Golomb G, Ezra V
School of Pharmacy, Hebrew University of Jerusalem, Israel.
Biomater Artif Cells Immobilization Biotechnol. 1992;20(1):31-41. doi: 10.3109/10731199209117856.
Calcification is the principal cause of the clinical failure of bioprosthetic heart valves (BHV). The hypothesis of this work was that an impaired balance between positively and negatively charged amino acids, due to the reaction with Lys and Hyl tissue-collagen residues, expose affinity sites to Ca++. We further hypothesized that regardless of the cause(s) of BHV calcification, positive charge modification of the tissue will prevent their propensity to calcify. Modification of BHV tissue was obtained by covalently binding protamine sulfate, a polybasic peptide, via glutaraldehyde. The modification procedure resulted in stable, covalent links of approximately 5.3% w/w protamine with undiminished anticalcification properties, even after long storage. Significant prevention of calcification was exhibited by the p-bound tissue in comparison to BHV tissue, 66.0 and 106.5 micrograms/mg calcium, respectively, after 30 days of subdermal implants in rats. The results support our hypotheses, and orthotopical heart valve replacements are required in order to completely evaluate the treatment efficacy and biocompatibility.
钙化是生物人工心脏瓣膜（BHV）临床失效的主要原因。这项研究的假设是，由于与赖氨酸（Lys）和羟赖氨酸（Hyl）组织胶原蛋白残基发生反应，带正电和负电的氨基酸之间的平衡受到破坏，从而使钙结合位点暴露给钙离子（Ca++）。我们进一步假设，无论BHV钙化的原因是什么，对组织进行正电荷修饰将阻止其钙化倾向。通过戊二醛将硫酸鱼精蛋白（一种多碱性肽）共价结合来实现对BHV组织的修饰。即使经过长时间储存，修饰过程也能产生稳定的共价连接，鱼精蛋白含量约为5.3%（重量/重量），且抗钙化性能未降低。与BHV组织相比，在大鼠皮下植入30天后，结合了鱼精蛋白的组织显著预防了钙化，钙化程度分别为66.0和106.5微克/毫克钙。结果支持了我们的假设，为了全面评估治疗效果和生物相容性，需要进行原位心脏瓣膜置换。
