Liao Qingyao, Yang Fang, Xiong Bo, Zheng Xiaoyu, Wang Yue, Qian Jun, Qiao Zhao, Huang Jing
Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Department of Clinical Medicine, Chongqing Medical and Pharmaceutical College, Chongqing, China.
Front Cardiovasc Med. 2021 Oct 14;8:739560. doi: 10.3389/fcvm.2021.739560. eCollection 2021.
The association between the treatment efficacy and safety of high-intensity focused ultrasound (HIFU)-based renal sympathetic denervation (RDN) and the acoustic energy dose applied has not been fully studied and may provide important understanding of the mechanism that led to failure of the WAVE IV trial. The objective of this study was to externally deliver different HIFU doses to canines for RDN treatment and to investigate the optimal energy dose for HIFU-based RDN. Thirty canines were divided into five RDN groups according to dose of acoustic energy applied, and a sham control group that consisted of four canines was used for comparisons. All animals in the RDN groups underwent the RDN procedure with different acoustic energy doses, while in the sham control group, renal arteries were harvested without being subjected to acoustic energy delivery and were imaged using color Doppler flow imaging (CDFI). Blood pressure (BP) was recorded, and blood samples were collected before the RDN procedure and at 28 days after the RDN procedure. Histological examinations and measurement of renal tissue norepinephrine concentration were performed in all retrieved samples. Suppression of BP was significant in the 300 W (15.17/8.33 ± 1.47/1.21 mmHg), 250 W (14.67/9.33 ± 1.21/1.37 mmHg), and 200 W (13.17/9.17 ± 2.32/1.84 mmHg) groups. Semiquantitative histological assessment of periarterial nerves around the kidney revealed that target nerves in the 300 W (9.77 ± 0.63), 250 W (9.42 ± 0.67), and 200 W (9.58 ± 0.54) groups had the highest nerve injury scores, followed by the 150 W group (5.29 ± 0.62). Furthermore, decreased renal tissue norepinephrine concentration, together with decreased expression of tyrosine hydroxylase in the 300, 250, and 200 W groups demonstrated effective sympathetic depression following sufficient acoustic energy deposition. However, the renal artery injury score in the 300 W group (0.93 ± 0.13) was significantly higher than in the other groups ( < 0.001). This study provides evidence that RDN effectiveness is based on the energy dose delivered and that 200-250 W is effective and safe in normal-sized canines.
基于高强度聚焦超声（HIFU）的肾交感神经去支配术（RDN）的治疗效果与安全性和所施加的声能剂量之间的关联尚未得到充分研究，这可能有助于深入理解导致WAVE IV试验失败的机制。本研究的目的是向犬只体外施加不同的HIFU剂量以进行RDN治疗，并探究基于HIFU的RDN的最佳能量剂量。30只犬根据所施加的声能剂量分为五个RDN组，并使用一个由4只犬组成的假手术对照组进行比较。RDN组中的所有动物均接受了不同声能剂量的RDN手术，而在假手术对照组中，采集了采集肾动脉但不施加声能，并使用彩色多普勒血流成像（CDFI）进行成像。记录血压（BP），并在RDN手术前和RDN手术后28天采集血样。对所有取回的样本进行组织学检查并测量肾组织去甲肾上腺素浓度。在300W（15.17/8.33±1.47/1.21mmHg）、250W（14.67/9.33±1.21/1.37mmHg）和200W（13.17/9.17±2.32/1.84mmHg）组中，血压抑制显著。对肾周围动脉周围神经的半定量组织学评估显示，300W（9.77±0.63）、250W（9.42±0.67）和200W（9.58±0.54）组的靶神经具有最高的神经损伤评分，其次是150W组（5.29±0.62）。此外，300、250和200W组中肾组织去甲肾上腺素浓度降低，同时酪氨酸羟化酶表达降低，表明在足够的声能沉积后交感神经受到有效抑制。然而，300W组的肾动脉损伤评分（0.93±0.13）显著高于其他组（<0.001）。本研究提供了证据，表明RDN的有效性基于所传递的能量剂量，并且200 - 250W在正常体型的犬中是有效且安全的。
