Proarrhythmic Effects of Sympathetic Activation Are Mitigated by Vagal Nerve Stimulation in Infarcted Hearts

OBJECTIVES The goal of this study was to evaluate whether intermittent VNS reduces electrical heterogeneities and arrhythmia inducibility during sympathoexcitation.& nbsp;BACKGROUND Sympathoexcitation increases the risk of ventricular tachyarrhythmias (VT). Vagal nerve stimulation (VNS) has been antiarrhythmic in the setting of ischemia-driven arrhythmias, but it is unclear if it can overcome the electrophysiological effects of sympathoexcitation in the setting of chronic myocardial infarction (MI).& nbsp;METHODS In Yorkshire pigs after chronic MI, a sternotomy was performed, a 56-electrode sock was placed over the ventricles (n = 17), and a basket catheter was positioned in the left ventricle (n = 6). Continuous unipolar electrograms from sock and basket arrays were obtained to analyze activation recovery interval (ARI), a surrogate of action potential duration. Bipolar voltage mapping was performed to define scar, border zone, or viable myocardium. Hemodynamic and electrical parameters and VT inducibility were evaluated during sympathoexcitation with bilateral stellate ganglia stimulation (BSS) and during combined BSS with intermittent VNS.& nbsp;RESULTS During BSS, global epicardial ARIs shortened from 384 +/- 59 milliseconds to 297 & PLUSMN; 63 milliseconds and endocardial ARIs from 359 +/- 36 milliseconds to 318 +/- 40 milliseconds. Dispersion in ARIs increased in all regions, with the greatest increase observed in scar and border zone regions. VNS mitigated the effects of BSS on border zone ARIs (from-18.3% +/- 6.3% to-2.1% +/- 14.7%) and ARI dispersion (from 104 ms(2) [1 to 1,108 ms(2)] to-108 ms2 [IQR:-588 to 30 ms2]). VNS reduced VT inducibility during sympathoexcitation (from 75%-40%; P < 0.05).& nbsp;CONCLUSIONS After chronic MI, VNS overcomes the detrimental effects of sympathoexcitation by reducing electrophysiological heterogeneities exacerbated by sympathetic stimulation, decreasing VT inducibility.