Abstract P245: Catheter-based Radiofrequency Renal Denervation In Normotensive Pigs Leads To Long-term Pathological Changes In Renal Nerves

Abstract

Objective: Pre-clinical data of renal nerve regrowth following radiofrequency (RF) renal denervation (RDN) are lacking. In this analysis of RF RDN in normotensive pigs, we assessed the specificity and durability of RF ablation to the perivascular tissues around the renal arteries. Design and Method: RF ablations were delivered to the renal arteries in pigs. To assess specificity, serial tissue samples were harvested from 6 pigs at day 7, and 8 pigs at day 28. Surrounding tissues (ureter, kidney, lymph nodes, skeletal muscle, adrenal glands, and renal nerves) were evaluated with a semi-quantitative scoring system ( Figure ). To assess durability, RF RDN was performed in a separate group of pigs with an additional control group. Serial tissue examination at day 7 (n=6 animals per group) and day 180 (n=8 per group) included quantification of cortical norepinephrine (NE) levels and renal cortical axon density, and evaluation for fibrosis, necrosis, and nerve fiber atrophy. Results: Disruption to non-target perivascular tissues was rare, whereas artery nerve disruption and axonal loss were sustained through 28 days ( Figure ). At 180 days, there was nerve atrophy from axonal destruction around the ablation regions. Necrosis was evident at day 7 but not day 180. Fibrosis was confined to the ablated regions. Renal cortical axon density and cortical NE levels were significantly reduced at 7 and 180 days in the RDN group vs. control. Conclusion: RF RDN specifically disrupted the renal nerves leading to axonal loss. Cortical axon density, NE reduction, and nerve atrophy were sustained through 180 days. These results support the existing clinical evidence of the specificity and durability of RF RDN.