[en] Objective: To study the effects and mechanism of ¹⁸⁸Re on apoptosis of cultured smooth muscle cells (SMCs), and to explore the value of radiation induced SMCs apoptosis for preventing restenosis. Methods: The SMCs cultured in vitro were irradiated by ¹⁸⁸Re with different doses. The trypan blue exclusion test, flow cytometry, JAM test, transmission electron microscopy and immunocytochemistry assay were used to investigate the effects of β-particles on apoptosis of SMCs, such as cell viability, cell apoptosis rate, DNA fragmentation, cell ultrastructural changes and related gene expression. Results: There were no significant changes of SMCs viability, cell apoptosis rate, DNA fragmentation and cellular ultrastructure in low-dose irradiation group, compared with control group. High-dose radiation (>2.96 GBq/L) on SMCs showed that viable cell proportion was markedly decreased, while cell apoptosis rate and DNA fragmentation were significantly increased, and cellular ultrastructure was destroyed. The expression of p53, bax gene was up regulated and bcl-2/bax was decreased while SMCs apoptosis occurred. Conclusions: Low-dose radiation on SMCs, which could inhibit completely SMCs proliferation, did not show any effects on cell viability, cell apoptosis rate, cell ultrastructure and DNA fragmentation. High-dose radiation could result in significant SMCs apoptosis. Up-regulated p53, bcl-2 and bax gene took a part in cell apoptosis induced by radiation. Low-dose and low-dose rate radiation appeared to be an ideal intravascular radiotherapy for preventing restenosis, which could not only inhibit SMCs proliferation, but also preserve cell viability and integrity

[en] To compare the effects of β-particle radiation on proliferation of smooth muscle cells and endothelial cells, and to explore the methods for protecting endothelial cells during endovascular radiotherapy, the smooth muscle cells and endothelial cells cultured in vitro were irradiated by ¹⁸⁸Re with different single doses. By means of proliferation cell count, cell cycle progression analysis, ³H-TdR incorporation, the effects of β-particle on proliferation of smooth muscle cells (SMCs) and endothelial cells (ECs) were studied and compared. SMCs proliferation, but not ECs, was significantly inhibited by β-particle irradiation with dose of 5.2 Gy. SMCs and ECs were inhibited similarly by β-particle irradiation with doses > 10.3 Gy and < 20 Gy. ECs appeared to be more radioresistant than SMCs at a lower dose. A safety window of treatment with ¹⁸⁸Re at a dose of 5.2 Gy was found between the smooth muscle cells and endothelial cells cultured in vitro

[en] Objective: To evaluate the effect and the mechanism of a new kind of ³²P stents used for prevention of the restenosis after percutaneous transluminal coronary angioplasty (PTCA); to observe the 'edge effect' caused by radioactive stents. Methods: Six ³²P-β-emitting stents made by compound plating, paired with 6 ³¹P nonradioactive(control) stents, were placed separately, one in one iliac artery in 6 rabbits, respectively. Animals were sacrificed after 30 d. Angiography, morphometry and immunohistochemistry work-up were performed. Results: There were no aneurysm or thrombosis in the arteries with stents placed. Morphometric measurements demonstrated that the mean minimum lumen diameter (MLD) was greater in ³²P stents than that in control stents (P<0.01); late loss of lumen area, loss index and percentage of in-stent restenosis were lower in 32 P stents than that in control stents (P<0.05). The lumen area in ³²P stents was greater than that in control stents, but the later had marked neointimal area than the former (P<0.01). The density of α-actin positive cells and proliferating cell nuclear antigen (PCNA) positive cells were lower in radioactive stents than that in control stents. Edge effect was observed in the radioactive stents. Conclusions: The ³²P-β-emitting stents made by compound plating could prevent in-stent restenosis significantly by inhibiting the neointimal growth even with low radioactivity; and it is safe, cheap and easy to make. But an unexpected increase in neointimal response, the so-called 'edge effect', was observed in the study

[en] Objective: To update the clinical and experimental evaluation of the effects of radioactive stents on the prevention of intimal proliferation. Methods: The stents were bombarded with suitably charged particles of adapted energy in the cyclotron to create a proper mixture of the radionuclides, ⁵⁹Fe, ⁶⁰Co, ⁵⁸Co, ⁵⁷Co, ⁵¹Cr and ⁵⁴Mn in them. The radioactive stents were implanted unilaterally in rabbit iliac arteries; and at the same time, non-radioactive stents were implanted in the contralateral iliac arteries of the same rabbits serving as controls. The effects of radioactive stents on prevention of restenosis were assessed by angiography, histo-morphometry and immunocytochemistry, Results: All the iliac arteries that had been implanted radioactive stents were clear on angiography and had no radiation complication during the 1-2 month follow-up. There was significant reduction in neo-intimal area [(0.37 +- 0.14) mm² vs. (0.81 +- 0.10) mm², P < 0.01], percent area stenosis [(6.70 +- 2.91)% vs. (13.15 +- 1.40)%, P < 0.01] and PCNA immunoreactive rate [(2.00 +- 1.58)% vs. (10.88 +- 6.98)%, P < 0.05] in the radioactive stents group compared with that in the control stents group. Conclusions: Radioactive stents with an activity of 33.819 - 61.189 kBq could inhibit the intimal proliferation in the animal model. The radioactive stents implantation is feasible for prevention of intimal proliferation

[en] Objective: To explore the effects and the mechanism of radionuclide on smooth muscle cells proliferation and apoptosis, and to investigate the effects of radioactive stents on prevention of restenosis. Methods: The effects and mechanism of radionuclide on the proliferation, apoptosis, and mutation of HPRT gene exon 7/8 in cultured smooth muscle cells were studied by cellular and molecular technique, and the prevention effects of radioactive stents on restenosis were investigated in animal model. Results: The proliferation of smooth muscle cells cultured in vitro could be inhibited markedly by β-particle radiation from radionuclide ¹⁸⁸Re, proliferation inhibition rate: [(100.0% vs 34.1%, t = 2.500, P < 0.05), (100.0% vs 27.7%, t = 2.744, P < 0.05), (100.0% vs 21.8%, t = 2.972, P < 0.05), (100.0% vs 18.1%, t = 3.121, P < 0.05)]; DNA synthesis inhibition rate: {[43.56 +- 2.32)% vs (23.80 +- 2.57)%, t = 11.416, P < 0.001], [(43.56 +- 2.32)% vs (11.82 +- 2.51)%, t = 18.566, P < 0.001], [(43.56 +- 2.32)% vs (6.04 +- 1.20)%, t = 28.734, P < 0.001], [(43.56 +- 2.32)% vs (3.30 +- 0.52)%, t = 33.892, P < 0.001], [(43.56 +- 2.32)% vs (1.49 +- 0.87)%, t = 33.991, P < 0.001]}. The apoptosis of smooth muscle cells could not be affected significantly by low-dose radiation. But there was an increase of apoptosis rate only in group 3.70 GBq/L [(2.89 +- 0.56)% vs (17.21 +- 2.56)%, t = 9.477, P < 0.001]. There was a positive relationship between the radiation dose and the mutation of HPRT gene and exon 7/8 (r = 0.993, P < 0.001; r = 0.947, P < 0.05). Radioactive stents could decrease neo-intimal area [(1.01 +- 0.37) mm² vs (0.60 +- 0.29) mm², t = 2.466, P < 0.05], and percent area of stenosis [(16.84 +- 6.61)% vs (10.05 +- 4.27)%, t = 2.448, P < 0.05] compared with non-radioactive stents in animal restenosis model. Conclusion: Endovascular radiotherapy in low-dose and low-dose rate was an ideal therapy selection for prevention of restenosis, which could inhibit cell proliferation significantly, but did not ruin the vessel structure. Radioactive stents could inhibit the restenosis in the animal model, and it is safe and feasible for prevention of restenosis

[en] Objective: To investigate the effects of intravascular β-irradiation with a liquid ¹⁸⁸Re-filled balloon on restenosis in rabbit model, and to evaluate the feasibility of the intravascular irradiation. Methods: The bilateral iliac arteries of 14 rabbits were injured by catheter balloon overdilation. A random side iliac artery of the rabbit was irradiated by a liquid ¹⁸⁸Re-filled balloon with the radioactivity of 15 Gy at a depth of 0.5 mm beneath the skin close to the artery, and the other iliac artery served as a control. At 12 weeks after operation, quantitative angiography, histopathology and immunohistochemistry analysis were performed in the injured iliac arteries to evaluate the effects of irradiation. Results: There was significant increase in iliac artery diameter [(1.94 +- 0.19) vs (1.77 +- 0.28) mm, P<0.05)], and significant decrease in neointimal area [(1.12 +- 0.75) vs (2.17 +- 1.21) mm², P<0.01], percent stenosis area [(19.23 +- 12.60)% vs (34.45 +- 17.49)%, P<0.01], and the proliferative cell nuclear antigen (PCNA) positive rate of vascular smooth muscle cells [(3.75+-2.09)% vs (5.64 +- 1.74)%, P<0.05] in ¹⁸⁸Re-filled balloon irradiation group compared with control group. Conclusions: Intravascular β-irradiation by a liquid ¹⁸⁸Re-filled balloon with 15 Gy at 0.5 mm tissue depth beneath the skin close to the artery in rabbit model could inhibit neointimal proliferation and prevent restenosis. The intravascular brachytherapy with irradiation for prevention of restenosis is technically feasible