Schleimer Karina, Jalaie Houman, Afify Mamdouh, Woitok Anna, Barbati Mohammad Esmaeil, Hoeft Konrad, Jacobs Michael, Tolba Rene H, Steitz Julia
Clinic of Vascular and Endovascular Surgery, Faculty of Medicine, RWTH Aachen University, 52074, Aachen, Germany.
Institute for Laboratory Animal Science, Faculty of Medicine, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
Acta Vet Scand. 2018 Jul 5;60(1):42. doi: 10.1186/s13028-018-0397-1.
In vascular surgery, novel synthetic prosthesis materials for patch-angioplasties, interpositions, bypasses and shunts are continuously under development and optimization. The characteristics of an ideal vascular prosthesis would display long-term patency, biocompatibility, durability, low porosity, lack of stich hole bleeding, ease of handling, kink resistance, infection resistance and reasonable costs. The aim of this study was to establish and report a reliable sheep model including potential pitfalls where those parameters could be analyzed. Before surgery, sheep were acclimatized for 4-8 weeks, during which parasite infections were treated and blood and serum parameters monitored. Twenty-four sheep underwent surgery, and carotid patch-angioplasties (n = 12), graft interpositions (n = 6) or arteriovenous prosthetic shunts (n = 6) were implanted. Half of the animals in each group were sacrificed after 2 weeks and the other half after 8 weeks. The implants were analyzed for patency, endothelialization, thrombogenicity and biocompatibility by clinical observation, blood flow measurement and pathological and histopathological (H&E, EvG) as well as immunohistochemical (Ki67, CD31) evaluations.
Health monitoring of the sheep revealed a parasitic burden with endoparasites in all animals. Some animals showed thereby infestations in the bile duct causing fibrotic cholangitis with calcifications in the liver. In addition, sarcosporidia were detected in histopathological specimen of the heart in all animals. Parasitic burden correlated with blood counts and serum bilirubin levels. Both were significantly reduced by albendazole treatment within the acclimatization time. Patches, interposition grafts, and straight shunts were successfully implanted bilaterally in all animals. The total average operation time was 136 ± 21 min. Most animals (23/24) showed good patency rates and general condition after implantation. Pathological and histopathological/immunohistochemical analyses were suitable to determine thrombogenicity, endothelialization, cellular/fibroblastic proliferation, biocompatibility, inflammatory cell infiltration, and thickness of neointima in the prosthesis material.
We have developed a suitable experimental protocol with standardized and successful anesthesia- and surgical-procedures for patch-angioplasty, graft interposition, and arteriovenous prosthetic shunts. This sheep model allows testing of new prosthetic materials for biocompatibility, thrombogenicity, and endothelialization.
在血管外科领域，用于补片血管成形术、血管间置术、旁路移植术和分流术的新型合成假体材料一直在不断研发和优化。理想的血管假体应具备长期通畅性、生物相容性、耐用性、低孔隙率、无缝合孔出血、易于操作、抗扭结、抗感染以及成本合理等特性。本研究的目的是建立并报告一种可靠的绵羊模型，包括可能存在的问题，以便对这些参数进行分析。手术前，绵羊需适应4 - 8周，在此期间治疗寄生虫感染并监测血液和血清参数。24只绵羊接受了手术，植入了颈动脉补片血管成形术（n = 12）、血管间置移植术（n = 6）或动静脉人工分流术（n = 6）。每组动物中一半在2周后处死，另一半在8周后处死。通过临床观察、血流测量以及病理和组织病理学（苏木精 - 伊红染色、弹力纤维染色）以及免疫组织化学（Ki67、CD31）评估，对植入物的通畅性、内皮化、血栓形成性和生物相容性进行分析。
对绵羊的健康监测发现所有动物体内均有内寄生虫负担。一些动物的胆管出现感染，导致肝纤维化胆管炎并伴有肝脏钙化。此外，在所有动物心脏的组织病理学标本中均检测到肉孢子虫。寄生虫负担与血细胞计数和血清胆红素水平相关。在适应期内，阿苯达唑治疗使两者均显著降低。补片、血管间置移植物和直管分流术在所有动物双侧均成功植入。总平均手术时间为136 ± 21分钟。大多数动物（23/24）植入后通畅率良好且总体状况良好。病理和组织病理学/免疫组织化学分析适用于确定假体材料中的血栓形成性、内皮化、细胞/成纤维细胞增殖、生物相容性、炎性细胞浸润以及新生内膜厚度。
我们已开发出一种适用于补片血管成形术、血管间置移植术和动静脉人工分流术的标准化且成功的麻醉和手术程序的合适实验方案。这种绵羊模型可用于测试新型假体材料的生物相容性、血栓形成性和内皮化。
