Change of Electrical Restitution Kinetics and Ventricular Fibrillation Threshold during Direct Autonomic Stimulation in Canine Heart

ABSTRACT

BACKGROUND AND OBJECTIVES: It is known that ventricular fibrillation (VF) can be enhanced by sympathetic activity and antagonized by vagal activity, and that the kinetics of electrical restitution is a key determinant of VF induction or maintenance. However, little is known about the effects of autonomic stimulation on electrical restitution. Therefore, we studied the effect of sympathetic (SS) and vagus nerve stimulation (VS) on the electrical restitution and VF induction. MATERIALS AND METHODS: A monophasic action potential (MAP) was simultaneously recorded from the endocardium and epicardium of the left ventricle in 12 open chest canine hearts. The restitution kinetics were studied using a single ventricular extra-stimuli (S2), following a 15 beat drive train (300 ms), down to the effective refractory period (ERP). S2-MAPD was plotted against the preceding diastolic intervals, fitted to exponential curves and the maximum restitution slope (Smax) measured. The VF threshold (VFT) was determined as the minimum current that would induce VF with rapid pacing (50x50 ms). Parameters were studied at the baseline (control) and separately during VS and SS. RESULTS: SS increased the Smax of the endocardium (1.14+/-0.37 vs. 0.80+/-0.25, p<0.001), but not that of the epicardium, and also increased the transmural dispersion of Smax and decreased the VFT (1.8+/-1.3 mA vs. 3.4+/-1.6 mA, p<0.05), even without significant shortening of the ERP, but VS had the opposite effects. There was a significant correlation between the endocardial Smax, transmural dispersion of the Smax and the VFT, respectively (r=-0.64, p<0.001 and r=-0.531, p=0.003). CONCLUSION: The role of the autonomic nervous system in ventricular arrhythmogenesis is by means of electrical restitution kinetics modulation.