The porcine coronary model of in‐stent restenosis: Current status in the era of drug‐eluting stents

Lowe, Harry C.; Schwartz, Robert S.; Neill, Briain D. Mac; Jang, Ik‐Kyung; Hayase, Motoya; Rogers, Campbell; Oesterle, Stephen N.

doi:10.1002/ccd.10705

Cited by 59 publications

(56 citation statements)

References 52 publications

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“…12) Through the femoral approach, 6 Fr Judkins right 4 catheters were used for both the left main and right ostia. After heparin administration (100 IU/ kg) and coronary angiography, each animal underwent placement of the stents in the coronary arteries.…”

Section: Methodsmentioning

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: Methodsmentioning

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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“…For interventional procedures, heparin is given once arterial access has been gained so as to reduce the risk of wire and stent thrombosis (Lowe et al, 2003). Although some authors have used doses as high as 10 000 U (Frimerman et al, 1999), we and others (Gunn et al, 2002), use a standard heparin dose of 2500 U for juvenile animals (which is approximately 100 U/kg) and have had no issues with acute stent thrombosis.…”

Section: Procedural Techniquementioning

confidence: 99%

“…It is important, if pressure fixation of the stented vessel(s) is to be performed, that the ascending aorta be removed intact, so that a watertight seal can be created around the fixation catheter. Vessel processing and analysis are beyond the scope of this article, but have been discussed in detail elsewhere (Lowe et al, 2003).…”

Section: Sacrificementioning

confidence: 99%

“…However, there are important differences between the two species in terms of responses to anaesthesia, pharmacotherapy, vascular access, catheter selection and angiographic views. Although guidelines exist (Schwartz et al, 2002;Lowe et al, 2003), there is no systematic description of the procedure in the literature, and most published reports only briefly summarise the methodology, thus providing insufficient detail for a researcher wishing to set up this model de novo, even if they have experience in human catheter-based coronary procedures.…”

Section: Introductionmentioning

confidence: 99%

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Coronary angiography and percutaneous coronary intervention in the porcine model: a practical guide to the procedure

Williams

Malik

Kingston

2012

Animal

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Assessment of safety and efficacy within the porcine coronary artery model remains a standard requirement for new therapies delivered to the coronary arteries before proceeding to clinical testing. Human coronary procedures carry a very low mortality rate; however, procedural mortality for porcine experiments is often high, despite these animals being young and free of atherosclerosis. Some of these deaths are due to poor technique, and therefore avoidable. However, despite the wide use of this model, a systematic description of the procedure has never been published. This article will detail how porcine angiography and stent implantation is performed in our institution and will discuss the relevant differences between humans and pigs with regard to anaesthesia, pharmacotherapy, vascular access, catheter selection and angiographic views. Important variations to the technique that have been reported are also covered.

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“…None has contrasted the central role of drug-eluting stents (10,11,12) although their long-term results seemingly limited by the delay in healing related to the risk of late stent thrombosis and hypersensitivity reactions (13,14,15).…”

Section: Introductionmentioning

confidence: 99%

Effect of a novel drug-eluted balloon coated with Genistein before stent implantation in porcine coronary arteries

et al. 2008

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This is an author version of the contribution published on: Questa è la versione dell'autore dell'opera: [Effect of a novel drug-eluted balloon coated with genistein before stent implantation in porcine coronary arteries.Sheiban I, Anselmino M, Moretti C, Biondi-Zoccai G, Galloni M, Vignolini C, Mattoni M, Sciuto F, Omedè P, Trevi GP. Clin Res Cardiol. 2008 Dec;97(12):891-8. doi: 10.1007/s00392-008-0705-2.] The definitive version is available at: La versione definitiva è disponibile alla URL: [http://link.springer.com/article/10.1007%2Fs00392-008-0705-2] Phone: +39-011-6334446. Fax: +39-0116967053. Email: isheiban@yahoo.com 3 Background. The major drawback of stent implantation in native human coronary vessels is the occurrence of restenosis. Drug-eluting stents significantly reduce restenosis after percutaneous coronary intervention (PCI), but may be associated with persistent local inflammation involved in the restenosis mechanisms. In this setting coating coronary devices with anti-inflammatory agents represents an intriguing alternative to stent-based local drug delivery. The aim of the present study was to test in a porcine model the safety and efficacy of a novel Genistein-eluting balloon preceding coronary stenting.Design. Female piglets underwent PCI in a randomized fashion with either a Genistein-eluting or a standard balloon angioplasty, followed in all vessels by bare-metal stent implantation. Pigs were sacrificed at different time points to appraise safety (i.e. endothelialization) and efficacy (i.e. antiinflammatory and anti-proliferative effects): 1, 4, and 6-8 weeks following PCI.Results. Overall analysis was conducted on 14 piglets. Twenty-five bare-metal stents were implanted preceded by angioplasty with a conventional balloon in 13 vessels and by the Genistein-eluted balloon in 12. No untoward effects were reported in either group. Healing and endothelialization appeared universal within four weeks. The Genistein-eluted balloon group disclosed a significant reduction, at four weeks from implantation, of the peri-stent inflammatory cells count (mononucleocytes 39±32 vs.96±29 per square millimetre, p=0.019. This effect did not clearly translate into a trend towards a reduced neointimal hyperplasia at six-eight weeks (0.13±0.11 vs. 0.14±0.09, p=0.835).Conclusion. This study provides the first in vivo demonstration of the anti-inflammatory effects of a Genistein-eluting balloon in PCI, warranting further research including the combination of a Genisteineluting balloon with standard drug-eluting stent.4

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The porcine coronary model of in‐stent restenosis: Current status in the era of drug‐eluting stents

Cited by 59 publications

References 52 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

Coronary angiography and percutaneous coronary intervention in the porcine model: a practical guide to the procedure

Effect of a novel drug-eluted balloon coated with Genistein before stent implantation in porcine coronary arteries

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