1197The development and validation of a novel transcatheter microwave renal denervation system

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P Qian ◽  
M A Barry ◽  
J Lu ◽  
A Mina ◽  
J Ryan ◽  
...  
Keyword(s):  
Renal Artery ◽  
Microwave Ablation ◽  
Renal Denervation ◽  
Arterial Injury ◽  
Renal Tissue ◽  
Local Health ◽  
Renal Nerve ◽  
Visceral Injury ◽  
Norepinephrine Content

Abstract Background Clinical studies of transcatheter radiofrequency renal denervation for treating hypertension have been hampered by the lack of consistent denervation efficacy. Microwave energy is well suited to renal denervation due to its capacity to spare vascular structures due to cooling from adjacent blood flow while enabling deep perivascular heating. Purpose We aimed to: 1) develop a transcatheter microwave system capable of safely delivering deep and circumferential perivascular renal nerve ablation, and 2) demonstrate the feasibility, short-term efficacy and safety of transcatheter microwave renal denervation. Method A novel 7F transcatheter microwave denervation system was designed, built, and iteratively prototyped in vitro and in 15 sheep. A histological grading system for microwave induced renal arterial and renal nerve injury was devised. The microwave denervation system was validated in an additional 9 sheep, which underwent unilateral renal denervation. Up to 2 microwave ablations were delivered to each artery with maximum power at 100–110W for 480s. Sheep were euthanised at 2–3 weeks post procedure. Gross microscopic histological examination as well as renal tissue norepinephrine content was analysed. Results Catheter deployment and ablation was successful in all 19 targeted vessel segments and ablation produced substantial circumferential perivascular injury; median ablation lesion area >395 (IQR 251–437) mm2, depth 17.1 (IQR 15.8–18.4) mm, length 16 (IQR 12–20) mm, without collateral visceral injury. Limiting power to 100W minimised arterial injury, while maintaining a deep circumferential perivascular ablation. At microwave ablation sites, a total of 292 nerve fascicles were identified, median distance from the renal artery of 4.2mm (IQR 2.1–8.8mm), of which 249 (85%) had sustained thermal injury with 128/249 (51%) showing grade 3–4 (moderate to severe) injury. Microwave denervation reduced median functional sympathetic nerve surface area at the renal hilum on anti-tyrosine hydroxylase staining by 100% (IQR 87%-100%), p=0.0039, and median renal cortical norepinephrine content by 83% (IQR 76%–92%), p=0.0078, compared to the paired control kidney. Conclusion Transcatheter microwave ablation can produce deep circumferential perivascular ablations over a long segment of the renal artery without significant arterial or collateral visceral injury to provide effective renal denervation. Clinical translation may enable more consistent and complete transcatheter renal denervation and antihypertensive efficacy. Acknowledgement/Funding University of Sydney; Western Sydney Local health District; National Health and Medical Research Council of Australia; National Heart Foundation (Au)

scholarly journals Early Morphologic Alterations in Renal Artery Wall and Renal Nerves in Response to Catheter-Based Renal Denervation Procedure in Sheep: Difference Between Single-Point and Multiple-Point Ablation Catheters

2017 ◽  
pp. 601-614 ◽  
Author(s):  
M. TÁBORSKÝ ◽  
D. RICHTER ◽  
Z. TONAR ◽  
T. KUBÍKOVÁ ◽  
A. HERMAN ◽  
...  
Keyword(s):  
Renal Artery ◽  
Resistant Hypertension ◽  
Renal Denervation ◽  
Single Point ◽  
Renal Tissue ◽  
Renal Nerves ◽  
Multiple Point ◽  
Renal Nerve ◽  
Jude Medical ◽  
Novel Strategy

Renal sympathetic hyperactivity is critically involved in hypertension pathophysiology; renal denervation (RDN) presents a novel strategy for treatment of resistant hypertension cases. This study assessed effects of two RDN systems to detect acute intravascular, vascular and peri-vascular changes in the renal artery, and renal nerve alterations, in the sheep. The procedures using a single-point or multi-point ablation catheters, Symplicity FlexTM, Medtronic versus EnligHTNTM, St. Jude Medical were compared; the intact contralateral kidneys served as controls. Histopathological and immunohistochemical assessments were performed 48 h after RDN procedures; the kidney and suprarenal gland morphology was also evaluated. Special staining methods were applied for histologic analysis, to adequately score the injury of renal artery and adjacent renal nerves. These were more pronounced in the animals treated with the multi-point compared with the single-point catheter. However, neither RDN procedure led to complete renal nerve ablation. Forty-eight hours after the procedure no significant changes in plasma and renal tissue catecholamines were detected. The morphologic changes elicited by application of both RDN systems appeared to be dependent on individual anatomical variability of renal nerves in the sheep. Similar variability in humans may limit the therapeutic effectiveness of RDN procedures used in patients with resistant hypertension.

scholarly journals Hemodynamic and neural responses to renal denervation of the nerve to the clipped kidney by cryoablation in two-kidney, one-clip hypertensive rats

2016 ◽  
Vol 310 (2) ◽  
pp. R197-R208 ◽  
Author(s):  
Noreen F. Rossi ◽  
Russell Pajewski ◽  
Haiping Chen ◽  
Peter J. Littrup ◽  
Maria Maliszewska-Scislo
Keyword(s):  
Renal Artery ◽  
Renal Denervation ◽  
Renal Tissue ◽  
Reflex Response ◽  
Ang Ii ◽  
Neural Responses ◽  
Sprague Dawley ◽  
Renal Nerve ◽  
Contralateral Kidney ◽  
Sprague Dawley Rats

Renal artery stenosis is increasing in prevalence. Angioplasty plus stenting has not proven to be better than medical management. There has been a reluctance to use available denervation methodologies in this condition. We studied conscious, chronically instrumented, two-kidney, one-clip (2K-1C) Goldblatt rats, a model of renovascular hypertension, to test the hypothesis that renal denervation by cryoablation (cryo-DNX) of the renal nerve to the clipped kidney decreases mean arterial pressure (MAP), plasma and tissue ANG II, and contralateral renal sympathetic nerve activity (RSNA). Five-week-old male Sprague-Dawley rats underwent sham (ShC) or right renal artery clipping (2K-1C), placement of telemetry transmitters, and pair-feeding with a 0.4% NaCl diet. After 6 wk, rats were randomly assigned to cryo-DNX or sham cryotreatment (sham DNX) of the renal nerve to the clipped kidney. MAP was elevated in 2K-1C and decreased significantly in both ShC cryo-DNX and 2K-1C cryo-DNX. Tissue norepinephrine was ∼85% lower in cryo-DNX kidneys. Plasma ANG II was higher in 2K-1C sham DNX but not in 2K-1C cryo-DNX vs ShC. Renal tissue ANG II in the clipped kidney decreased after cryo-DNX. Baseline integrated RSNA of the unclipped kidney was threefold higher in 2K-1C versus ShC and decreased in 2K-1C cryo-DNX to values similar to ShC. Maximum reflex response of RSNA to baroreceptor unloading in 2K-1C was lower after cryo-DNX. Thus, denervation by cryoablation of the renal nerve to the clipped kidney decreases not only MAP but also plasma and renal tissue ANG II levels and RSNA to the contralateral kidney in conscious, freely moving 2K-1C rats.

scholarly journals Technical advance in silico and in vitro development of a new bipolar radiofrequency ablation device for renal denervation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Noel Pérez ◽  
Karl Muffly ◽  
Stephen E. Saddow
Keyword(s):  
Radiofrequency Ablation ◽  
Renal Artery ◽  
Resistant Hypertension ◽  
In Silico ◽  
Renal Denervation ◽  
Bipolar Electrode ◽  
Ablation Zone ◽  
Catheter Design ◽  
Basket Catheter

Abstract Background Renal denervation with radiofrequency ablation has become an accepted treatment for drug-resistant hypertension. However, there is a continuing need to develop new catheters for high-accuracy, targeted ablation. We therefore developed a radiofrequency bipolar electrode for controlled, targeted ablation through Joule heating induction between 60 and 100 °C. The bipolar design can easily be assembled into a basket catheter for deployment inside the renal artery. Methods Finite element modeling was used to determine the optimum catheter design to deliver a minimum ablation zone of 4 mm (W) × 10 mm (L) × 4 mm (H) within 60 s with a 500 kHz, 60 Vp-p signal, and 3 W maximum. The in silico model was validated with in vitro experiments using a thermochromic phantom tissue prepared with polyacrylamide gel and a thermochromic ink additive that permanently changes from pink to magenta when heated over 60 °C. Results The in vitro ablation zone closely matched the size and shape of the simulated area. The new electrode design directs the current density towards the artery walls and tissue, reducing unwanted blood temperature increases by focusing energy on the ablation zone. In contrast, the basket catheter design does not block renal flow during renal denervation. Conclusions This computational model of radiofrequency ablation can be used to estimate renal artery ablation zones for highly targeted renal denervation in patients with resistant hypertension. Furthermore, this innovative catheter has short ablation times and is one of the lowest power requirements of existing designs to perform the ablation.

1196Transvascular pace-capture of aorticorenal ganglia provides a testable procedural endpoint for transcatheter renal artery denervation and identifies a novel therapeutic ablation target for denervation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P C Qian ◽  
M A Barry ◽  
J Lu ◽  
J Pouliopoulos ◽  
A Mina ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Artery ◽  
Sympathetic Nerve ◽  
Renal Denervation ◽  
Vena Cava ◽  
Renal Sympathetic Denervation ◽  
Local Health ◽  
Renal Vasoconstriction ◽  
Arterial Blood ◽  
Renal Sympathetic

Abstract Background Transcatheter renal denervation procedures often produces incomplete renal denervation and inconsistent antihypertensive effect. The lack of an intraprocedural method for renal sympathetic nerve function assessment has precluded a rational and physiologically based approach to ensure adequate denervation has been achieved at the time of the procedure. Purpose To demonstrate that it is possible to localise aorticorenal ganglia via transvascular pacing to provide: 1) a testable procedural endpoint for transcatheter renal denervation and, 2) a novel ablation target for renal denervation. Methods High frequency pacing in the inferior vena cava and aorta, invasive blood pressure measurements and renal angiography was performed in sheep (N=19) to identify ARG pace-capture sites by concurrent hypertensive and renal vasoconstrictive responses. Group A (N=5) underwent ink injection labelling at the ARG pace-capture site for histological verification; Group B (N=6) received unilateral irrigated radiofrequency ablation of ARG pace-capture sites and assessment of renal innervation at 1week post-procedure; and Group C (N=8) had ARG pacing performed prior to and 2–3 weeks after unilateral transcatheter microwave renal denervation. Results ARG pace-capture responses were observed at paired discrete sites in the posterior IVC and anterolateral aorta approximately 40mm above the ipsilateral renal artery. Pacing elicited a mean arterial blood pressure change of 22.2 [IQR 15.5–34.3] mmHg, p<0.001, together with ipsilateral renal vasoconstriction with main renal artery calibre change of −0.42mm [IQR −0.64mm to −0.24mm] measured with quantitative coronary analysis (QCA), p<0.0001, and branch renal artery median pixel density index change −10.4% [IQR −22.7% to −3.0%], p=0.003. Contralateral renal arterial vasoconstriction was not observed consistently at either the main or branch renal artery level. Sympathetic ganglionic tissue was observed at ARG pace-capture sites, and ganglion ablation caused significant ipsilateral renal denervation with a median hilar functional sympathetic nerve area reduction of 51% [IQR 24%–52%], p=0.043, and renal cortical norepinephrine reduction of 54% [IQR 36%–59%], p=0.043. Circumferential renal denervation resulted in immediate and sustained abolition of ARP pacing induced renal vasoconstriction and significant ipsilateral renal denervation. Conclusion Localisation of ARG using transvascular pacing is feasible with pace-capture demonstrated by concurrent hypertensive and ipsilateral renal arterial vasoconstrictive responses. Abolition of ARG pacing induced renal arterial vasoconstriction may indicate successful renal sympathetic denervation, providing a physiological procedural endpoint to guide transcatheter renal denervation. Additionally, ablation of ARG could provide an alternative or adjunctive method for renal denervation. Acknowledgement/Funding University of Sydney; Western Sydney Local health District; National Health and Medical Research Council of Australia; National Heart Foundation (Au)

Transcatheter microwave ablation can deliver deep and circumferential perivascular nerve injury without significant arterial injury to provide effective renal denervation

2019 ◽  
Vol 37 (10) ◽  
pp. 2083-2092 ◽  
Author(s):  
Pierre C. Qian ◽  
Michael A. Barry ◽  
Juntang Lu ◽  
Sara Al-Raisi ◽  
Ashraf Mina ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Microwave Ablation ◽  
Renal Denervation ◽  
Arterial Injury

scholarly journals Afferent renal innervation in anti-Thy1.1 nephritis in rats

2020 ◽  
Vol 319 (5) ◽  
pp. F822-F832
Author(s):  
Kristina Rodionova ◽  
Roland Veelken ◽  
Karl F. Hilgers ◽  
Eva-Maria Paulus ◽  
Peter Linz ◽  
...  
Keyword(s):  
Renal Tissue ◽  
In Vitro Assays ◽  
Renal Nerves ◽  
Dual Function ◽  
Sprague Dawley ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Cgrp Release ◽  
Renal Nerve Activity

Afferent renal nerves exhibit a dual function controlling central sympathetic outflow via afferent electrical activity and influencing intrarenal immunological processes by releasing peptides such as calcitonin gene-related peptide (CGRP). We tested the hypothesis that increased afferent and efferent renal nerve activity occur with augmented release of CGRP in anti-Thy1.1 nephritis, in which enhanced CGRP release exacerbates inflammation. Nephritis was induced in Sprague-Dawley rats by intravenous injection of OX-7 antibody (1.75 mg/kg), and animals were investigated neurophysiologically, electrophysiologically, and pathomorphologically 6 days later. Nephritic rats exhibited proteinuria (169.3 ± 10.2 mg/24 h) with increased efferent renal nerve activity (14.7 ± 0.9 bursts/s vs. control 11.5 ± 0.9 bursts/s, n = 11, P < 0.05). However, afferent renal nerve activity (in spikes/s) decreased in nephritis (8.0 ± 1.8 Hz vs. control 27.4 ± 4.1 Hz, n = 11, P < 0.05). In patch-clamp recordings, neurons with renal afferents from nephritic rats showed a lower frequency of high activity following electrical stimulation (43.4% vs. 66.4% in controls, P < 0.05). In vitro assays showed that renal tissue from nephritic rats exhibited increased CGRP release via spontaneous (14 ± 3 pg/mL vs. 6.8 ± 2.8 pg/ml in controls, n = 7, P < 0.05) and stimulated mechanisms. In nephritic animals, marked infiltration of macrophages in the interstitium (26 ± 4 cells/mm2) and glomeruli (3.7 ± 0.6 cells/glomerular cross-section) occurred. Pretreatment with the CGRP receptor antagonist CGRP8–37 reduced proteinuria, infiltration, and proliferation. In nephritic rats, it can be speculated that afferent renal nerves lose their ability to properly control efferent sympathetic nerve activity while influencing renal inflammation through increased CGRP release.

scholarly journals Evaluation of Later Morphologic Alterations in Renal Artery Wall and Renal Nerves in Response to Catheter-Based Renal Denervation in Sheep: Comparison of the Single-Point and Multiple-Point Ablation Catheters

2018 ◽  
pp. 891-901 ◽  
Author(s):  
M. TÁBORSKÝ ◽  
D. RICHTER ◽  
Z. TONAR ◽  
T. KUBÍKOVÁ ◽  
A. HERMAN ◽  
...  
Keyword(s):  
Renal Artery ◽  
Renal Denervation ◽  
Single Point ◽  
Renal Nerves ◽  
Multiple Point ◽  
Artery Wall ◽  
Renal Nerve ◽  
Extensive Evaluation ◽  
Kidney Morphology ◽  
Renal Nerve Ablation

This study evaluated the subacute morphologic alterations in renal artery wall and renal nerves in response to catheter-based renal denervation (RDN) in sheep and also compared the efficiency of single-point and multiple-point ablation catheters. Effect of each ablation catheter approved for the clinical use (Symplicity FlexTM, Medtronic, Inc., or EnligHTNTM, St. Jude Medical, INC.) was compared to intact contralateral renal artery in 12 sheep by histopathology and immunohistochemistry evaluation after a 10-day period post-RDN procedure. The safety was verified by extensive evaluation of kidney morphology. Vascular wall lesions and nerve injuries were more pronounced in those animals treated with multi-point EnligHTN catheter when compared with animals treated with single-point Symplicity Flex catheter. However, neither RDN procedure led to complete renal nerve ablation. Both systems, tested in the present study, provided only incomplete renal nerve ablation in sheep. Moreover, no appreciable progression of the nerve disintegration in subacute phase post-RDN procedure was observed. This study further supports the notion that the effectiveness remains fully dependent on anatomical inter-individual variability of the sympathetic nerve plexus accompanying the renal artery. Therefore, new systems providing deeper penetrance to targeted perivascular structure would be more efficient.

scholarly journals Microdissection of the Human Renal Nervous System

Hypertension ◽  
2020 ◽  
Vol 76 (4) ◽  
pp. 1240-1246 ◽  
Author(s):  
Arturo García-Touchard ◽  
Eva Maranillo ◽  
Blanca Mompeo ◽  
José Ramón Sañudo
Keyword(s):  
Nervous System ◽  
Renal Artery ◽  
Renal Denervation ◽  
Left Kidney ◽  
Renal Nerves ◽  
Renal Nerve ◽  
Main Renal Artery ◽  
Area Under Roc Curve ◽  
Human Cadavers ◽  
The Right

Despite the use of renal denervation to treat hypertension, the anatomy of the renal nervous system remains poorly understood. We performed a detailed quantitative analysis of the human renal nervous system anatomy with the goal of optimizing renal denervation procedural safety and efficacy. Sixty kidneys from 30 human cadavers were systematically microdissected to quantify anatomic variations in renal nerve patterns. Contrary to current clinical perception, not all renal innervation followed the main renal artery. A significant portion of the renal nerves (late arriving nerves) frequently reached the kidney (73% of the right kidney and 53% of the left kidney) bypassing the main renal artery. The ratio of the main renal artery length/aorta-renal hilar distance proved to be a useful variable to identify the presence/absence of these late arriving nerves (odds ratio, 0.001 (95% CI, 0.00002–0.0692; P : 0.001) with a cutoff of 0.75 (sensitivity: 0.68, specificity: 0.83, area under ROC curve at threshold: 0.76). When present, polar arteries were also highly associated with the presence of late arriving nerve. Finally, the perivascular space around the proximal main renal artery was frequently occupied by fused ganglia from the solar plexus (right kidney: 53%, left kidney: 83%) and/or by the lumbar sympathetic chain (right kidney: 63%, left kidney: 60%). Both carried innervation to the kidneys but importantly also to other abdominal and pelvic organs, which can be accidentally denervated if the proximal renal artery is targeted for ablation. These novel anatomic insights may help guide future procedural treatment recommendations to increase the likelihood of safely reaching and destroying targeted nerves during renal denervation procedures.

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