Background: Several epidemiologic studies have showed that the air pollution particulate matter (PM) increases arrhythmia. However, the arrhythmogenic mechanism of PM was not still revealed. Recently, we found that the PM can directly induce triggered activity and arrhythmia in Langendorff-perfusion isolated rat hearts via the mechanism of oxidative stress and calcium calmodulin kinase II (CaMKII) acivition. This study was performed whether the PM can increase tissue electrical heterogeneity and inducibility of arrhtythmia via the same mechanism.
Methods: In Langendorff-perfused Adult Sprague-Dawley rat hearts (n=25), arrhythmic events and mechanism were evaluated after treatment with diesel exhaust product (DEP) using optical mapping technique. To remove the effect of agglomeration, the DEP was sonificated for 20 minutes, and confirmed the particle size less than 100 nm with electronic microscope.
Results: DEP induced ROS generation in time and dose dependant manner, showing that 67% myocyte generated ROS at 400㎍/ml after 6hr exposure. In Langendorff-perfused rat hearts (n=10), DEP infusion of 12.5 mg/L for 10 minutes significantly prolonged APD90 at the base (from 104 ± 24 to 152 ± 30 ms, p=0.01), but not at the apex (from 92 ± 25 to 102 ± 23 ms, p=0.38) of left ventricle at the pacing cycle length (CL) of 200 ms. Compared with baseline, apicobasal APD90 difference (APD base-apex) increased at pacing CL of 300 ms (13 ± 6, vs. 82 ± 24 ms, p=0.001) 200ms (13 ± 4, vs. 50 ± 11 ms, p=0.001), and 160 ms (10 ± 5, vs. 32 ± 10 ms, p=0.01) after DEP, producing significant apico-basal APD gradients. However, the APD restitution slope was not changed significantly by DEP. After DEP infusion, the concordant (148 ± 10, vs. 107 ± 13 ms, p=0.001), discordant alternans (123 ± 17, vs. 78 ± 8 ms, p=0.001) and conduction block (120 ± 18 ms, vs. 79 ± 9 ms, p=0.006) were also easily observed at longer CL than baseline. Ventricular tachyarrhythmias (VT) were induced in 7 (70%) hearts at the mean pacing CL of 122 ± 76 ms after DEP treatment, while they were not induced at baseline until CL of 70 ms. Among the total 37 VT episodes, the apicobasal reentry was observed in 22 (60%) episodes. The pretreatment with N-acetylcystein (5 mmol/L, n=5) and the CaMKII inhibitor KN 93 (1 μmol/L, n=5) successfully prevented DEP-induced APD prolongation and VT. However, its inactive analogue KN 92 (1 μmol/L, n=5) showed no difference in APD prolongation and VT.
Conclusion: Air pollution increased apicobasal repolarization gradients and reenty via oxidative stress and CaMKII activation in Langendorff-perfused rat heart.
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