Effects of renal sympathetic denervation on the stellate ganglion and brain stem in dogs

Abstract

Background Renal sympathetic denervation (RD) is a promising method of neuromodulation for the management of cardiac arrhythmia. Objective We tested the hypothesis that RD is antiarrhythmic in ambulatory dogs because it reduces the stellate ganglion nerve activity (SGNA) by remodeling the stellate ganglion (SG) and brain stem. Methods We implanted a radiotransmitter to record SGNA and electrocardiogram in 9 ambulatory dogs for 2 weeks, followed by a 2nd surgery for RD and 2 months SGNA recording. Cell death was probed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Results Integrated SGNA at baseline, 1 and 2 months after RD were 14.0±4.0, 9.3±2.8 and 9.6±2.0 μV, respectively (p=0.042). The SG from RD but not normal control (N=5) dogs showed confluent damage. An average of 41±10% and 40±16% of ganglion cells in the left and right SG, respectively, were TUNEL-positive in RD dogs compared with 0% in controls dogs (p= 0.005 for both). Left and right SG from RD dogs had more tyrosine hydroxylase-negative ganglion cells than left SG of control dogs (p= 0.028 and 0.047 respectively). Extensive TUNEL positive neurons and glial cells were also noted in the medulla, associated with strongly positive glial fibrillary acidic protein staining. The distribution was heterogeneous, with more cell death in the medial than lateral aspects of the medulla. Conclusion Bilateral RD caused significant central and peripheral sympathetic nerve remodeling and reduced SGNA in ambulatory dogs. These findings may in part explain the antiarrhythmic effects of RD.

Atrial fibrillation reduction by renal sympathetic denervation: 12 months’ results of the AFFORD study

“…Besides the antihypertensive effects of RDN, an experimental study by Tsai and colleagues showed the antiarrhythmic effects of RDN in six ambulatory dogs by measuring lower nerve activity at the level of the stellate ganglion with also a decrease in paroxysmal atrial tachycardia episodes and duration after RDN as compared to controls [ 10 ]. Moreover, two clinical studies assessed the antiarrhythmic effect of RDN in addition to PVI in hypertensive patients with symptomatic AF.…”

Sympathetic Activation in Hypertensive Chronic Kidney Disease – A Stimulus for Cardiac Arrhythmias and Sudden Cardiac Death?

“…It is also possible that several different routes (i.e. carotid sinus) contribute with collapse between synapses (Tsai et al, 2017), as afferent renal nerve ganglionic cells situated in lumbar and thoracic dorsal root ganglia of the spinal cord also connect to hypothalamic nucleispecifically the posterior and lateral areas, and the locus ceruleus (Campese and Kogosov, 1995;Jansen et al, 1995). Together these data suggest that long-term RDN results may possibly occur due to remodeling of crucial brainstem sites and both SG.…”

“…Renal denervation may blunt sympathetic overactivity and arrhythmogenic foci, thereby potentially reducing arrhythmogenic activity. Preclinical data have shown remodeling of the stellate ganglion (SG) and the brain stem ∼2 months post-RDN, likely medaited by afferent renal nerve signaling interruption (Tsai et al, 2017). Also, a reduction of 18 FDGuptake, SG sympathetic traffic and atrial tachyarrhythmias were correlated to neural modifications of these structures.…”

“…Also, a reduction of 18 FDGuptake, SG sympathetic traffic and atrial tachyarrhythmias were correlated to neural modifications of these structures. Therefore, such remodeling could at least in part explain the antiarrhythmic effects of RDN (Tsai et al, 2017). Even 1 year following a trauma, the central and peripheral nervous system may continue to impact on the damaged site and in distant zones of the brain (Bramlett and Dietrich, 2007).…”

Effects of sympathetic modulation in metabolic disease

“…Animal studies have shown that bilateral RDN led to substantial neuronal remodeling in the brain stem and stellate ganglia following the RDN procedure. [34][35][36][37] The renal efferent sympathetic nerves arising from the second sympathetic ganglion form a network within the renal artery adventitia 38 that is regulated by the rostral ventrolateral medulla, the destruction of which substantially reduces BP. 39 Accordingly, the RDN procedure was introduced to disrupt the sympathetic crosstalk from the kidneys to the brain and vice versa as well as between the two kidneys.…”