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)
Smooth muscle cell (SMC) proliferation is a key event in the development of restenosis after balloon angioplasty, and it is thought that macrophages play an important role in the complex process of activation of SMCs after vascular injury induced by balloon angioplasty. The study was designed to determine the time course of the accumulation of macrophages in the intimal layer following experimental balloon angioplasty. To determine the extent and time course of the accumulation of macrophages after experimental balloon angioplasty, an intimal atheroma was produced by repeated weak electrical stimulation of the right carotid artery of 45 male New Zealand White rabbits. Additionally, the animals received an 0.5% cholesterol diet during the 28 days of plaque development. Transluminal balloon angioplasty was subsequently performed. At 3, 7, 14, 21, 28 and 42 days after balloon treatment the vessels from at least five animals from each group were excised and analysed for the presence of macrophages using immunocytochemical techniques. In one group of five animals plaque development occurred without subsequent balloon angioplasty; the animals were killed after 21 days (sham group). SMCs were identified by immunohistological staining of alpha-actin. Intimal thickening increased after dilatation from 137 +/- 62 microns (control group without balloon treatment) to 244 +/- 47 microns in the 42 days after angioplasty (P < 0.05). The percentage of macrophages in the intimal layer displayed a significant increase (P < 0.01) at 14 days after angioplasty (9.1 +/- 4.3% vs 2.0 +/- 1.7% in the control group).(ABSTRACT TRUNCATED AT 250 WORDS)
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