The effects of chronic vagal nerve stimulation on autonomic function and the electrocardiogram

Physiology 2014 (London, UK) (2014) Proc Physiol Soc 31, PCA013

Poster Communications: The effects of chronic vagal nerve stimulation on autonomic function and the electrocardiogram

E. Radcliffe1

1. University of Manchester, Manchester, United Kingdom.

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Vagal nerve stimulation (VNS) poses a promising approach to the treatment of heart failure. Now in human clinical trial [1], VNS has been shown to improve left ventricular ejection fraction, reduce New York Heart Association Classification and improve quality of life in patients with chronic heart failure [2]. Such findings could be attributed to a bradycardia induced improvement in diastolic filling of the ventricles. However, given that little is known about the underlying mechanisms of VNS we have sought to characterise its effects in the ovine heart. Specifically we aimed to assess the chronic effects of VNS on (i) autonomic function and (ii) the electrocardiogram.Welsh mountain sheep (female, aged 18 ± 6 months, 26-40kg) were anaesthetised with isofluorane (1-4% isofluorane v/v in oxygen). VNS devices (Cyberonics, Houston, Texas) were placed around the right cervical vagus nerve. Following a two week recovery period, animals were subject to six weeks VNS. VNS burst amplitudes were set to induce a 20-30% reduction in heart rate. Animals were fitted with telemetry jackets (EMKA, Paris, France) throughout to provide 24 hour ECG measurements. Autonomic function was assessed pre and post stimulation in conscious, gently restrained animals using intravenous infusion of dobutamine, propranolol and atropine. All ECG analysis was performed using automatic wave detection software (LabChart, AD Instruments, Oxford) and checked manually. Statistical significance was assessed using paired T-tests and values of p < 0.05 were considered significant. Values are expressed as mean ± SEM.Six weeks VNS produced no chronic changes in vagal tone (n = 8, p=0.51) or dobutamine stress test response (n = 6, p=0.79) in these animals. VNS induced a chronic tachycardic effect on natural sinus rhythm, altering heart rate from 64± 5bpm pre-stimulation to 84±5bpm post-stimulation (n = 6, p<0.01). This was accompanied by a reduction in PR interval from 117±7ms to 109±6ms (n=6, p<0.05). These data indicate that there is no chronic change in underlying vagal tone and dobutamine response associated with six weeks VNS in the healthy heart. Hoverer, a VNS induced increase in sinus heart rate and a shortening of the PR interval. Further work will be required to corroborate these findings in the diseased heart.



Where applicable, experiments conform with Society ethical requirements.

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