Our data show that paclitaxel inhibits haSMC proliferation and migration in a dose-dependent manner in monocultures and cocultures even in the presence of mitogens. Furthermore, paclitaxel prevents neointima formation in rabbits after balloon angioplasty. The long-lasting effect after just several minutes' exposure time makes this lipophilic substance a promising candidate for local antiproliferative therapy of restenosis.

Local delivery of paclitaxel resulted in reduced neointimal stenosis and enlargement in vessel size. Both these effects contribute to a preservation of vessel shape and are likely to be caused by a structural alteration of the cytoskeleton.

The mean effective dose for MSCT coronary angiography was significantly higher than that for conventional angiography. As MSCT cardiac scanners become increasingly available, operators must be aware of the radiation dose and the factors that affect it.

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Smooth muscle cell (SMC) proliferation is known to be an important factor for the development of restenosis after percutaneous transluminal coronary angioplasty. To determine the time course of intimal and medial SMC proliferation and morphological changes after experimental angioplasty, an intimal atheroma was produced with repeated weak electrical stimulations in the right carotid artery of 45 male New Zealand White rabbits. Angioplasty was subsequently performed in 35 rabbits, and the proliferative responses were analyzed with histomorphological and immunohistological criteria at 3, 7, 14, 21, 28, and 42 days after intervention. A hemodynamic relevant stenosis after angioplasty was found in eight (23%) of 35 dilated arteries. In five rabbits the stenosis was due to a mural thrombus, and in three animals restenosis was caused by intimal SMC proliferation. In all dilated arteries the intimal wall thickness increased from 13 +/- 5 intimal cell layers (after electrical stimulation) to 33 +/- 14 cell layers during 28 days after angioplasty (p less than 0.05). Later than 4 weeks after angioplasty, no additional increase of intimal thickening occurred. Application of bromodeoxyuridine 18 and 12 hours before excision of the vessels allowed determination of the percent of cells undergoing DNA synthesis in the intima and media using monoclonal antibody against bromodeoxyuridine. SMCs were identified by alpha-actin staining. Immunohistological quantification of intimal SMC proliferation showed a maximum of cells undergoing DNA synthesis within the first 7 days after angioplasty (p less than 0.01). In contrast, medial proliferation of SMCs was delayed and showed a small but significant increase 21 days after dilatation (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Background-Stent-based antiproliferative therapy appears to decrease in-stent restenosis. However, alternative approaches might produce equivalent efficacy with better long-term safety. In previous work, an adenovirus capable of expressing the tissue inhibitor of metalloproteinase-3 (RAdTIMP-3) inhibited neointima formation in cell cultures and porcine saphenous vein grafts. RAdTIMP-3 decreased smooth muscle cell migration, stabilized the extracellular matrix, and uniquely promoted apoptosis. The current study developed eluting stent technology to deliver RAdTIMP-3 during stenting of pig coronary arteries. Methods and Results-Binding of virus to and elution from stents and transduction of pig coronary arteries were confirmed using ␤-galactosidase as a reporter gene in vitro and in vivo. Deployment of RAdTIMP-3-coated stents increased apoptosis and reduced neointimal cell density, but did not increase inflammation or proliferation compared with ␤-galactosidase-expressing adenovirus (RAdlacZ

Background. The proliferative response induced by balloon angioplasty is known to be an important factor in the development of restenosis after successful coronary angioplasty.Methods and Results. To study the effects of low-molecular-weight heparin (LMWH) on cellular proliferation after experimental balloon angioplasty, LMWH (3.9 kd, 400 anti-Xa units/kg/day) was given to 20 male New Zealand White rabbits. After an intimal fibromuscular plaque was induced by electrical stimulation in the right carotid artery, LMWH was applied during the 7 days after balloon dilatation. As the control group, 20 other rabbits underwent balloon angioplasty without application of LMWH. The vessels were excised 3, 7, 14, and 28 days after balloon treatment. During the final 18 hours before the rabbits were killed, bromodeoxyuridine was applied. Intimal wall thickness increased from 13±5 cell layers (preangioplasty control group) to 20±6 cell layers in the LMWH-treated group at 28 days (p<0.05). In contrast, histological examination of control animals 28 days after angioplasty revealed a significant increase to 35±+15 cell layers (p<0.01). Immunohistological quantification showed a significant increase (p<0.001) of cells undergoing DNA synthesis at 3 (10.2±4.2%) and 7 (7.7±4.8%) days after balloon dilatation in control animals. In contrast, at 3 and 7 days after balloon treatment, the percentage of cells undergoing DNA synthesis in LMWH-treated rabbits was lower (3 days, 2.7±1.8%; 7 days, 1.9+0.3%) than the corresponding untreated controls but showed a significant increase (p<0.01) compared with the preangioplasty controls. The differences between the two groups were statistically significant, however (3 days, p<0.01; 7 days, p<0.05). As early as 14 days after angioplasty, the extent of

The purpose of this experimental in vivo study was to determine the time course of smooth muscle cell proliferation early and late after intravascular stenting compared to conventional balloon angioplasty in normal vessels. A balloon expandable 2.0 mm tantalum Strecker stent was placed in the right carotid artery of 33 male New Zealand White rabbits after they had been fed a 0.5% cholesterol diet for 28 days. In addition, balloon angioplasty was performed in 27 of the animals; 19 contralateral vessels served as controls without treatment. The vessels were excised at 7, 14, 28, 42 or 90 days after treatment. During the final 18 h before the rabbits were killed, bromodeoxyuridine (BrdU) was applied and proliferating cells were detected by using a monoclonal antibody against BrdU. In histological cross sections the proportion of cells undergoing DNA synthesis was determined. Analysis was performed separately in the intimal and medial layers. Additionally, the area adjacent to the stent wire was compared with the intermediate area. Smooth muscle cells were identified by alpha-actin staining. Intimal wall thickness increased from 23 +/- 28 microns (control group without intervention) to 323 +/- 84 microns within 42 days after stenting (P < 0.01), and to 81 +/- 82 microns at day 42 after balloon angioplasty (P < 0.05). However, between 42 and 90 days following stent implantation a significant (P < 0.05) decrease in neointimal thickness was observed (90 days: 215 +/- 15 microns).(ABSTRACT TRUNCATED AT 250 WORDS)