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Effect of Ranolazine on Ventricular Vulnerability and Defibrillation Threshold in the Intact Porcine Heart
Author(s) -
KUMAR KAPIL,
NEARING BRUCE D.,
BARTOLI CARLO R,
KWAKU KEVIN F,
BELARDINELLI LUIZ,
VERRIER RICHARD L
Publication year - 2008
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.2008.01204.x
Subject(s) - ranolazine , medicine , defibrillation threshold , cardiology , ventricular fibrillation , defibrillation , effective refractory period , implantable cardioverter defibrillator , fibrillation , qt interval , ventricular tachycardia , anesthesia , refractory period , atrial fibrillation
: Extensive in vitro studies and clinical evidence (MERLIN trial) indicate an antiarrhythmic potential of ranolazine, a novel antianginal agent. Programmed electrophysiologic testing was performed to quantify ranolazine's effects on ventricular vulnerability and defibrillation thresholds and to gain insights into mechanisms.Methods and Results:Effects of ranolazine (9.2 ± 2.1 μM, plasma level) on surface ECG, right ventricular effective refractory period (ERP), and repetitive extrasystole (RE), ventricular fibrillation (VF), and defibrillation (DFT) thresholds were determined in 29 normal closed‐chest anesthetized pigs. The single extrastimulus method was employed for ERP and for RE and VF thresholds. DFT 50 was determined using an up‐down testing protocol with an implantable cardioverter‐defibrillator. Ranolazine increased rate‐corrected QT interval from 490 ± 30 to 527 ± 24 ms (P < 0.05) but did not alter T peak ‐T end interval (59 ± 8 to 62 ± 11, P = 0.65). ERP increased by 40 ± 6 ms (P < 0.001). Compared with baseline, ranolazine raised RE threshold from 20 ± 6 to 34 ± 9 mA (P < 0.001) and VF threshold from 38 ± 4 to 48 ± 10 mA (P < 0.05). DFT 50 was unchanged (baseline: 14 ± 2 J; ranolazine: 14 ± 2 J; P = 0.6), whereas diastolic pacing threshold increased from baseline pulse width of 0.07 ± 0.03 to 0.17 ± 0.07 ms (P < 0.01) with 1V pulse amplitude.Conclusions:Ranolazine, at therapeutic concentrations, produces a mild increase in QT interval and a marked increase in both RE and VF thresholds. Thus, ranolazine does not augment and may improve dispersion of ventricular repolarization, suggesting a potential antiarrhythmic action. Ranolazine is unlikely to affect the margin of safety of defibrillation, given no significant effect on DFT, but could result in a mild increase in pacing threshold.