scholarly journals Noninvasive Stereotactic Radiotherapy for Renal Denervation in a Swine Model

2019 ◽  
Vol 74 (13) ◽  
pp. 1697-1709 ◽  
Author(s):  
Xingxing Cai ◽  
Yuli Yang ◽  
Yichen Shen ◽  
Wei Wang ◽  
Li Qian ◽  
...  
Keyword(s):  
Stereotactic Radiotherapy ◽  
Renal Denervation ◽  
Swine Model

Abstract P195: No Functional Nerve Recovery To 6 Months Post Renal Denervation With Rf Energy In A Normotensive Pig Model

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Andrew Sharp ◽  
Stefan Tunev ◽  
Markus P Schlaich ◽  
David P LEE ◽  
Aloke Finn ◽  
...  
Keyword(s):  
Animal Studies ◽  
Renal Denervation ◽  
Blood Pressure Reduction ◽  
Immunohistochemical Analysis ◽  
Swine Model ◽  
Renal Nerve ◽  
Tissue Samples ◽  
Axon Density ◽  
Rf Energy

Background: The safety and efficacy of catheter-based radio frequency (RF) renal denervation (RDN) have been demonstrated in randomized, sham-controlled trials. Long-term durability of blood pressure reduction following RDN has also been demonstrated by all-comer registries, although published pre-clinical reports of functional renal nerve regrowth are not consistent. We quantified the processes that support RDN procedural durability utilizing animal models. Methods: Animal studies were conducted in accordance with published guidelines. RDN was performed (4 lesions in the main renal artery) in normotensive swine using the Symplicity Spyral™ RDN system (Medtronic, Santa Rosa, CA, USA). Two additional groups not undergoing RDN served as control. Serial histological tissue samples were obtained in separate groups at 7 (n=12/group) and 180 (N=16/group) days post-procedure in all animals followed by bioanalytical quantification of cortical norepinephrine (NE) levels and immunohistochemical analysis of renal cortical axon density in matched samples. Results: Renal cortical axon density and NE levels were significantly reduced at 7 days and persisted through 180 days following RDN compared with control ( Figure ). Nerve fibrosis and necrosis were observed in the region of ablation, while nerve body atrophy was apparent distal to ablation location at 180 days. Conclusions: Reductions in both NE and renal cortical axon density were sustained at 7 and 180 days post-RDN procedure using RF renal denervation in a normotensive swine model. These data confirm and extend other pre-clinical and clinical evidence of long-term durability of the RDN procedure using RF energy.

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.

scholarly journals Stereotactic Radiotherapy for Renal Denervation

2019 ◽  
Vol 74 (13) ◽  
pp. 1710-1713 ◽  
Author(s):  
Felix Mahfoud ◽  
Elazer Edelman ◽  
Nikhilesh Bhatt
Keyword(s):  
Stereotactic Radiotherapy ◽  
Renal Denervation

scholarly journals TCT CONNECT-418 Evaluation of Nerve Injury and Regrowth Following Renal Denervation in Swine Model

2020 ◽  
Vol 76 (17) ◽  
pp. B179
Author(s):  
Andrew Sharp ◽  
Stefan Tunev ◽  
Markus Schlaich ◽  
David Lee ◽  
Aloke Finn ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Renal Denervation ◽  
Swine Model

scholarly journals TCT-30 Renal Denervation Improves Cardiac Function in a Swine Model of Heart Failure

2018 ◽  
Vol 72 (13) ◽  
pp. B14
Author(s):  
Tom Sharp ◽  
David Polhemus ◽  
Zhen Li ◽  
Pablo Spaletra ◽  
John Reilly ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Renal Denervation ◽  
Swine Model

scholarly journals Renal Denervation by Noninvasive Stereotactic Radiotherapy Induces Persistent Reduction of Sympathetic Activity in a Hypertensive Swine Model

2021 ◽  
Author(s):  
Xingxing Cai ◽  
Yichen Shen ◽  
Yuli Yang ◽  
Wei Wang ◽  
Li Qian ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Nerve Regeneration ◽  
Nerve Injury ◽  
Sympathetic Activity ◽  
Renal Denervation ◽  
Blood Pressure Response ◽  
Sympathetic Nerves ◽  
Swine Model ◽  
Renal Nerve ◽  
Deoxycorticosterone Acetate

Background We have previously reported the feasibility of noninvasive stereotactic body radiotherapy (SBRT) as a novel approach for renal denervation. Methods and Results Herein, from a translational point of view, we assessed the antihypertensive effect and chronological evolution of SBRT‐induced renal nerve injury within 6 months in a hypertensive swine model. Hypertension was induced in swine by subcutaneous implantation of deoxycorticosterone acetate pellets in combination with a high‐salt diet. A single dose of 25 Gy with SBRT was delivered for renal denervation in 9 swine within 3.4±1.0 minutes. Blood pressure levels at baseline and 1 and 6 months post‐SBRT were comparable to control (n=5), whereas renal norepinephrine was significantly lower at 6 months ( P <0.05). Abdominal computed tomography, performed before euthanasia and renal function assessment, remained normal. Standard semiquantitative histological assessment showed that compared with control (1.4±0.4), renal nerve injury was greater at 1 month post‐SBRT (2.3±0.3) and peaked at 6 months post‐SBRT (3.2±0.8) ( P <0.05), along with a higher proportion of active caspase‐3–positive nerves ( P <0.05). Moreover, SBRT resulted in continuous dysfunction of renal sympathetic nerves and low level of nerve regeneration in 6 months by immunohistochemistry analysis. Conclusions SBRT delivering 25 Gy for renal denervation was safe and related to sustained reduction of sympathetic activity by aggravating nerve damage and inhibiting nerve regeneration up to 6 months; however, its translation to clinical trial should be cautious because of the negative blood pressure response in the deoxycorticosterone acetate–salt hypertensive swine model.

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