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: 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
• Journal: Toxicology and applied pharmacology (Toxicol Appl Pharmacol) Vol. 259 Issue 1 Pg. 66-73 (Feb 15 2012) ISSN: 1096-0333 [Electronic] United States
• PMID: 22197715 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Air Pollutants
• Particulate Matter
• Reactive Oxygen Species
• Vehicle Emissions
• Calcium-Calmodulin-Dependent Protein Kinase Type 2
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Action Potentials (drug effects)
• Air Pollutants (toxicity)
• Animals
• Animals, Newborn
• Apoptosis (drug effects)
• Arrhythmias, Cardiac (chemically induced, enzymology, metabolism, prevention & control)
• Calcium-Calmodulin-Dependent Protein Kinase Type 2 (metabolism)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Enzyme Activation
• Immunoblotting
• Immunohistochemistry
• Male
• Myocytes, Cardiac (drug effects, metabolism)
• Oxidative Stress (drug effects)
• Particulate Matter (toxicity)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Vehicle Emissions (toxicity)
• Ventricular Premature Complexes (chemically induced, enzymology, metabolism, prevention & control)
• Voltage-Sensitive Dye Imaging