Three-dimensional mapping of an arrhythmogenic substrate of ventricular fibrillation modulated by autonomic nerve activity

在我们的室性心律失常（VA）的实验模型中，使用多极跳水针电极记录通过心室壁的单极电图。通过分析脑电图的激活-恢复间隔（ARI）估计局部心室复极。自主神经活动通过电刺激星状神经节和颈迷走交感干或静脉注射肾上腺素来调节。利用体表心电图数据进行频谱分析。在对照状态下，静脉注射肾上腺素或电刺激星状神经节诱导室性早搏和/或非持续性室性早搏，在E4031模型中，这些早搏触发室性早搏。另一方面，在贝必地尔模型中，交感神经活动的增强使室性早搏数量减少，室性早搏很少发生。在延长QT间期的花胸膜素- a （AP-A）模型中，低输出量的s…更多的交感神经刺激或低剂量的肾上腺素静脉注射缩短了QT间期，使心脏心室复极均匀化，而不诱导持续的室间隔。然而，高输出的交感神经刺激或大剂量的肾上腺素注射可引起VF。采用AP-A模型研究了硫酸镁（Mg^<++>）对VA的治疗作用及自主神经系统在Mg^<++>作用中的作用。静脉注射Mg^<++>可迅速消除自终止型多态VA和所有分离性室性早搏。Mg^<++>在所有记录点引起ARI的适度缩短，尽管这种影响是短暂的。由于ARI缩短的幅度在心肌中部比其他心室部位更大，Mg^<++>注射后，平均ARI跨壁弥散度降低。Mg^<++>-在药物诱导的自主神经阻滞后也有类似的效果。除了抑制诱发的过早活动外，经壁心室复极均匀化与静脉注射Mg^<++>的抗心律失常作用有关。在该模型中，Mg^<++>的抗心律失常作用可归因于其直接的药理特性，而不是环境自主神经活动的改变。双丙酰胺和贝必地尔能减弱迷走神经刺激对心房心肌的作用，这与迷走神经刺激诱发心房颤动的治疗效果有关。心率变异性是评价抗心律失常药物对自主神经系统影响的一个有用参数。少

In our experimental models of ventricular arrhythmia (VA), unipolar electrograms through the ventricular wall were recorded using multipolar plunge needle electrodes. Local ventricular repolarization was estimated by analyzing the activation-recovery interval (ARI) from the electrograms. Autonomic nerve activity was modulated by electrical stimulation of the stellate ganglions and cervical vagosympathetic trunks or intravenous administration of epinephrine. Spectrum analysis was performed using the data from body surface ECG.In the control state, intravenous administration of epinephrine or electrical stimulation of the stellate ganglions induced ventricular premature beats (PVCs) and/or non-sustained VA. In the model of E4031, these PVCs triggered VF. On the other hand, in the model of bepridil, the numbers of PVCs were decreased and VF was seldom induced by the augmentation of sympathetic nerve activity. In an anthopleurin-A (AP-A.) model of the prolonged QT interval, low output of s … More ympathetic nerve stimulation or a low dose of epinephrine by intravenous administration abbreviated the QT interval and homogenized ventricular repolarization in the heart without induction of sustained VA. However, high output of sympathetic nerve stimulation or a larger dose of epinephrine injection provoked VF.The therapeutic effect of magnesium sulfate (Mg^<++>) for VA and the role played by the autonomic nervous system in the effects of Mg^<++> were studied in an AP-A model. Intravenous administration of Mg^<++> rapidly eliminated self-terminating polymorphic VA and all isolated PVCs. Mg^<++> caused a modest shortening of ARI at all recording sites although this effect was transient. Since the magnitude of ARI shortening was greater at mid-myocardial sites than at other ventricular sites, mean transmural ARI dispersion decreased after Mg^<++> injection. Similar effects of Mg^<++>- were observed after drug-induced autonomic block. Besides suppression of triggered premature activity, homogenization of transmural ventricular repolarization was associated with the antiarrhythmic effects of intravenous Mg^<++>. The antiarrhythmic effects of Mg^<++> in this model were attributable to its direct pharmacological properties, and not to changes in ambient autonomic nervous activity.Disopyramide and bepridil attenuated the effect of vagal stimulation in the atrial myocardium, and this was associated with the therapeutic effects for the vagal stimulation induced atrial fibrillation. Heart rate variability is a useful parameter for evaluation of the effect of anti-arrhythmic drugs on the autonomic nerve system. Less