Légaré J F, Ross D B, Issekutz T B, Ruigrok W, Creaser K, Hirsch G M, Lee T D
Departments of Surgery, Pathology, and Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
J Thorac Cardiovasc Surg. 2001 Aug;122(2):310-7. doi: 10.1067/mtc.2001.112336.
Allograft heart valves are commonly used in cardiac surgery. Despite mounting evidence that these valves are immunogenic, leading to premature failure, current clinical practice does not attempt to minimize or control such a response. The objective of this study was to evaluate immune modulatory approaches to ameliorate allograft valve failure in a rat model.
Aortic valve grafts were implanted infrarenally into Lewis rat recipients (n = 32). There were 4 transplant groups: syngeneic grafts (Lewis to Lewis), untreated allografts (Brown Norway to Lewis), allograft recipients treated with cyclosporine (INN: ciclosporin) (10 mg/kg per day for 7 or 28 days), and allograft recipients treated with anti-alpha4 integrin and anti-beta2 integrin monoclonal antibodies for 7 days. At 7 and 28 days the valves were examined for structural integrity and cellular infiltration.
Both cyclosporine and anti-alpha4/beta2 integrin treatment resulted in significant reduction in leaflet infiltration by macrophages (ED1(+)), T cells (CD3(+)), and CD8(+) T cells at 7 days with preservation of structural integrity when compared with control allografts. Twenty-eight days after implantation, daily treatment with cyclosporine preserved leaflet structural integrity and inhibited cellular infiltration. However, a short course of cyclosporine (7 days) failed to prevent destruction of the valves at 28 days.
Immune modulatory approaches aimed at T-cell activation or trafficking decrease leaflet cellular infiltration and prevent allograft valve structural failure. However, short-course therapy does not appear to be sufficient and must be maintained to allow long-term preservation of leaflet structural integrity (28 days).
同种异体心脏瓣膜常用于心脏手术。尽管越来越多的证据表明这些瓣膜具有免疫原性，会导致过早失效，但目前的临床实践并未试图将这种反应降至最低或加以控制。本研究的目的是评估免疫调节方法对改善大鼠模型同种异体瓣膜失效的作用。
将主动脉瓣膜移植到Lewis大鼠受体的肾下部位（n = 32）。有4个移植组：同基因移植组（Lewis大鼠之间）、未处理的同种异体移植组（棕色挪威大鼠到Lewis大鼠）、接受环孢素（国际非专利药品名称：环孢菌素）治疗的同种异体移植受体组（每天10 mg/kg，持续7天或28天），以及接受抗α4整合素和抗β2整合素单克隆抗体治疗7天的同种异体移植受体组。在第7天和第28天，检查瓣膜的结构完整性和细胞浸润情况。
与对照同种异体移植组相比，环孢素和抗α4/β2整合素治疗均导致第7天时巨噬细胞（ED1(+)）、T细胞（CD3(+)）和CD8(+) T细胞对瓣叶的浸润显著减少，同时保持了结构完整性。植入后28天，每天用环孢素治疗可保持瓣叶结构完整性并抑制细胞浸润。然而，短期使用环孢素（7天）未能在第28天时防止瓣膜破坏。
针对T细胞活化或迁移的免疫调节方法可减少瓣叶细胞浸润并防止同种异体瓣膜结构失效。然而，短期治疗似乎并不足够，必须持续进行以实现瓣叶结构完整性的长期维持（28天）。
