Division of Electrophysiology, Department of Cardiovascular Medicine, University Hospital of Münster, Albert-Schweitzer Campus 1, Münster, Germany.
Europace. 2013 May;15(5):761-9. doi: 10.1093/europace/eus399. Epub 2013 Feb 1.
In several clinical and pre-clinical studies, application of ranolazine (RAN) led to suppression of atrial fibrillation (AF). The aim of the present study was to investigate whether RAN can suppress AF in an experimental rabbit whole heart model, in which acute haemodynamic changes trigger AF. Ranolazine was compared with flecainide and sotalol as established antiarrhythmic agents.
In 60 Langendorff-perfused, isolated rabbit hearts, AF episodes were evoked by burst pacing with a fixed number of stimuli at baseline and following acute atrial stretch. Data were obtained in the absence and presence of acute dilatation of the left atrium (20 mmHg) at baseline and after drug application (RAN 10 µM, n = 10; flecainide 2 µM, n = 10; sotalol 50 µM, n = 10). Application of sotalol, but not RAN or flecainide increased the atrial action potential duration at 90% repolarization (aAPD90); however, both RAN (+8 ms) and flecainide (+13 ms) increased interatrial conduction time. All three drugs caused a significant increase in atrial effective refractory period (aERP) and, thus, an increase in atrial post-repolarization refractoriness (aPRR: +11 ms each, P < 0.05). Acute dilatation of the left atrium reduced aAPD90 and aERP. The described drug effects were preserved in the setting of acute atrial dilatation. Acute atrial dilatation significantly increased the incidence of AF. Ranolazine and flecainide, but not sotalol, decreased the number of responses.
Ranolazine-related sodium channel block is preserved upon acute atrial stretch. Ranolazine suppresses stretch-induced AF by increasing interatrial conduction time and aPRR. These results shed further evidence on the potential role of RAN in the prevention of AF. This might also apply to clinical conditions that are associated with haemodynamic or mechanical disorders, leading to acute dilatation of the atria.
在几项临床和临床前研究中，雷诺嗪（RAN）的应用导致了心房颤动（AF）的抑制。本研究的目的是研究雷诺嗪是否可以在实验性兔全心脏模型中抑制 AF，在该模型中，急性血液动力学变化引发 AF。将雷诺嗪与氟卡尼和索他洛尔作为已建立的抗心律失常药物进行比较。
在 60 个 Langendorff 灌注、分离的兔心中，在基线和急性心房拉伸后，通过固定刺激数量的爆发起搏诱发 AF 发作。在基线和药物应用后（RAN 10 µM，n = 10；氟卡尼 2 µM，n = 10；索他洛尔 50 µM，n = 10）获得无急性左心房扩张（20 mmHg）和存在急性左心房扩张的数据。应用索他洛尔而非雷诺嗪或氟卡尼增加了心房动作电位复极 90%时程（aAPD90）；然而，雷诺嗪（+8 ms）和氟卡尼（+13 ms）均增加了房间隔传导时间。三种药物均导致心房有效不应期（aERP）显著增加，从而导致心房复极后不应期（aPRR）增加（各增加 11 ms，P < 0.05）。急性左心房扩张减少了 aAPD90 和 aERP。在急性心房扩张的情况下，描述的药物作用得以保留。急性心房扩张显著增加了 AF 的发生率。雷诺嗪和氟卡尼而非索他洛尔减少了反应次数。
雷诺嗪相关的钠通道阻滞在急性心房拉伸时得以保留。雷诺嗪通过增加房间隔传导时间和 aPRR 抑制拉伸诱导的 AF。这些结果进一步证明了 RAN 在预防 AF 中的潜在作用。这也可能适用于与血液动力学或机械障碍相关的临床情况，导致心房急性扩张。
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