Anatomic Conformation of Renal Sympathetic Nerve Fibers in Living Human Tissues

Abstract

Renal denervation using radiofrequency catheter ablation is known to eliminate the renal sympathetic nerve and to lower blood pressure in patients with resistant hypertension. We sought to investigate the detailed anatomic conformation of the peri-renal arterial sympathetic nerve fibers with living human specimens. Peri-renal arterial tissue was harvested from patients undergoing elective radical or simple nephrectomy. Digital images of each section from the distal arterial bifurcation to the proximal margin were obtained and analyzed after immunohistochemical staining with anti-tyrosine hydroxylase antibodies. A total of 3,075 nerve fibers were identified from 84 sections of peri-renal arterial tissue from 28 patients (mean age 62.5 ± 10.2 years, male 68%). Overall, 16% of nerve fibers were located at distances greater than 3 mm from the endoluminal surface of the renal artery. The median distance from the arterial lumen to the nerve fibers of the proximal, middle, and distal renal arterial segments was 1.51 mm, 1.48 mm, and 1.52 mm, respectively. The median diameter of the nerve fibers was 65 μm, and there was no significant difference between the segments. A substantial proportion of the sympathetic nerve fibers were located deeper in the peri-arterial soft tissue than in the lesion depth created by the conventional catheter-based renal sympathetic denervation system.

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

“…In addition, because the sympathetic nerve fibers around the renal artery were distributed far from the arterial wall, a catheter-based ablation would not be sufficiently effective [10]. In our animal model and human tissue studies, we found that the sympathetic nerve fibers were located 3 to 5 mm from the luminal surface and 8 mm from the center of the renal artery [11,12]. In addition, according to renal angiographic studies using computed tomography angiography, more than 30% of patients had anatomical variants of renal arteries, such as an accessory artery and early branching arteries [13].…”

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

“…In addition, the system is flexible and adaptable and thus can accommodate renal sympathetic nerves plexus of various sizes. Since the system has the ability to accesses sympathetic nerve directly, it can treat sympathetic nerves located in any proximity of renal artery, e.g., nerves located far from the lumen in the proximal segment of a renal artery, nerves located close to the arterial wall, and nerves inside tunica adventitia of artery [21]. The previous approach, such as the catheter-based RDN, does not have such flexibility and were of limited use.…”

“…In in-vivo simulation, the artery 3D, as shown in Fig. 5 was designed based on previous histological studies where the diameter of the artery, the diameter of the lumen, and thickness of the artery wall were 5 mm, 2mm, and 1.5 mm, respectively [17,21]. The arterial wall was composed of tunica media and adventitia.…”

“…We set 50 ℃ as an isothermal line, which is the thermal lesion boundary, or a nonviable volume [27]. Typically the renal nerves distributed in tunica adventitia and periarterial connective tissue [20,21]. Therefore, the ideal thermal lesion boundary should be located in the border between tunica media and adventitia while preventing thermal damage to tunica intima or lumen.…”

“…While it cannot be generalized, the lesion depth for the catheter-based RDN was found to be about 2 mm for a cadaver [16] and 6 mm for animal models [17][18][19] from multiple studies, but 31% of renal nerves are located 2-10 mm away from the endoluminal surface [20,21]. Thus, it cannot completely ablate renal sympathetic nerves outside the arterial wall.…”