Una Buckley1, Ray W Chui2, Pradeep S Rajendran2, Tina Vrabec3, Kalyanam Shivkumar2, Jeffrey L Ardell4. 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.
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.
Authors: Marmar Vaseghi; Jean Gima; Christopher Kanaan; Olujimi A Ajijola; Alexander Marmureanu; Aman Mahajan; Kalyanam Shivkumar Journal: Heart Rhythm Date: 2013-11-28 Impact factor: 6.343
Authors: Joseph Hadaya; Una Buckley; Nil Z Gurel; Christopher A Chan; Mohammed A Swid; Niloy Bhadra; Tina L Vrabec; Jonathan D Hoang; Corey Smith; Kalyanam Shivkumar; Jeffrey L Ardell Journal: Am J Physiol Heart Circ Physiol Date: 2021-12-03 Impact factor: 4.733