CVPath Institute, Inc., 19 Firstfield Road, Gaithersburg, MD 20878, United States of America; Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany.
CVPath Institute, Inc., 19 Firstfield Road, Gaithersburg, MD 20878, United States of America.
Cardiovasc Revasc Med. 2022 Feb;35:129-138. doi: 10.1016/j.carrev.2021.03.023. Epub 2021 Apr 8.
Cytokine storm-related hypercoagulation may be important in the pathogenesis of stent thrombosis in patients with SARS-CoV-2. Whether stent polymers behave differently under such conditions has never been explored.
Fluorinated polymer-nanocoated and uncoated COBRA stents (CeloNova), BioLinx-polymer-coated Resolute Onyx stents (Medtronic), and Synergy stents (Boston Scientific), which are abluminally coated with a bioabsorbable polymer, were exposed to human blood from healthy donors which was supplemented with 400 pg/mL IL-6 and 100 pg/mL TNF-α, similar to what is seen in cytokine storm caused by SARS-CoV-2. Platelet adhesion and neutrophil activation, assessed by immunofluorescence, were compared under cytokine storm and control conditions (untreated blood) (n = 4 experimental runs).
Platelet adhesion values, defined as %platelet-covered area x staining intensity, were significantly lower in coated and uncoated COBRA and in Resolute Onyx than in Synergy under control conditions (1.28 × 10 ± 0.43 × 10 vs. 2.92 × 10 ± 0.49 × 10 vs. 3.57 × 10 ± 0.73 × 10 vs. 9.94 × 10 ± 0.99 × 10; p ≤0.0001). In cytokine storm, platelet adhesion values remained low in coated COBRA-PzF (1.78 × 10 ± 0.38 × 10) compared to all other devices (uncoated COBRA: 5.92 × 10 ± 0.96 × 10; Resolute Onyx: 7.27 × 10 ± 1.82 × 10; Synergy: 11.28 × 10 ± 1.08 × 10; p ≤ 0.0001). Although cytokine storm conditions significantly increased neutrophil activation in all stents, it was significantly less in coated and uncoated COBRA, and in Resolute Onyx than in Synergy.
Blood-biomaterials interactions may determine the thrombogenic potential of stents. Under simulated cytokine storm conditions, fluoropolymer-coated stents showed the most favorable anti-thrombogenic and anti-inflammatory properties.
细胞因子风暴相关的高凝状态可能在 SARS-CoV-2 患者的支架血栓形成发病机制中起重要作用。在这种情况下,支架聚合物的行为是否不同,尚未得到探索。
用健康供体的人血(补充了 400pg/mL 的白细胞介素-6 和 100pg/mL 的肿瘤坏死因子-α)处理氟聚合物纳米涂层和未涂层的 COBRA 支架(CeloNova)、BioLinx 聚合物涂层的 Resolute Onyx 支架(美敦力)和 Synergy 支架(波士顿科学),这些支架的内表面涂有生物可吸收聚合物,使其暴露于类似 SARS-CoV-2 引起的细胞因子风暴的条件下。通过免疫荧光法评估血小板黏附和中性粒细胞激活,并在细胞因子风暴和对照条件(未处理的血液)下进行比较(n=4 个实验运行)。
在对照条件下,与 Synergy 支架相比,涂层和未涂层的 COBRA 和 Resolute Onyx 支架的血小板黏附值(定义为血小板覆盖面积×染色强度)显著降低(1.28×10±0.43×10 比 2.92×10±0.49×10 比 3.57×10±0.73×10 比 9.94×10±0.99×10;p≤0.0001)。在细胞因子风暴中,与其他所有器械相比,涂层 COBRA-PzF 的血小板黏附值仍较低(1.78×10±0.38×10)(未涂层 COBRA:5.92×10±0.96×10;Resolute Onyx:7.27×10±1.82×10;Synergy:11.28×10±1.08×10;p≤0.0001)。尽管细胞因子风暴条件显著增加了所有支架中的中性粒细胞激活,但在涂层和未涂层的 COBRA 以及 Resolute Onyx 中,其程度明显低于 Synergy。
血液-生物材料相互作用可能决定支架的血栓形成潜力。在模拟细胞因子风暴条件下,氟聚合物涂层支架显示出最有利的抗血栓形成和抗炎特性。