Intermittent vagus nerve stimulation allows preventing the “escape” effect of heart rhythm changes

Background.Vagus nerve stimulation has been proposed for the treatment of a number of diseases. The positive effects of vagus nerve stimulation on ischemic and reperfusion myocardial injury has been tested in experimental models. However, the escape effect of vagus activation on heart rate and the methodology to overcome this effect have not been reported properly.Objective. The purpose of the study is to evaluate parameters of prolonged stimulation that decrease heart rate and allow overcoming the escape effect of vagus nerve activation.Design and methods. We used Wistar rats (n = 9). Cervical section was performed under general anesthesia. Left vagus nerve isolated from adjacent tissue was contacted with custom stimulation electrodes and a custom pulse generator. Blood pressure was measured in the right common carotid artery. Limb electrocardiogram was continuously recorded. First, stimulation parameters repeatedly evoking vagal reaction (decrease in heart rate) without nerve damage were evaluated. Second, parameters of intermittent stimulation that allowed repeat and consistent heart rate decrease were assessed.Results. During experiments, in 5 animals the following parameters leading to sustained 30 ± 20 % heart rate reduction were found: rectangular pulse, 30 Hz, 0,5 ms, 1–2 V (0,6– 0,8 mA). Stimulation with 50 Hz frequency led to nerve damage in 1 case. Stimulation with 20 Hz frequency led to heart rate over-suppression of heart rate and blood pressure. Intermittent nerve stimulation was tested in 4 animals and led to repeated heart rate decrease by 38 ± 15 %. The parameters which helped to avoid escape effect on heart rate change were the following: the length of stimulation episode of 45 s and interruption of stimulation for 15 s.Conclusion. Intermittent electrical stimulation evokes vagal reactions on heart rate and allows overcoming the escape effect of vagal activation.

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Vagus Nerve Stimulation for Blood Pressure and Heart Rate Regulation

2018 Design of Medical Devices Conference ◽

10.1115/dmd2018-6847 ◽

2018 ◽

Author(s):

George D. O’Clock ◽

Bruce H. KenKnight ◽

Elena G. Tolkacheva

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Mechanical Compression ◽

Non Invasive ◽

Heart Rate Regulation ◽

Health Care Applications ◽

Surgical Conditions

For more than 27 years, implanted vagus nerve stimulation (VNS) devices, with electric current outputs in the 1 to 3.5 mA range, have been developed for many health care applications, including epilepsy and heart disease [1]. Mechanical compression approaches for VNS were administered under surgical conditions, using forceps, in the 1800’s [2]. Outcomes such as Electrocardiogram (ECG) data, blood pressure (BP), and heart rate (HR) were evaluated. Also, non-invasive (NI) mechanical compression of the vagus nerve for various nervous system disorders using hand, thumb, finger and belt pressure was popular in the 1800’s [3]. Cyberonics (now LivaNova) received the first FDA clearance for a surgically implanted electrical VNS device to treat refractory epilepsy in 1997.

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Blood pressure and heart rate relationships during cervical sympathetic and vagus nerve stimulation in streptozotocin diabetic rats

Brain Research ◽

10.1016/0006-8993(93)91343-q ◽

1993 ◽

Vol 629 (2) ◽

pp. 342-344 ◽

Cited By ~ 7

Author(s):

Shinji Homma ◽

Yuko Yamazaki ◽

Takeo Karakida

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Diabetic Rats ◽

Streptozotocin Diabetic Rats ◽

Cervical Sympathetic

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Implanted vagus nerve stimulation in 126 patients: surgical technique and complications

Perspectives in Surgery ◽

10.33699/pis.2020.99.7.304-310 ◽

2020 ◽

Vol 99 (7) ◽

Keyword(s):

Vagus Nerve ◽

Vocal Cord ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Pulse Generator ◽

Operative Procedure ◽

Intractable Epilepsy ◽

Vagal Nerve ◽

University Hospital ◽

Nerve Stimulator

Introduction: Vagus nerve stimulation is a palliative treatment for patients with refractory epilepsy to reduce the frequency and intensity of seizures. A bipolar helical electrode is placed around the left vagus nerve at the cervical level and is connected to the pulse generator placed in a subcutaneous pocket, most commonly in the subclavian region. Methods: Between March 1998 and October 2019, we performed 196 procedures related to the vagal nerve stimulation at the Neurosurgery Department in Motol University Hospital. Of these, 126 patients were vagal nerve stimulator implantation surgeries for intractable epilepsy. The cases included 69 female and 57 male patients with mean age at the time of the implantation surgery 22±12.4 years (range 2.1−58.4 years). Results: Nine patients (7.1%) were afflicted by complications related to implantation. Surgical complications included postoperative infection in 1.6%, VNS-associated arrhythmias in 1.6%, jugular vein bleeding in 0.8% and vocal cord paresis in 2.4%. One patient with vocal cord palsy also suffered from severe dysphagia. One patient (0.8%) did not tolerate extra stimulation with magnet due to a prolonged spasm in his throat. The extra added benefit of vagus stimulation in one patient was a significant reduction of previously regular severe headaches. Conclusion: Vagus nerve stimulation is an appropriate treatment for patients with drug-resistant epilepsy who are not candidates for focal resective surgery. Implantation of the vagus nerve stimulator is a relatively safe operative procedure.

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Impact of Subthreshold Transcutaneous Auricular Vagus Nerve Stimulation on the Heart Rate Variability and Atrial Arrhythmias

2020 43rd International Convention on Information, Communication and Electronic Technology (MIPRO) ◽

10.23919/mipro48935.2020.9245390 ◽

2020 ◽

Author(s):

R. Trobec ◽

M. Linden ◽

M. Sinkovec

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Atrial Arrhythmias

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Long Term Effects of Low Frequency (10 Hz) Vagus Nerve Stimulation on EEG and Heart Rate Variability in Crohn's Disease: A Case Report

Brain Stimulation ◽

10.1016/j.brs.2014.08.001 ◽

2014 ◽

Vol 7 (6) ◽

pp. 914-916 ◽

Cited By ~ 26

Author(s):

Didier Clarençon ◽

Sonia Pellissier ◽

Valérie Sinniger ◽

Astrid Kibleur ◽

Dominique Hoffman ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Crohn’S Disease ◽

Case Report ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Low Frequency ◽

Long Term Effects

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Effect of defibrillation on the performance of an implantable vagus nerve stimulation system

Bioelectronic Medicine ◽

10.1186/s42234-021-00064-w ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Imad Libbus ◽

Scott R. Stubbs ◽

Scott T. Mazar ◽

Scott Mindrebo ◽

Bruce H. KenKnight ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Function ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Pulse Generator ◽

High Energy ◽

Implantable Pulse Generator ◽

Defibrillation Pulse ◽

Stimulation System

Abstract Background Vagus Nerve Stimulation (VNS) delivers Autonomic Regulation Therapy (ART) for heart failure (HF), and has been associated with improvement in cardiac function and heart failure symptoms. VNS is delivered using an implantable pulse generator (IPG) and lead with electrodes placed around the cervical vagus nerve. Because HF patients may receive concomitant cardiac defibrillation therapy, testing was conducted to determine the effect of defibrillation (DF) on the VNS system. Methods DF testing was conducted on three ART IPGs (LivaNova USA, Inc.) according to international standard ISO14708-1, which evaluated whether DF had any permanent effects on the system. Each IPG was connected to a defibrillation pulse generator and subjected to a series of high-energy pulses. Results The specified series of pulses were successfully delivered to each of the three devices. All three IPGs passed factory electrical tests, and interrogation confirmed that software and data were unchanged from the pre-programmed values. No shifts in parameters or failures were observed. Conclusions Implantable VNS systems were tested for immunity to defibrillation, and were found to be unaffected by a series of high-energy defibrillation pulses. These results suggest that this VNS system can be used safely and continue to function after patients have been defibrillated.

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