Long-term effects of polymer-based, slow-release, sirolimus-eluting stents in a porcine coronary model

Carter, Andrew J.; Aggarwal, Meenakshi; Kopia, Gregory A.; Tio, Fermin O.; Tsao, Philip S.; Kolata, Ron; Yeung, Alan C.; Llanos, Gerald; Dooley, John; Falotico, Robert

doi:10.1016/j.cardiores.2004.04.029

Cited by 259 publications

(168 citation statements)

References 14 publications

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“…Thus, we presume the second generation DES should also confront the old problem of delayed neointimal hyperplasia that has been reported in previous brachytherapy 15) and permanent polymer-coated DES studies. 16) Altogether randomized clinical trials with longer term observation are necessary to document a sustained benefit for these novel drug-eluting stents.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Effects of Novel Biodegradable, Polymer-Coated, Sirolimus-Eluting Stents on Neointimal Formation in a Porcine Coronary Model

et al. 2009

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SummaryThe postulated relationship between nonbiodegradable polymers and late stent thrombosis has led to a concerted effort to seek alternative biodegradable polymers for drug delivery. The purpose of this study was to evaluate the long-term effects of novel sirolimuseluting stents (SES) with biodegradable polylactic-co-glycolic acid (PLGA) polymer on neointimal thickening in a porcine coronary model. Three types of stents were implanted in different coronary arteries of the same mini-swine: bare cobalt-chromium stents (BMS); PLGA-coated-only stents (PCOS); and PLGA-coated, sirolimus-eluting stents (PCSES). A total of 26 animals underwent successful placement of 78 oversized stents (each stentgroup, n = 26) in the coronary arteries with histopathologic analysis and Western blot at 28 days, 3 months, or 1 year. At 28 days and 3 months, the mean neointimal area was about two-fold lower in PCSES versus BMS or PCOS. At 1 year, the mean intimal area was similar for PCSES (1.76 ± 0.28 mm 2 ) and BMS (2.06 ± 0.23 mm 2 , P = 0.051). Western blot analysis demonstrated decreased expression of p27 kip1 in the vessel wall 3 months after PCSES implantation as compared with 28 days. PCSES effectively reduced in-stent neointimal formation for the first 3 months in this porcine coronary model. Beyond 3 months, neointimal proliferation was not substantially inhibited by PCSES. The observed delayed neointimal hyperplasia with PCSES may be partly related to the potential side effects of sirolimus and/or late insufficient arterial drug levels. (Int Heart J 2009; 50: 811-822) Key words: Bioabsorbable, Polymer, PLGA, Sirolimus-eluting stents, Restenosis IT has been proven beyond doubt that the first generation drug-eluting stents (DESs) are more effective than bare-metal stents in reducing restenosis and related target vessel revascularization mainly by limiting intimal hyperplasia. 1,2)However, concerns regarding the long-term safety of the current DESs usingFrom the

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Section: Discussionmentioning

confidence: 99%

Long-Term Effects of Novel Biodegradable, Polymer-Coated, Sirolimus-Eluting Stents on Neointimal Formation in a Porcine Coronary Model

et al. 2009

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“…However, DES have been associated with a higher frequency of very late stenosis and re-infarction (more than 1 year) compared with bare metal stents, 1.9% versus 0.6% per year, respectively. 1,2 In addition, animal studies have shown that DES can cause local toxicity to the vessel wall in the form of medial necrosis, intimal proliferation, chronic inflammation and delayed re-endothelialization of the stents. [1][2][3] Thus, although DES reduce the risk of restenosis, they are associated with delayed re-endothelialization.…”

Section: Introductionmentioning

confidence: 99%

“…1,2 In addition, animal studies have shown that DES can cause local toxicity to the vessel wall in the form of medial necrosis, intimal proliferation, chronic inflammation and delayed re-endothelialization of the stents. [1][2][3] Thus, although DES reduce the risk of restenosis, they are associated with delayed re-endothelialization. 4,5 An optimal therapeutic approach would involve a strategy, which inhibits intimal hyperplasia while promoting re-endothelialization and suppressing stent-or vector-related inflammatory side effects.…”

Section: Introductionmentioning

confidence: 99%

Gene-eluting stents: non-viral, liposome-based gene delivery of eNOS to the blood vessel wall in vivo results in enhanced endothelialization but does not reduce restenosis in a hypercholesterolemic model

et al. 2011

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Although successful, drug-eluting stents require significant periods of dual anti-platelet therapy with a persistent risk of late stent thrombosis due to inhibition of re-endothelialization. Endothelial regeneration is desirable to protect against in-stent thrombosis. Gene-eluting stents may be an alternative allowing inhibition of neointima and regenerating endothelium. We have shown that adenoviral endothelial nitric oxide synthase (eNOS) delivery can result in significantly decreased neointimal formation and enhanced re-endothelialization. Here, we examined non-viral reporter and therapeutic gene delivery from a stent. We coated lipoplexes directly onto the surface of stents. These lipostents were then deployed in the injured external iliac artery of either normal or hypercholesterolemic New Zealand White rabbits and recovered after 28 days. Lipoplexes composed of lipofectin and a reporter lacZ gene or therapeutic eNOS gene were used. We demonstrated efficient gene delivery at 28 days post-deployment in the media (21.3 ± 7.5%) and neointima (26.8 ± 11.2%). Liposomal delivery resulted in expression in macrophages between the stent struts. This resulted in improved re-endothelialization as detected by two independent measures compared with vector and stent controls (Po0.05 for both). However, in contrast to viral delivery of eNOS, liposomal eNOS does not reduce restenosis rates. The differing cell populations targeted by lipoplexes compared with adenoviral vectors may explain their ability to enhance re-endothelialization without affecting restenosis. Liposome-mediated gene delivery can result in prolonged and localized transgene expression in the blood vessel wall in vivo. Furthermore, lipoeNOS delivery to the blood vessel wall results in accelerated re-endothelialization; however, it does not reduce neointimal formation. Gene Therapy (2012) 19, 321-328; doi:10.1038/gt.2011.92; published online 30 June 2011Keywords: endothelialization; coronary artery stents; restenosis; late stent thrombosis; liposome INTRODUCTION Drug-eluting stents (DES) are now routinely used for occlusive atherosclerotic coronary lesions to reduce the problem of restenosis. However, DES have been associated with a higher frequency of very late stenosis and re-infarction (more than 1 year) compared with bare metal stents, 1.9% versus 0.6% per year, respectively. 1,2 In addition, animal studies have shown that DES can cause local toxicity to the vessel wall in the form of medial necrosis, intimal proliferation, chronic inflammation and delayed re-endothelialization of the stents. 1-3 Thus, although DES reduce the risk of restenosis, they are associated with delayed re-endothelialization. 4,5 An optimal therapeutic approach would involve a strategy, which inhibits intimal hyperplasia while promoting re-endothelialization and suppressing stent-or vector-related inflammatory side effects.Gene-eluting stents have the potential to provide an alternative treatment strategy for the prevention of restenosis. The safety and feasibility of viral-medi...

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“…This phenomenon repeated itself with brachytherapy. No long-term benefit was seen in animal models but humans did benefit [263,[265][266][267][268][269]. Serruys et al state: "Finally, because the results of experiments in animal models cannot be directly translated to humans, specific clinical trials of safety and efficacy are required for each device [DES] [270].…”

Section: Palmaz Et Al First Employed Stents In Peripheral Arteries Imentioning

confidence: 99%

A Discussion of the Role of Complex Evolved Systems in the Development of Invasive Cardiovascular Interventions as Illustrated by the Blalock- Taussig Shunt and Intra-Arterial Stents

Greek¹

2014

Biol Syst Open Access

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Scientific disciplines normally thought of as outside the sphere of medical science have experienced advances over the past twenty years that currently have profound implications for medical care and medical research. Evolutionary and developmental biology, complexity and chaos science, along with the Human Genome Project and spinoff projects, have dramatically altered our understanding of how the human body functions and what can be expected from research methods like animal modeling. In this article, I summarize these advances and examine one historical medical development, the Blalock-Taussig shunt, in order to ascertain whether historically accepted representations of this development are consistent with current knowledge. I also examine an ongoing technology-intra-arterial stent development-to compare human data to the known animal data and place this comparison in the context of the aforementioned advances.

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Long-term effects of polymer-based, slow-release, sirolimus-eluting stents in a porcine coronary model

Cited by 259 publications

References 14 publications

Long-Term Effects of Novel Biodegradable, Polymer-Coated, Sirolimus-Eluting Stents on Neointimal Formation in a Porcine Coronary Model

Long-Term Effects of Novel Biodegradable, Polymer-Coated, Sirolimus-Eluting Stents on Neointimal Formation in a Porcine Coronary Model

Gene-eluting stents: non-viral, liposome-based gene delivery of eNOS to the blood vessel wall in vivo results in enhanced endothelialization but does not reduce restenosis in a hypercholesterolemic model

A Discussion of the Role of Complex Evolved Systems in the Development of Invasive Cardiovascular Interventions as Illustrated by the Blalock- Taussig Shunt and Intra-Arterial Stents

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