Role of Sympathetic Nerve Activity for Modulation of Transmural Ventricular Repolarization and Initiation of Ventricular Fibrillation

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Unipolar electrograms through the ventricular wall (endocardial layer, mid-myocardial layer : Mid, and epicardial layer : Epi) 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 altered using electrical stimulation of both sides of stellate ganglions and cervical vagosympathetic trunks of canine experimental models of ventricular tachyarrhythmia(VTA). To evaluate the autonomic nerve activity, spectrum analysis (Mem Calc method) was performed using the data from body surface ECG.Electrical stimulation of the left stellate ganglion induced non-sustained VTA in the control state. After administration of E4031,VTA occasionally degenerated into ventricular fibrillation(VF) whereas sotalol prevented induction of VTA. In an anthopleurin-A(AP-A) model of a prolonged QT interval, low output of sympathetic stimulation abbreviated QT interval … More and homogenized the ventricular repolarization in the heart, but high output stimulation provoked VF.Sympathetic nerve activity gradually increased after cassation of vagal stimulation, and T wave alternans(TWA), and sometimes, VF were induced in an AP-A model. TWA created a large spatial dispersion of the ventricular repolarization in the heart, and initiation of VF was associated with a delayed condition and/or functional conduction block at the Mid layer. Different electrophysiological characteristics between the Mid and Epi layers ; ARI restitution kinetics (larger ΔARI and τ at Mid) and diastolic intervals, contributed to initiate concordant TWA. Furthermore, discordant TWA which created a much larger spatial dispersion of ventricular repolarization developed between the Mid and Epi layers when QT interval shortening occurred in two successive beats at the Mid or Epi layers. Mexiletine shortened baseline QT interval in an AP-A model and prevented initiation of TWA and VF associated with sympathetic nerve activity. Intracardiac autonomic nerve activity was reasonably represented on the parameters of spectrum analysis of body surface ECG. Less