Experimental Study To Evaluate The Safety And Efficacy Of The Novel Polymer-Free Drug-eluting Stents

Objective: It has been approved that the late adverse events after drugeluting stent implantation associated with the residual polymer coating inlong term. The purpose of this study is to evaluate the safety andefficacy of the novel polymer-free drug-eluting stents compared with thebare metal stent or the first generation DES in porcine. Additionally, wealso evaluate the feasibility of optical cohehence tomography (OCT) forassessing neointimal response after stent implantation compared withintravascular ultrasound (IVUS) and histopathology.Method: a bare metal stent, a first generation drug-eluting stent and4types novel polymer-free drug-eluting stents were implanted in porcinecoronary arteries:①bare metal stent(BMS group, n=9);②first generationsirolimus-eluting stent(SES group, n=10);③NANOTMpolymer-freesirolimus-eluting stent(NANO group, n=10);④YUKONTMpolymer-freesirolimus-eluting stent(YUKON group, n=5)⑤YUKONTMpolymer-freesirolimus-and probucol-eluting stent(DD group, n=5);⑥endothelialprogenitor cells capture anti-CD34antibody and sirolimus-elutingcombination stent(EPC group, n=10). Morphometric evaluation usingOCT and IVUS were performed in all stented arteries at14days and28days after stents implantation. endothelium-dependent vasomotor function were assessed at28days. Each porcine was euthanized, andhistopathological morphometric analysis was performed and correlatedOCT and IVUS. In addition, the vessel wall inflammatory response wereanalyzed using histopathological measurement.Result: at14days after implantation, mean lumen area, mineral lumenarea were all significantly higher in all polymer-free drug-eluting stentsgroups than in the BMS group or the SES group. In contract, lumenstenosis, late lumen loss, neointimal thickness and neointimal area wereless in the4types polymer-free drug-eluting stents than in BMS or SES,but no significant differences existed among4types polymer-freedrug-eluting stents. In addition, OCT observed that uncovered struts andstent malapposition were higher than other groups(1.28%，0.29%，P<0.05). Inflammatory response was detected in all of groups, but thepercentage of3degree of inflammation score was significantly higher inSES group（NANO group18.9%，DD group6.7%，YUKON6.8%，EPCgroup4.4%，SES30%，P<0.05）.At28days after implantation, OCT, IVUS and histopathology revealedthat the neointimal thickness and neointimal area were increased in allgroups compared with that at14days. The mean lumen area, minerallumen area were higher, as well as lumen stenosis, late lumen loss,neointimal thickness and neointimal area were lower in NANO group andEPC group than that in BMS and SES groups. While OCT demonstrated that the lumen stenosis rate in NANO group was lower then than in EPCgroup(23.31±0.79%，31.74±1.02%， P<0.05).The histopathologyidentified significant reductions in the inflammatory response in all ofgroups compared with that at14days, but the percentage of3degree ofinflammation score was still higher in SES group than in other groups(SES11.1%，NANO6.5%，EPC2.2%，P<0.05）. Compared with SESand NANO groups, the inflammatory cell density in EPC group werelower(SES10,75±3.37，NANO8.36±1.34VS. EPC5.48±1.01，P<0.05).Endothelial function examination showed that endothelium-dependentrelaxation to substance P was decreased in SES and NANO groupscompared with BMS and EPC groups.The lumen area and stent lumen area measured by OCT were larger thanhistopathology, and lower than IVUS（4.56±1.24mm2VS.2.85±2.41mm2，3.03±1.26mm2，6.34±1.39mm2VS.4.16±1.2mm2,24.16±1.16mm2，P<0.05，P<0.05，respectively）.Although accuracy of OCT for theevaluation of mean neointimal thickness and uncovered struts weresimilar to histopathology（4.21±1.23mm2，4.16±1.16mm2，P>0.05）,whereas there was a poor correlation between OCT and histopathologywhen neointimal thickness was below80μm(80-60μm3.35%VS.1.84%,60-40μm4.76%VS.1.88%,40-20μm4.37%VS.2.35%,>20μm4.21%VS.4.41%, P<0.05, respectively). IVUS can not detected the uncoveredstruts and the neointimal thickness below100μm. In addition, OCT observed that the homogenous signals was more in BMS group（93.3%VS.31.3%，P<0.05）, on the contrary the heterogeneous signals was morein SES group（68.7%VS.6.3%，P<0.05）. Compared with histopathology,the level of inflammatory response in homogenous neointima was greaterthan in homogenous neointima.Conclusion:1. novel polymer-free drug-eluting stents are associated withhigh anti-restenostic efficacy and saftey.2. the study demonstrated that the polymer-free drug-eluting stentscombined with probucol or CD34antibody exhibited the low uncoveredstruts rate and inflammatory response.3. OCT has a high accuracy for assessment of neointimal proliferation,struts coverage, and also can be used to assess the component change ofneointimal after stent implantation in order to predict long-term safetyand efficacy of stent.