Investig Clin Urol.  2020 Jan;61(1):107-113. 10.4111/icu.2020.61.1.107.

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

Affiliations
  • 1Department of Urology, Seoul National University Hospital, Seoul, Korea. drboss@gmail.com
  • 2Department of Urology, Pusan National University Yangsan Hospital, Yangsan, Korea.
  • 3Department of Creative IT Engineering, Pohang University of Science and Technology (POSTECH), Pohang, Korea.
  • 4Department of Prototype Production, Osong Medical Innovation Foundation, Cheongju, Korea.
  • 5Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.

Abstract

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℃ 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.
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℃ to 90℃ within 180 seconds. However, further developments are necessary before its clinical use.

Keyword

Animals; Denervation; Hypertension; Laparoscopy; Renal artery

MeSH Terms

Animals*
Arteries
Denervation*
GAP-43 Protein
Humans
Hypertension*
Laparoscopy
Male
Models, Animal*
Nerve Fibers
Renal Artery
Surgical Instruments
Swine
GAP-43 Protein

Figure

  • Fig. 1 (A) Schematic of the proposed laparoscopy-based renal denervation (RDN) surgical approach and (B) concept design of the surgical instrument for laparoscopy-based RDN. A, curling tip of RDN device.

  • Fig. 2 Real-time energy delivery-controlling generator (A) using a smart algorithm with temperature-monitoring feedback (B). RF, radiofrequency; Amp, amplifier.

  • Fig. 3 Animal experiment using the novel surgical instrument for laparoscopy-based renal denervation (RDN). a:The electrode is wrapped 360° around the artery. b:Temperature wire electrode. c:Surgical instrument for laparoscopy-based RDN.


Reference

1. GBD 2015 Risk Factors Collaborators. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016; 388:1659–1724. PMID: 27733284.
2. World Health Organization. A global brief on hypertension: silent killer, global public health crisis [Internet]. Geneva: WHO;2013. cited 2018 Jun 4. Available from: https://www.who.int/cardiovascular_diseases/publications/global_brief_hypertension/en/.
3. Achelrod D, Wenzel U, Frey S. Systematic review and metaanalysis of the prevalence of resistant hypertension in treated hypertensive populations. Am J Hypertens. 2015; 28:355–361. PMID: 25156625.
Article
4. Tsioufis CP, Papademetriou V, Dimitriadis KS, Kasiakogias A, Tsiachris D, Worthley MI, et al. Catheter-based renal denervation for resistant hypertension: twenty-four month results of the EnligHTN I first-in-human study using a multi-electrode ablation system. Int J Cardiol. 2015; 201:345–350. PMID: 26301677.
Article
5. Krum H, Schlaich M, Whitbourn R, Sobotka PA, Sadowski J, Bartus K, et al. Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study. Lancet. 2009; 373:1275–1281. PMID: 19332353.
Article
6. Gordan R, Gwathmey JK, Xie LH. Autonomic and endocrine control of cardiovascular function. World J Cardiol. 2015; 7:204–214. PMID: 25914789.
Article
7. Chen PS, Chen LS, Fishbein MC, Lin SF, Nattel S. Role of the autonomic nervous system in atrial fibrillation: pathophysiology and therapy. Circ Res. 2014; 114:1500–1515. PMID: 24763467.
8. Flack JM, Bhatt DL, Kandzari DE, Brown D, Brar S, Choi JW, et al. SYMPLICITY HTN-3 Investigators. An analysis of the blood pressure and safety outcomes to renal denervation in African Americans and Non-African Americans in the SYMPLICITY HTN-3 trial. J Am Soc Hypertens. 2015; 9:769–779. PMID: 26362830.
Article
9. Bhatt DL, Kandzari DE, O'Neill WW, D'Agostino R, Flack JM, Katzen BT, et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014; 370:1393–1401. PMID: 24678939.
Article
10. Vink EE, Goldschmeding R, Vink A, Weggemans C, Bleijs RL, Blankestijn PJ. Limited destruction of renal nerves after catheter-based renal denervation: results of a human case study. Nephrol Dial Transplant. 2014; 29:1608–1610. PMID: 24875664.
Article
11. Choe WS, Song WH, Jeong CW, Choi EK, Oh S. Anatomic conformation of renal sympathetic nerve fibers in living human tissues. Sci Rep. 2019; 9:4831. PMID: 30886195.
Article
12. Atherton DS, Deep NL, Mendelsohn FO. Micro-anatomy of the renal sympathetic nervous system: a human postmortem histologic study. Clin Anat. 2012; 25:628–633. PMID: 21976355.
Article
13. Tarzamni MK, Nezami N, Rashid RJ, Argani H, Hajealioghli P, Ghorashi S. Anatomical differences in the right and left renal arterial patterns. Folia Morphol (Warsz). 2008; 67:104–110. PMID: 18521808.
14. Olsen LK, Kamper AL, Svendsen JH, Feldt-Rasmussen B. Renal denervation. Eur J Intern Med. 2015; 26:95–105. PMID: 25676808.
Article
15. Ye E, Baik J, Lee S, Ryu SY, Yang S, Choi EK, et al. Design and simulation of novel laparoscopic renal denervation system: a feasibility study. Int J Hyperthermia. 2018; 35:9–18. PMID: 29772927.
Article
16. Gill IS. Retroperitoneal laparoscopic nephrectomy. Urol Clin North Am. 1998; 25:343–360. PMID: 9633590.
Article
17. Kuntz C, Wunsch A, Bödeker C, Bay F, Rosch R, Windeler J, et al. Effect of pressure and gas type on intraabdominal, subcutaneous, and blood pH in laparoscopy. Surg Endosc. 2000; 14:367–371. PMID: 10790557.
Article
18. Gettman MT, Box G, Averch T, Cadeddu JA, Cherullo E, Clayman RV, et al. Consensus statement on natural orifice transluminal endoscopic surgery and single-incision laparoscopic surgery: heralding a new era in urology? Eur Urol. 2008; 53:1117–1120. PMID: 18304726.
Article
19. Lee JK, Oh JJ, Lee S, Lee SB, Byun SS, Lee SE, et al. A new sliding-loop technique in renorrhaphy for partial nephrectomy: a feasibility study in a porcine model. Surg Innov. 2016; 23:130–133. PMID: 26169258.
20. Jung JW, Cha WH, Lee BK, Lee S, Lee SB, Lee SE, et al. Laparoendoscopic single-site surgery using innovative articulating instruments: preclinical evaluation of the prototype. J Endourol. 2014; 28:281–285. PMID: 24090367.
Article
21. Choi EK, Shen MJ, Han S, Kim D, Hwang S, Sayfo S, et al. Intrinsic cardiac nerve activity and paroxysmal atrial tachyarrhythmia in ambulatory dogs. Circulation. 2010; 121:2615–2623. PMID: 20529998.
Article
22. Táborský M, Richter D, Tonar Z, Kubíková T, Herman A, Peregrin J, et al. 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. Physiol Res. 2017; 66:601–614. PMID: 28406699.
Article
Full Text Links
  • ICU
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr