Optimal Strategy for HIFU-Based Renal Sympathetic Denervation in Canines

Abstract

Background: 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.Methods: 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.Results: 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 (p < 0.001).Conclusion: 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.

Non-Invasive Heat-Induced Numerous Tissue Ablation Simulation in a Medical Environment Using Different Focal Length High Intensity Focused Ultrasound Apparatus

“…This analysis also includes the ideal height of each tissue. Tissue heights are 480 mm for the bone, 93 mm for the brain, 120 mm for the heart, 140 mm for kidney, 70 mm for liver and 176 mm for skull respectively [36][37][38]. Figure 4 shows the best positive pressure readings obtained from soft and hard tissues using relative pressure probes.…”

Advances in Renal Denervation in the Treatment of Hypertension

“…Swine or canines were used, because their renal systems are similar to those of humans. Several experimental studies [60][61][62][63][64] have shown that extracorporeal focused ultrasound ablation of the renal artery and nerve is safe and effective.…”