Simon P, Kasimir M T, Seebacher G, Weigel G, Ullrich R, Salzer-Muhar U, Rieder E, Wolner E
Department of Cardiothoracic Surgery, AKH-University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria.
Eur J Cardiothorac Surg. 2003 Jun;23(6):1002-6; discussion 1006. doi: 10.1016/s1010-7940(03)00094-0.
The first tissue engineered decellularized porcine heart valve, Synergraft (Cryolife Inc., USA) was introduced in Europe as an alternative to conventional biological valves. This is the first report of the rapid failure of these new grafts in a small series.
In 2001, 2 model 500 and 2 model 700 Synergraft valves were implanted in four male children (age 2.5-11 years) in the right ventricular outflow tract as a root. Two patients had a Ross operation and two had a homograft replacement.
The cryopreserved Synergraft valves appeared macroscopically unremarkable at implantation. Recovery from surgery was uneventful and good valve function was demonstrated postoperatively. Three children died, two suddenly with severely degenerated Synergraft valves 6 weeks and 1 year after implantation. The third child died on the 7th day due to Synergraft rupture. Subsequently the fourth graft was explanted prophylactically 2 days after implantation. Macroscopically all four grafts showed severe inflammation starting on the outside (day 2 explant) leading to structural failure (day 7 explant) and severe degeneration of the leaflets and wall (6 weeks and 1 year explant). Histology demonstrated severe foreign body type reaction dominated by neutrophil granulocytes and macrophages in the early explants and a lymphocytic reaction at 1 year. In addition significant calcific deposits were demonstrated at all stages. Surprisingly pre-implant samples of the Synergraft revealed incomplete decellularization and calcific deposits. No cell repopulation of the porcine matrix occurred.
The xenogenic collagen matrix of the Synergraft valve elicits a strong inflammatory response in humans which is non-specific early on and is followed by a lymphocyte response. Structural failure or rapid degeneration of the graft occurred within 1 year. Calcific deposits before implantation and incomplete decellularization may indicate manufacturing problems. The porcine Synergraft treated heart valves should not be implanted at this stage and has been stopped.
首个组织工程去细胞猪心脏瓣膜Synergraft（美国Cryolife公司）作为传统生物瓣膜的替代品在欧洲推出。本文首次报道了在一小系列病例中这些新型移植物的快速失效情况。
2001年，将2个500型号和2个700型号的Synergraft瓣膜作为根部植入4名男性儿童（年龄2.5 - 11岁）的右心室流出道。2例患者接受了Ross手术，2例接受了同种异体移植瓣膜置换术。
冷冻保存的Synergraft瓣膜在植入时肉眼观察无明显异常。手术恢复顺利，术后显示瓣膜功能良好。3名儿童死亡，2名在植入后6周和1年时因Synergraft瓣膜严重退变突然死亡。第3名儿童在第7天因Synergraft瓣膜破裂死亡。随后，第4个移植物在植入后2天被预防性取出。肉眼观察，所有4个移植物均显示从外部开始（植入后2天取出）出现严重炎症，导致结构失效（植入后7天取出）以及瓣叶和瓣膜壁严重退变（植入后6周和1年取出）。组织学检查显示，早期取出的标本中以中性粒细胞和巨噬细胞为主的严重异物型反应，1年后出现淋巴细胞反应。此外，在所有阶段均发现显著的钙化沉积。令人惊讶的是，Synergraft瓣膜植入前的样本显示去细胞不完全和钙化沉积。猪基质中未发生细胞再填充。
Synergraft瓣膜的异种胶原基质在人体内引发强烈的炎症反应，早期是非特异性的，随后是淋巴细胞反应。移植物在1年内发生结构失效或快速退变。植入前的钙化沉积和去细胞不完全可能表明存在制造问题。现阶段不应植入经猪Synergraft处理的心脏瓣膜，该产品已停止使用。
