Department of Physiology, Faculty of Medicine, University of Thessaly, Larissa, Greece.
Department of Cardiac & Thoracic Surgery, University Hospital of Larissa, Faculty of Medicine, University of Thessaly, Larissa, Greece.
J Interv Card Electrophysiol. 2021 Oct;62(1):153-159. doi: 10.1007/s10840-020-00865-0. Epub 2020 Sep 30.
Previous clinical studies have shown that ranolazine (RAN) added to amiodarone (AMIO) might accelerate the termination of recent-onset atrial fibrillation. This study was undertaken to delineate possible mechanisms that contribute to the enhancement of the antiarrhythmic efficacy of RAN-AMIO coadministration.
Ten rabbits were anesthetized and two monophasic action potential (MAP) catheters were sequentially inserted into the right atrium. One MAP electrode was used to pace and record; the other electrode was used only for recording MAP from an adjacent atrial region. Intraatrial conduction time (IACT), 2:1 intraatrial conduction block (IACB), and atrial post-repolarization refractoriness (aPRR) were consecutively determined by high-rate atrial burst pacing and programmed stimulation, respectively. All parameters were evaluated during baseline and following AMIO (3 mg/kg iv) or AMIO+RAN (2.4 mg/kg iv bolus +0.134 mg/kg/min maintenance infusion).
The IACT remained unchanged post AMIO compared with baseline (37.6 ± 3.8 vs 36.4 ± 2.4 ms), whereas the addition of RAN to AMIO significantly prolonged IACT (50.4 ± 3.6 ms, p < .001). The pacing cycle length producing 2:1 IACB was 101.2 ± 21.7 ms at baseline , 117.5 ± 15 ms after AMIO (p = 0.265), and 150 ± 14 ms after AMIO+RAN (p < .001). Baseline aPRR was longer following AMIO treatment (35 ± 5 vs 50 ± 9 ms, p < .01) but remarkably prolonged with RAN supplementation (105 ± 11 ms, p < .001).
RAN significantly prolonged the propagation time of rapid atrial depolarizations and potentiated the AMIO-induced moderate increases in aPRR. These mechanisms possibly contribute to the earlier termination of atrial fibrillation when RAN is co-administered with AMIO.
先前的临床研究表明，雷诺嗪（RAN）联合胺碘酮（AMIO）可能会加速近期发作的心房颤动的终止。本研究旨在阐明可能有助于增强 RAN-AMIO 联合给药的抗心律失常疗效的机制。
10 只兔子被麻醉，先后插入两个单相动作电位（MAP）导管到右心房。一个 MAP 电极用于起搏和记录；另一个电极仅用于记录相邻心房区域的 MAP。通过高频率心房爆发起搏和程控刺激，依次确定心房内传导时间（IACT）、2:1 心房内传导阻滞（IACB）和心房后除极不应期（aPRR）。在基线和给予 AMIO（3mg/kg 静脉注射）或 AMIO+RAN（2.4mg/kg 静脉推注+0.134mg/kg/min 维持输注）后，分别评估所有参数。
与基线相比，给予 AMIO 后 IACT 保持不变（37.6±3.8 比 36.4±2.4ms），而将 RAN 加入 AMIO 后显著延长 IACT（50.4±3.6ms，p<0.001）。产生 2:1 IACB 的起搏周期长度在基线时为 101.2±21.7ms，在给予 AMIO 后为 117.5±15ms（p=0.265），在给予 AMIO+RAN 后为 150±14ms（p<0.001）。AMIO 治疗后 aPRR 较长（35±5 比 50±9ms，p<0.01），但用 RAN 补充后明显延长（105±11ms，p<0.001）。
RAN 显著延长了快速心房去极化的传播时间，并增强了 AMIO 引起的 aPRR 的适度增加。这些机制可能有助于当 RAN 与 AMIO 联合给药时，心房颤动更早终止。
