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

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.