Combined effects of nifekalant and lidocaine on the spiral-type re-entry in a perfused 2-dimensional layer of rabbit ventricular myocardium
Combined effects of nifekalant and lidocaine on the spiral-type re-entry in a perfused 2-dimensional layer of rabbit ventricular myocardium
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DOI：
10.1253/circj.69.576
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发表时间：
2005-05-01
影响因子：
3.3
通讯作者：
Kodama, I
中科院分区：
文献类型：
--
作者：
Amino, M;Yamazaki, M;Kodama, I
背景螺旋折返在室性心动过速和心室颤动（VT/VF）的发生中起主要作用。特异性 I-Kr 阻滞剂尼非卡康 (NIF) 通常与利多卡因 (LID) 联合使用，最近在日本被用于预防复发性 VT/VF，但这些药物对螺旋折返的联合作用从未被研究过。 方法和结果 通过冷冻程序从 13 只 Langendorff 灌注的兔心脏中获取心室心外膜片，并 使用高分辨率光学映射系统分析心外膜兴奋。 Nifekakant (0.5 μmol/L) 引起动作电位持续时间 (APD) 显着延长，LID (3 μmol/L) 减弱 APD 延长而不影响传导速度。通过交叉场刺激在 6 颗心脏中诱导 VT，并且在 VT 期间观察到围绕可变功能块线循环的单环或双环螺旋。 Nifekakant 缩短了 VT 周期长度，并导致与螺旋动力学不稳定相关的提前终止（功能阻滞线延长、频繁的局部传导阻滞和广泛的蜿蜒）。添加LID可以防止NIF对螺旋型折返VT的这些修饰。结论LID逆转了NIF对螺旋激发的影响。当这些药物联合使用治疗 VT/VF 时，应考虑到这种相互作用。
Background Spiral re-entry plays the principal role in the genesis of ventricular tachycardia and ventricular fibrillation (VT/VF). The Specific I-Kr blocker, nifekakant (NIF) has, often in combination with lidocaine (LID), recently been used in Japan to prevent recurrent VT/VF, but the combined effects of these drugs on spiral reentry had never been investigated.Methods and Results A ventricular epicardial sheet was obtained from 13 Langendorff-perfused rabbit hearts by means of a cryoprocedure, and epicardial excitations were analyzed with a high-resolution optical mapping system. Nifekakant (0.5 mu mol/L) caused significant prolongation of action potential duration (APD) and LID (3 mu mol/L) attenuated the APD prolongation without affecting the conduction velocity. VT were induced in 6 hearts by cross-field stimulation, and single- or double-loop spirals circulating around variable functional block lines were visualized during the VT. Nifekakant reduced VT cycle length and caused early termination in association with destabilization of the spiral dynamics (prolongation of functional block line, frequent local conduction block, and extensive meandering). These modifications of spiral-type re-entrant VT by NIF were prevented by addition of LID.Conclusions The effects of NIF on the spiral excitations are reversed by LID. This interaction should be taken into account when these drugs are used in combination to treat VT/VF.