The Experiment Study Of Arsenic Trioxide Eluting Stent Preventing Post-PTA Restenosis

Part IThe Experiment Study of the Apoptosis-inducing Effect of Arsenic Trioxide (As₂O₃) on Canine Iliac Artery Smooth Muscle CellObjective To study the possible apoptosis—inducing effect of arsenic trioxide (As₂0₃) on canine artery smooth muscle cell. To assess the most effective concentration of Arsenic Trioxide.Material and methods1. Canine iliac artery vascular smooth muscle cells (VSMC) were cultured in vitro.2. VSMC stained with HE were observed by the optical microscope, immunohistochemical staining of α-actin protein in VSMC were observed with the optical microscope.3. MTT test was undergone in all groups, the growing features of VSMC in different As₂O₃ concentration were observed.4. Inhibiting growth curve of the VSMC cultured in different As₂0₃ were described.5. The ultrastructure changes of VSMC apoptosis by As₂O₃ were observed with transmission electron microscope.Results1. Growth rate of VSMC was inhibited by As₂0₃, the inhibiting effect became more obviously in dosage-time dependent manner.2. With the increasing As₂O₃ concentration, the VSMC apoptosis became evident, the VSMC growth rate decreased, the number of the remained survival VSMC decreased, respectively.3. Transmission electron microscope appearance of induced apoptosis by As₂O₃ demonstrated apoptotic VSMC cellular shrinkage, membrane blebbing, formation of vesicle, and formation of apoptotic body.Conclusions1. There were evident inhibiting effects of As₂O₃ on VSMC proliferation, the mechanism of the effect due to that As₂O₃ could induce apoptosis of VSMC and could use to prevent restenosis post-PTA.2. As₂O₃ could decrease VSMC DNA synthesizing, proliferation of VSMC, and keep VSMC to stay at the DAN synthesizing phrase or post DNA synthesizing stage.3. The minimum concentration of As₂O₃ inducing VSMC apoptosis was2. Oumol/L, 4. Oumol/L with evident inducing VSMC apoptosis effect; 5.Oumol/L could promote VSMC death dramatically, in dosage-time dependent manner respectively.Part II Making of Arsenic Trioxide Eluting StentObjective to make polymer of Morpheline-2, 5-dione and Lactide, preparing the arsenic trioxide eluting stent with this polymer, measure the weights of the coating and drug of eluting stents. Material and methods1. Self-made the polymer of Morpheline-2, 5-dione and Lactide.2. Preparing the arsenic trioxide eluting stents, rapamycin eluting stents and no-drug eluting stents.3. Measure the weights of the coating and drug of eluitng stents. Results1. Successful making the polymer of Morpheline-2, 5-dione and Lactide2. Total 12 arsenic trioxide eluting stents were made, the average weight of coating of the arsenic trioxide eluting stents was 186ug, with carrying dosage of arsenic trioxide 46.58ug; 6 rapamycin eluting stents were made, the average weight of coating of those stents was 178. 5ug, with carrying dosage of rapamycin was 402.7ug; 6 no-drug eluting stents were made, the average weight of coating of those stents was 187. 7ug.Conclusions1. The synthesis of polymer of Morpheline-2, 5-dione and Lactide is successful.2. Preparing the arsenc trioxide eluting stents and no-drug eluting stents are successful.Part III The Experimental Study of Arsenic Trioxide Eluting Stent PreventingPost-PTA Restenosis in VivoObjective to evaluate the effect of arsenic trioxide eluting stent preventing post PTA restenosis, to verify the assumption that whether or not the arsenic trioxide eluting stent can prevent post-PTA restenosis, is there any difference between the arsenic trioxide eluting stent and rapamycin eluting stent on preventing post-PTA restenosis.Material and method Total 24 common iliac arteries of 12 mongrel dogs were underwent PTA, then implanted 24 stents; all stents divided into 3 groups, including 6 no-drug eluting stents, 6 rapamycin eluting stent, 12 arsenic trioxide eluting stents. After 4 to 12 weeks intervals of follow-up, the animals were performed quantitative angiography and then killed, stents with vessel were isolated and section into slice, stain with eosin, and each slide was measured by microscope, the thickness and area of the neointima was quantified.Result At 4^th week follow-up 12 stents were patent, 12^th weeks there were marked in-stent restenosis in the no-drug eluting stents, slightly in-stent restenosis in the arsenic trioxide and rapamycin eluting stents angiographically, compared with no-drug eluting stents there were statistic significant difference between drug eluting stents and no-drug eluting stents. At the end of 12 weeks follow-up the historical slides presented there were mild proliferation of neointima in the arsenic trioxide and rapamycin eluting stents, marked proliferation of neointima in the no-drug eluting stents, the thickness and area of neointima had significant difference between drug eluting stents and no-drug elutingstents, no significant difference between arsenic trioxide eluting stentsand rapamycin eluting stents, statistically.Conclusion1. The arsenic trioxide eluting stents were implanted into the canine iliac arteries which was feasiable and safe interventionaly.2. At 4^th week angiography follow-up there were no evident in-stent restenosis in the drug eluting stents and no-drug eluting stents.3. Both arsenic trioxide and rapamycin eluting stents could effectively reduce the proliferation of neointima.4. The arsenic trioxide and rapamycin eluting stents had no effect on the reendothelization of the vessels with stents at 12^th week.