Heart Rhythm
Volume 6, Issue 2 , Pages 244-250, February 2009

Relationship between right cervical vagus nerve stimulation and atrial fibrillation inducibility: Therapeutic intensities do not increase arrhythmogenesis

  • Youhua Zhang, MD, PhD

      Affiliations

    • Department of Molecular Cardiology, Cleveland Clinic, Cleveland, Ohio
  • ,
  • Itamar Ilsar, DVM

      Affiliations

    • Henry Ford Health System, Detroit, Michigan
  • ,
  • Hani N. Sabbah, PhD

      Affiliations

    • Henry Ford Health System, Detroit, Michigan
  • ,
  • Tamir Ben David, PhD

      Affiliations

    • BioControl Medical, Inc., Yehud, Israel
  • ,
  • Todor N. Mazgalev, PhD, FHRS

      Affiliations

    • Department of Molecular Cardiology, Cleveland Clinic, Cleveland, Ohio
    • Corresponding Author InformationAddress reprint requests and correspondence: Todor N. Mazgalev, Ph.D., Cleveland Clinic, Research Building NE61, 9500 Euclid Avenue, Cleveland, Ohio 44195

Received 7 October 2008; accepted 29 October 2008. published online 10 November 2008.

Background

Strong vagus nerve stimulation (VNS) is routinely used to induce and maintain atrial fibrillation (AF) in acute animal studies. Taken as a surrogate of increased vagal tone, such observations suggest an arrhythmogenic role of VNS in AF. In contrast, VNS has been demonstrated to have profound therapeutic effects in heart failure and other ailments.

Objective

The purpose of this study was to examine the relationship between right cervical VNS and AF, especially the potential arrhythmogenic effects of therapeutic VNS.

Methods

The relationship between VNS intensities and AF inducibility was studied in eight acute dogs at baseline and four different levels of VNS, which were set to prolong spontaneous sinus cycle length (SCL) by 20%, 40%, 60%, or 100%. The effect of mild VNS treatment on AF induction was further investigated in six chronically instrumented conscious dogs. These dogs were implanted with right cervical VNS stimulators and specialized atrial pacemakers. VNS intensity was titrated to slow the sinus rate by 10%.

Results

In acute studies, it was found that mild to moderate VNS (i.e., producing ≤40% SCL prolongation) did not increase AF inducibility, while strong VNS (i.e., producing ≥60% SCL prolongation) did. In chronic studies, compared with controls, AF induction did not change during the 4-week VNS treatment.

Conclusions

AF inducibility by right cervical VNS is intensity dependent: strong VNS (producing ≥60% SCL prolongation) facilitates AF, while moderate VNS (producing ≤40% SCL prolongation) appears not to affect AF. The nonarrhythmogenic effect of therapeutic chronic VNS was further verified in conscious animals. We conclude that VNS with moderate intensities can be used to deliver therapeutic benefits without arrhythmogenic risk.

Keywords: Atrial fibrillation, Vagus nerve, Vagal stimulation, Heart rate, Electrophysiology

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 This study was supported by the Atrial Fibrillation Innovation Center, the State of Ohio Wright Center of Innovation, and a Biomedical Research and Technology Transfer Partnership Award (Ohio's Third Frontier Project).

PII: S1547-5271(08)01080-1

doi:10.1016/j.hrthm.2008.10.043

Heart Rhythm
Volume 6, Issue 2 , Pages 244-250, February 2009