<b>Commentary: Rat Restenosis Models:</b>Means for Thorough Restenosis Research

Langeveld, Bas; Roks, Anton J.M.

doi:10.1583/04-1466.1

Cited by 4 publications

(3 citation statements)

References 20 publications

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“…75,79,133 The rates of vascular healing in rat carotid arterial and aortic models appear to parallel those of models utilizing larger species qualitatively; however, the vascular response in the rat has similar salient features as mice, including only sparse thrombus formation and fibrin deposition, minimal inflammation, and a lack of remodeling. 11,77,104,105,186 Murine models have promise for elucidating pathophysiologic mechanisms related to atherosclerosis and ISR; nonetheless, the cumulative shortcomings of these models warrant their careful application and critical interpretation. First, murine arteries suitable for the evaluation of ISR are mostly elastic, which are less prone to injury and have only modest neointimal responses following vascular injury when compared to muscular arteries.…”

Section: Rodentsmentioning

confidence: 99%

Preclinical Models of Restenosis and Their Application in the Evaluation of Drug-Eluting Stent Systems

Perkins

2010

Vet Pathol

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Coronary arterial disease (CAD) is the leading cause of death in the United States, the European Union, and Canada. Percutaneous coronary intervention (PCI) has revolutionized the treatment of CAD, and it is the advent of drug-eluting stent (DES) systems that has effectively allayed much of the challenge of restenosis that has plagued the success of PCI through its 30-year history. However, DES systems have not been a panacea: There yet remain the challenges associated with interventions involving bare metallic stents as well as newly arisen concerns related to the application of DES systems. To effectively address these novel and ongoing issues, animal models are relied on both to project the safety and efficacy of endovascular devices and to provide insight into the pathophysiology underlying the vascular response to injury and mechanisms of restenosis. In this review, preclinical models of restenosis are presented, and their application and limitation in the evaluation of device-based interventional technologies for the treatment of CAD are discussed.Keywords restenosis, stent, animal models, coronary artery disease Coronary artery disease (CAD) is the progressive accumulation of atherosclerotic plaque within the lumen of a coronary artery, with the typical result being luminal narrowing, reduced compliance of the vessel wall, and either a gradual reduction or a dramatic and sudden loss of blood supply to the myocardium. It is the leading cause of death in the United States, the European Union, and Canada, singly accounting for the death of 1 in 5 Americans. 117,185 In treatment options for symptomatic CAD, percutaneous coronary intervention (PCI) is the foremost modality, being based on the nonsurgical placement of a bare metallic scaffold, or stent, to prop open the artery to regain patency. However, there are drawbacks to coronary stenting, with restenosis being the Achilles' heel, accounting for a rate of failure up to 15 to 25%.18,124 Drug-eluting stents (DESs) have revolutionized PCI by effectively reducing restenosis rates to the single digits over standard bare metallic stents.DES systems combine mechanical and pharmacological approaches to assuage one or more events in the cascade that results in restenosis. These combination products consist of an intravascular scaffolding device that presents or releases single or multiple bioactive agents or pharmaceuticals into the bloodstream and arterial wall. Traditional DESs have consisted of a platform (stent), a carrier (usually a polymer), and an antirestenotic agent that is delivered locally to avert the need for high, systemically administered doses. The fundamental goal of the DES is to restore lumen patency while curtailing the diseased vessel's innate and often exuberant response to the implanted foreign material (stent) and to stent-induced injury. Despite the success of current DESs at achieving these goals, concerns have surfaced with their accruing clinical use. Such concerns pertain to vascular healing and late stent thrombosis, biocompat...

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Section: Rodentsmentioning

confidence: 99%

Preclinical Models of Restenosis and Their Application in the Evaluation of Drug-Eluting Stent Systems

Perkins

2010

Vet Pathol

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“…Rats have been used for studying in vivo degradation processes; stent implantation into the abdominal aorta of rats has been proven a reliable model for stent evaluation 10–12…”

Section: Introductionmentioning

confidence: 99%

“…Building on this model, we aimed to establish an animal model which transforms the BMS scaffolding approach to a small animal model. Here, we present the combination of the double‐stent layer approach with a high‐throughput rodent model as described previously by Langeveld and colleagues 10, 11. To establish the rat model, a newly developed heat‐fixated 3D‐braided nondegradable polyurethane (PU) stent which was presented earlier by our group14 was tested for EPC adhesive capacity and mechanical properties, and, subsequently, was implanted in the novel animal model.…”

Section: Introductionmentioning

confidence: 99%

Introduction of a high‐throughput double‐stent animal model for the evaluation of biodegradable vascular stents

et al. 2012

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Current stent system efficacy for the treatment of coronary artery disease is hampered by in-stent restenosis (ISR) rates of up to 20% in certain high-risk settings and by the risk of stent thrombosis, which is characterized by a high mortality rate. In theory, biodegradable vascular devices exhibit crucial advantages. Most absorbable implant materials are based on poly-L-lactic acid (PLLA) owing to its mechanical properties; however, PLLA might induce an inflammatory reaction in the vessel wall. Evaluation of biodegradable implant efficacy includes a long-term examination of tissue response; therefore, a simple in vivo tool for thorough biocompatibility and biodegradation evaluation would facilitate future stent system development. Rats have been used for the study of in vivo degradation processes, and stent implantation into the abdominal aorta of rats is a proven model for stent evaluation. Here, we report the transformation of the porcine double-stent animal model into the high-throughput rat abdominal aorta model. As genetic manipulation of rats was introduced recently, this novel method presents a powerful tool for future in vivo biodegradable candidate stent biocompatibility and biodegradation characterization in a reliable simple model of coronary ISR.

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