Biological effect on drug distribution and vascular healing via paclitaxel-coated balloon technology in drug eluting stent restenosis swine model.

OBJECTIVES: To evaluate the biological effect of a paclitaxel-coated balloon (PCB) technology on vascular drug distribution and healing in drug eluting stent restenosis (DES-ISR) swine model. BACKGROUND: The mechanism of action and healing response via PCB technology in DES-ISR is not completely understood. METHODS: A total of 27 bare metal stents were implanted in coronary arteries and 30 days later the in-stent restenosis was treated with PCB. Treated segments were harvested at 1 hr, 14 days and 30 days post treatment for the pharmacokinetic analysis. In addition, 24 DES were implanted in coronary arteries for 30 days, then all DES-ISRs were treated with either PCB (n = 12) or uncoated balloon (n = 12). At day 60, vessels were harvested for histology following angiography and optical coherence tomography (OCT). RESULTS: The paclitaxel level in neointimal tissue was about 18 times higher (P = 0.0004) at 1 hr Cmax , and retained about five times higher (P = 0.008) at day 60 than that in vessel wall. A homogenous distribution of paclitaxel in ISR was demonstrated by using fluorescently labeled paclitaxel. Notably, in DES-ISR, both termination OCT and quantitative coronary angioplasty showed a significant neointimal reduction and less late lumen loss (P = 0.05 and P = 0.03, respectively) post PCB versus post uncoated balloon. The PES-ISR + PCB group displayed higher levels of peri-strut inflammation and fibrin scores compared to the -limus DES-ISR + PCB group. CONCLUSIONS: In ISR, paclitaxel is primarily deposited in neointimal tissue and effectively retained over time following PCB use. Despite the presence of metallic struts, a uniform distribution was characterized. PCB demonstrated an equivalent biological effect in DES-ISR without significantly increasing inflammation. © 2015 Wiley Periodicals, Inc.

Comparison of the vascular responses to balloon-expandable stenting in the coronary and peripheral circulations: long-term results in an animal model using the TriMaxx stent.

OBJECTIVE: The clinical results after stenting in the coronary and peripheral circulations are vastly different. Possible explanations for this discrepancy include generally longer and more complex lesions in the periphery, variable vascular responses to injury according to anatomic location, disparate blood flow rates, and impedance in coronary vs skeletal smooth muscle beds, or phenotypic differences in neointimal hyperplasia and remodeling. This study examined the long-term results (6 months) after implantation of phosphorylcholine-coated balloon-expandable stents in a porcine model of experimental in-stent coronary and peripheral arterial restenosis. METHODS: Forty-eight stainless steel-tantalum-stainless steel composite balloon-expandable stents coated with phosphorylcholine (TriMaxx stent, Abbott Laboratories, Abbott Park, Ill) were implanted in the coronary (3.0 x 15 mm) or larger femoral arteries (4.0 x 38 mm) of Yorkshire crossbred swine to achieve a 1.1:1 stent-to-artery ratio. After 28, 90, or 180 days, the arteries were excised, perfusion-fixed at 100 mm Hg, sectioned, and stained with hematoxylin and eosin for morphometric evaluation. RESULTS: One animal did not survive to euthanasia; all arteries in surviving animals were patent. No significant differences were found in mean injury or inflammation scores among the groups or time points. The larger femoral arteries generated more neointimal area over time than the coronary arteries. The neointimal area in coronary arteries was 2.76 +/- 0.71, 1.75 +/- 0.42, and 1.83 +/- 0.19 mm(2) at 28, 90, and 180 days, respectively, and 5.20 +/- 0.97, 3.11 +/- 0.53, and 5.10 +/- 0.80 mm(2) in the femoral arteries (P < .05 coronary vs femoral at 180 days). This led to statistically significantly increased percent area stenosis at 180 days (coronary 27% +/- 4% vs femoral 45% +/- 5%; P < .05). CONCLUSIONS: The vascular response to balloon-expandable stenting in the coronary and peripheral circulations is different. After 6 months, neointimal hyperplasia and stent-induced stenosis were increased in peripheral porcine arteries compared with coronary arteries.