Effect of ranolazine on ventricular vulnerability and defibrillation threshold in the intact porcine heart
Effect of ranolazine on ventricular vulnerability and defibrillation threshold in the intact porcine heart
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DOI：
10.1111/j.1540-8167.2008.01204.x
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发表时间：
2008-10-01
影响因子：
2.7
通讯作者：
Verrier, Richard L.
中科院分区：
文献类型：
--
作者：
Kumar, Kapil;Nearing, Bruce D.;Verrier, Richard L.
雷诺嗪与VF易感性简介：广泛的体外研究和临床证据（MERLIN试验）表明雷诺嗪（一种新型抗心绞痛药物）具有抗心绞痛潜力。进行程序化电生理测试以量化雷诺嗪对心室易损性和除颤阈值的影响，并深入了解其机制。方法和结果：雷诺嗪的作用（9.2 +/- 2.1 μ M，血浆水平），右心室有效不应期（ERP）和重复性期外收缩（RE），室颤（VF），在29只正常闭胸麻醉猪上测定了心脏除颤阈值。ERP、RE和VF阈值采用单次刺激法。DFT 50是使用上下测试协议与植入式心律转复除颤器确定的。雷诺嗪使心率校正的QT间期从490 +/- 30增加到527 +/- 24 ms（P < 0.05），但没有改变T峰-T末间期（59 +/- 8到62 +/- 11，P = 0.65）。ERP增加40 +/- 6 ms（P < 0.001）。与基线相比，雷诺嗪使RE阈值从20 +/- 6提高到34 +/- 9 mA（P < 0.001），VF阈值从38 +/- 4提高到48 +/- 10 mA（P < 0.05）。DFT 50不变（基线：14 +/- 2 J;雷诺嗪：14 +/- 2 J; P = 0.6），而舒张期起搏阈值从基线脉宽0.07 +/- 0.03增加到0.17 +/- 0.07 ms结论：雷诺嗪在治疗浓度下可使QT间期轻度延长，RE和VF阈值显著增加。因此，雷诺嗪不增加，并可能改善心室复极的离散度，这表明一个潜在的抗心律失常作用。雷诺嗪不太可能影响除颤的安全范围，因为对DFT没有显著影响，但可能导致起搏阈值轻度升高。
Ranolazine and Vulnerability to VF. Introduction: 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 mu M, 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. DFT50 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). DFT50 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.