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在成年家族性高胆固醇血症猪模型中,药物洗脱支架植入术后,斑块负担与最小内膜覆盖相关。

Plaque burden is associated with minimal intimal coverage following drug-eluting stent implantation in an adult familial hypercholesterolemia swine model.

机构信息

Department of Cardiology, Erasmus MC, Dr. Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.

Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.

出版信息

Sci Rep. 2023 Jul 1;13(1):10683. doi: 10.1038/s41598-023-37690-0.

Abstract

Safety and efficacy of coronary drug-eluting stents (DES) are often preclinically tested using healthy or minimally diseased swine. These generally show significant fibrotic neointima at follow-up, while in patients, incomplete healing is often observed. The aim of this study was to investigate neointima responses to DES in swine with significant coronary atherosclerosis. Adult familial hypercholesterolemic swine (n = 6) received a high fat diet to develop atherosclerosis. Serial OCT was performed before, directly after, and 28 days after DES implantation (n = 14 stents). Lumen, stent and plaque area, uncovered struts, neointima thickness and neointima type were analyzed for each frame and averaged per stent. Histology was performed to show differences in coronary atherosclerosis. A range of plaque size and severity was found, from healthy segments to lipid-rich plaques. Accordingly, neointima responses ranged from uncovered struts, to minimal neointima, to fibrotic neointima. Lower plaque burden resulted in a fibrotic neointima at follow-up, reminiscent of minimally diseased swine coronary models. In contrast, higher plaque burden resulted in minimal neointima and more uncovered struts at follow-up, similarly to patients' responses. The presence of lipid-rich plaques resulted in more uncovered struts, which underscores the importance of advanced disease when performing safety and efficacy testing of DES.

摘要

冠状动脉药物洗脱支架(DES)的安全性和疗效通常在健康或轻度患病的猪中进行临床前测试。这些猪通常在随访时显示出明显的纤维性新生内膜,而在患者中,常观察到不完全愈合。本研究旨在研究在患有严重冠状动脉粥样硬化的猪中 DES 对新生内膜的反应。成年家族性高胆固醇血症猪(n=6)接受高脂肪饮食以发展动脉粥样硬化。在 DES 植入前(n=14 个支架)、直接植入后和 28 天后进行了一系列 OCT 检查。对每个支架进行了管腔、支架和斑块面积、未覆盖的支架、新生内膜厚度和新生内膜类型的分析,并对每个支架进行了平均。进行了组织学检查以显示冠状动脉粥样硬化的差异。发现斑块大小和严重程度的范围从健康节段到富含脂质的斑块。因此,新生内膜反应范围从未覆盖的支架、最小的新生内膜到纤维性新生内膜。较低的斑块负担导致随访时出现纤维性新生内膜,类似于轻度患病猪的冠状动脉模型。相比之下,较高的斑块负担导致随访时出现最小的新生内膜和更多未覆盖的支架,与患者的反应相似。富含脂质的斑块的存在导致更多的未覆盖支架,这凸显了在进行 DES 的安全性和疗效测试时,存在严重疾病的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/74b4/10314904/d74506f48cf5/41598_2023_37690_Fig1_HTML.jpg

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