The Effect Of Local Delivery Of Paclitaxel After Angioplasty:an Experimental And Clinical Sutdy

Objective①to evaluate the effect of local delevery of paclitaxel on neointimal hyperplasia and endothelialization;②to compare the effect of different doeses and time of administration of paclitaxel on neointimal hyperplasia and endothelialization;③to evaluate the efficacy and safty of local delevery of paclitaxel to inhibit restenosis after stent implantationMaterials and methods1. Establishment of experimental common carotid artery injury model in the rat. Local intra-arterial administration(240μg/40μl、120μg/40μl) was applied. The neointimal thickness and area, medial thickness and area, the ratio of intimal area to medial area, internal elastic lamina area, and external elastic lamina area were measured or calculated14and28days after injury respectively, which were compared to those of controls, to estimate the change of the vessel wall. Proliferating cells could be indentified as smooth muscle cells(SMCs) with immunohistological a-actin, and mocrophages were detected with RAM11antibody. vWF antibody was used to label the endothelial cells to evaluste the effect of anti-proliferative agents on endothelialization.2. We conducted a prospective, randomized trial comparing the local delivery of paclitaxel after bare metal stent implantation (group Ⅰ) with the implantation of bare metal stent (group Ⅱ) of the superficial femoral artery. The primary end point was minimal lumen diameter, in-stent late lumen loss, ankle brachial index(ABI) and target lesion revascularization. The aim of the study was to evaluate safty of local delevery of paclitaxel.Relults1.14and28days after injury, the neointimal thickness and area, the ratio of intimal area to medial area were significantly decreased in paclitaxel groups compared to control group(P<0.01), and the neointimal thickness and area the ratio of intimal area to medial area were the least in paclitaxel high concentration(240μg/μl) lOmin group(P<0.01). No significant difference of the internal and exrernal elastic lamina area could be seen between paclitaxel experimental groups and controls; compared to controls, the smooth muscle cell proliferation was significantly inhibited in paclitaxel experimental groups, especially the high concentration(240μg/μl)10min group(P<0.01).30days after injury, endothelialization of the vessel wall was completed in paclitaxel experimental groups; mocrophages were not observed in paclitaxel experimental groups and controls.2. After intervention, there are no significant differences in lesion charactrtostocs such as ankle branchial index loss and late lumen loss between treatment groups(P>0.05). There are a improvement of number of white blood cell in the group treated with local delivery of paclitaxel. There are no complications in all patients. At6months, there are no significant differences in ankle branchial index loss and late lumen loss between the group treated with local delivery of paclitaxel and the control group.Conclusion1. A short-term release of paclitaxel with local intra-arterial administration could effectively suppress the neointimal hyperplasia in the long term(28days in the experiment), especially the high concentration(240μg/μl)10min group.2. A short-term release of paclitaxel with local intra-arterial administration could significantly inhibit the smooth muscle cell proliferation, meanwhile, have no influence on the expression of endothelialization and inflammation.3. In this pilot trial, local delivery of paclitaxel with balloon catheter did not reduce restenosis in patients undergoing bare metal stenting of femoropopliteal arteries.4. Local delivery of paclitaxel with balloon catheter was safe and caused no obvious adverse events.