Laparoscopic-based perivascular renal sympathetic nerve denervation: a feasibility study in a porcine model

Abstract

Background: This study aims to evaluate the effects and safety of laparoscopic-based perivascular renal sympathetic nerve denervation (RDN) in a porcine model fed a high-fat diet. Method: Thirty-six high-fat diet-fed Bama minipigs were randomly divided into an RDN group (n = 18), in which minipigs received laparoscopic-based perivascular RDN, and a sham group (n = 18). All pigs were fed the high-fat diet after the operation to establish a model of obesity-induced hypertension. Bama pigs in the RDN and sham groups were killed at 3 time points [2 days after RDN (n = 6), day 90 (n = 6) and day 180 (n = 6)]. Result: The systolic blood pressure (SBP) and noradrenaline (NE) concentration in the kidney tissue were significantly lower in the RDN group than in the sham group at 2 days (113.83 ± 3.26 mmHg vs 129.67 ± 3.32 mmHg, P = 0.011, and 112.02 ± 17.34 ng/g vs 268.48 ± 20.61 ng/g, P < 0.001, respectively), 90 days (116.83 ± 3.88 mmHg vs 145.00 ± 4.22 mmHg, P = 0.001, respectively) and 180 days (129.33 ± 2.87 mmHg vs 168.57 ± 2.86 mmHg, P < 0.001, and 152.15 ± 16.61 ng/g vs 318.97 ± 24.84 ng/g, P < 0.001, respectively) after the operation. The diastolic blood pressure (DBP) was significantly lower in the RDN group than in sham group at 90 and 180 days after the operation (72.17 ± 2.7 mmHg vs 81.50 ± 2.22 mmHg, P = 0.037, and 76.83 ± 2.75 mmHg vs 86.33 ± 2.22 mmHg P = 0.021, respectively). Based on the pathological evaluation, the renal sympathetic nerve fascicles were successfully disrupted by radiofrequency energy after laparoscopic-based perivascular RDN, but the intima was intact. Tyrosine hydroxylase (TH) expression was decreased, while the expression of the S100 protein was increased in treated renal arteries after RDN. Conclusions: Laparoscopic-based perivascular RDN prevented the occurrence and development of hypertension, and thus it may be an efficient and safe method for controlling blood pressure in an experimental model.

Reply

“…Data from our team's previous studies suggest that intima-RDN may induce or trigger renal artery injury or stenosis. [1][2][3][4] Therefore, similar to the opinion of Dr. Donatella Schiavone and colleagues, even if intima-RDN can control blood pressure, it is not worth promoting.…”

“…It also questions whether the existing RDN from the intima of the renal artery (intima-RDN) can reduce blood pressure and, subsequently, long-term cardiovascular events.Evidently, intimal injury is the initiating factor of atherosclerosis.Data from our team's previous studies suggest that intima-RDN may induce or trigger renal artery injury or stenosis. [1][2][3][4] Therefore, similar to the opinion of Dr. Donatella Schiavone and colleagues, even if intima-RDN can control blood pressure, it is not worth promoting.In 2012, a rare opportunity for our team to implement RDN from the adventitia of the renal artery (adventitia-RDN) in a patient with resistant hypertension produced surprising results. 5 To date, the patient's blood pressure remains well controlled, and he has recovered well from preoperative stroke, cerebral hemorrhage, and neurological dysfunction.…”

“…6,7 Although the antihypertensive mechanism of adventitia-RDN remains unclear, several basic studies from our team and others' have preliminarily explored the feasibility and effectiveness of adventitia-RDN. [1][2][3][4] According to investigations, the mechanisms to consider may involve: (1) The severance of the sympathetic nerve distributed around the renal artery in the process of blunt separation of the renal artery and the exposure of its adventitia; (2) The removal of a part of the renal peripheral adipose tissue, thus reducing its influence in secreting unknown substances, secreted by adipocytes, on the sympathetic nerves; and (3) The reduction in sympathetic neurotransmitter release in the renal artery as adventitia-RDN is more conducive than intima-RDN, as shown by a study, which illustrated the renal sympathetic nerve being mainly distributed in the adventitia of the renal artery. 8 Regarding the inclusion criteria, we complied with the American Heart Association definition of resistant hypertension.…”

Laparoscopic Ablation System for Complete Circumferential Renal Sympathetic Denervation

“…To overcome the shortcomings of the catheter-based RDN, a laparoscopic approach has been introduced as an optimized strategy, which improves the efficacy over catheter-based modality and reduces the invasiveness over the surgical sympathectomy [17,[20][21][22]. The laparoscopic approach, which is a minimally invasive surgery, is operated in the abdomen with small incisions and can directly approach the peripheral regions of the renal arteries.…”

“…The laparoscopic RDN can ablate nerves both at the proximal and distal end of the renal artery, independent of artery size, and reduces thermal damage to the endothelial layer [17]. 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].…”