Selective control of physiological responses by temporally-patterned electrical stimulation of the canine vagus nerve

Vagus nerve stimulation (VNS) is effective for treating epilepsy and depression, and has emerging indications for anxiety and heart failure. However, stimulation-evoked side effects remain a challenge for long-term compliance. We investigated the feasibility of reducing VNS side effects by using a temporally-modified stimulation pattern. In 4 anesthetized canines, we measured changes in both the heart rate and evoked laryngeal muscle activity. Compared to baseline, we found that a 5% duty cycle (measured by the number of pulses per second of stimulation) could still evoke a 21% reduction in heart rate; whereas compared to continuous stimulation (3 mA, 300 μs pulsewidth, 20 Hz) the same 5% duty cycle reduced the evoked laryngeal muscle activity by 90%. The results of this study indicate that temporally-patterned stimulation may provide an effective tool for optimizing VNS therapy.

[1]  Warren M. Grill,et al.  Excitation properties of the right cervical vagus nerve in adult dogs , 2011, Experimental Neurology.

[2]  D. Woodbury,et al.  Effects of Vagal Stimulation on Experimentally Induced Seizures in Rats , 1990, Epilepsia.

[3]  R. Kuzniecky,et al.  Vagus Nerve Stimulation for Treatment of Partial Seizures: 3. Long‐Term Follow‐Up on First 67 Patients Exiting a Controlled Study , 1994, Epilepsia.

[4]  E. Ben-Menachem,et al.  Vagus Nerve Stimulation for Treatment of Partial Seizures: 1. A Controlled Study of Effect on Seizures , 1994, Epilepsia.

[5]  A. Brodal,et al.  Neurological Anatomy in Relation to Clinical Medicine , 1950 .

[6]  R. Kuzniecky,et al.  Vagus nerve stimulation for treatment of partial seizures: 3. Long-term follow-up on first 67 patients exiting a controlled study. First International Vagus Nerve Stimulation Study Group. , 1994, Epilepsia.

[7]  A. Milby,et al.  Vagus nerve stimulation for epilepsy and depression , 2011, Neurotherapeutics.

[8]  A. Boyer,et al.  The composition of the vagus nerve of the cat , 2004, Cell and Tissue Research.

[9]  D. Evans,et al.  Histological and functional studies on the fibre composition of the vagus nerve of the rabbit. , 1954, Journal of anatomy.

[10]  P. Schwartz,et al.  Vagal stimulation for heart failure: background and first in-man study. , 2009, Heart rhythm.

[11]  J. Dean,et al.  Prevention of Intractable Partial Seizures by Intermittent Vagal Stimulation in Humans: Preliminary Results , 1990, Epilepsia.

[12]  E. Ben-Menachem,et al.  Vagus nerve stimulation for treatment of partial seizures: 1. A controlled study of effect on seizures. First International Vagus Nerve Stimulation Study Group. , 1994, Epilepsia.

[13]  Markus Zabel,et al.  Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure. , 2011, European heart journal.

[14]  J G McLeod,et al.  Abnormalities in the vagus nerve in canine acrylamide neuropathy. , 1982, Journal of neurology, neurosurgery, and psychiatry.

[15]  Hani N. Sabbah,et al.  RIGHT VAGUS NERVE STIMULATION IMPROVES LEFT VENTRICULAR FUNCTION IN DOGS WITH HEART FAILURE , 2010 .

[16]  P. Huttenlocher Neurological Anatomy in Relation to Clinical Medicine , 1970, The Yale Journal of Biology and Medicine.

[17]  Peter H Veltink,et al.  An indirect component in the evoked compound action potential of the vagal nerve , 2010, Journal of neural engineering.

[18]  Zoran B. Popović,et al.  Chronic Vagus Nerve Stimulation Improves Autonomic Control and Attenuates Systemic Inflammation and Heart Failure Progression in a Canine High-Rate Pacing Model , 2009, Circulation. Heart failure.

[19]  Luigi Tavazzi,et al.  Long term vagal stimulation in patients with advanced heart failure First experience in man , 2008, European journal of heart failure.

[20]  Masaru Sugimachi,et al.  Vagal Nerve Stimulation Markedly Improves Long-Term Survival After Chronic Heart Failure in Rats , 2003, Circulation.

[21]  A. Paintal,et al.  Vagal sensory receptors and their reflex effects. , 1973, Physiological reviews.

[22]  Hani N. Sabbah,et al.  Vagus nerve stimulation in experimental heart failure , 2011, Heart Failure Reviews.

[23]  P. Schwartz,et al.  Chronic vagal stimulation in patients with congestive heart failure , 2009, 2009 Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[24]  Peter J. Schwartz,et al.  Sympathetic–parasympathetic interaction in health and disease: abnormalities and relevance in heart failure , 2011, Heart Failure Reviews.