The Mechanism Of Biodegradable External Stent Reducing Intimal Hyperplasia Of Autologous Vein Graft

Objective: Coronary artery bypass grafting(CABG) using saphenous vein conduits remains thestandard for treatment of intractable angina due to coronary artery occlusive disease.However, its long-term clinical success is limited. Late vein graft failure is the result ofmedial and intimal thickening consequent upon medial vascular smooth muscle cellmigration, proliferation and extracellular matrix deposition, followed later by superimposedatherosclerosis. Vein graft wall thickening (ie, remodeling), may represent an adaptationimposed by arterial hemodynamic factors. It has been proved that external stent outsidesupporting on the vein grafting can reduces intimal hyperplasia, total wall thickness andatherosclerosis. Although there are a few short-time studies about biodegradable externalstent on vein grafting, the changes of vein grafting is unknow in a long time and themechanism of biodegradable external stent on vein grafting is unclear. We speculated thatthe protective effects of biodegradable external stent on vein grafting persistently exist afterstent biodegraded. Thus, in the present study, a poly(lactic acid/glycolic acid)(PLGA)biodegradable external stent was used outside of vein graft and the changes of vein graft wallmorphology, the character of mechanical property, and the proliferation and apoptosis, theenzymes relatived with ECM are estimated, in order to estimation of the feasibility and themechanism of the PLGA biodegradable external stent on reducing the intimal hypertrophy ofvein graft.Methods:1.The biological safety evaluation of PLGA According to the standards of biological evaluation of medical treatment ISO10993-1992 and GB/T16886.1-1997, we have made the research of the biological safety forPLGA in vitro and in vivo. The cytotoxicity test and subcutaneous implanting test wereconducted to evaluate the cytotoxicity, biocompatibility.2. The establishment of animal vein grafting model with the biodegradable external stent The compliant, biodegradable prostheses were prepared from 85/15(wt,v/v%) PLGA.The prosthesis had an internal diameter of 4 mm and a length of 8 cm. 20 dogs weighting15-20kg were used in the present study. Animals were anesthesized with intravenousinjection of sodium barbiturate. The femoral veins of both sides were harvested withno-touch technique and were inversely interposed to the artery of the same side with end toend anastomosis. In the stent group, the prosthesis was put out of the vein graft afterproximal anastomosis was finished (stent group). In the another side, the vein was onlytransplanted(control group). The grafts were evaluated at 3 days, 2 weeks, 4 weeks, 6weeks,12weeks after operation(n=4). All grafts were carefully harvested. Each of the specimenswas divided into three segments for rutine pathology,electron microscopy and westernblotting examination. Light microscopy was used for morphologic evaluation of the graftwalls. Scanning electron microscopy was used for evaluation of the endothelial lining.Human VIII factor relative antigen and smooth muscle cell α-actin antigen were examinedto evaluation endothelial cell line and smooth muscle cells.3. The machinal mechanism of PLGA external stent reducing intimal hyperplasia of veingraft The 5 dogs weighting 15-20kg were used in the present study. The animal model wassimilar with that in the second part. The veins were interposed in the same length. The bloodpressure was measured before and after vein transplantation. The blood velocity anddiameter were measured with echo after implantation, 12 weeks after operation. The wallshear stress(WSS) were calculated. The circumferential strain(CS) was assessed by P-V testbefore implantation and at 12weeks after implantation. Finally, the WSS and CS werecompared between stent and control groups.4. The biological mechanism of PLGA external stent reducing intimal hyperplasia of veingraft The same animal model was used in this experiment. The vein grafts were harveste...