Local paclitaxel delivery after coronary stenting in an experimental animal model

SummaryThe goal of this study was to test the safety and efficacy of local paclitaxel delivery via a newly designed application catheter in an experimental animal study. Drug-eluting stents reduce restenosis in comparison to bare-metal stents. The drug-eluting polymer, however, may exert potential thrombogenic and inflammatory effects. A catheter-based local paclitaxel delivery offers further advantages, particularly a homogenous drug transfer into the vessel wall and a pharmacotherapy of the stent edges. In 30 pigs, both bare-metal stent (3.0 × 13mm) implantation and balloon angioplasty were performed. Ten pigs received subsequent local delivery of paclitaxel-solution via a newly designed catheter (Genie™, ACROSTAK corp., Switzerland), 10 animals served as a sham group and received vehicle (0.9% NaCl solution) and 10 animals were used as a control group. All animals were treated with aspirin and clopidogrel to prevent stent thrombosis. After final angiography the vessels were excised 42 days after intervention and prepared for histological and histomorphometric analysis. All coronary arteries showed complete endothelialization 42 days following treatment. Paclitaxel treatment led to a marked reduction of neointimal proliferation either post stent implantation (neointimal area: 1.04 ± 0.10 mm2 vs. 2.37 ± 0.23 mm2, p<0.001) or post balloon dilatation (neontimal area: 0.35 ± 0.14 mm2, vs. 0.68 ± 0.24 mm2, p<0.01).There were no significant angiographic or histomorphometric differences between the control and the sham group. In both paclitaxel groups neither angiographic edge phenomena nor a significant histomorphometric inflammatory response were found in the treated vessel segments. In conclusion, the local application of paclitaxel via the Genie™ catheter is safe and effective to significantly reduce the proliferative response post-stent implantation or balloon dilatation in an experimental animal model.

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COMPARISON OF 4 YEARS CLINICAL OUTCOME OF STENT IMPLANTATION IN RENAL FAILURE PATIENTS WITH DIALYSIS: COMPARISON WITH BARE METAL, STENTS, FIRST GENERATION DRUG-ELUTING STENT AND SECOND GENERATION DRUG-ELUTING STENTS

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(11)61894-9 ◽

2011 ◽

Vol 57 (14) ◽

pp. E1894 ◽

Cited By ~ 1

Author(s):

Sunao Nakamura ◽

Shotaro Nakamura ◽

Hisao Ogawa ◽

Jang-Ho Bae ◽

Yeo H. Cahyadi ◽

...

Keyword(s):

Renal Failure ◽

Clinical Outcome ◽

Stent Implantation ◽

First Generation ◽

Bare Metal Stents ◽

Drug Eluting Stents ◽

Drug Eluting Stent ◽

Metal Stents ◽

Bare Metal ◽

Drug Eluting

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Abstract 2955: Increased Luminal Diameter With Drug-eluting Versus Bare-metal Stenting Of The Piglet Ductus Arteriosus

Circulation ◽

10.1161/circ.116.suppl_16.ii_660 ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Kyong-Jin Lee ◽

Aleksander Hinek ◽

Claudia Almeida ◽

Rajiv Chaturvedi ◽

Lee Benson

Keyword(s):

Stent Implantation ◽

Cellular Proliferation ◽

Ductus Arteriosus ◽

Metal Stents ◽

Type I ◽

External Diameter ◽

Bare Metal ◽

Luminal Diameter ◽

Extracellular Matrix Components ◽

Drug Eluting

Introduction: Maintaining ductus arteriosus (DA) patency by stent implantation may be advantageous in congenital heart disease management algorithms. Rapamycin, an immuno-suppressant drug, has anti-proliferative properties, inhibits smooth muscle cell (SMC) migration and may deter intimal hyperplasia occurring during spontaneous closure and post stent implantation of the DA. Methods: 16 Yorkshire piglets (age 7–11 days old, weight 2.2– 4.9 kg) underwent stent implantation of the DA (rapamycin-eluting (n = 8), bare metal (n = 8) stents, (3.5 mm diameter) and were sacrificed at 2, 4 and 6 weeks. Dissected DA were analyzed for SMC and extracellular matrix components (elastin, collagen and glycosaminoglycans). External diameter, wall thickness and lumen diameter were analyzed by morphometric software. DA-derived SMC were isolated and cultured for 7 days in the presence or absence of 100mM of rapamycin. Cellular proliferation rates were assessed by proliferative antigen Ki-67 detection and [ 3 H]-thymidine incorporation. Specific antibodies to elastin, collagen type I, and chondroitin sulfate-containing glycosaminoglycans were analyzed. Results: Rapamycin-eluting stents significantly inhibited neointimal formation compared with bare metal stents at 4 and 6 weeks resulting in larger luminal diameters (p<0.001). The in vitro studies demonstrated rapamycin-treated cultures of the DA-derived SMC had 50% lower proliferation rates (p<0.001). Conclusions : Rapamycin has anti-proliferative actions on the DA. Drug-eluting stents may be a more efficient tool for prolonging patency of the DA in neonates palliated for future correctional surgery.

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Endothelial Recovery in Bare Metal Stents and Drug-Eluting Stents on a Single-Cell Level

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.121.316472 ◽

2021 ◽

Author(s):

Anne Cornelissen ◽

Liang Guo ◽

Raquel Fernandez ◽

Michael C. Kelly ◽

Christine Janifer ◽

...

Keyword(s):

Single Cell ◽

Balloon Angioplasty ◽

Stent Implantation ◽

Bare Metal Stents ◽

Drug Eluting Stents ◽

Metal Stents ◽

Bare Metal ◽

Single Cell Rna Sequencing ◽

Drug Eluting ◽

Plain Old Balloon Angioplasty

Objective: Healing processes, particularly reendothelialization, are essential for vascular homeostasis after plain old balloon angioplasty and stent implantation. Drug-eluting stents (DES) are commonly used for percutaneous coronary intervention because restenosis rates are reduced as compared with bare metal stents. However, in addition to understanding the nature of regenerated endothelial cells, concerns over incomplete stent healing persist, and the molecular effects of antiproliferative drug coatings on endothelium remain poorly understood. Approach and Results: We used the rabbit iliac artery model to analyze differences in stent endothelialization in bare metal stents and DES. Histology and immunohistochemistry confirmed that stent coverage was significantly greater in bare metal stents than in DES at 30 days after stent implantation. Single-cell RNA sequencing revealed a more immature transcriptomic signature of neointimal endothelial cell harvested from stented arteries in comparison with native and plain old balloon angioplasty–treated arteries. Whereas the genetic signature of bare metal stents was overall proangiogenic with enrichment of genes involved in endothelial proliferation, sprouting, and migration, as well as extracellular matrix assembly, DES-derived endothelial cell showed upregulation of genes associated with angiogenesis inhibition and endothelial activation. Conclusions: Single-cell RNA sequencing analysis identified unique transcriptional changes within regenerated endothelium after plain old balloon angioplasty and stent implantation. These data suggest unique endothelial transcriptional differences, which characterize the different response of the endothelium to vascular injury and may help explain why long-term responses in DES remain suboptimal.

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