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Radiofrequency renal denervation (RDN) is under investigation for treatment of hypertension with variable success. We developed preclinical models to examine the dependence of ablation biomarkers on RDN treatment parameters and anatomical variables. 129 porcine renal arteries were denervated with an irrigated RF catheter with multiple helically arrayed electrodes. Nerve effects and ablation geometries at 7d were characterized histomorphometrically and correlated with associated renal norepinephrine (NEPI) levels. NEPI exhibited a threshold dependence on the percentage of affected nerves (%AN) across the range of treatment durations (30–60sec) and power set-points (6–20W). For 15W/30sec treatments, NEPI reduction and %AN tracked with number of electrode treatments, confirming additive effects of helically staggered ablations. Threshold effects were only attained when ≥four electrodes were powered. Histomorphometry and computational modeling both illustrated that RF treatments directed at large neighboring veins resulted in sub-average ablation areas, and therefore contributed suboptimally to efficacy. Account for measured nerve distribution patterns and the annular geometry of the artery revealed that, regardless of treatment variables, total ablation area and circumferential coverage were the prime determinants of RDN efficacy, with increased efficacy at smaller diameters. SUMMARY: Large animal experiments supported by computational and statistical models that account for arterial microanatomy and nerve distribution explain the dependence of RDN efficacy on procedural parameters, e.g. number of electrode treatments, and anatomic parameters, e.g. arterial diameter and the proximity of veins to ablation sites.

Background— The long-term efficacy of radiofrequency ablation of renal autonomic nerves has been proven in nonrandomized studies. However, long-term safety of the renal artery (RA) is of concern. The aim of our study was to determine if cooling during radiofrequency ablation preserved the RA while allowing equivalent nerve damage. Methods and Results— A total of 9 swine (18 RAs) were included, and allocated to irrigated radiofrequency (n=6 RAs, temperature setting: 50°C), conventional radiofrequency (n=6 RAs, nonirrigated, temperature setting: 65°C), and high-temperature radiofrequency (n=6 RAs, nonirrigated, temperature setting: 90°C) groups. RAs were harvested at 10 days, serially sectioned from proximal to distal including perirenal tissues and examined after paraffin embedding, and staining with hematoxylin-eosin and Movat pentachrome. RAs and periarterial tissue including nerves were semiquantitatively assessed and scored. A total of 660 histological sections from 18 RAs were histologically examined by light microscopy. Arterial medial injury was significantly less in the irrigated radiofrequency group (depth of medial injury, circumferential involvement, and thinning) than that in the conventional radiofrequency group ( P P =0.003 for thinning). Severe collagen damage such as denatured collagen was also significantly less in the irrigated compared with the conventional radiofrequency group ( P P =0.36), there was a trend toward less nerve damage in the irrigated compared with conventional. Compared to conventional radiofrequency, circumferential medial damage in highest-temperature nonirrigated radiofrequency group was significantly greater ( P Conclusions— Saline irrigation significantly reduces arterial and periarterial tissue damage during radiofrequency ablation, and there is a trend toward less nerve damage.