For peripheral endovascular intervention, self-expanding (SE) stents are commonly oversized in relation to target arteries to assure optimal wall apposition and prevent migration. However, the consequences of oversizing have not been well studied. The purpose of this study was to examine the effects of SE stent oversizing (OS) with respect to the kinetics of late stent expansion and the long-term histological effects of OS. Pairs of overlapped 8 x 28-mm Nitinol SE stents were implanted into the iliofemoral arteries of 14 Yucatan swine. Due to variations in target artery size, the stent-to-artery ratio ranged from 1.2:1 to 1.9:1. Lumen and stent diameters were assessed by quantitative angiography at the time of implantation. Following angiographic assessment at 6 months, stented arteries were perfusion-fixed, sectioned, and stained for histological analysis. Immediately following implantation, the stents were found to be expanded to a range of 4.7-7.1 mm, largely conforming to the diameter of the recipient target artery. The stents continued to expand over time, however, and all stents had enlarged to nearly their 8-mm nominal diameter by 6 months. The histological effects of OS were profound, with marked increases in injury and luminal area stenosis, including a statistically significant linear correlation between stent-to-artery ratio and area stenosis. In this experimental model of peripheral endovascular intervention, oversized Nitinol SE stents are constrained by their target artery diameter upon implantation but expand to their nominal diameter within 6 months. Severe OS (stent-to-artery ratio >1.4:1) results in a profound long-term histological response including exuberant neointimal proliferation and luminal stenosis.

Nitinol self-expanding stents undergo both axial and bending deformation when implanted into the superficial femoral and popliteal arteries. Commercially available stents exhibit a variable ability to withstand chronic deformation in vitro, and their response is highly dependent on the type of deformation applied.

A B S T R A C TBackground: Calcific atherosclerosis is a major challenge to intraluminal drug delivery in peripheral artery disease (PAD). Objectives: We evaluated the effects of orbital atherectomy on intraluminal paclitaxel delivery to human peripheral arteries with substantial calcified plaque. Methods: Diagnostic angiography and 3-D rotational imaging of five fresh human lower limbs revealed calcification in all main arteries. The proximal or distal segment of each artery was treated using an orbital atherectomy system (OAS) under simulated blood flow and fluoroscopy. Explanted arterial segments underwent either histomorphometric assessment of effect or tracking of 14 C-labeled or fluorescent-labeled paclitaxel.Radiolabeled drug quantified bulk delivery and fluorescent label established penetration of drug over finer spatial domain in serial microscopic sections. Results were interpreted using a mathematical model of bindingdiffusion mediated arterial drug distribution. Results: Lesion composition affected paclitaxel absorption and distribution in cadaveric human peripheral arteries. Pretreatment imaging calcium scores in control femoropopliteal arterial segments correlated with a loglinear decline in the bulk absorption rate-constant of 14 C-labeled, declining 5.5-fold per calcified quadrant (p = 0.05, n = 7). Compared to controls, OAS-treated femoropopliteal segments exhibited 180 μm thinner intima (p < 0.001), 45% less plaque calcification, and 2 log orders higher paclitaxel bulk absorption rate-constants. Correspondingly, fluorescent paclitaxel penetrated deeper in OAS-treated femoropopliteal segments compared to controls, due to a 70% increase in diffusivity (p < 0.001).Conclusions: These data illustrate that calcified plaque limited intravascular drug delivery, and controlled OAS treatment of calcific plaques resulted in greater drug permeability and improved adjunct drug delivery to diseased arteries.

Background Drug-coated balloons are increasingly utilized for peripheral vascular disease and yet, mechanisms of tissue uptake and retention remain poorly characterized. Most systems to date have used Paclitaxel, touting its propensity to associate with various excipients that can optimize its transfer and retention. We examined Zotarolimus pharmacokinetics. Methods and results Animal studies, bench-top experiments and computational modeling were integrated to quantify arterial distribution after Zotarolimus-coated balloon (ZCB) use. Drug diffusivity and binding parameters for use in computational modeling were estimated from kinetics of Zotarolimus uptake into excised porcine femoral artery specimens immersed in radiolabeled drug solutions. Like Paclitaxel, Zotarolimus exhibited high partitioning into the arterial wall. Exposure of intimal tissue to drug revealed differential distribution patterns, with Zotarolimus concentration decreasing with transmural depth as opposed to multiple peaks displayed by Paclitaxel. Drug release kinetics was measured by inflating ZCBs in whole blood. In vivo drug uptake in swine arteries increased with inflation time but not with balloon size. Simulations coupling transmural diffusion and reversible binding to tissue proteins predicted arterial distribution that correlated with in vivo uptake. Diffusion governed drug distribution soon after balloon expansion but binding determined drug retention. Conclusions Large bolus of Zotarolimus releases during balloon inflation, some of which pervades the tissue and a fraction of the remaining drug adheres to the tissue-lumen interface. As a result, duration of delivery modulates tissue uptake where diffusion and reversible binding to tissue proteins determine drug transport and retention, respectively.