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 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.

Renal denervation: current implications and future perspectives

2013 ◽  
Vol 126 (1) ◽  
pp. 41-53 ◽  
Author(s):  
Jianzhong Xu ◽  
Dagmara Hering ◽  
Yusuke Sata ◽  
Antony Walton ◽  
Henry Krum ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Resistant Hypertension ◽  
Renal Denervation ◽  
Interventional Procedure ◽  
Strong Association ◽  
Blood Pressure Reduction ◽  
Pressure Control ◽  
Renal Nerves ◽  
Renal Nerve ◽  
Disease States

SNS (sympathetic nervous system) activation is a common feature of arterial hypertension and has been demonstrated to contribute to the development and progression of the hypertensive state. Persuasive evidence suggests a strong association between SNS overactivity and variety of disease states, including chronic renal failure, insulin resistance, congestive heart failure, sleep apnoea, ventricular arrhythmias and others. Although sympatholytic agents are available to target SNS overactivity pharmacologically, they are not widely used in clinical practice, leaving the SNS unopposed in many patients. The recent introduction of catheter-based renal denervation as an alternative approach to target the SNS therapeutically has been demonstrated to result in a clinically relevant blood pressure reduction in patients with resistant hypertension, presumably through its effects on both efferent and afferent renal nerve traffic. Available data on this interventional procedure demonstrate a favourable vascular and renal safety profile. Preliminary data obtained primarily from small and mostly uncontrolled studies in related disease states often characterized by overactivity of the SNS are promising, but require confirmation in appropriately designed clinical trials. In the present paper, we briefly review the physiology of the renal nerves and their role in hypertension and other relevant disease states, summarize the data currently available from clinical studies pertaining to the safety and efficacy of renal denervation in resistant hypertension, discuss potential future implications and the available data supporting such a role for renal denervation, and describe some of the newer devices currently under investigation to achieve improved blood pressure control via renal denervation.

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 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.

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)

Abstract 13272: Efficacy and Safety of Non-invasive Renal Denervation Study Using Externally Delivered Focused Ultrasound in Severe Resistant Hypertension

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Roland E Schmieder ◽  
John A Ormiston ◽  
Petr Neuzil ◽  
Zdenek Stárek ◽  
Patrick Kay ◽  
...  
Keyword(s):  
Resistant Hypertension ◽  
Renal Denervation ◽  
Focused Ultrasound ◽  
Surrounding Tissue ◽  
Renal Nerves ◽  
Antihypertensive Medications ◽  
Serious Adverse Events ◽  
Sound System ◽  
Invasive Approach ◽  
Non Invasive

Background: Invasive catheter based techniques for renal denervation have been extensively examined in treating patients with resistant hypertension, with mixed results and some periprocedural complications. New evidence suggested that not all renal nerves are in the range of invasive procedures limited to a distance 4 to 6 mm from the lumen. Aims: To evaluate the safety and efficacy of an entirely non-invasive approach to renal denervation using externally delivered focused ultrasound to the peri-renal artery tissue with real time Doppler-based image guidance. Methods and results: Twenty-seven patients with severe, treatment resistant hypertension, defined as persistent systolic blood pressure (BP) > 160 mmHg despite 3 or more antihypertensive medications, were treated non-invasively with the Kona Medical Surround Sound System™. Focused ultrasound energy was delivered to the renal arteries bilaterally and surrounding tissue using Doppler-based imaging and continuous tracking with automatic correction for kidney motion throughout treatment. Patients received conscious sedation during the treatment period. At this time, all patients have completed 24 weeks and 23 patients 52 weeks of follow up. Post-denervation, the mean changes from baseline BP (175/92 mmHg) were -16.8/-8.6 mmHg at 3 weeks, -23.2/-10.8 mmHg at 6 weeks, -29.7/-13.1 mmHg at 12 weeks, -21.6/-8.7 mmHg at 24 weeks and -25.6/-10.1 mmHg at 52 weeks . No serious device-related events have been reported to date. Forty-one percent of subjects (11/27) reported mild back pain immediately following the denervation treatment. The majority of cases (7/11) completely resolved within three days post treatment without any significant intervention and no case was associated with any motor, sensory deficits. Conclusions: This is the first study in humans using a non-invasive renal denervation system in severe resistant hypertension. Results showed clinically meaningful reductions from baseline in office BP through 52 weeks post-denervation. The procedure was well-tolerated with no serious adverse events. This technology should enable patients to benefit from renal denervation therapy without the invasive risks associated with catheter based techniques.

Abstract P203: Insights To Lesion Formation For Percutaneous Renal Denervation: Human And Porcine Histological Analyses

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
David Kandzari ◽  
Stefan Tunev ◽  
Markus P Schlaich ◽  
David P LEE ◽  
Aloke Finn ◽  
...  
Keyword(s):  
Renal Denervation ◽  
Renal Arteries ◽  
Renal Nerves ◽  
Swine Model ◽  
Renal Nerve ◽  
Perivascular Adipose Tissue ◽  
Human Cadavers ◽  
Procedural Outcomes ◽  
Maximal Reduction ◽  
Conduction Properties

Background: The safety and efficacy of radiofrequency (RF) renal denervation (RDN) have been demonstrated in multiple randomized trials. We performed histological analyses in a swine model and human cadavers to investigate RF lesion geometry, morphology and location in the context of local anatomic structures and describe their impact on procedural outcomes. Methods: The Symplicity Spyral catheter was used to perform RDN in 164 renal arteries from healthy swine terminated at 7 days post-treatment. Lesion characteristics were determined by semi-quantitative histology. Renal nerve functionality was measured by quantitative immunohistochemistry and correlated to renal norepinephrine. In addition, we investigated the retroperitoneal space in 10 human cadavers to determine the relative location of extravascular tissues. Results: In the swine model, RF lesions developed exclusively in the perivascular adipose tissue which contains the renal nerves. Lesions were irregularly shaped due to inherent sparing of surrounding perfused structures, such as veins and lymph nodes. Maximum depth of the irregularly shaped RF lesions was 6.8±2.5 mm, and mean depth was 3.9±2.4 mm. Renal norepinephrine levels were lowest when >80% of renal nerves were ablated ( Figure ). Reendothelialization of the lesion area was >99% within 7 days. In humans, only 0.3% of renal nerves were localized on the opposite side of the renal veins. Conclusion: Patterns of RF RDN are uniquely influenced by electrical and thermal conduction properties of tissues surrounding the renal arteries. Maximal reduction of renal norepinephrine content requires ablation of at least 80% of the renal nerves.

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