The hemocompatibility of a nitric oxide generating polymer that catalyzes S-nitrosothiol decomposition in an extracorporeal circulation model.
The hemocompatibility of a nitric oxide generating polymer that catalyzes S-nitrosothiol decomposition in an extracorporeal circulation model.
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一氧化氮产生聚合物的血流相容性，该聚合物在体外循环模型中催化S-硝基硫醇分解。
DOI：
10.1016/j.biomaterials.2011.03.036
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发表时间：
2011-09
期刊：
影响因子：
14
通讯作者：
Bartlett, Robert H.
中科院分区：
文献类型：
--
作者：
Major, Terry C.;Brant, David O.;Burney, Charles P.;Amoako, Kagya A.;Annich, Gail M.;Meyerhoff, Mark E.;Handa, Hitesh;Bartlett, Robert H.
关键词：
先前已证明，一氧化氮（NO）生成（NOGen）材料通过含铜（Cu）聚合物涂层催化分解血液S-亚硝基硫醇（RSNO），可局部增加NO浓度，并可改善体外循环（ECC）血液相容性。在这项工作中，NOGen聚合物涂层组成的CuO-纳米粒子（80 nm）-含有亲水性聚氨酯（SP-60 D-60）与RSNO，S-亚硝基-N-乙酰青霉胺（SNAP）的静脉输注，在4小时兔血栓形成模型中进行了评估，并研究了抗血栓形成机制。含有10重量%的聚合物膜与全身SNAP施用（0.1182 μmol/kg/min）同时使用涂覆在ECC回路的内壁上的Cu 〇-纳米颗粒，以产生与聚合物对照+全身SNAP或10重量%在4小时血液暴露后，Cu NOGen +全身盐水（0.4 ± 0.2 NOGen/SNAP vs 4.9 ± 0.5对照/SNAP或3.2 ± 0.2像素/cm 2 NOGen/盐水）。与对照/SNAP或NOGen/盐水组相比，NOGen/SNAP组合在4小时血液暴露后，血小板计数（3.9 ± 0.7 NOGen/SNAP vs 1.8 ± 0.1对照/SNAP或3.0 ± 0.2 × 108/ml NOGen/盐水）和血浆纤维蛋白原水平得以保持。在NOGen/SNAP和NOGen/盐水组中，通过聚集测定法测量的血小板功能（51 ± 9 NOGen/SNAP对49 ± 3%NOGen/盐水）显著降低，而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小时后没有降低（26 ± 2NOGen/SNAP对29 ± 1 MFI基线）。蛋白质印迹法显示，在用NOGen/SNAP的ECC上4小时后，通过Aγ二聚体表达评估的纤维蛋白原活化减少（68 ± 7 vs 83 ± 3%对照/SNAP）。这些结果表明，与SNAP输注组合的NOGen聚合物涂层通过减弱活化的纤维蛋白原和防止血小板聚集来保护暴露于ECC的血液中的血小板。当存在足够水平的RSNO时，这些NO介导的血小板变化显示出改善NOGen聚合物涂覆的ECC的抗血栓性。
Nitric oxide (NO) generating (NOGen) materials have been shown previously to create localized increases in NO concentration by the catalytic decomposition of blood S-nitrosothiols (RSNO) via copper (Cu)-containing polymer coatings and may improve extracorporeal circulation (ECC) hemocompatibility. In this work, a NOGen polymeric coating composed of a Cuo-nanoparticle (80 nm)-containing hydrophilic polyurethane (SP-60D-60) combined with the intravenous infusion of an RSNO, S-nitroso-N-acetylpenicillamine (SNAP), is evaluated in a 4 h rabbit thrombogenicity model and the anti-thrombotic mechanism is investigated. Polymer films containing 10 wt.% Cuo-nanoparticles coated on the inner walls of ECC circuits are employed concomitantly with systemic SNAP administration (0.1182 μmol/kg/min) to yield significantly reduced ECC thrombus formation compared to polymer control + systemic SNAP or 10 wt.% Cu NOGen + systemic saline after 4 h blood exposure (0.4 ± 0.2 NOGen/SNAP vs 4.9 ± 0.5 control/SNAP or 3.2 ± 0.2 pixels/cm2 NOGen/saline). Platelet count (3.9 ± 0.7 NOGen/SNAP vs 1.8 ± 0.1 control/SNAP or 3.0 ± 0.2 × 108/ml NOGen/saline) and plasma fibrinogen levels were preserved after 4 h blood exposure with the NOGen/SNAP combination vs either the control/SNAP or the NOGen/saline groups. Platelet function as measured by aggregometry (51 ± 9 NOGen/SNAP vs 49 ± 3% NOGen/saline) significantly decreased in both the NOGen/SNAP and NOGen/saline groups while platelet P-selectin mean fluorescence intensity (MFI) as measured by flow cytometry was not decreased after 4 h on ECC to ex vivo collagen stimulation (26 ± 2 NOGen/SNAP vs 29 ± 1 MFI baseline). Western blotting showed that fibrinogen activation as assessed by Aγ dimer expression was reduced after 4 h on ECC with NOGen/SNAP (68 ± 7 vs 83 ± 3% control/SNAP). These results suggest that the NOGen polymer coating combined with SNAP infusion preserves platelets in blood exposure to ECCs by attenuating activated fibrinogen and preventing platelet aggregation. These NO-mediated platelet changes were shown to improve thromboresistance of the NOGen polymer-coated ECCs when adequate levels of RSNOs are present.
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DOI：
10.1073/pnas.142136499
发表时间：
2002-07-09
影响因子：
11.1
作者：
Akhter, S;Vignini, A;Mutus, B
通讯作者：
Mutus, B
影响因子：
--
作者：
Massaguer, A;Engel, P;Pizcueta, P
通讯作者：
Pizcueta, P
影响因子：
14
作者：
Major, Terry C.;Brant, David O.;Reynolds, Melissa M.;Bartlett, Robert H.;Meyerhoff, Mark E.;Handa, Hitesh;Annich, Gail M.
通讯作者：
Annich, Gail M.
影响因子：
7.3
作者：
Batchelor, MM;Reoma, SL;Meyerhoff, ME
通讯作者：
Meyerhoff, ME
影响因子：
3
作者：
Burg, A;Cohen, H;Meyerstein, D
通讯作者：
Meyerstein, D