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 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 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.

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.

Mechanism of effect of diphenylhydantoin on renal renin release

1984 ◽  
Vol 247 (3) ◽  
pp. F418-F422
Author(s):  
P. Cadnapaphornchai ◽  
C. Pontes ◽  
F. D. McDonald
Keyword(s):  
Renal Artery ◽  
Renal Denervation ◽  
Secretion Rate ◽  
Renin Secretion ◽  
Separate Group ◽  
Renin Release ◽  
Renal Nerves ◽  
Percent Increase ◽  
Anesthetized Dogs

This study was undertaken to delineate the mechanism of the effect of diphenylhydantoin (DPH) on renal renin release. DPH at a dose of 0.18 mg X kg-1 X min-1 was infused for 30 min into the renal artery of anesthetized dogs with acute unilateral renal denervation. In the innervated kidney, DPH infusion increased renin secretion rate (RSR) from 189 +/- 54 to 939 +/- 279 ng ANG I X h-1 X min-1. In the contralateral denervated kidneys, RSR did not change. An identical study was done in a second group of dogs in which unilateral renal denervation was done 24 h prior to DPH infusion. In this group, DPH infusion increased RSR from 63 +/- 57 to 643 +/- 180 ng ANG I X h-1 X min-1 in the innervated kidneys. In the contralateral denervated kidneys, RSR did not change. In a separate group of indomethacin-treated nondenervated dogs, intrarenal infusion of DPH increased RSR from 131 +/- 32 to 452 +/- 88 ng ANG I X h-1 X min-1. The percent increase in RSR in the indomethacin-treated dogs was not significantly different from the non-indomethacin-treated dogs. These data suggest that the stimulatory effect of DPH on renin release is mediated by or requires the presence of renal nerves. The step(s) after the renal nerves is (are) not mediated by prostaglandins.

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.

The renal afferent nerves in the pathogenesis of hypertension

1987 ◽  
Vol 65 (8) ◽  
pp. 1548-1558 ◽  
Author(s):  
Suzanne Oparil ◽  
Wanida Sripairojthikoon ◽  
J. Michael Wyss
Keyword(s):  
Renal Denervation ◽  
Genetic Model ◽  
Spontaneously Hypertensive Rat ◽  
Plasma Renin ◽  
Urinary Sodium Excretion ◽  
Experimental Models ◽  
Renal Nerves ◽  
Renal Nerve ◽  
Afferent Nerves ◽  
Hypertensive Rat

The renal nerves play a role in the pathogenesis of hypertension in a number of experimental models. In the deoxycorticosterone acetate – salt (DOCA–NaCl) hypertensive rat and the spontaneously hypertensive rat (SHR) of the Okamoto strain, total peripheral renal denervation delays the development and blunts the severity of hypertension and causes an increase in urinary sodium excretion, suggesting a renal efferent mechanism. Further, selective lesioning of the renal afferent nerves by dorsal rhizotomy reduces hypothalamic norepinephrine stores without altering the development of hypertension in the SHR, indicating that the renal afferent nerves do not play a major role in the development of hypertension in this genetic model. In contrast, the renal afferent nerves appear to be important in one-kidney, one-clip and two-kidney, one-clip Goldblatt hypertensive rats (1K, 1C and 2K, 1C, respectively) and in dogs with chronic coarctation hypertension. Total peripheral renal denervation attenuates the severity of hypertension in these models, mainly by interrupting renal afferent nerve activity, which by a direct feedback mechanism attenuates systemic sympathetic tone, thereby lowering blood pressure. Peripheral renal denervation has a peripheral sympatholytic effect and alters the level of activation of central noradrenergic pathways but does not alter sodium or water intake or excretion, plasma renin activity or creatinine clearance, suggesting that efferent renal nerve function does not play an important role in the maintenance of this form of hypertension. Selective lesioning of the renal afferent nerves attenuates the development of hypertension, thus giving direct evidence that the renal afferent nerves participate in the pathogenesis of renovascular hypertension.

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