Hagen P O, Wang Z G, Mikat E M, Hackel D B
Ann Surg. 1982 Mar;195(3):328-39. doi: 10.1097/00000658-198203000-00014.
While the use of prosthetic grafts in small diameter arterial reconstruction is required when suitable autogenous graft material is unavailable, late occlusion of prosthetic grafts caused by proliferative lesions has been described. This study evaluated the suitability of 3-mm (ID) microporous polytetrafluoroethylene (PTFE) Gore-Tex grafts inserted in the abdominal aorta of eight nonhuman primates (Macaca fascicularis), and the effects of prolonged antiplatelet treatment on both graft patency and the development of intimal hyperplasia in the adjacent vasculature. Four monkeys received antiplatelet medication consisting of aspirin (163 mg twice daily) and dipyridamole (25 mg twice daily). When killed at four months following graft insertion, all four grafts in the antiplatelet medicated group were patent, while in the control group, only two of four grafts were patent. Histologic examination and quantitative photogravitometric evaluation of the degree of luminal narrowing were performed on all grafts and the adjacent vasculature. These studies revealed that while all graft and aortic segments showed varying amounts of intimal thickening, occlusions in the control animals were related to intimal hyperplasia in the host aorta at the site of the distal anastomosis. Intimal hyperplasia in all aortic segments examined distal to the graft was significantly reduced by antiplatelet therapy. Electronmicroscopy showed that smooth muscle cells were the predominant cells of the intimal thickening of the aorta (intimal hyperplasia), and that proliferation of these cells did not extend into the graft itself. The predominant cell population of the intimal thickening of the graft were of the myofibroblast type (neointimal hyperplasis). The luminal surface of the graft was lined with cells that had some but not all of the characteristics of mature endothelial cells. In vitro studies confirmed global interference with platelet function and arachidonic acid metabolism in medicated animals. Medication inhibited platelet cyclo-oxygenase without affecting platelet lipoxygenase, thromboxane synthetase, or prostacyclin-like activity in undisturbed arteries. This study shows that severe intimal hyperplasia develops rapidly in the recipient vessel adjacent to small diameter Gore-Tex grafts, and that the severity of the response is reduced by antiplatelet agents. Histologic examination revealed that the intimal thickening in the graft and the adjacent aortic segments were composed of cells that were not morphologically identical, suggesting two separate aetiologies and the possible need to use different approaches in their prevention.
当无法获得合适的自体移植材料时,小直径动脉重建就需要使用人工血管,但人工血管因增殖性病变导致的晚期闭塞已有报道。本研究评估了内径3毫米的微孔聚四氟乙烯(PTFE)戈尔特斯人工血管植入8只食蟹猴腹主动脉的适用性,以及长期抗血小板治疗对人工血管通畅性和相邻血管内膜增生发展的影响。4只猴子接受了由阿司匹林(每日2次,每次163毫克)和双嘧达莫(每日2次,每次25毫克)组成的抗血小板药物治疗。在植入人工血管4个月后处死动物时,抗血小板药物治疗组的4根人工血管均保持通畅,而对照组的4根人工血管中只有2根通畅。对所有人工血管及其相邻血管进行了组织学检查和管腔狭窄程度的定量光密度测定评估。这些研究表明,虽然所有人工血管段和主动脉段都显示出不同程度的内膜增厚,但对照组动物的闭塞与远端吻合口处宿主主动脉的内膜增生有关。抗血小板治疗显著减少了人工血管远端所有检查的主动脉段的内膜增生。电子显微镜显示,平滑肌细胞是主动脉内膜增厚(内膜增生)的主要细胞,且这些细胞的增殖未延伸至人工血管本身。人工血管内膜增厚的主要细胞群是肌成纤维细胞类型(新生内膜增生)。人工血管的管腔表面衬有具有一些但并非全部成熟内皮细胞特征的细胞。体外研究证实,用药动物的血小板功能和花生四烯酸代谢受到全面干扰。药物抑制了血小板环氧化酶,而不影响未受干扰动脉中的血小板脂氧化酶、血栓素合成酶或前列环素样活性。本研究表明,小直径戈尔特斯人工血管相邻的受体血管中会迅速出现严重的内膜增生,且抗血小板药物可减轻这种反应的严重程度。组织学检查显示,人工血管和相邻主动脉段的内膜增厚由形态不同的细胞组成,提示有两种不同的病因,可能需要采用不同的预防方法。