Effects of external crushing forces on a novel below-the-knee vascular implant.

Background: The Tack Endovascular System is a novel vascular implant designed to focally treat dissections with low radial force and minimal metal burden. As there are currently no approved below-the-knee (BTK) implants in the USA, a unique, 3-stage model was developed to characterize crush deformation and fracture potential of the Tack Endovascular System in BTK arteries.

Methods: First, 35 Tack implants were deployed bilaterally in the posterior tibial, anterior tibial, and peroneal arteries of 3 cadavers, and clinically relevant external forces were applied to simulate BTK crushing deformation including focal load, leg crossing, and leg bending.

An Animal Model of Human Peripheral Arterial Bending and Deformation.

Background: Designing peripheral arterial stents has proved challenging, as implanted devices will repetitively and unpredictably deform and fatigue during movement. Preclinical testing is often inadequate, given the lack of relevant animal models. The purpose of this study was to test the hypothesis that deformation of the human peripheral vasculature could be qualitatively and quantitatively modeled using an experimental animal.

Calcified plaque modification alters local drug delivery in the treatment of peripheral atherosclerosis.

Background: 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.

Assessment of self-expanding nitinol stent deformation after chronic implantation into the femoropopliteal arteries.

Aims: The purpose of this prospective clinical investigation was to quantify the degree and range of compressive and bending deformations sustained by self-expanding nitinol stents when implanted into the femoropopliteal arteries of patients with symptomatic peripheral vascular disease (PVD).

Methods And Results: Twenty-three nitinol self-expanding stents (Absolute; Abbott Vascular, Santa Clara, CA, USA) with diameters ranging from 5-10 mm and lengths ranging from 40-100 mm were implanted in 19 lesions in 18 extremities of 17 patients. Two days following implantation, in vivo stent compression and bending were assessed by measurement of stent length and deflection angle via lateral view radiographs.

Mechanisms of tissue uptake and retention in zotarolimus-coated balloon therapy.

Background: Drug-coated balloons are increasingly used 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.

Inhibition of experimental neointimal hyperplasia and neoatherosclerosis by local, stent-mediated delivery of everolimus.

Introduction: A novel self-expanding, drug-eluting stent (DES) was designed to slowly release everolimus in order to prevent restenosis after percutaneous peripheral intervention. The purpose of this experimental animal study was to test the hypothesis that long-term local, stent-mediated delivery of everolimus would reduce neointimal hyperplasia in porcine iliac arteries.

Methods: The iliac arteries of 24 Yucatan mini-swine were percutaneously treated with overlapping 8- × 28-mm self-expanding nitinol stents loaded with everolimus (225 μg/cm2 stent surface area) formulated in a poly(ethylene-co-vinyl alcohol) copolymer intended to deliver the drug in a sustained fashion over about 6 months (DES).

Vascular response to zotarolimus-coated balloons in injured superficial femoral arteries of the familial hypercholesterolemic Swine.

Background: Drug-coated balloons are rapidly emerging as a therapeutic alternative for the interventional treatment of peripheral vascular disease. The purpose of this study was to test the hypothesis that an angioplasty balloon coated with the mTOR inhibitor zotarolimus (ZCB) would inhibit neointimal hyperplasia in a novel injury-based superficial femoral artery model in the familial hypercholesterolemic swine.

Methods And Results: A total of 44 familial hypercholesterolemic swine were included (12 designated to study tissue pharmacokinetics and 32 to study safety and efficacy).

Respiration-induced kidney motion on cobalt-chromium stent fatigue resistance.

During normal breathing, the kidneys move up and down due to the diaphragm motion and the renal artery subsequently experiences bending at or close to its point of fixation to the aorta. The impact of this kidney motion on implanted stent fatigue performance was not well understood in the past. Previous study from the authors on an 18-mm long single cobalt-chromium stent showed that the change in bending angle was minor during simulated respiration-induced kidney motion on cadavers.

Late stent expansion and neointimal proliferation of oversized Nitinol stents in peripheral arteries.

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.

Fracture of self-expanding nitinol stents stressed in vitro under simulated intravascular conditions.

Objective: The use of intravascular stents in the superficial femoral artery (SFA) continues to be controversial due to the potential for compression and fracture in the tortuous physical environment of the adductor canal. The purpose of this study was to (1) characterize the types and ranges of stent distortion theoretically produced by extremity movement and (2) use these ranges as parameters for in vitro long-term fatigue testing of commercially available self-expanding nitinol stents.

Methods: Nitinol self-expanding stents were placed in the SFAs of cadavers and lateral view radiographs were obtained with the limb in various degrees of hip and knee flexion.

Sustained high-level expression of human factor IX (hFIX) after liver-targeted delivery of recombinant adeno-associated virus encoding the hFIX gene in rhesus macaques.

The feasibility, safety, and efficacy of liver-directed gene transfer was evaluated in 5 male macaques (aged 2.5 to 6.5 years) by using a recombinant adeno-associated viral (rAAV) vector (rAAV-2 CAGG-hFIX) that had previously mediated persistent therapeutic expression of human factor IX (hFIX; 6%-10% of physiologic levels) in murine models.