Oei F B, Welters M J, Bonthuis F, Vaessen L M, Marquet R L, Zondervan P E, Weimar W, Bogers A J
Department of Thoracic Surgery, University Hospital Rotterdam-Dijkzigt, Rotterdam, The Netherlands.
J Surg Res. 1999 Dec;87(2):239-44. doi: 10.1006/jsre.1999.5763.
Structural failure of cardiac valve allografts may be related to technical factors such as size mismatch, resulting in early intimal proliferation and fibrosis or immunological reactions against the transplanted valves, featuring lymphocytic infiltration.
To develop a heterotopic aortic valve implantation model in the rat to study the immunological factors leading to graft failure in the setting of a technical adaptation for size mismatch.
Syngeneic (WAG-WAG or DA-DA) and allogeneic (WAG-BN or WAG-DA) rat strain combinations were used to study the effect of the allogeneic response on valve properties. An end-to-side anastomosis was made between the U-shaped aortic root graft and the recipient's abdominal aorta to resolve the problems of size matching.
No animals suffered from ischemic or neurological complications during the study period. One hundred percent survival and patency of the aortic grafts were achieved at the end of a 21-day observation period. In the syngeneic group 9 of 10 valves were still competent when assessed during retrograde injection. In contrast, 2 of 10 allogeneic valve grafts were competent on postoperative Day 21. Microscopic evaluation revealed no fibrosis or intimal thickening in the syngeneic valve grafts while the allogeneic valve grafts demonstrated rejection-like morphology.
The absence of fibrosis and intimal thickening in the syngeneic transplanted valve grafts indicates that this implantation model is not influenced by nonimmunological-based structural changes. Therefore, this new model enables us to study the association between donor-directed immune responses and allograft degeneration in a technically unbiased manner.
心脏瓣膜同种异体移植的结构失败可能与技术因素有关,如尺寸不匹配,导致早期内膜增殖和纤维化,或针对移植瓣膜的免疫反应,其特征为淋巴细胞浸润。
建立大鼠异位主动脉瓣植入模型,以研究在尺寸不匹配的技术适应情况下导致移植物失败的免疫因素。
使用同基因(WAG-WAG或DA-DA)和异基因(WAG-BN或WAG-DA)大鼠品系组合来研究同种异体反应对瓣膜特性的影响。在U形主动脉根部移植物与受体腹主动脉之间进行端侧吻合,以解决尺寸匹配问题。
在研究期间,没有动物出现缺血或神经并发症。在21天观察期结束时,主动脉移植物的存活率和通畅率均达到100%。在同基因组中,逆行注射评估时10个瓣膜中有9个仍功能良好。相比之下,10个异基因瓣膜移植物中有2个在术后第21天功能良好。显微镜评估显示同基因瓣膜移植物中没有纤维化或内膜增厚,而异基因瓣膜移植物表现出类似排斥的形态。
同基因移植瓣膜移植物中没有纤维化和内膜增厚,表明该植入模型不受基于非免疫的结构变化影响。因此,这个新模型使我们能够以技术上无偏差的方式研究供体导向的免疫反应与同种异体移植物退变之间的关联。