Laparoscopic Renal Denervation Research Articles

Novel laparoscopic renal denervation immediately reduces atrial fibrillation inducibility: a swine model study

Catheter-based approaches may have inherent limitations in achieving effective renal denervation (RDN) and treatment of atrial fibrillation (AF). This study aimed to investigate the acute effects of novel laparoscopic RDN on modulating AF inducibility using a swine model. Four and five swine were randomly allocated to the sham and RDN groups, respectively. Each swine underwent measurement of the atrial effective refractory period (AERP) and AF induction tests using burst atrial pacing before and immediately after sham or RDN procedures with and without vagal nerve stimulation (VNS). A laparoscopic RDN procedure circumferentially ablated the renal nerves round the renal arteries using radiofrequency energy. There was no significant difference in the baseline AERP between the two groups (p > 0.05). Under VNS, AERP was significantly increased by 20 ms after laparoscopic RDN (95% CI = 0–30, p = 0.004). Compared to the sham group, the RDN group showed significantly reduced AF inducibility [OR (95% CI) = 0.32 (0.13–0.76) and 0.24 (0.11–0.57) with and without VNS, respectively]. After laparoscopic RDN, the duration of inducible AF episodes was significantly shortened from 28 (10–77) s to 7 (3–11) s (p < 0.001). The novel laparoscopic RDN can immediately reduce AF inducibility in a swine model.

Laparoscopic approach for renal denervation: an experimental study on animals

Aim. To study the efficacy and safety of laparoscopic mechanical renal denervation.Methods. Thirty sheep with mean weight 92.3±2.1 kg were divided in 2 groups: control group (group I, n=15) and mechanical laparoscopic renal denervation group (group II, n=15). The follow-up period was 6 months. The following parameters were assessed: blood pressure in response to high-frequency electrical intraluminal stimulation, creatinine, blood urea nitrogen test (BUN), damage to the renal arteries according to the result of angiography, the degree of destruction of nerve fibers according to histological examination.Results. All animals were alive during the entire observation period. The creatinine and BUN were within the normal ranges during the observation period. Angiography of the renal arteries did not reveal iatrogenic stenotic lesions. After 6 months in group 2 there was hypertensive response of blood pressure to high-frequency electrical stimulation (in-creased systolic blood pressure ∆70.27±5.31 (p&gt;0.005), diastolic blood pressure ∆49.87±6.05 (p&gt;0.005)). After 6 months, the animals were euthonised, further histological examination was completed. Histological examination: in the group II, there was swelling and vacuolization of the nerve fiber without signs of demyelination.Conclusions. Laparoscopic mechanical renal denervation is a safe technique. However, the hypotensive effect is short-term.

Combined method of renal denervation in an animal model

Background: Currently, intra-arterial radiofrequency renal denervation is an only interventional treatment for resistant hypertension. However, available data are controversial since this method does not provide the long-term hypotensive effect.Objective: To compare the safety and efficacy of laparoscopic mechanical renal denervation and laparoscopic combined renal denervation using a radiofrequency clamp.Methods: Thirty sheep weighing 93.00 ± 3.72 kg were divided into two groups for mechanical laparoscopic renal denervation (group I, n = 15) and combined laparoscopic renal denervation with a radiofrequency clamp (group II, n = 15). The observation period lasted for six months. We assessed the following parameters: blood pressure (BP) in response to high-frequency electric stimulation from the lumen of the vessel, creatinine and uric acid levels, iatrogenic damage to the renal arteries based on angiography findings, and destruction of nerve fibers based on histological findings.Results: All the animals survived throughout the observation period. Creatinine and uric acid levels were within the normal ranges. Renal angiography did not reveal any iatrogenic stenosis. After six months, we found some BP response (elevated systolic BP ∆66.73 ± 6.63 mm Hg [p &lt; 0.001], elevated diastolic BP ∆47.27 ± 5.98 mm Hg [p &lt; 0.001]) to high-frequency electric stimulation in group I and no hypertensive response in group II. After six months, the animals were withdrawn for further histological assessment. Histology revealed complete destruction of the nerve fiber (demyelination) in group II and vacuolized swollen nerve fibers without any signs of demyelination in group I.Conclusion: Laparoscopic combined renal denervation is a safe and efficacious method with a stable hypotensive effect after six months in an animal model as compared to laparoscopic mechanical renal denervation. Received 30 March 2022. Revised 5 December 2022. Accepted 9 December 2022. Funding: The study did not have sponsorship. Conflict of interest: Authors declare no conflict of interest. Contribution of the authorsConception and study design: D.I. Bashta, L.I. Vilenskiy, A.B. RomanovData collection and analysis: D.I. Bashta, Yu.S. Krivosheev, A.A. SimonyanStatistical analysis: D.I. Bashta, Yu.S. KrivosheevDrafting the article: D.I. Bashta, Yu.S. Krivosheev Critical revision of the article: L.I. Vilenskiy, Yu.S. Krivosheev, A.B. Romanov Final approval of the version to be published: D.I. Bashta, L.I. Vilenskiy, Yu.S. Krivosheev, A.A. Simonyan, A.B. Romanov

PO-690-05 NOVEL LAPAROSCOPY-BASED RENAL DENERVATION FOR MODULATING AF INDUCIBILITY USING A SWINE MODEL

Renal denervation (RDN) may control atrial fibrillation (AF) by modulating autonomic tone. The study aimed to validate the acute effects of a novel laparoscopy-based RDN for modulating AF inducibility using a swine model. Each 4 swine were assigned for the sham operation and laparoscopy-based RDN. Vagal nerve stimulation (VNS; 10 Hz, 50 ms, 5-20 V, 30 sec) was performed at the right vagal nerve to enhance AF inducibility. Burst atrial pacing (100 ms, 1-5 V, 90 sec) at the right atrium was used to induce AF. Atrial effective refractory period (AERP) and AF duration were compared before and after the sham operation or RDN. Laparoscopy-based RDN was done using an instrument with linear bipolar electrodes that wraps around the renal artery (Figure 1A). It delivers the radiofrequency energy to the adventitia to ablate renal sympathetic nerves. Both proximal and distal parts of renal artery were ablated (Figure 2A). Renal arterial biopsy was done and stained with tyrosine hydroxylase to identify sympathetic nerves and compared between both groups. For the sham group, VNS significantly reduced AERP from median 180 to 150 ms and 170 to 150 ms before and after the sham operation, respectively (both p =0.009) (Figure 2A). VNS numerically increased AF duration from median 4.5 to 10.5 sec and 6.0 to 9.5 sec before and after the sham operation (p =0.06 and 0.11, respectively) (Figure 2B). The effect of VNS on AF duration was significant (p =0.005), while the sham operation did not (p =0.79). For the RDN group, VNS numerically reduced AERP from 160 to 130 ms and 180 to 160 ms before and after RDN (p =0.24 and 0.54, respectively) (Figure 2A). VNS did not induce significant difference in AF duration regardless of RDN. However, RDN significantly reduced AF duration regardless of VNS (from mean 23.0 to 4.8 sec; difference between means 18.3 sec (95% CI 6.4-30.1 sec); p =0.03) (Figure 2B). The effect of RDN on AF duration was significant (p =0.003). In histology analysis, renal sympathetic nerve tissue was degenerated after laparoscopic RDN, whereas normal renal sympathetic nerves were intact in the sham group (Figure 2B). A novel laparoscopy-based RDN significantly reduced AF inducibility in swine models. The long-term effect of this novel laparoscopy-based RDN would be investigated.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Circular Radio-Frequency Electrode With MEMS Temperature Sensors for Laparoscopic Renal Sympathetic Denervation.

Laparoscopic renal denervation (LRDN) ablates sympathetic nerves on the outer wall of a renal artery to treat autonomic nervous system disorders such as hypertension and arrhythmia. Here, we developed a new circular radio frequency (RF) electrode for LRDN using micro-electro-mechanical systems (MEMS) technology. The electrode consists of a parallel bipolar MEMS electrode, two MEMS thermocouples, and a shape-memory alloy (SMA) substrate. The electrode is automatically wrapped and unwrapped under actuation controlled by the heat generated by RF energy on the electrode-tissue interface. The electrode was designed through a computational simulation analysis, and its actuation and temperature-sensing performance were tested in laboratory experiments and a porcine animal study. In an in-vivo study of porcine renal arteries, the electrode could automatically wrap and unwrap around an artery during LRDN. The bipolar MEMS electrode required 13 Vrms for heat generation up to 60°C, while the two MEMS thermocouples reliably measured the temperature without noise signals (a temperature coefficient of 38.3 or 38.5 µV/°C and an accuracy of ±0.44 or ±0.49°C). As revealed in a histological analysis using hematoxylin and eosin staining and Masson's trichrome staining, the renal artery was intact after LRDN. The circular RF electrode improves the safety of LRDN by reliably measuring the electrode temperature of the electrode during RDN and enhances the effectiveness of LRDN by reducing the complicated manipulations of the surgical instrument. The developed circular RF electrode will pave the way for LRDN treatment of autonomic nervous system disorders.

Pain Management Techniques for Loin Pain Hematuria Syndrome Case Report

Background: Loin pain hematuria syndrome (LPHS) is a rare syndrome presenting with chronic unilateral or bilateral flank pain and gross or microscopic hematuria. Case Report: We present a case of LPHS in a male with past medical history of atrial fibrillation, Barrett’s esophagus, and loin pain hematuria syndrome who initially presented to our medical facility with gross hematuria, intractable left flank pain, and non-bloody emesis. Our case exemplifies the challenge in managing patients with LPHS. Conclusion: Without a definitive mechanism for LPHS, current treatment focuses on symptom management. Analgesics (non-opioid and opioid) may be used orally or intravenous depending on the presence of concomitant nausea and vomiting. For patients at risk of opioid dependence, targeting afferent pain fibers originating from the kidneys and ureters has proven a successful analgesic strategy. Surgical options for renal denervation include: endovascular radiofrequency ablation, laparoscopic renal denervation, and renal auto transplant. Treatment options for this disease process include intra-ureteric bupivacaine, renal denervation, and possible spinal cord stimulation. Key words: Flank pain, loin pain hematuria syndrome, renal denervation, spinal cord stimulation

Laparoscopic Renal Denervation System for Treating Resistant Hypertension: Overcoming Limitations of Catheter-Based Approaches.

In a pivotal clinical trial, the percutaneous catheter-based renal denervation system developed to treat resistant hypertension did not show effectiveness in reducing blood pressure because of its fundamental limitation to ablate deeper nerves present around the renal artery. We propose a new renal denervation strategy called laparoscopicdenervation system (LDS) based-on laparoscopy procedure to ablate the renal nerves completely but inhibit the thermal arterial damage.The system has flexible electrodes to bend around the arterial wall to ablate nervesThe simulation study using validated in-silico models evaluated the heat distributionon the outer arterial wall,and an acute animal study (swine model) was conducted to demonstrate the feasibility of LDS in vivo. The simulation studyconfirmedthat LDS could localize the heat distributionbetween the electrode and the outer arterial wall. In the animal study, we could maximize nerve denervation by the localizing ablation energy within the renal nerves and achieve nerve denaturationand decrease in neural density by 20.78% (P < 0.001), while maintaining a constant tip temperature of 65 °C for the duration of 70 s treatment. The study confirmed intact lumen artery through histological analysis and acute reduction in systolic blood pressure by 9.55 mmHg (p < 0.001) Conclusion: The LDS presented here has potential to effectively and safely ablate the renal nerves, independent of anatomical variation and nerve distribution, to control hypertension in real clinical conditions. LDS approach is innovative, inventive, and presents a novel technique totreat hypertension.

Development of a nitinol-actuated surgical instrument for laparoscopic renal denervation: feasibility test in a swine survival model

Purpose In this study, we developed a novel nitinol-actuated surgical instrument to conduct laparoscopic renal denervation for the treatment of resistant hypertension. We investigated whether shape and temperature settings of nitinol specimens fit well into the design goals. Furthermore, we conducted a pilot study to validate the mechanical and physiological performance of nerve ablation without damaging the renal artery. Method Tensile tests were performed to observe temperature-dependent thermomechanical properties and the original shape of nitinol specimens was set considering our design goal. We performed strain gage experiments to measure bending strain. We developed surgical instrument and operated laparoscopic renal denervation in a swine model. Subsequent impedance spectroscopy experiments were conducted to measure changes in impedance magnitudes during the operation and histological analyses were performed to visualize thermogenic damage to arteries and nerves. Results Tensile testing showed that the shape memory effect begins above 37 °C. Measured strains on nitinol surfaces were 2.10% ± 0.769%, below the strain limit of 8%. Impedance spectroscopy experiments showed decreases in magnitude in all six trials. After operation of laparoscopic renal denervation following the protocol, renal arteries and nerves were harvested and thermogenic damage was observed in nerves but not arteries. Conclusion We developed a novel nitinol-actuated surgical instrument with which to perform laparoscopic renal denervation. The feasibility of our device was verified using thermomechanical analyses of nitinol, and assessments of mechanical and physiological performance. Our device could be used in other laparoscopic procedures that require large degrees of freedom while restricting to trocar size.

Animal model evaluation of a novel renal denervation system for future laparoscopic treatment of resistant hypertension.

PurposeAlthough percutaneous catheter-based ablation of renal sympathetic nerve fibers has been used in the treatment of patients with resistant hypertension, a recent phase III study did not confirm its efficacy. In this study, we developed a novel laparoscopic renal denervation system and evaluated its safety and initial feasibility using an animal model.Materials and MethodsA novel surgical instrument that uses a smart algorithm with temperature-monitoring feedback was developed. We used 4 male pigs (6 weeks old, weighing approximately 45 kg each) to evaluate the safety and efficacy of the laparoscopic renal denervation system. We performed immunohistochemical staining analysis after renal denervation using various tip temperatures and over various durations through an open approach.ResultsWhen the temperature of the outer wall of the renal artery was maintained at 90℃ for 180 seconds, the artery was completely denervated without damaging its inner layer, as evaluated using Masson's trichrome staining. When the temperature ranged from 70℃ to 90℃ and the duration ranged from 90 to 420 seconds, partial or complete denervation without significant vessel injury was confirmed with anti- growth-associated protein 43 and anti-S100 staining.ConclusionsThis animal study confirmed the safety and feasibility of the novel laparoscopic renal denervation system. A safe and effective protocol was developed with ablation at a constant tissue temperature of 70℃ to 90℃ within 180 seconds. However, further developments are necessary before its clinical use.

Developing a Computational Model of Renal Nerves and Surgical System for Laparoscopic Renal Denervation.

The sympathetic nervous system was known to play an important role in resistant hypertension. Surgical sympathectomy for renal sympathetic nerve removal were performed since the 1930s. Although effective, it had many serious side effects and complications due to non-selective property. Recently, catheter based RDN system using radiofrequency (RF) ablation was developed and considered promising, however, it failed in sham controlled trial. Therefore, there are needs for safe and effective RDN strategies considering the anatomical structure of the renal arteries and sympathetic nerves. In this paper, we propose a novel surgical instruments for laparoscopic renal denervation (RDN) to treat of resistant hypertension through a 3D realistic model using nephrectomy tissues. Laparoscopic RDN is a new surgical approach to remove renal sympathetic nerves.

Design and simulation of novel laparoscopic renal denervation system: a feasibility study

Purpose: In this study, we propose a novel laparoscopy-based renal denervation (RDN) system for treating patients with resistant hypertension. In this feasibility study, we investigated whether our proposed surgical instrument can ablate renal nerves from outside of the renal artery safely and effectively and can overcome the depth-related limitations of the previous catheter-based system with less damage to the arterial walls.Method: We designed a looped bipolar electrosurgical instrument to be used with laparoscopy-based RDN system. The tip of instrument wraps around the renal artery and delivers the radio-frequency (RF) energy. We evaluated the thermal distribution via simulation study on a numerical model designed using histological data and validated the results by the in vitro study. Finally, to show the effectiveness of this system, we compared the performance of our system with that of catheter-based RDN system through simulations.Results: Simulation results were within the 95% confidence intervals of the in vitro experimental results. The validated results demonstrated that the proposed laparoscopy-based RDN system produces an effective thermal distribution for the removal of renal sympathetic nerves without damaging the arterial wall and addresses the depth limitation of catheter-based RDN system.Conclusions: We developed a novel laparoscope-based electrosurgical RDN method for hypertension treatment. The feasibility of our system was confirmed through a simulation study as well as in vitro experiments. Our proposed method could be an effective treatment for resistant hypertension as well as central nervous system diseases.

AB031. Laparoscopic renal denervation and cyst decortication for autosomal dominant polycystic kidney disease related hypertension and pain in adult

BackgroundWe present our initial experience with laparoscopic renal denervation and cyst decortication for ADPKD related hypertension and pain.MethodsTwelve patients 36 to 67 years old previously diagnosed with ADPKD presented with hypertension and Pain. These 12 patients underwent laparoscopic renal denervation and cyst decortication of 12 kidneys.ResultsMean operative time was 78 minutes and mean hospital stay was 5.6 days. Mean systolic pressure decline was 21 mmHg, and mean diastolic pressure decline was 13 mmHg at a mean follow up of 15 months. All patients were pain-free at discharge home and remained pain-free at a mean follow up of 15 months.ConclusionsWe believe that laparoscopic renal denervation plus cyst decortication is a promising option for uncontrolled ADPKD related hypertension and pain in adult population.

Transperitoneal laparoscopic renal denervation for the management of loin pain haematuria syndrome

Objectives: To assess the role of laparoscopic renal denervation as a surgical option in loin pain-haematuria syndrome (LPHS), refractory to conservative treatment. Material and methods: Nine patients between 2000 and 2010 with a diagnosis of LPHS following extensive investigations. The data collection from medical records and electronic databases included demographic details, details of surgical procedures, perioperative outcomes, pain recurrences and ongoing analgesia requirements. A telephone follow-up was conducted after at least one year after the procedure for each patient using the Pain Impact Questionnaire (PIQ-6TM) to assess impact of pain on their quality of life. Results: Nine patients (nine women; median age 37 years) underwent 11 laparoscopic denervations. The median follow-up was 28 months. The median operative time was 150 min. There were no significant postoperative complications. In four patients (44%) laparoscopic denervation procedures were curative (median follow-up 70.5 months). The analgesic requirement was significantly reduced in 22% of patients. Telephone follow-up confirmed that 66.66% of the patients had better quality of life after the procedure. Conclusions: Laparoscopic renal denervation is a feasible and safe alternative to open procedures in patients with refractory LPHS, producing good outcomes in terms of pain-free rates and quality of life impact.

How Does Acute Urolithiasis Present After Renal Denervation?

To present our experience with the acute presentation of urolithiasis after laparoscopic renal denervation and nephropexy for intractable renal pain in the pediatric patient. Five patients aged 8 to 16 years (mean age 11.4 years) with a history of laparoscopic renal denervation presented with acute abdominal symptoms; obstructing urolithiasis was diagnosed. There were a total of 12 episodes of acute urolithiasis in this cohort. All five patients presented with periumbilical and epigastric discomfort when the stone was on the denervated side. During the episodes, of the five patients, three (60%) also presented with vomiting; four (80%) had at least one episode of gross hematuria; and five (100%) had microscopic hematuria during episodes on the denervated side. None of the patients presented with flank discomfort on the denervated side. Stone-related pain in patients undergoing laparoscopic renal denervation and nephropexy is not a typical presentation, and one needs to be wary of vague abdominal pain in this population.

Follow-up for Laparoscopic Renal Denervation and Nephropexy for Autosomal Dominant Polycystic Kidney Disease–Related Pain in Pediatrics

To present our medium-term experience with laparoscopic renal denervation and nephropexy for autosomal dominant polycystic kidney disease (ADPKD)-related pain in the pediatric patient. Twelve patients aged 8 to 19 years (mean age 12.4 years) with ADPKD presented with chronic pain refractory to narcotic analgesics. These 12 patients underwent laparoscopic renal denervation of 16 kidneys. Mean operative time was 152 minutes and mean hospital stay was 2.17 days. All patients were pain-free at discharge and remain pain-free at a mean follow-up of 25.5 months. Three adolescent patients each had an episode of flank pain. One was associated with pyelonephritis, another with stones, and the third with trauma and a hematoma. Laparoscopic renal denervation and nephropexy is a promising option for pediatric patients with uncontrolled ADPKD-related pain.

Laparoscopic Renal Denervation and Nephropexy for Autosomal Dominant Polycystic Kidney Disease Related Pain in Adolescents

We present our initial experience with laparoscopic renal denervation and nephropexy for ADPKD related pain in the adolescent population. Four patients 15 to 19 years old previously diagnosed with ADPKD presented with chronic pain refractory to narcotic analgesics. These 4 patients underwent laparoscopic renal denervation of 5 kidneys. Mean operative time was 136 minutes and mean hospital stay was 2.75 days. All patients were pain-free at discharge home and remained pain-free at a mean followup of 11.5 months. We believe that laparoscopic renal denervation plus nephropexy is a promising option for uncontrolled ADPKD related pain in the adolescent population.

Analysis of tissue and arterial blood temperatures in the resting human forearm. 1948.

Analysis of tissue and arterial blood temperatures in the resting human forearm. 1948.