Department of Pharmacological Sciences, Medical School, University of Tampere, Finland.
Heart Rhythm. 2011 Apr;8(4):608-14. doi: 10.1016/j.hrthm.2010.11.029. Epub 2010 Nov 19.
Clinical evidence suggests that the antianginal agent ranolazine has antiarrhythmic properties, but its effects on vulnerability to ventricular fibrillation (VF) and T-wave alternans (TWA) during coronary artery stenosis have not been measured.
We investigated whether the antiarrhythmic effect of ranolazine during acute coronary stenosis could be quantified by measuring VF threshold and TWA magnitude.
Electrode catheters placed in the left ventricular apex were used to determine VF threshold during ventricular pacing at 130 beats/min, and TWA was quantified from epicardial electrograms using modified moving average method (N = 18). Left anterior descending coronary flow was reduced with a balloon occluder by 75% for 10 minutes. The I(Kr) blocker E-4031 was used to distinguish effects of late I(Na) and I(Kr) inhibition by ranolazine.
Before stenosis, ranolazine and E-4031 increased VF threshold from 32 ± 4 mA to 46 ± 4 mA (mean ± SEM), P = .02, and from 33 ± 5 mA to 40 ± 9 mA, P = .02, respectively. During stenosis, ranolazine increased VF threshold from 19 ± 2 mA to 33 ± 3 mA (P = .02), whereas E-4031 decreased VF threshold from 21 ± 3 mA to 15 ± 3 mA (P = .02). The ischemia-induced increase in TWA was suppressed by ranolazine but not by E-4031, consistent with effects of these agents on VF threshold.
Ranolazine exerts significant antifibrillatory effects during coronary stenosis through direct effects on cardiac electrical properties independent of coronary flow. Ranolazine's antifibrillatory action during myocardial ischemia does not appear to be mediated by blockade of I(Kr) but rather by inhibition of late I(Na). TWA changes paralleled vulnerability to VF as indicated by VF threshold testing.
临床证据表明，雷诺嗪作为一种抗心绞痛药物具有抗心律失常特性，但尚未测量其在冠状动脉狭窄期间对室颤（VF）和 T 波交替（TWA）易感性的影响。
我们研究了雷诺嗪在急性冠状动脉狭窄期间的抗心律失常作用是否可以通过测量 VF 阈值和 TWA 幅度来量化。
使用放置在左心室心尖部的电极导管，在心室起搏 130 次/分时确定 VF 阈值，使用改良移动平均法（N = 18）从心外膜电图量化 TWA。用球囊阻塞器将左前降支冠状动脉血流减少 75%，持续 10 分钟。使用 I(Kr) 阻滞剂 E-4031 来区分雷诺嗪对晚期 I(Na)和 I(Kr)抑制的作用。
在狭窄之前，雷诺嗪和 E-4031 将 VF 阈值从 32 ± 4 mA 增加到 46 ± 4 mA（平均值 ± SEM，P =.02）和从 33 ± 5 mA 增加到 40 ± 9 mA，P =.02）。在狭窄期间，雷诺嗪将 VF 阈值从 19 ± 2 mA 增加到 33 ± 3 mA（P =.02），而 E-4031 将 VF 阈值从 21 ± 3 mA 降低至 15 ± 3 mA（P =.02）。雷诺嗪抑制缺血引起的 TWA 增加，但 E-4031 则没有，这与这些药物对 VF 阈值的影响一致。
雷诺嗪通过独立于冠状动脉血流的直接作用对心脏电生理特性产生显著的抗纤颤作用，在冠状动脉狭窄期间发挥作用。雷诺嗪在心肌缺血期间的抗纤颤作用似乎不是通过阻断 I(Kr)介导的，而是通过抑制晚期 I(Na)介导的。TWA 变化与 VF 易感性平行，如 VF 阈值测试所示。
