The attenuation of platelet and monocyte activation in a rabbit model of extracorporeal circulation by a nitric oxide releasing polymer.
The attenuation of platelet and monocyte activation in a rabbit model of extracorporeal circulation by a nitric oxide releasing polymer.
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DOI：
10.1016/j.biomaterials.2009.12.028
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发表时间：
2010-04
期刊：
影响因子：
14
通讯作者：
Annich, Gail M.
中科院分区：
文献类型：
--
作者：
Major, Terry C.;Brant, David O.;Reynolds, Melissa M.;Bartlett, Robert H.;Meyerhoff, Mark E.;Handa, Hitesh;Annich, Gail M.
关键词：
一氧化氮（NO）已被证明通过减少血小板和单核细胞的表面糖蛋白，P-选择素和整合素，CD 11b，分别激活减少血栓形成。为了防止暴露于体外循环（ECC）时的血小板和单核细胞活化，使用流式细胞术在4小时家兔血栓形成模型中评价了由增塑聚氯乙烯（PVC）与亲脂性N-二醇二氮烯鎓混合组成的一氧化氮释放（NORel）聚合物涂层。在4小时血液暴露后，与聚合物对照相比，NORel聚合物显著减少ECC血栓形成（2.8 ± 0.7 NORel对比6.7 ± 0.4像素/cm 2对照）。在NORel与对照ECC中暴露4小时后，血小板计数（3.4 ± 0.3 NORel vs 2.3 ± 0.3 × 108/ml对照）和通过聚集测定法测量的功能（71 ± 3 NORel vs 17 ± 6%对照）保持不变。NORel组和对照组血浆纤维蛋白原水平均显著降低。通过流式细胞术测量的血小板P-选择素平均荧光强度（MFI）在ECC至离体胶原刺激4小时后减弱（27 ± 1 NORel vs 40 ± 2 MFI对照）。在使用NORel聚合物的ECC上4小时后，单核细胞CD 11b表达降低（87 ± 14 NORel vs 162 ± 30 MFI对照）。这些结果表明，NORel聚合物涂层减弱了暴露于ECC的血液中血小板P-选择素和单核细胞CD 11b整联蛋白表达的增加。这些NO介导的血小板和单核细胞的变化显示出改善这些用于生物医学装置的NORel聚合物涂覆的ECC的抗血栓性。
Nitric oxide (NO) has been shown to reduce thrombogenicity by decreasing platelet and monocyte activation by the surface glycoprotein, P-selectin and the integrin, CD11b, respectively. In order to prevent platelet and monocyte activation with exposure to an extracorporeal circulation (ECC), a nitric oxide releasing (NORel) polymeric coating composed of plasticized polyvinyl chloride (PVC) blended with a lipophilic N-diazeniumdiolate was evaluated in a 4 hour rabbit thrombogenicity model using flow cytometry. The NORel polymer significantly reduced ECC thrombus formation compared to polymer control after 4 hours blood exposure (2.8 ± 0.7 NORel vs 6.7 ± 0.4 pixels/cm2 control). Platelet count (3.4 ± 0.3 NORel vs 2.3 ± 0.3 × 108/ml control) and function as measured by aggregometry (71 ± 3 NORel vs 17 ± 6 % control) were preserved after 4 hours exposure in NORel versus control ECC. Plasma fibrinogen levels significantly decreased in both NORel and control groups. Platelet P-selectin mean fluorescence intensity (MFI) as measured by flow cytometry was attenuated after 4 hours on ECC to ex vivo collagen stimulation (27 ± 1 NORel vs 40 ± 2 MFI control). Monocyte CD11b expression was reduced after 4 hours on ECC with NORel polymer (87 ± 14 NORel vs 162 ± 30 MFI control). These results suggest that the NORel polymer coatings attenuate the increase in both platelet P-selectin and monocytic CD11b integrin expression in blood exposure to ECCs. These NO-mediated platelet and monocytic changes were shown to improve thromboresistance of these NORel-polymer-coated ECCs for biomedical devices.
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