seungsanno, Seodaemun-gu, Seoul and Joung, Boyoung, E-mail: cby6908@yuhs.ac},
abstractNote = {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 μg/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 μg/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 μmol/L, n = 5), and active Ca{sup 2+}/calmodulin-dependent protein kinase II (CaMKII) blockade, KN 93 (1 μmol/L, n = 5), but not by thapsigargin (200 nmol/L) plus ryanodine (10 μmol/L, n = 5) and inactive CaMKII blockade, KN 92 (1 μmol/L, n = 5). In neonatal rat cardiomyocytes, DEP provoked ROS generation in dose dependant manner. DEP (12.5 μg/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. -- Highlights: ► The ambient PM consistently prolonged repolarization. ► The ambient PM induced triggered activity and ventricular arrhythmia. ► These effects were prevented by antioxidants, I{sub CaL} blockade and CaMKII blockade. ► The ambient PM can induce arrhythmia via oxidative stress and activation of CaMKII.},
doi = {10.1016/J.TAAP.2011.12.007},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 259,
place = {United States},
year = {2012},
month = {2}
}