Bioelectronic neuromodulation of the paravertebral cardiac efferent sympathetic outflow and its effect on ventricular electrical indices

Una Buckley; Ray W Chui; Pradeep S Rajendran; Tina Vrabec; Kalyanam Shivkumar; Jeffrey L Ardell

doi:10.1016/j.hrthm.2017.02.020

Bioelectronic neuromodulation of the paravertebral cardiac efferent sympathetic outflow and its effect on ventricular electrical indices

Heart Rhythm. 2017 Jul;14(7):1063-1070. doi: 10.1016/j.hrthm.2017.02.020. Epub 2017 Feb 20.

Authors

Una Buckley¹, Ray W Chui², Pradeep S Rajendran², Tina Vrabec³, Kalyanam Shivkumar², Jeffrey L Ardell⁴

Affiliations

¹ University of California - Los Angeles (UCLA) Cardiac Arrhythmia Center, David Geffen School of Medicine, Los Angeles, California; UCLA Neurocardiology Research Center of Excellence, David Geffen School of Medicine, Los Angeles, California.
² University of California - Los Angeles (UCLA) Cardiac Arrhythmia Center, David Geffen School of Medicine, Los Angeles, California; UCLA Neurocardiology Research Center of Excellence, David Geffen School of Medicine, Los Angeles, California; Molecular, Cellular, & Integrative Physiology Program, UCLA, Los Angeles, California.
³ Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio.
⁴ University of California - Los Angeles (UCLA) Cardiac Arrhythmia Center, David Geffen School of Medicine, Los Angeles, California; UCLA Neurocardiology Research Center of Excellence, David Geffen School of Medicine, Los Angeles, California; Molecular, Cellular, & Integrative Physiology Program, UCLA, Los Angeles, California. Electronic address: jardell@mednet.ucla.edu.

Abstract

Background: Neuromodulation of the paravertebral ganglia by using symmetric voltage controlled kilohertz frequency alternating current (KHFAC) has the potential to be a reversible alternative to surgical intervention in patients with refractory ventricular arrhythmias. KHFAC creates scalable focal inhibition of action potential conduction.

Objective: The purpose of this article was to evaluate the efficacy of KHFAC when applied to the T1-T2 paravertebral chain to mitigate sympathetic outflow to the heart.

Methods: In anesthetized, vagotomized, porcine subjects, the heart was exposed via a midline sternotomy along with paravertebral chain ganglia. The T3 paravertebral ganglion was electrically stimulated, and activation recovery intervals (ARIs) were obtained from a 56-electrode sock placed over both ventricles. A bipolar Ag electrode was wrapped around the paravertebral chain between T1 and T2 and connected to a symmetric voltage controlled KHFAC generator. A comparison of cardiac indices during T3 stimulation conditions, with and without KHFAC, provided a measure of block efficacy.

Results: Right-sided T3 stimulation (at 4 Hz) was titrated to produce reproducible ARI changes from baseline (52 ± 30 ms). KHFAC resulted in a 67% mitigation of T3 electrical stimulation effects on ARI (18.5 ± 22 ms; P < .005). T3 stimulation repeated after KHFAC produced equivalent ARI changes as control. KHFAC evoked a transient functional sympathoexcitation at onset that was inversely related to frequency and directly related to intensity. The optimum block threshold was 15 kHz and 15 V.

Conclusion: KHFAC applied to nexus (convergence) points of the cardiac nervous system produces a graded and reversible block of underlying axons. As such, KHFAC has the therapeutic potential for on-demand and reversible mitigation of sympathoexcitation.

Keywords: Axonal modulation therapy; Kilohertz frequency alternating current (KHFAC); Paravertebral chain; Stellate ganglion; Sympathetic efferent; Ventricular electrical indices.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Action Potentials / physiology
Animals
Arrhythmias, Cardiac* / physiopathology
Arrhythmias, Cardiac* / therapy
Disease Models, Animal
Heart Rate / physiology
Heart Ventricles* / innervation
Heart Ventricles* / physiopathology
Neural Conduction / physiology
Stellate Ganglion / physiology*
Swine
Transcutaneous Electric Nerve Stimulation / methods*

Grants and funding

F31 HL127974/HL/NHLBI NIH HHS/United States