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

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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