Composite Of Bfgf In The Pcl / Plga Heparinized Stent Revascularization Experimental Research

Objective.Coronary artery disease remains the leading cause of morbidity and mortality in the world.Approximately 12%of patients with coronary artery disease,because of unfavorable characteristics such as diffuse coronary atherosclerosis,small distal vessels or lack of suitable bridge vessels,are not amenable to coronary artery bypass grafting(CABG) or percutaneous coronary intervention(PCI).In this setting,transmyocardial laser revascularization(TMLR) derived from the idea of myocardial sinusoids has been explored, however,histologic observations in experimental specimens and clinical postmortem studies have demonstrated initial thrombus and eventually entire obliteration of the channels.The objective of this study,by producing transmural channels of 3.0mm in diameter and then implanting heparinized bFGF-incorporating PCL/PLGA stentts,is to investigate the potentiality of channel patency and new vessels density,and further study the concomitant efficacy in improving myocardial perfusion and function.Methods.(1) By electrospinning technology,solvent casting and surface spraying,a kind of novel heparinized bFGF-incorporating PCL/PLGA bilayer stent was fabricated.(2) Evaluate the feasibility of transmyocardial drilling revascularization(TMDR) and stent implantation,and the potential injury to the heart.(3) After myocardial infarction model,the miniswines were grouped:Control Group, TMDR Group,TMDR with Blank Stentt Group(TMDR-BS group) and TMDR with Heparinized Stent Group(TMDR-HS Group),and investigated the channel patency and myocardial perfusion improvement.(4) Based on the long-term patency of the heparinized channel,the miniswines were grouped:TMDR with Blank Stent Group(TMDR-BS Group),TMDR with Heparinized Stentt Group(TMDR-HS Group),and TMDR with Heparinized bFGF-incorporating Stentt Group(TMDR-HBS Group),and evaluated whether heparinized bFGF-incorporating stent could further enhance myocardial perfusion and function by the biologically synergetic role of bFGF and heparin.Results.(1) Each PCL/PLGA stent,with 25mg heparin and 15μg bFGF,could keep original shape and maintain control-release of heparin and bFGF for 4 weeks.(2) Both TMDR and stent implantation were accomplished readily,without any side effects,such as embolism,bleeding,and hemodynamic abnormality.(3) In TMDR and TMDR-BS group,the channels were occluded 6 weeks later. However,heparinized stent could keep the channel patent and induce luminal endothelialization.In TMDR-HS group,the neovascular density significantly increased, mass defect percentage(MDP%) of myocardial perfusion and fractional shortening(FS%) in TMDR-HBS group also revealed significant improvements compared with other groups (P＜0.05).(4) In TMDR-HBS group,pro-angiogenic factors ofVEGF,vWF,TGF-β3,IL-1βmarkedly expressed.Vascular density and MDP%significantly increased compared with TMDR-BS and TMDR-HS group(P＜0.05).FS%in both TMDR-HBS and TMDR-HS group significantly improved compared with TMDR-BS group(P＜0.001),however,there existed a trend towards improvement between TMDR-HBS and TMDR-HS group (P=0.058),although no statistical difference was revealed.Conclusions.PCL/PLGA bilayer stent could withstand recurrent crushing in vivo and maintain original contour.The stent with heparinized procedure could keep the channel open and promote luminal endothelialization by continuous anticoagulation.The control-released heparin and bFGF promoted neovascular formation and collateral development,and further improved cardiac function by increasing blood flow perfusion of ischemic "hibernated" myocardium.