LOW-DOSE, BETA-PARTICLE EMISSION FROM STENT WIRE RESULTS IN COMPLETE, LOCALIZED INHIBITION OF SMOOTH-MUSCLE CELL-PROLIFERATION

Article

关键词: LUMINAL CORONARY ANGIOPLASTY;    INTIMAL HYPERPLASIA;    BALLOON ANGIOPLASTY;    RADIATION-THERAPY;    ARTERIAL INJURY;    TIME COURSE;    RESTENOSIS;    IRRADIATION;    PREVENTION;    INDUCTION;   

DOI  :  10.1161/01.CIR.90.6.2956

来源: SCIE

【 摘 要 】

Background Restenosis after catheter-based revascularization has been demonstrated to be primarily caused by medial and/or intimal smooth muscle cell (SMC) proliferation. The objective of this study was investigate the ability of local emission of P-particles from a P-32-impregnated titanium ''stent'' wire source to inhibit vascular SMC and endothelial cell proliferation in cell culture and to determine the dose-response characteristics of this inhibition. Methods and Results A series of experiments were performed using 0.20-mm-diameter titanium wires that were impregnated with varying low concentrations of P-32 (activity range, 0.002 to 0.06 mu Ci/cm wire, n=47) or P-31 (nonradioactive control, n=28) in cultures of rat and human aortic SMCs and in cultured bovine aortic endothelial cells. The zone of complete cell growth inhibition (in millimeters from stent wire) was measured using light microscopy in the cultures exposed to the radioactive (P-32) or control (P-31) wires at 6 and 12 days after plating. In both rat and human SMC cultures there was a distinct 5.5- to 10.6-mm zone of complete SMC inhibition at wire activity levels greater than or equal to 0.006 mu Ci/cm. In contrast, there was no zone of inhibition surrounding the control (P-31 impregnated) wires (P<.001 versus P-32 wires at all wire activities greater than or equal to 0.006 mu Ci/cm for human and rat SMCs). Proliferating bovine endothelial cells were more radioresistant than SMCs, with no zone of inhibition observed at wire activity levels up to 0.019 mu Ci/cm (P<.001 versus SMCs at 0.006 mu Ci/cm and 0.019 mu Ci/cm). Conclusions We conclude that very low doses of beta-particle emission from a P-32-impregnated stent wire (activity levels as low as 0.006 mu Ci/cm of wire) completely inhibit the growth and migration of both rat and human SMCs within a range of 5.5 to 10.6 mm from the wire. Endothelial cells appear to be much more radioresistant than SMCs. These data suggest that an intra-arterial stent impregnated with a low concentration of P-32 may have a salutary effect on the restenosis process. Whether this approach can be used successfully and safely to inhibit restenosis in vivo and in the clinical setting is under investigation.

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