Abstract 15981: Long-Term Vagus Nerve Stimulation Improves Electrophysiological Properties and Prevents Ventricular Fibrillation in Heart Failure Rats
Introduction: Sudden cardiac death in chronic heart failure (CHF) patients causes excess morbidity and mortality and may be attributed to autonomic imbalance. Augmentation of parasympathetic activation through chronic, intermittent vagus nerve stimulation (VNS) has emerged as a viable therapy for CHF. To elucidate the mechanisms responsible for the cardioprotective effects of VNS, we investigated the cardiac electrophysiological remodeling that occurs in rat ventricle.
Methods: Sprague Dawley rats (300g) were placed in either Active (n=5) or Control (n=5) groups. In both groups, CHF was induced by permanent ligation of the left anterior descending coronary artery, and VNS stimulators and leads (right vagus) were implanted. However, only Active group received VNS treatment (20 Hz, 0.75-1.0 mA) consisting of continuously-cyclic therapy. Hearts were removed at 13 weeks and mounted on a Langendorff perfusion system for high resolution optical mapping experiments. Hearts were stimulated at decreased cycle length (CL), from 250 ms to 30 ms or until ventricular fibrillation (VF) was induced. Images were obtained from the epicardial surface of the right ventricle, and the following parameters were determined: action potential duration (APD), APD heterogeneity (μ), conduction velocity (CV) and maximum slope of the CV (CVmax) and APD (Sdyn) restitution curves.
Results: Chronic VNS provided significant protection against VF induction. Sustained VF was induced in 5/5 hearts from Control and 0/5 hearts from Active groups. The minimum CL preceding loss of capture was significantly smaller for Active (66 2 ms) than for Control (108 ms; p<0.05) group. The following changes in the electrophysiological properties were observed for Active vs. Control group: increase of Sdyn (4.17 0.16 vs. 0.65 0.2; p<0.05) and CVmax (0.9 .6 cm/s2 vs. 0.4 0.1 cm/s2, p<0.05); and decrease of μ (for CL=140 ms: 0.22 0.03 vs. 0.53 0.10, p<0.05), However, no changes in CV (62 3 cm/s vs. 51 04 cm/s, p=N/S) and mean APD (70 ms vs. 67 ms, p=N/S) were observed (data for CL=140ms.)
Conclusion: Chronic, continuously-cyclic VNS provides beneficial anti-arrhythmic effect to CHF rats and is associated with electrophysiologic remodeling of ventricular myocardium.
- © 2013 by American Heart Association, Inc.