Comparison of Histopathologic Analysis Following Renal Sympathetic Denervation Over Multiple Time Points

Background-The pathology of radiofrequency-derived sympathetic renal denervation has not been studied over time and may provide important understanding of the mechanisms resulting in sustained blood pressure reduction. The purpose of this study was to investigate chronological changes after radiofrequency-renal denervation in the swine model. Methods and Results-A total of 49 renal arteries from 28 animals with 4 different time points (7, 30, 60, and 180 days) were examined. Semiquantitative histological assessment of arteries and associated tissue was performed to characterize the chronological progression of the radiofrequency lesions. Arterial medial circumferential injury (%) was greatest at 7 days (38 +/- 13%), followed by 30 days (31 +/- 6%) and 60 days (31 +/- 15%), and least at 180 days (21 +/- 12%) (P=0.046). Nerve injury score was significantly greater (P<0.001) at 7 days (3.9 +/- 0.4) compared with 30 days (2.5 +/- 0.5), 60 days (2.6 +/- 0.5), and 180 days (1.9 +/- 0.9). Tyrosine hydroxylase score, which assesses functional nerve damage, was significantly less after 7 (1 +/- 1) and 30 days (0.7 +/- 0.6) compared with 60 (2.7 +/- 0.6) and 180 days (2.7 +/- 0.6; P=0.01). Focal nerve regeneration at the sites of radiofrequency ablation was observed in 17% of renal arteries at 60 days and 71% of 180 days. Conclusions-Nerve injury after radiofrequency ablation was greatest at 7 days, with maximum functional nerve damage sustained <= 30 days. Focal terminal nerve regeneration was observed only at the sites of ablation as early as 60 days and continued to 180 days. Renal artery and peri-arterial soft tissue injury is greatest in the subacute phase, and least in the chronic phase, suggesting gradual recovery of the renal arterial wall and surrounding tissue.