P372Electrophysiological changes in chronic heart failure rat hearts induced by vagal nerve stimulation

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Intermittent vagal nerve stimulation (VNS) has recently been shown to reduce arrhythmia in animals and humans with chronic heart failure (CHF). The electrophysiological changes underpinning these benefits remain largely uncharacterized. Therefore, we aimed to investigate the electrophysiological remodeling resulting from long-term intermittent VNS therapy in the CHF rat. Myocardial infarction (MI) was induced via LAD ligation in n=10 male Sprague-Dawley rats (250-300g). Rats were randomized into two groups: MI-SS rats (n = 5) were implanted with non-functional VNS stimulators, and MI-VNS rats (n = 5) were implanted with functional VNS stimulators and received chronic intermittent VNS treatment during 12 weeks. In Sham rats (n = 4) neither MI nor VNS were performed. At 13 weeks, hearts were explanted and Langendorff perfused. Optical mapping of right ventricle (RV) during periodic pacing and right atrium (RA) during sinus rhythm was then performed. First, we confirmed that long-term intermittent VNS therapy has clear antiarrhythmic benefits. Indeed, our results demonstrate that no MI-VNS rats (0/5) exhibited ventricular fibrillation, compared to Sham (2/4) and MI-SS (5/5) rats. Nevertheless, the maximum slope of the RV action potential duration (APD) restitution curve was larger (2.07±0.63) in MI-VNS rats compared to MI-SS (0.65±0.19, p<0.05) and Sham (0.59±0.13, p<0.05) rats. Most importantly, all MI-VNS rats displayed mean APD restitution slope greater than 1, while none of MI-SS or Sham rats had slope exceeding 1 (p < 0.05). Furthermore, MI-VNS rats exhibited significantly lower RV APD heterogeneity index (0.225±0.032) compared to MI-SS (0.538±0.107) rats. However, long-term intermittent VNS does not affect APD, and has moderate-to-no effect on conduction velocity of electrical propagation in RV. In RA during sinus rhythm, MI-VNS rats showed significantly larger APD (27.74±0.59 ms) compared to MI-SS (23.53±0.39 ms, p<0.05), but not different from Sham (26.41 ± 0.42, p=NS). However, APD heterogeneity indexes for both MI-VNS (0.562±0.038) and MI-SS (0.542±0.017) rats were similar, but significantly higher when compared to Sham (0.331±0.055). Our results suggest that the VNS therapy prevents VF through a remodeling of the electrophysiological properties of the myocardium.

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