Liao K, Seifter E, Factor S M, Yellin E L, Frater R W
Department of Cardiothoracic Surgery, Albert Einstein College of Medicine, Bronx, New York 10461.
J Surg Res. 1992 Oct;53(4):349-56. doi: 10.1016/0022-4804(92)90060-d.
Calcification is a major cause of glutaraldehyde-fixed bioprosthetic valve failure. Recent studies have shown that dystrophic calcification shares basic features with normal bone mineralization, including crystal initiation through the mediation of cell membranes, usually in the form of extracellular vesicles. In this study, we observed that calcification of the myocardium of DBA/2J mice was inhibited or reversed by diets supplemented with 100 mg/kg diet diphenylhydantoin (dilantin) for 70 days, with a calcification incidence of 25% in the dilantin group versus 58% in control. We further studied the effects of dilantin on bioprosthetic valve calcification. Three groups of young male Sprague-Dawley rats (100 g, 9/group) were implanted subcutaneously with 1-cm2 pieces of glutaraldehyde-fixed bovine pericardium. Controls were fed a ground chow for 45 or 90 days postimplantation; experimentals received the same chow for the first 45 days postimplantation and then were fed the same diet supplemented with 1000 mg dilantin/kg for the succeeding 45 days. Calcium content (microgram/mg dry weight) of the implants in the dilantin group was 137 +/- 18.6 versus 214 +/- 34.3 in 90 days control and 79.9 +/- 41.5 in 45 days control (mean +/- SD, P < 0.01 and P < 0.05 respectively, t test). The tibia calcium content of the dilantin group was not significantly different from 90 days control. We conclude that orally administered dilantin inhibits calcification of glutaraldehyde-fixed bovine pericardial implants preferentially. It does not cause decalcification either of implants that have already calcified or of the bones. The anti-calcification effect of dilantin may be associated with its anti-vitamin D effect.
钙化是戊二醛固定生物瓣膜失效的主要原因。最近的研究表明，营养不良性钙化与正常骨矿化具有基本特征，包括通过细胞膜介导的晶体起始，通常以细胞外囊泡的形式。在本研究中，我们观察到，饮食中补充100mg/kg苯妥英钠（大仑丁）70天可抑制或逆转DBA/2J小鼠心肌的钙化，大仑丁组的钙化发生率为25%，而对照组为58%。我们进一步研究了大仑丁对生物瓣膜钙化的影响。将三组年轻雄性Sprague-Dawley大鼠（100g，每组9只）皮下植入1cm2的戊二醛固定牛心包片。对照组在植入后45天或90天喂食普通饲料；实验组在植入后的前45天喂食相同的饲料，然后在接下来的45天喂食补充有1000mg大仑丁/kg的相同饲料。大仑丁组植入物的钙含量（微克/毫克干重）为137±18.6，而90天对照组为214±34.3，45天对照组为79.9±41.5（平均值±标准差，t检验，P分别<0.01和P<0.05）。大仑丁组的胫骨钙含量与90天对照组无显著差异。我们得出结论，口服大仑丁优先抑制戊二醛固定牛心包植入物的钙化。它不会导致已钙化的植入物或骨骼脱钙。大仑丁的抗钙化作用可能与其抗维生素D作用有关。
