Krupski W C, Bass A, Anderson J S, Kelly A B, Harker L A
Department of Medicine, Emory University School of Medicine, Atlanta, Ga.
Surgery. 1990 Aug;108(2):283-90; discussion 290-1.
We have compared the acute antithrombotic effects of aspirin-treated versus normal endothelial cell (EC) coverage of endarterectomized baboon aortic segments (EAS) incorporated into chronic exteriorized arteriovenous shunts in baboons. Human ECs grown in culture were incubated in control medium or medium containing aspirin (100 mumols/ml) and then attached at saturation density by incubating EC suspensions (6 x 10(5) cells/100 microliters) within EAS for 20 minutes. Nonendarterectomized aortic segments and untreated EAS served as negative and positive controls, respectively. The inhibitory effect of aspirin treatment on EC production of prostacyclin was confirmed by radioimmunoassay of its stable metabolic breakdown product, 6-keto-prostaglandin F1 alpha in supernatant medium. Thrombus formation in vivo was measured as the accumulation of indium 111-labeled platelets on endarterectomy sites in real time by scintillation camera imaging. 111In-labeled platelets were deposited rapidly, reaching a plateau by 60 minutes of 4.40 +/- 0.89 x 10(9) platelets/cm, compared with 111In-labled platelet deposition on nonendarterectomized segments of 0.89 +/- 0.26 x 10(9) platelets/cm (p = 0.008). Coverage of EAS with normal cultured ECs significantly reduced platelet deposition on EAS (1.05 +/- 0.45 x 10(9) platelets/cm; p = 0.009 at 1 hour compared with EAS not incubated with ECs). Aspirin-treated ECs also produced a marked reduction in platelet disposition (0.71 +/- 0.24 x 10 platelets/cm; p = 0.007 compared with EAS without ECs) that was equivalent to the effect of non-aspirin-treated ECs (p greater than 0.5). Scanning and transmission electron microscopy confirmed the antithrombotic effects of attached ECs. We conclude that endarterectomy of normal arteries produces a highly thrombogenic surface and the thrombogenicity is abolished by acutely attaching cultured human ECs.
我们比较了阿司匹林处理的与正常内皮细胞（EC）覆盖的狒狒动脉内膜切除术后主动脉段（EAS）的急性抗血栓形成作用，这些主动脉段被植入狒狒慢性外置动静脉分流术中。将培养的人内皮细胞在对照培养基或含阿司匹林（100μmol/ml）的培养基中孵育，然后通过在EAS内孵育EC悬液（6×10⁵细胞/100微升）20分钟以饱和密度附着。未进行动脉内膜切除术的主动脉段和未处理的EAS分别作为阴性和阳性对照。通过对上清液培养基中其稳定代谢分解产物6-酮-前列腺素F1α进行放射免疫测定，证实了阿司匹林处理对EC产生前列环素的抑制作用。通过闪烁相机成像实时测量体内血栓形成，即铟111标记的血小板在动脉内膜切除部位的积聚。铟111标记的血小板迅速沉积，到60分钟时达到平台期，为4.40±0.89×10⁹血小板/cm，相比之下，铟111标记的血小板在未进行动脉内膜切除术的段上的沉积为0.89±0.26×10⁹血小板/cm（p = 0.008）。用正常培养的EC覆盖EAS显著减少了血小板在EAS上的沉积（1.05±0.45×10⁹血小板/cm；与未与EC孵育的EAS相比，1小时时p = 0.009）。经阿司匹林处理的EC也使血小板沉积显著减少（0.71±0.24×10血小板/cm；与没有EC的EAS相比，p = 0.007），这与未用阿司匹林处理的EC的效果相当（p＞0.5）。扫描和透射电子显微镜证实了附着的EC的抗血栓形成作用。我们得出结论，正常动脉的动脉内膜切除术产生高度血栓形成的表面，而通过急性附着培养的人EC可消除血栓形成性。
