Fishbein M C, Levy R J, Ferrans V J, Dearden L C, Nashef A, Goodman A P, Carpentier A
J Thorac Cardiovasc Surg. 1982 Apr;83(4):602-9.
To study the process of calcification in bioprosthesis, 108 glutaraldehyde-treated porcine aortic valve leaflets were implanted subcutaneously in rabbits and removed 1 day to 6 months later; morphologic findings were correlated with biochemically determined levels of calcium (Ca++) and gamma-carboxyglutamic acid (Gla), a vitamin K-dependent Ca++-binding amino acid known to be present in a variety of tissues with pathological calcification. Gla and Ca++ levels began to increase about 2 months after implantation and increased progressively with time. Ca/Gla molar ratios were comparable to those in leaflets of bioprostheses explanted from patients, 22 to 64 months after implantation. Morphologically evident calcification began at the same time that Gla and Ca++ increases were detected biochemically and also increased in severity with time. Electron microscopy showed that calcification primarily involved the surface of collagen fibrils and the interfibrillar spaces. The biochemical and morphological findings in this experimental system are similar to those described in calcified porcine bioprosthetic valve leaflets removed from patients, but occurred much more rapidly. As with pathological calcification of other tissues, progressive calcification was accompanied by increased Gla levels, suggesting that Gla plays a role in the calcification of the leaflets. This model allows rapid comparative evaluation of large numbers of valve leaflets maintained under similar host conditions.
为研究生物假体中的钙化过程，将108片经戊二醛处理的猪主动脉瓣叶皮下植入兔体内，于1天至6个月后取出；形态学结果与通过生化方法测定的钙（Ca++）和γ-羧基谷氨酸（Gla）水平相关，γ-羧基谷氨酸是一种维生素K依赖的与Ca++结合的氨基酸，已知存在于多种发生病理性钙化的组织中。Gla和Ca++水平在植入后约2个月开始升高，并随时间逐渐增加。Ca/Gla摩尔比与植入后22至64个月从患者体内取出的生物假体瓣膜叶中的比值相当。形态学上明显的钙化在生化检测到Gla和Ca++增加的同时开始，且严重程度也随时间增加。电子显微镜显示钙化主要累及胶原纤维表面和纤维间间隙。该实验系统中的生化和形态学结果与从患者体内取出的钙化猪生物假体瓣膜叶中描述的结果相似，但发生速度要快得多。与其他组织的病理性钙化一样，进行性钙化伴随着Gla水平升高，提示Gla在瓣膜叶钙化中起作用。该模型允许在相似的宿主条件下对大量瓣膜叶进行快速比较评估。
