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达比加群的围手术期三联疗法可改善猪冠状动脉支架置入模型中的血管运动并促进内皮化。

Peri-interventional Triple Therapy With Dabigatran Improves Vasomotion and Promotes Endothelialization in Porcine Coronary Stenting Model.

作者信息

Hemetsberger Rayyan, Farhan Serdar, Lukovic Dominika, Zlabinger Katrin, Hajagos-Toth Judit, Bota Judit, Garcia-Garcia Hector M, Ay Cihan, Samaha Eslam, Gaspar Robert, Garamvölgyi Rita, Huber Kurt, Gyöngyösi Mariann, Spannbauer Andreas

机构信息

Department of Cardiology and Angiology, University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany.

Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

出版信息

Front Cardiovasc Med. 2021 Jul 2;8:690476. doi: 10.3389/fcvm.2021.690476. eCollection 2021.

Abstract

We evaluated the short and long-term effect of peri-interventional dabigatran therapy on vasomotion, endothelialization, and neointimal formation in a porcine coronary artery stenting model. Stenting of coronary arteries induces local inflammation, impairs vasomotion and delays endothelialization. Twenty-eight animals underwent percutaneous coronary intervention (PCI) with drug eluting stents. Sixteen pigs started dabigatran therapy 4 days prior to PCI and continued for 4 days post-stenting, while 12 animals served as controls. Post-stenting dual antiplatelet therapy (75 mg clopidogrel and 100 mg aspirin) was continued in both groups until termination. Immediately post-stenting and at day 3 optical coherence tomography (OCT) was performed in all animals, followed by euthanasia of 8 dabigatran and 4 control animals. The remaining pigs (8 of each group) were followed up for 1 month, with control angiography and OCT. Tissue burden (degree of peri-strut structure-thrombus and/or fibrin) was evaluated. After euthanasia coronary arteries were harvested for myometry and histology. Thrombin generation was lower ( < 0.001) and tissue burden (0.83 ± 0.98 vs. 3.0 ± 2.45; = 0.031) was significantly decreased in dabigatran treated animals. After 3 days post-PCI endothelium-dependent vasodilation was significantly improved (77 ± 40% vs. 41 ± 31%, = 0.02) in dabigatran animals. Neither quantitative angiography nor histomorphometry showed differences between the groups. Endothelialization was faster in the dabigatran group as compared with controls ( = 0.045). Short-term peri-interventional triple therapy with dabigatran, aspirin, and clopidogrel led to an enhanced endothelium dependent vasodilation and faster endothelialization. However, neointimal formation 1-month after stent implantation was comparable between groups.

摘要

我们在猪冠状动脉支架置入模型中评估了围介入期达比加群治疗对血管运动、内皮化和新生内膜形成的短期和长期影响。冠状动脉支架置入会引发局部炎症,损害血管运动并延迟内皮化。28只动物接受了药物洗脱支架的经皮冠状动脉介入治疗(PCI)。16头猪在PCI前4天开始使用达比加群治疗,并在支架置入后持续4天,而12只动物作为对照。两组均持续进行支架置入后双联抗血小板治疗(75毫克氯吡格雷和100毫克阿司匹林)直至实验结束。所有动物在支架置入后即刻和第3天进行光学相干断层扫描(OCT),随后对8只接受达比加群治疗的动物和4只对照动物实施安乐死。其余猪(每组8只)随访1个月,进行对照血管造影和OCT检查。评估组织负荷(支架周围结构 - 血栓和/或纤维蛋白的程度)。安乐死后,采集冠状动脉用于肌测法和组织学检查。达比加群治疗的动物凝血酶生成较低(<0.001),组织负荷显著降低(0.83±0.98对3.0±2.45;P = 0.031)。PCI后3天,达比加群治疗的动物内皮依赖性血管舒张显著改善(77±40%对41±31%,P = 0.02)。定量血管造影和组织形态计量学在两组之间均未显示出差异。与对照组相比,达比加群组的内皮化更快(P = 0.045)。围介入期短期使用达比加群、阿司匹林和氯吡格雷三联疗法可增强内皮依赖性血管舒张并加快内皮化。然而,支架植入后1个月两组之间新生内膜形成情况相当。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ab2/8300015/e72ba9903b6f/fcvm-08-690476-g0001.jpg

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