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

Jin Bae Kim, Changsoo Kim, Eunmi Choi, Sanghoon Park, Hyelim Park, Hui Nam Pak, Moon Hyoung Lee, Dong Chun Shin, Ki Chul Hwang, Boyoung Joung

Research output: Contribution to journalArticle

34 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)66-73
Number of pages8
JournalToxicology and Applied Pharmacology
Volume259
Issue number1
DOIs
Publication statusPublished - 2012 Feb 15

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Calcium-Calmodulin-Dependent Protein Kinases
Oxidative stress
Air Pollution
Air pollution
Cardiac Arrhythmias
Oxidative Stress
Chemical activation
Calcium
Particulate Matter
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Ventricular Tachycardia
Action Potentials
Rats
Ryanodine
Thapsigargin
Ventricular Premature Complexes
Acetylcysteine
Nifedipine
1-(2-(dodecyloxy)ethyl)pyrrolidine hydrochloride
Cardiac Myocytes

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

Cite this

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. / Particulate air pollution induces arrhythmia via oxidative stress and calcium calmodulin kinase II activation. In: Toxicology and Applied Pharmacology. 2012 ; Vol. 259, No. 1. pp. 66-73.
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Particulate air pollution induces arrhythmia via oxidative stress and calcium calmodulin kinase II activation. / 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.

In: Toxicology and Applied Pharmacology, Vol. 259, No. 1, 15.02.2012, p. 66-73.

Research output: Contribution to journalArticle

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T1 - Particulate air pollution induces arrhythmia via oxidative stress and calcium calmodulin kinase II activation

AU - Kim, Jin Bae

AU - Kim, Changsoo

AU - Choi, Eunmi

AU - Park, Sanghoon

AU - Park, Hyelim

AU - Pak, Hui Nam

AU - Lee, Moon Hyoung

AU - Shin, Dong Chun

AU - Hwang, Ki Chul

AU - Joung, Boyoung

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N2 - 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.

AB - 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.

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