UCLA Cardiac Arrhythmia Center & Neurocardiology Research Program of Excellence, University of California, Los Angeles, California.
UCLA Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California.
Heart Rhythm. 2021 Oct;18(10):1745-1757. doi: 10.1016/j.hrthm.2021.06.1192. Epub 2021 Jun 26.
Clinical trials for renal artery (RA) ablation have shown limited efficacy.
The purpose of this study was to investigate whether the aorticorenal ganglion (ARG) can be targeted for renal denervation.
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.
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.
Our findings indicate that the ARG may be a novel target for renal neuromodulation. Further studies are warranted to validate these findings.
肾动脉 (RA) 消融的临床试验显示疗效有限。
本研究旨在探讨主动脉肾神经节 (ARG) 是否可作为去肾神经的靶点。
28 头猪在异氟烷或α-氯醛糖麻醉下，观察 RA 或 ARG 刺激时的血流动力学反应和儿茶酚胺释放。为评估 ARG 消融的疗效，我们将 16 头猪随机分为假手术、RA 或 ARG 消融组，随后结扎左前降支冠状动脉 (LAD)。结扎 LAD 后评估血流动力学反应、心脏电生理参数和心律失常/心脏性猝死。刺激后无血流动力学反应证实 ARG 或 RA 消融。记录星状神经节的神经活动以评估心脏交感神经信号。进行尸体解剖以定位人类的 ARG，与猪进行比较。
ARG 是一个纯粹的交感神经节，具有胆碱能传入和贯穿感觉传入纤维。与 RA 刺激相比，ARG 刺激在 α-氯醛糖麻醉下引起更大的血流动力学反应。然而，在异氟烷下两个部位均无明显反应。ARG 的射频消融消除了对 RA 和 ARG 刺激的反应，而 RA 消融并不能消除对 ARG 刺激的反应。ARG 消融不会影响肾脏或肾上腺。与对照组和 RA 消融组相比，ARG 消融对室性心律失常和心脏性猝死有保护作用。人与猪的 ARG 位置相似，位于主动脉肾区。
我们的研究结果表明，ARG 可能是肾脏神经调节的一个新靶点。需要进一步的研究来验证这些发现。
