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

Hye Jin Hwang, huinam pak, Moon Hyoung Lee, Boyoung Joung, Jin Bae Kim

Research output: Contribution to journalArticle

Abstract

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±30ms (p=0.01). However, ranolazine pretreatment (n=8, 20 pmol/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±5ms to 41 ±19 ms (p=0.01), it was prevented by pretreatment with ranolazine (12±13 ms). Rranolazine 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.

Original languageEnglish
Number of pages1
Journaljournal of arrhythmia
Volume27
Issue number4
DOIs
Publication statusPublished - 2011 Jan 1

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Air Pollutants
Vehicle Emissions
Cardiac Arrhythmias
pamidronate
Tachycardia
Action Potentials
Particulate Matter
Anti-Arrhythmia Agents
Ranolazine
Incidence

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

@article{842ac68ac8734309b9168be826a77dbb,
title = "Protective Effects of Ranolazine on Air Pollutant-Induced Ventricular Arrhythmia through Late INa Inhibition",
abstract = "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±30ms (p=0.01). However, ranolazine pretreatment (n=8, 20 pmol/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±5ms to 41 ±19 ms (p=0.01), it was prevented by pretreatment with ranolazine (12±13 ms). Rranolazine 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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Protective Effects of Ranolazine on Air Pollutant-Induced Ventricular Arrhythmia through Late INa Inhibition. / Hwang, Hye Jin; pak, huinam; Lee, Moon Hyoung; Joung, Boyoung; Kim, Jin Bae.

In: journal of arrhythmia, Vol. 27, No. 4, 01.01.2011.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Protective Effects of Ranolazine on Air Pollutant-Induced Ventricular Arrhythmia through Late INa Inhibition

AU - Hwang, Hye Jin

AU - pak, huinam

AU - Lee, Moon Hyoung

AU - Joung, Boyoung

AU - Kim, Jin Bae

PY - 2011/1/1

Y1 - 2011/1/1

N2 - 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±30ms (p=0.01). However, ranolazine pretreatment (n=8, 20 pmol/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±5ms to 41 ±19 ms (p=0.01), it was prevented by pretreatment with ranolazine (12±13 ms). Rranolazine 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.

AB - 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±30ms (p=0.01). However, ranolazine pretreatment (n=8, 20 pmol/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±5ms to 41 ±19 ms (p=0.01), it was prevented by pretreatment with ranolazine (12±13 ms). Rranolazine 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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