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

Abstract

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 laparoscopic denervation 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 nerves The simulation study using validated in-silico models evaluated the heat distribution on the outer arterial wall, and an acute animal study (swine model) was conducted to demonstrate the feasibility of LDS in vivo. Results: The simulation study confirmed that LDS could localize the heat distribution between 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 denaturation and decrease in neural density by 20.78 % (P<0.001), while maintaining a constant tip temperature of 65 ℃ 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 to treat hypertension.

Laparoscopic Ablation System for Complete Circumferential Renal Sympathetic Denervation

“…1B) should curve to completely cover an artery and ablate the entire renal sympathetic nerves using RF energy. To realize the system with the above principle of operation, the ablation electrode of the proposed laparoscopic instrument uses electrical energy through an RF energy delivery system to generate heat at the electrode-tissue interface [23]. In addition, since the electrode is made of a Nitinol substrate with a shape memory effect, it changes its shape from straight to circular at the desired temperature to surround the artery [24].…”

“…The electrodes connected to the newly developed radiofrequency (RF) system modulates the transmitted RF energy by feeding back the temperature of the thermocouple to maintain the constant heat level. Our preliminary study showed that the RF system maintained a constant ablation temperature after reaching 90 % of the preset tip temperature within 7.1 ± 3.5 s [23,25].…”

“…1C); 2) transmit RF energy to generate heat at the electrode-tissue interface; 3) the Nitinol substrate forms a round shape at 50 ℃ and automatically wraps the renal artery (Fig. 1D); 4) maintain the ablation temperature at 65 ℃ for 70 s [23]; and 5) after the treatment, when the temperature of the Nitinol decreases and its tensile strength becomes weak, the FPCB is pulled to release the Nitinol from the artery.…”

“…Histologic sections were examined under a digital pathology slide scanner (Aperio ImageScope, Leica). Artery and nerve damage was evaluated and quantified using ImageJ (software, National Institute of Health) [34]; percent medial area affected, the intensity of immunohistochemical staining, and the gap at the ablation pattern using ImageJ [23].…”

“…However, surgical nerve dissection with conventional laparoscopic instruments requires expertise due to many nerves located near or in the tunica adventitia [14] and also limited of surgical movement [22]. In our preliminary study, we proposed a laparoscopic ablation system optimized for RDN consisting of a laparoscopic instrument with a parallel bipolar electrode and a radiofrequency (RF) energy delivery system controlling ablation temperature [23]. Although this study presented feasibility of the laparoscopic RDN with immediate BP reduction after ablation, it was lack of analysis on effectiveness of complete RDN as well as BP changes in a long term.…”