Randomised, blinded and controlled comparative study of chemical and radiofrequency-based renal denervation in a porcine model.

AIMS: The blood pressure-lowering effect of percutaneous renal denervation (RDN) is controversial. The success of RDN may be device-dependent. We sought to compare the efficacy of RDN by chemical neurolysis using alcohol (Peregrine System Infusion Catheter; Ablative Solutions, Inc., Menlo Park, CA, USA) to RDN by radiofrequency (RF) ablation with the single-electrode RF catheter (Symplicity Flex; Medtronic, Minneapolis, MN, USA) in a porcine model. METHODS AND RESULTS: This was a prospective, randomised, blinded study. Pigs were assigned to undergo bilateral RF ablation or chemical neurolysis. Primary endpoints were ablation depth and renal tissue norepinephrine (NE) concentrations at three-month follow-up. Twelve pigs underwent RF ablation (n=4) or chemical neurolysis by infusion of 0.3 mL (n=4) or 0.6 mL (n=4) alcohol. Ninety days after RF ablation and chemical neurolysis with 0.3 mL and 0.6 mL of alcohol, mean maximal tissue injury depth was 3.9±1.2 mm, 6.6±1.7 mm and 8.2±2.2 mm, respectively (p<0.001 for either dose of alcohol vs. RF ablation). Compared with historical controls, median renal tissue NE concentration reductions were 66%, 78% and 83% after RF ablation and chemical neurolysis using 0.3 mL and 0.6 mL alcohol, respectively (p=0.107 for chemical neurolysis vs. RF ablation). Mean total ablation area was significantly greater in both (0.3 mL and 0.6 mL) alcohol groups (p=0.0001 for both) than the RF ablation group (30.8±13.7 mm2, 41.6±12.4 mm2 and 11.0±7.5 mm2, respectively). CONCLUSIONS: RDN is more effective using chemical neurolysis than single-electrode RF ablation. Our findings suggest that the efficacy of RDN may be device-dependent.

Ethanol-mediated perivascular renal sympathetic denervation: preclinical validation of safety and efficacy in a porcine model.

AIMS: We report the use of a novel endovascular approach using chemical neurolysis, via periadventitial injection of dehydrated ethanol (EtOH) to perform renal artery denervation. METHODS AND RESULTS: A novel, three-needle delivery device was introduced into the renal arteries of adult swine using fluoroscopic guidance. EtOH was injected bilaterally with one injection per artery, via the three needles into the adventitial and periadventitial space, using EtOH doses 0.15 ml/artery; n=3, 0.30 ml/artery; n=3, and 0.60 ml/artery; n=3, with saline injection as a sham control (0.4 ml/artery; n=3), and naive subjects (n=7) as a true negative control. The renal parenchymal norepinephrine (NE) concentration at two-week follow-up was the primary efficacy endpoint. The mean renal NE reduction was 54%, 78% and 88% at doses of 0.15 ml, 0.30 ml and 0.60 ml, respectively (p<0.0001 vs. controls). Histological examination revealed marked, and deep, circumferential renal nerve injury at depths of 2-8 mm from the intimal surface. There was no evidence of device-related or EtOH-induced injury to the intimal layers. In some samples at the higher EtOH doses, there was focal loss of smooth muscle cells in the outer media. Angiography at 45 days demonstrated normal appearing renal arteries with no detectable stenoses (n=8). CONCLUSIONS: Circumferential adventitial delivery of very low doses of EtOH may be a promising alternative to energy-based systems to achieve dose-dependent, and predictable renal denervation. Further study is warranted.