Detrusor nerve radiofrequency ablation (DENERA): Experimental study of safety and efficacy in an ovine model.

PURPOSE: The subtrigonal perivesical nerve plexus contains a large proportion of the bladder's innervation. A transurethral radiofrequency ablation approach has successfully denervated this region to alleviate overactive bladder symptoms, with some urothelial heat injury. We report a novel transvaginal RFA device (DENERA) and assess its feasibility and efficacy in denervating the perivesical nerve plexus of in vivo sheep. METHODS: In 14 adult female in vivo sheep, pulsed radiofrequency energy was applied transvaginally for three cycles of 4 min, maintaining the tissue temperature at 45°C, with 30 s of rest between each cycle. The control group (n = 4) was sacrificed without ablation, and various groups were sacrificed 1 week (n = 3), 4 weeks (n = 4), and 12 weeks (n = 3) after ablation. The bladder subtrigones were harvested then analyzed with H&E, S100, and TH immunostaining to quantify their neural density and neural vacuolization. RESULTS: The ablation procedure increased the neural vacuolization the most at 1 week and decreased the neural density the most at 4 weeks, with both variables displaying a significant change followed by a slight rebound towards baseline at 12 weeks. The H&E analysis showed that the needles penetrated deep into the subtrigonal detrusor muscle. The sheep recovered from the procedure with no complications or damage in the bladder wall or urothelium. CONCLUSIONS: This study shows that one DENERA treatment can cause subtrigonal denervation with some rebound afterwards and no complications. DENERA may become a promising OAB treatment option that can ablate the perivesical plexus without harming the urothelium.

Initial Evaluation of a Novel Modulated Radiofrequency-based Bladder Denervation Device.

OBJECTIVE: To determine if targeted and modulated radiofrequency ablation (RFA) of the urinary bladder using our novel ablation device (Denerblate) reduces bladder nerve density, potentially leading to a novel strategy for the management of overactive bladder. METHODS: Fifteen pigs were divided into 4 groups: control (n = 3), 1-week (n = 4), 4-week (n = 4) and 12-week (n = 4) survival times. Denerblate was deployed on the trigone area of the bladder. Three 240-second cycles of modulated RFA were applied with 30 seconds between cycles. At the end of each survival term, urinary bladders were harvested for histopathologic evaluation. Nerve count and density were manually calculated. RESULTS: All procedures were successfully completed, and all animals survived to the desired time points. Mean nerve density (nerves/mm2) was highest in the control and 1-week survival group compared to the 4-week and 12-week groups, both of which demonstrated significant diminishment. Nerve density in the bladder neck at control, 1 week, 4 weeks, and 12 weeks were 1.8, 1.35, 0.87, and 0.12, respectively (P <.001). Nerve density in the bladder trigone area at control, 1 week, 4 weeks, and 12 weeks were 1.5, 0.98, 0.65, and 0.112, respectively (P <.001). Epithelial heat injury was observed in 14.3% at 1 week, 10.7% at 4 weeks, but completely resolved by 12 weeks. CONCLUSION: In the porcine model, modulated RFA delivered by our novel device reduced nerve density in the bladder neck and trigone by 88.6% and 88.9% at 12 weeks without evidence of lasting epithelial injury.