Endotracheal Exposure of Particulate Matter Induces Arrhythmia via Oxidative Stress and Calcium Calmodulin Kinase II Activation

Backgrounds: Air pollution particulate matter (PM) could induce arrhythmia. We evaluated the arrhythmogenic mechanism of endotracheal exposure of PM. Methods: We compared the arrhythmic events in rats endotracheally exposed to diesel exhaust product (DEP) of 200 mg/L (DEP group, n=11), control (n=9) and DEP + N-acetylcysteine of 5 mmol/L (NAC group, n=3). Optical mapping was performed the day after in vivo experiment. Results: After endotracheal DEP exposure of 200 mg/L, PR (83 ±16 vs. 63 ±5 ms, p=0.02) and QT intervals (142 ±18, vs. 115±14 ms, p=0.02) were increased than baseline. However, compared with control, PR (73 ±6 ms, p=NS) and QT intervals (103 ±6 ms, p=NS) were not prolonged in NAC group. In DEP group, APD prolonged only at LV base (127±17, vs. 100±12 ms, p=0.002), increasing apicobasal APD (22±10, vs. 5± 11 ms, p=0.01) than control (n=8). Discordant alternans (94±12, vs. 128± 11 ms, p=0.001) were also easily induced at longer pacing cycle length in DEP group than in control. Ventricular arrhythmia was more frequently induced in DEP (67%) than control group (0%, p=0.01). Inhibition of calcium calmodulin kinase II (CaMKII) with KN 93 effectively protected cells from DEP-induced apotosis, whereas inactive KN 93 analogue, KN 92 had no protective effect. Conclusion: Endotracheal exposure of PM prolonged repolarization and induced arrhythmia via oxidative stress and CAMKII activation.