Yuichi Hori1, Taro Temma1, Christian Wooten1, Christopher Sobowale1, Sarah Tahmasian1, Christopher Chan1, Mohammed A Swid1, Jonathan E Zuckerman2, Warwick Peacock3, Olujimi A Ajijola4. 1. UCLA Cardiac Arrhythmia Center & Neurocardiology Research Program of Excellence, University of California, Los Angeles, California. 2. UCLA Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California. 3. UCLA Surgical Science Laboratory, Department of Neurosurgery, University of California, Los Angeles, California. 4. UCLA Cardiac Arrhythmia Center & Neurocardiology Research Program of Excellence, University of California, Los Angeles, California. Electronic address: oajijola@mednet.ucla.edu.
Abstract
BACKGROUND: Clinical trials for renal artery (RA) ablation have shown limited efficacy. OBJECTIVE: The purpose of this study was to investigate whether the aorticorenal ganglion (ARG) can be targeted for renal denervation. METHODS: Twenty-eight pigs were studied under isoflurane or alpha-chloralose to examine hemodynamic responses and catecholamine release in response to RA or ARG stimulation. To assess the efficacy of ARG ablation, we randomized 16 pigs to either sham, RA, or ARG ablation, followed by occlusion of the left anterior descending coronary artery (LAD). Hemodynamic responses, cardiac electrophysiological parameters, and arrhythmias/sudden cardiac death were assessed following LAD occlusion. Absent hemodynamic responses to stimulation confirmed ARG or RA ablation. In vivo stellate ganglion neural activity was recorded to assess cardiac sympathetic signaling. Cadaveric dissections were performed to localize the ARG in humans for comparison to swine. RESULTS: The ARG is a purely sympathetic ganglion with cholinergic inputs and pass-through sensory afferent fibers. Compared to RA stimulation, ARG stimulation yielded greater hemodynamic responses during alpha-chloralose anesthesia. However, neither site yielded significant responses under isoflurane. Radiofrequency ablation of the ARG eliminated responses to both RA and ARG stimulation, whereas RA ablation did not eliminate responses to ARG stimulation. Ablation of the ARG did not impact the kidneys or adrenal glands. Compared to control and RA ablation, ARG ablation was protective against ventricular arrhythmias and sudden death. Human and swine ARG are similarly located in the aorticorenal region. CONCLUSION: Our findings indicate that the ARG may be a novel target for renal neuromodulation. Further studies are warranted to validate these findings.
BACKGROUND: Clinical trials for renal artery (RA) ablation have shown limited efficacy. OBJECTIVE: The purpose of this study was to investigate whether the aorticorenal ganglion (ARG) can be targeted for renal denervation. METHODS: Twenty-eight pigs were studied under isoflurane or alpha-chloralose to examine hemodynamic responses and catecholamine release in response to RA or ARG stimulation. To assess the efficacy of ARG ablation, we randomized 16 pigs to either sham, RA, or ARG ablation, followed by occlusion of the left anterior descending coronary artery (LAD). Hemodynamic responses, cardiac electrophysiological parameters, and arrhythmias/sudden cardiac death were assessed following LAD occlusion. Absent hemodynamic responses to stimulation confirmed ARG or RA ablation. In vivo stellate ganglion neural activity was recorded to assess cardiac sympathetic signaling. Cadaveric dissections were performed to localize the ARG in humans for comparison to swine. RESULTS: The ARG is a purely sympathetic ganglion with cholinergic inputs and pass-through sensory afferent fibers. Compared to RA stimulation, ARG stimulation yielded greater hemodynamic responses during alpha-chloralose anesthesia. However, neither site yielded significant responses under isoflurane. Radiofrequency ablation of the ARG eliminated responses to both RA and ARG stimulation, whereas RA ablation did not eliminate responses to ARG stimulation. Ablation of the ARG did not impact the kidneys or adrenal glands. Compared to control and RA ablation, ARG ablation was protective against ventricular arrhythmias and sudden death. Human and swine ARG are similarly located in the aorticorenal region. CONCLUSION: Our findings indicate that the ARG may be a novel target for renal neuromodulation. Further studies are warranted to validate these findings.