Abstract
Cardiovascular disease degrades the regulatory function of the autonomic nervous system. Cyclic vagus nerve stimulation (VNS) is an already FDA‐approved therapy for drug‐resistant epilepsy and depression, and has been shown to normalize autonomic function and improve objective measures of heart function and subjective measures of heart failure symptoms. However, it remains unclear whether VNS may induce negative effects in patients with potentially healthy hearts where VNS can be used for epileptic patients. Hence, this study aims to investigate the effects of VNS on the hearts of healthy rats with normal autonomic balance. Sprague–Dawley rats were implanted with stimulators and randomized to either Sham or VNS groups. Rats in VNS group received 10 weeks of chronic intermittent VNS via stimulation of the right cervical vagus nerve. Echocardiography was performed at Baseline (prior to VNS), Week 2, and Week 9. After 10 weeks, high‐resolution optical mapping was performed in ex vivo perfused hearts to evaluate the electrophysiological remodeling that occurs in the heart as a result of the VNS therapy. Chronic VNS modified the electrophysiological properties of healthy rat hearts by reducing the action potential duration at 50% (APD 50) and 80% (APD 80) repolarization. Chronic VNS also affected the restitution properties of the heart at the APD 50 level and increased myocardial conduction velocity (CV). VNS did not induce any significant changes to ventricular ejection fraction (EF) and spatial dispersion of APD, thus indicating that VNS did not negatively affect cardiac function. VNS also reduced the susceptibility to ventricular arrhythmias (ventricular fibrillation [VF] and ventricular tachycardia [VT]) during ex vivo programmed electrical stimulation. In summary, chronic application of cyclic VNS induces changes to the electrophysiological properties of healthy rat hearts. The observed decrease in APD and increase in CV suggest that the beneficial effects of VNS do not require the presence of existing autonomic imbalance.
Highlights
Vagus nerve stimulation (VNS) is an approved clinical therapy for drug-refractory epilepsy and depression, and more than 130,000 vagus nerve stimulation (VNS) therapy systems have been implanted since 1995 (Shuchman 2007)
We investigated the effects of chronic, cyclic VNS on healthy rat hearts
Heart, including reduction of APD at larger basic cycle length (BCL) and an increase of conduction velocity (CV) at all BCLs; (2) VNS did not induce any detrimental effects to the heart: neither affecting the left ventricle (LV) function of the heart verified via echocardiography nor increasing the spatial dispersion of APD (l); (3) VNS significantly affected the restitution properties of the heart at the APD50, but not at the APD80, levels; (4) VNS had anti-arrhythmic effects that has been previously only reported for diseased hearts (Annoni et al 2015; Beaumont et al 2015)
Summary
Vagus nerve stimulation (VNS) is an approved clinical therapy for drug-refractory epilepsy and depression, and more than 130,000 VNS therapy systems have been implanted since 1995 (Shuchman 2007). Several preclinical and clinical studies have demonstrated the beneficial effects of VNS on cardiovascular diseases via parasympathetic nervous system activity modulation (De Ferrari and Schwartz 2011; Sabbah 2011; Beaumont et al 2015). Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
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