Preclinical restenosis models and drug-eluting stents

Abstract

Percutaneous coronary intervention continues to revolutionize the treatment of coronary atherosclerosis. Restenosis remains a significant problem but may at last be yielding to technologic advances. The examination of neointimal hyperplasia in injured animal artery models has helped in our understanding of angioplasty and stenting mechanisms, and as drug-eluting stent (DES) technologies have arrived, they too have been advanced through the study of animal models. These models are useful for predicting adverse clinical outcomes in patients with DESs because suboptimal animal model studies typically lead to problematic human trials. Similarly, stent thrombosis in animal models suggests stent thrombogenicity in human patients. Equivocal animal model results at six or nine months occasionally have been mirrored by excellent clinical outcomes in patients. The causes of such disparities are unclear but may result from differing methods, including less injury severity than originally described in the models. Ongoing research into animal models will reconcile apparent differences with clinical trials and advance our understanding of how to apply animal models to clinical stenting in the era of DESs.

Impact of Stent Size Selection on Acute and Long-Term Outcomes After Drug-Eluting Stent Implantation in De Novo Coronary Lesions

“…[27][28][29] Although one study reported that arterial injury as assessed by the balloon-toartery ratio was not associated with the amount of neointimal hyperplasia in sirolimus-eluting stents and paclitaxel-eluting stents, 30 the exact impact of stent oversizing has not been well investigated in DES. In the present study, stent oversizing resulted in no significant increase of neointimal proliferation in large target vessels.…”

Design and Optimization of a Blood Vessel Mimic Bioreactor System for the Evaluation of Intravascular Devices in Simple and Complex Vessel Geometries

“…Animal studies, however, are a valuable tool and much of what is known about restenosis and the healing response after stent implantation has been gathered from the study of both healthy and atherosclerotic animal models (Touchard and Schwartz 2006;Schwartz, Chronos and Virmani 2004;Wieneke, et al 1999).…”

“…More importantly, it should closely mimic the human pathophysiology of neointimal proliferation and remodeling (Russell and Proctor 2006;Kantor, et al 1999). Current animal models for preclinical intravascular device testing include mice, rats, rabbits, pigs, dogs, and primates (Russell and Proctor 2006;Touchard and Schwartz 2006;Schwartz, Chronos and Virmani 2004).…”

“…Rats and rabbits are small and relatively inexpensive, providing a fast and reliable animal model for preclinical testing. One disadvantage is that rats and rabbits are highly resistant to the development of atherosclerosis, necessitating the use of either a high cholesterol diet or vessel injury to mimic coronary lesions (Schwartz, Chronos and Virmani 2004;Wieneke, et al 1999). However, even healthy rat and rabbit models provide important information regarding the vascular healing response that occurs after device implantation.…”

“…In addition to rats and rabbits, the pig has become a widely used species for assessing treatments of restenosis because its coronary anatomy and physiology are similar to those of humans and are susceptible to atherosclerosis, developing thick neointimal lesions in response to injury (Russell and Proctor 2006;Schwartz, Chronos and Virmani 2004). Large animas, such as dogs and primates, are also useful models but are not commonly used due to high cost, ethical considerations, and long life spans.…”