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Optical Coherence Tomography Combined Pathological Evaluation Of Drug-eluting Stenting Delayed Intimal Healing And Atorvastatin Improve Neointimal Healing

Posted on:2013-01-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:T J WangFull Text:PDF
GTID:1114330374973838Subject:Internal Medicine
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Background:Delayed neointimal coverage and re-endothelialization after drug-eluting stent implantation are thought to be the underlying mechanisms of late stent thrombosis (LST).Methods and Results:Forty-five Chinese minipigs were divided into three groups (n=15each):bare metal stent (BMS), SES, and SES and atorvastatin treatment (SES+ator). Neointimal coverage and endothelium coverage were evaluated separately by optical coherence tomography (OCT), pathology, and scanning electron microscopy (SEM) at days7,14and28. OCT showed that SES significantly delayed neointimal coverage compared with BMS and the percentage of uncovered struts in the SES+ator group was significantly decreased on days7(42.7±1.3%vs56.8±5.7%, P<0.01) and14(24.8±4.3%vs45.3±2.8%, P<0.01) compared with the SES group. However, re-endothelialization was even more seriously delayed than the neointima formation after SES deployed (P<0.05). Pathology and SEM revealed improved re-endothelialization on the neointima by atorvastatin therapy in terms of more struts covered by endothelium, less platelet adhesion, and higher eNOS expression of the endothelial cells in the SES+ator group. Flow cytometry illustrated that the SES+ator group had more mobilized EPCs compared with the SES group at day7(0.21+0.02%vs0.11±0.03%, P=0.022).Conclusions:Atorvastatin pretreatment can accelerate both neointimal coverage and re-endothelialization after SES implantation which may be mediated by the mobilization of EPC and enhancement of the endothelial function of the neointima. Objective:To investigate whether monotherapy by clopidogrel without aspirin after drug-eluting stent implantation (DES) was effective to inhibite platelets activation and prevent stent thrombosis formation.Methods:Eighteen Chinese mini-porcine were randomized into3groups of bare metal stent (BMS)(n=6), sirolimus-eluting stent (SES)(control; n=6), and SES plus Ator group(atorvastatin; n=6). Each animal accepted300mg aspirine and300mg clopidogrel before stent implantation and100mg aspirin and75mg clopidogrel per day for7days after stent implantation. Then aspirine therapy was stopped and only75mg clopidogrel was given. Inhabitation of platelet was evaluated by platelet affregation test before PCI and at7days,14days,21days, and28days after PCI. The rate of stent thrombosis was observed by coronary angiography and optical coherence tomography (OCT). Stent thrombosis was then confirmed by pathology and the adhension of platelets on stents was evaluated by scanning electron microscopy (SEM).Results:The percentage of stent thrombosis was0%in the BMS group (0/6),16.7%in the SES group (1/6),33.3%in the SES+ator group (2/6), respectively. Although the BMS group and the SES+ator group showed better neointima coverage compared with the SES group at14days after PCI, there was no signigicant difference about the rate of stent thrombosis between the SES group and the SES+ator group (P=1.0). the percentage of stent coverage was77.3±8.0%,54.7±6.2%, and75.2±9.5%in the BMS, SES, and SES+ator group respectively. The result of pathology showed that the stent thrombosis was mainly formed on the stent struts without neointimal coverage. SEM revealed that the number of platelet adhension was9.7±9.7,21.9±17.9and18.0±20.9in the three groups respectively. The SES group and the SES+ator group had more platelets adhension than the BMS group at28days(P=0.014and P=0.052). there was no significant difference between the SES and the SES+ator group (P=0.41).Conclusion:mono antiplatelet therapy by clopigrel could not completely prevent stent thrombosis formation after DES implantation. although acceralted neointimal coverage was observed by atorvastatin therapy, no decrease of stent thrombosis was shown. Objective:To evaluate the neointimal coverage at the very early phase after sirolimus-(SES) and everolimus-eluting stent (EES) implantation using optical coherence tomography (OCT).Background:Previous studies usually focus on the delayed neointimal coverage at long term follow-up after drug-eluting stent (DES) implantation. The very early neointimal hyperplasia is seldom studied.Methods:Thirty-seven multi-vessel coronary artery disease patients who accepted OCT examination both at immediately post-intervention and follow-up were classified into either the7-day group (n=18patients,36stents) or the3-month group (n=19patients,33stents). The stent coverage and malapposition was analyzed using OCT.Results:18.7±16.6%and77.3±16.0%of the struts were covered at7days and3months, respectively. SES and hypertension were associated with a significantly lower percentage of stent coverage at3months (69.8±3.7%in SES vs85.6±5.9%in EES, P=0.003;64.5±4.2%vs80.9±4.2%, P=0.02, respectively). The stepwise linear regression analyses showed that the percentage of immediately malapposed struts (beta coefficient:0.3%,95%confidence interval:0.1%to0.5%, P=0.002) and chronic total occlusion (CTO)(beta coefficient:1.3%,95%confidence interval:0.2%to2.4%, P=0.018) could increase the percentage of struts malapposition in the3months follow-up.Conclusion:Neointimal coverage could be detected at one week after DES implantation by OCT. However, EES showed better neointimal coverage compared with SES. Hypertension could impact the neointimal coverage in the first3months. The rate of stent malapposition immediately after intervention and CTO may increase struts malapposition in the very early phase after DES implantation.
Keywords/Search Tags:optical coherence tomography, statins, drug-eluting stent, endothelialprogenitor cell, late stent thrombosis, eNOSatorvastatin, clopidogrel, opticalcoherence tomographyDrug-eluting stent, Optical coherence tomography, Neointimal coverage
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