Protective Effects of Ranolazine on Air Pollutant-Induced Ventricular Arrhythmia through Late INa Inhibition

DOI
  • Hwang HyeJin
    Cardiology Division, Yonsei Cardiovascular Center and Cardiovascular Research Institute
  • Kim Jin-Bae
    Cardiology Division, Kyounghee University
  • Pak Hui-Nam
    Cardiology Division, Yonsei Cardiovascular Center and Cardiovascular Research Institute
  • Lee Moon-Hyoung
    Cardiology Division, Yonsei Cardiovascular Center and Cardiovascular Research Institute
  • Joung Boyoung
    Cardiology Division, Yonsei Cardiovascular Center and Cardiovascular Research Institute

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Introduction: The objective of this study is to examine whether ranolazine, a novel inhibitor of late INa, can reduce particulate matter (PM)-induced ventricular arrhythmia. Methods: In Langendorff-perfused rat hearts, arrhythmic events were analyzed after diesel exhaust product (DEP) infusion and pretreatment with ranolazine. Results: In Langendorff-perfused rat hearts (n=10), DEP infusion of 12.5 mg/L for 20 min prolonged action potential duration (APD90) from 104±24 to 152±30 ms (p=0.01). However, ranolazine pretreatment (n=8, 20 µmol/L) prevented DEP induced-APD prolongation (104±24, vs. 115±26 ms, p=0.03) without affecting conduction velocity (0.53±0.15, vs. 0.54±0.16 m/s, p=0.9) compared to DEP alone. While the APD dispersion was significantly increased by DEP alone from 10±5 ms to 41±19 ms (p=0.01), it was prevented by pretreatment with ranolazine (12±13 ms). Ranolazine also completely prevented triggered activity (70% vs. 0%, p=0.03), decreased the incidence of spontaneous ventricular tachyarrhythmia (VT) (60% vs. 13%, p=0.05), and increased the frequency of spontaneous termination of VT (13% vs. 90%, p=0.01). Ranolazine pretreatment decreased dominant frequency (11±4 Hz, vs. 25±9 Hz, p=0.03) and mean wavelets number/cm2 (1.7±0.7/cm2 vs. 3.1±0.8/cm2, p=0.06). Conclusion: Ranolazine prevented action potential prolongation and suppressed triggered effect by inhibiting an increase of late Na current due to DEP exposure. Ranolazine has anti-arrhythmic effect to prevent air pollutant induced arrhythmia and to suppress its perpetuation.

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