Suppression of re-entrant and multifocal ventricular fibrillation by the late sodium current blocker ranolazine.
Suppression of re-entrant and multifocal ventricular fibrillation by the late sodium current blocker ranolazine.
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DOI：
10.1016/j.jacc.2010.07.045
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发表时间：
2011-01-18
影响因子：
24
通讯作者：
Karagueuzian, Hrayr S.
中科院分区：
文献类型：
--
作者：
Morita, Norishige;Lee, Jong Hwan;Xie, Yuanfang;Sovari, Ali;Qu, Zhilin;Weiss, James N.;Karagueuzian, Hrayr S.
关键词：
本研究的目的是验证晚钠电流阻滞剂雷诺嗪抑制折返性和多灶性室颤（VF）的假设。室颤可由折返性或局灶性机制引起。在24只离体灌流的老年大鼠心脏上同时进行了左心室心外膜表面电压和细胞内Ca+2光学标测沿着微电极记录。快速起搏和暴露于0.1 mM过氧化氢（H2 O2）的氧化应激诱导折返性VF和多灶性VF。快速起搏引起8只老年大鼠心脏中7只出现持续性室颤，表现为2 ~ 4个宽波阵面。雷诺嗪显著降低了动作电位时程恢复曲线的最大斜率（p < 0.05），并使所有7个心脏的持续性VF转化为非持续性VF，持续时间为24 ± 8 s。暴露于H2 O2启动早期后除极（EAD）介导的触发活动，导致持续性VF 8 8个老年心脏。VF的特征为多个病灶，平均每100 ms出现6.8 ± 3.2个病灶，局限于平均2.8 ± 0.85 mm 2的小区域，并在平均43 ± 16 ms后消失。（当在H2 O2之前给药时）并通过减少病灶数量抑制H2 O2介导的埃兹，导致8个心脏中的8个心脏VF终止。二维组织中EAD介导的多灶性VF的模拟显示，通过阻断晚期Na电流，病灶数量逐渐减少，VF终止。雷诺嗪晚期钠电流阻滞可有效抑制起搏诱导的折返性VF和EAD介导的多灶性VF。
The purpose of this study was to test the hypothesis that the late Na current blocker ranolazine suppresses re-entrant and multifocal ventricular fibrillation (VF). VF can be caused by either re-entrant or focal mechanism. Simultaneous voltage and intracellular Ca+2 optical mapping of the left ventricular epicardial surface along with microelectrode recordings was performed in 24 isolated-perfused aged rat hearts. Re-entrant VF was induced by rapid pacing and multifocal VF by exposure to oxidative stress with 0.1 mM hydrogen peroxide (H2O2). Rapid pacing induced sustained VF in 7 of 8 aged rat hearts, characterized by 2 to 4 broad propagating wavefronts. Ranolazine significantly (p < 0.05) reduced the maximum slope of action potential duration restitution curve and converted sustained to nonsustained VF lasting 24 ± 8 s in all 7 hearts. Exposure to H2O2 initiated early afterdepolarization (EAD)-mediated triggered activity that led to sustained VF in 8 out of 8 aged hearts. VF was characterized by multiple foci, appearing at an average of 6.8 ± 3.2 every 100 ms, which remained confined to a small area averaging 2.8 ± 0.85 mm2 and became extinct after a mean of 43 ± 16 ms. Ranolazine prevented (when given before H2O2) and suppressed H2O2-mediated EADs by reducing the number of foci, causing VF to terminate in 8 out of 8 hearts. Simulations in 2-dimensional tissue with EAD-mediated multifocal VF showed progressive reduction in the number of foci and VF termination by blocking the late Na current. Late Na current blockade with ranolazine is effective at suppressing both pacing-induced re-entrant VF and EAD-mediated multifocal VF.
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影响因子：
15.9
作者：
Kim, YH;Garfinkel, A;Chen, PS
通讯作者：
Chen, PS
影响因子：
15.9
作者：
BOLLI, R;PATEL, BS;MCCAY, PB
通讯作者：
MCCAY, PB
DOI：
10.1111/j.1540-8167.2008.01204.x
发表时间：
2008-10-01
影响因子：
2.7
作者：
Kumar, Kapil;Nearing, Bruce D.;Verrier, Richard L.
通讯作者：
Verrier, Richard L.
影响因子：
20.1
作者：
Ide, T;Tsutsui, H;Takeshita, A
通讯作者：
Takeshita, A
影响因子：
64.5
作者：
Erickson, Jeffrey R.;Joiner, Mei-ling A.;Anderson, Mark E.
通讯作者：
Anderson, Mark E.