Mechanisms of destabilization and early termination of spiral wave reentry in the ventricle by a class III antiarrhythmic agent, nifekalant
Mechanisms of destabilization and early termination of spiral wave reentry in the ventricle by a class III antiarrhythmic agent, nifekalant
复制标题
DOI：
10.1152/ajpheart.00640.2006
复制
发表时间：
2007-01-01
影响因子：
4.8
通讯作者：
Kodama, Itsuo
中科院分区：
文献类型：
--
作者：
Yamazaki, Masatoshi;Honjo, Haruo;Kodama, Itsuo
III类抗心律失常药尼非卡兰使心室螺旋波折返不稳定和提前终止的机制。美国生理学杂志心脏循环生理学292：H539-H548，2007年。首次发表于2006年8月25日; doi：10.1152/ajpheart. 00640.2006.-尼非卡兰（NF）是一种新型III类抗心律失常药，可有效预防危及生命的室性心动过速/室颤（VT/VF）。我们使用高分辨率光学动作电位标测系统，在Langendorff灌注的兔心脏（n=21）的二维心外膜心肌层中研究NF对螺旋型折返性VT的不稳定和早期终止的机制。在基础刺激期间，NF（0.1 μ M）引起动作电位时程（APD）的均匀延长，而不影响传导速度和APD恢复斜率的增加。在NF存在下由直流电刺激诱导的VT持续时间较短（VT> 30 s：2/54 NF vs. 19/93对照）。在VT控制期间（可见旋翼），波前以一定距离（复极化区）追逐自己的尾巴，它们很少相遇。相位奇点（PS）点的平均数量为1.31 +/- 0.14/665 ms（n = 7）。在NF的存在下，波前经常遇到自己的尾巴，导致螺旋波的瞬时破裂或旋转中心的突然移动（PS的空间跳跃）。NF后每665 ms平均PS数增加到1.63 +/-0.22（n = 7，P < 0.05）。在大多数情况下（9/10，90.0%），控制转子的自发终止模式是相互湮灭的结果，反向旋转波前。在NF中，转子常因波前与房室沟碰撞而终止（12/19，63.2%）或因螺旋尖端陷在不应区而终止（7/19，36.8%）。NF引起的螺旋波折返的不稳定和早期终止是复极调制后可兴奋组织比例有限的结果。
Mechanisms of destabilization and early termination of spiral wave reentry in the ventricle by a class III antiarrhythmic agent, nifekalant. Am J Physiol Heart Circ Physiol 292: H539-H548, 2007. First published August 25, 2006; doi:10.1152/ajpheart. 00640.2006.-Nifekalant (NF) is a novel class III antiarrhythmic agent that is effective in preventing life-threatening ventricular tachycardia/fibrillation (VT/VF). We investigated mechanisms of destabilization and early termination of spiral-type reentrant VT by NF in a two-dimensional subepicardial myocardial layer of Langendorff-perfused rabbit hearts (n=21) using a high-resolution optical action potential mapping system. During basic stimulation, NF (0.1 mu M) caused uniform prolongation of action potential duration (APD) without affecting conduction velocity and an increase of APD restitution slope. VTs induced by direct current stimulation in the presence of NF were of shorter duration (VTs > 30 s: 2/54 NF vs. 19/93 control). During VTs in control (with visible rotors), the wave front chased its own tail with a certain distance (repolarized zone), and they seldom met each other. The average number of phase singularity (PS) points was 1.31 +/- 0.14 per 665 ms (n = 7). In the presence of NF, the wave front frequently encountered its own tail, causing a transient breakup of the spiral wave or sudden movement of the rotation center (spatial jump of PS). The average number of PS was increased to 1.63 +/- 0.22 per 665 ms (n = 7, P < 0.05) after NF. The mode of spontaneous termination of rotors in control was in most cases (9/10, 90.0%) the result of mutual annihilation of counterrotating wave fronts. With NF, rotors frequently terminated by wave front collision with the atrioventricular groove (12/19, 63.2%) or by trapping the spiral tip in a refractory zone (7/19, 36.8%). Destabilization and early termination of spiral wave reentry induced by NF are the result of a limited proportion of excitable tissue after modulation of repolarization.