Robert J. Melder

Evaluation of Polymer-Based Comparator Drug-Eluting Stents Using a Rabbit Model of Iliac Artery Atherosclerosis

Background—Although atherosclerotic models, especially in the rabbit, have existed for a long time, a comparative study of various drug-eluting stent (DES) implantations in atherosclerotic arteries have not been systematically studied. Methods and Results—New Zealand White rabbits (n=44) with induced atheroma received bilateral iliac artery stents: bare metal stent (BMS) (Driver) or a stent eluting zotarolimus (ZES) (Endeavor), sirolimus (SES) (Cypher), or everolimus (EES) (Xience V). After 28 days, tissues were harvested for histomorphometric analyses, en face analysis of endothelial coverage, and expression of endothelial nitric oxide synthase (eNOS). Area measurements of external elastic lamina and stent area were similar. Neointimal area was significantly less in all DES versus BMS, which was least in SES and EES; similar trends were noted for cell proliferation. Uncovered struts were greater for SES and EES and least in BMS, whereas ZES were in between and associated with the least fibrin. Macrophages of the neointima were significantly less for all DES relative to BMS. Plaque calcification underneath stents, however, was significantly greater in SES and ZES than in BMS. Although endothelial coverage in between struts was comparable between BMS and DES, there was significantly greater expression of eNOS in BMS and ZES relative to EES and SES. Conclusions—The rabbit atherosclerotic model of stenting showed delayed healing and significantly greater reduction of neointima following implantation of SES and EES; however, delayed healing was less in ZES with greater neointima (but less than BMS), endothelial regrowth, and eNOS expression.

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.

Efficacy and Safety of Catheter-Based Radiofrequency Renal Denervation in Stented Renal Arteries

Background—In selected patients with hypertension, renal artery (RA) stenting is used to treat significant atherosclerotic stenoses. However, blood pressure often remains uncontrolled after the procedure. Although catheter-based renal denervation (RDN) can reduce blood pressure in certain patients with resistant hypertension, there are no data on the feasibility and safety of RDN in stented RA. Methods and Results—We report marked blood pressure reduction after RDN in a patient with resistant hypertension who underwent previous stenting. Subsequently, radiofrequency ablation was investigated within the stented segment of porcine RA, distal to the stented segment, and in nonstented RA and compared with stent only and untreated controls. There were neither observations of thrombus nor gross or histological changes in the kidneys. After radiofrequency ablation of the nonstented RA, sympathetic nerves innervating the kidney were significantly reduced, as indicated by significant decreases in sympathetic terminal axons and reduction of norepinephrine in renal tissue. Similar denervation efficacy was found when RDN was performed distal to a renal stent. In contrast, when radiofrequency ablation was performed within the stented segment of the RA, significant sympathetic nerve ablation was not seen. Histological observation showed favorable healing in all arteries. Conclusions—Radiofrequency ablation of previously stented RA demonstrated that RDN provides equally safe experimental procedural outcomes in a porcine model whether the radiofrequency treatment is delivered within, adjacent, or without the stent struts being present in the RA. However, efficacious RDN is only achieved when radiofrequency ablation is delivered to the nonstented RA segment distal to the stent.