4.4 Article

Effects of subcutaneous nerve stimulation with blindly inserted electrodes on ventricular rate control in a canine model of persistent atrial fibrillation

Journal

HEART RHYTHM
Volume 18, Issue 2, Pages 261-270

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.hrthm.2020.09.009

Keywords

Atrial fibrillation; Autonomic nervous system; Neuro-modulation; Rate control; Subcutaneous nerve stimulation

Funding

  1. National Institutes of Health (NIH) [R42DA043391]
  2. NIH [R56 HL71140, TR002208-01, R01 HL139829, 1OT2OD028190]
  3. Krannert Institute of Cardiology
  4. Medtronic-Zipes Endowment
  5. Indiana University Health-Indiana University School of Medicine Strategic Research Initiative

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This study conducted a comparative study of high-output and low-output ScNS in a canine model, finding that high-output ScNS significantly reduced ventricular rate and stellate ganglion nerve activity, improved left ventricular ejection fraction, reduced atrial fibrosis, while low-output ScNS had no significant effects.
BACKGROUND Subcutaneous nerve stimulation (ScNS) delivered directly to large subcutaneous nerves can be either antiarrhythmic or proarrhythmic, depending on the stimulus output. OBJECTIVE The purpose of this study was to perform a prospective randomized study in a canine model of persistent AF to test the hypothesis that high-output ScNS using blindly inserted subcutaneous electrodes can reduce ventricular rate (VR) during persistent atrial fibrillation (AF) whereas low-output ScNS would have opposite effects. METHODS We prospectively randomized 16 male and 15 female dogs with sustained AF (.48 hours) induced by rapid atrial pacing into 3 groups (sham, 0.25 mA, 3.5 mA) for 4 weeks of ScNS (10 Hz, alternating 20-seconds ON and 60-seconds OFF). RESULTS ScNS at 3.5 mA, but not 0.25 mA or sham, significantly reduced VR and stellate ganglion nerve activity (SGNA), leading to improvement of left ventricular ejection fraction (LVEF). No differences were found between the 0.25-mA and sham groups. Histologic studies showed a significant reduction of bilateral atrial fibrosis in the 3.5-mA group compared with sham controls. Only 3.5mA ScNS had significant fibrosis in bilateral stellate ganglions. The growth-associated protein 43 (GAP43) staining of stellate ganglions indicated the suppression of GAP43 protein expression in the 3.5-mA group. There were no significant differences of nerve sprouting among all groups. There was no interaction between sex and ScNS effects on reduction of VR and SGNA, LVEF improvement, or results of histologic studies. CONCLUSION We conclude that 3.5-mA ScNS with blindly inserted electrodes can improve VR control, reduce atrial fibrosis, and partially improve LVEF in a canine model of persistent AF.

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