Neuromatous regeneration as a nerve response after catheter-based renal denervation therapy in a large animal model: immunohistochemical study.

BACKGROUND: Renal denervation (RDN) emerged as a therapeutic option for resistant hypertension. Nerve regrowth after RDN has been questioned. We aimed to characterize the nerve response after RDN. METHODS AND RESULTS: Swine underwent bilateral RDN and were followed up for 7, 30, and 90 days and evaluated with S100 (Schwann cell), tyrosine hydroxylase (TH; efferent nerves), and growth-associated protein 43 (neurite regeneration) markers. At 7 days, nerve changes consisted of necrosis associated with perineurial fibrosis and distal atrophy with inflammation. At 30 days changes were substituted by healing changes (ie, fibrosis). This response progressed through 90 days resulting in prominent neuroma formation. Immunohistochemistry at 7 days: TH staining was strongly decreased in treated nerves. Early regenerative attempts were observed with strongly TH and growth-associated protein 43 positive and weak S100 disorganized nerve sprouts within the thickened perineurium. Distal atrophic nerves show weak staining for all 3 markers. At 30 days, affected nerves show a weak TH and S100 staining. Evident growth-associated protein 43+ disorganized neuromatous tangles in the thickened perineurium of severed nerves were observed. At 90 days, some TH expression was observed together with prominent S100+ and growth-associated protein 43+ neuromatous tangles with disorganized architecture. The potential for regenerative activity is unlikely based on the disrupted architecture of these neuromatous tangles at the radiofrequency lesion sites. CONCLUSIONS: This study is the first documentation that a progressive regenerative response occurs as early as 7 days after RDN, resulting in a poorly organized neuromatous regeneration. This finding is of paramount importance to further establish the potential functional significance of a regeneration after RDN.

Vasomotor function after paclitaxel-coated balloon post-dilation in porcine coronary stent model.

OBJECTIVES: The purpose of this study was to evaluate endothelial function after post-dilation of bare-metal stents with paclitaxel-coated balloons (PCB) or non-drug-coated balloons (non-DCB) in a porcine model. BACKGROUND: DCB are an attractive alternative to drug-eluting stents because they provide short duration of drug exposure, while potentially inhibiting in-stent restenosis. Drug-eluting stents are associated with impaired endothelial function. It is unknown whether this abnormal vasomotor function is mitigated by reduced duration of drug exposure. METHODS: Thirteen pigs underwent bare-metal stent implantation (arteries, n = 30), followed by post-dilation with either PCB (SeQuent Please, B. Braun Melsungen AG, Berlin, Germany) (n = 17) or non-DCB (n = 13). Five pigs with unstented arteries (n = 14) were controls. Coronary vasomotion was assessed 1 month after stent implantation, using acetylcholine (Ach) and nitroglycerin. Measurements were obtained for distal segments. RESULTS: Angiographic late loss and histological area stenosis were similar between PCB and non-DCB. However, the percentage of diameter change in response to Ach was diminished with PCB (p < 0.05), when compared with either non-DCB or naive arteries. There was no difference between non-DCB and naive arteries. Inflammatory score and intramural fibrin grading were significantly greater in PCB than non-DCB (p < 0.05). Additionally, inflammatory cell infiltration in the stented segments correlated with the degree of percentage of diameter change in response to Ach, at distal regions. CONCLUSIONS: Post-dilation of bare-metal stents with PCB was associated with impaired vasodilatory response to Ach distal to the treated segments. Vasodilatory response after post-dilation with non-DCB was similar to control arteries.