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

Goal: 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. Methods: 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. Results: 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 degrees 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. Significance: LDS approach is innovative, inventive, and presents a novel technique totreat hypertension.11Yscopu

Modularized Electrosurgical System with a Hybrid CPU-FPGA Chip for Real-Time Thermal Lesion Approximation

Electrosurgery that ablates the target tissues such as tumor and nerve cells using radio-frequency (RF) heating has been widely employed in the medical industry. Although the thermal lesion plays a key role in the efficacy and safety for this method, it is still difficult to identify the depth and size of the lesion during the treatment using recent electrosurgical systems. Herein, we propose a novel electrosurgical instrument for real-time approximation of thermal lesions during RF ablation (RFA). Thermal lesions were numerically calculated based on theoretical thermal models using a hybrid central processing unit (CPU)-field-programmable gate array (FPGA) chip. Other functions such as RF control, voltage, and temperature measurements were implemented using RF components in a modular manner. It can solve voltage distribution in 6 ms by repeating the calculation 5000 times and can anticipate the thermal lesion in 15.6 ms within a time step in real-time simulations. As a real-world validation, the feasibility of the system was demonstrated through an animal study using a swine model. The system is modularly designed using off-the-shelf chips and RF components to improve flexibility and scalability. It can be easily compatible with existing RF surgical applications and medical imaging devices and can improve the efficacy of RFA therapy.11Nsciescopu

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

Purpose: Although 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 Methods: A 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. Results: When the temperature of the outer wall of the renal artery was maintained at 90 degrees C for 180 seconds, the artery was completely denervated without damaging its inner layer, as evaluated using Masson&apos;s trichrome staining. When the temperature ranged from 70 degrees C to 90 degrees C 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. Conclusions: This 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 degrees C to 90 degrees C within 180 seconds. However, further developments are necessary before its clinical use.1

Laparoscopic Ablation System for Complete Circumferential Renal Sympathetic Denervation

Goal: The catheter-based renal denervation (RDN) showed promising results for patients in lowering BP, but there were also many non-responders. One of the possible reasons was the incomplete neural ablation due to the ablation of renal nerves at random sites resulting in asymmetric innervation patterns along the renal artery. Methods: We developed a laparoscopic ablation system that is optimized for complete RDN regardless of renal arterial innervation and size. To demonstrate its effectiveness, we evaluated the system using computational simulation and 28-day survival model using pigs. Results: The ablations were focused around the tunica externa, and the ablation patterns could be predicted numerically during RDN treatment. In the animal study, the mean reduction of systolic BP and diastolic BP in the bilateral main renal arteries was 22.8 mmHg and 14.4 mmHg (P<0.001), respectively. The respond to immunostaining targeting tyrosine hydroxylase was significantly reduced at treatment site (108.2 +/- 7.5 (control) vs. 63.4 +/- 8.7 (treatment), P<0.001), and an increased degree of sympathetic signals interruption to kidneys was associated with the efficacy of RDN. Conclusion: The laparoscopic ablation system achieved complete circumferential RDN at the treatment site and could numerically predict the ablation patterns. Significance: These findings clearly suggest that the proposed system can significantly improve the RDN effectiveness by reducing the variation to the percentage of injured nerves and open up a new opportunity to treat uncontrolled hypertension.11Nsciescopu