Vyavahare N R, Chen W, Joshi R R, Lee C H, Hirsch D, Levy J, Schoen F J, Levy R J
Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, Michigan USA.
Hebrew University of Jerusalem, Jerusalem, Israel.
Cardiovasc Pathol. 1997 Jul;6(4):219-29. doi: 10.1016/S1054-8807(97)00017-3.
The use of bioprosthetic valves fabricated from fixed heterograft tissue (porcine aortic valves or bovine pericardium) in heart valve replacement surgery is limited because of calcification-related failures. The mechanism of calcification of bioprosthetic valves is quite complex and has a variety of determinants, including host factors, tissue fixation conditions, and mechanical effects. Currently, there is no effective therapy to prevent calcification in clinical settings. This article reviews a variety of anticalcification strategies that are under investigation either in advanced animal models or in clinical trials. Bisphosphonates, such as ethan hydroxybisphosphonate (EHBP), inhibit calcium phosphate crystal formation. However, because of their systemic toxicity, they are used as either tissue treatments or polymeric site-specific delivery systems. Detergent treatment, such as sodium dodecyl sulfate (SDS), extracts almost all phospholipids from bioprosthetic heart valve cuspal tissue. Procedures, such as amino oleic acid pretreatment, inhibit calcium uptake. Polyurethane trileaflet valves, investigated as alternatives to bioprosthetic or mechanical valve prostheses, undergo intrinsic and thrombus-related calcification and degradation. Calcification- and thrombus-resistant polyurethanes synthesized in our laboratory by covalent linking of EHBP or heparin (either in bulk or on surface) by unique polyepoxidation chemistry are attractive candidates for further research. Tissue-engineered heart valves may have an important place in the future.
在心脏瓣膜置换手术中,使用由固定的异种移植组织(猪主动脉瓣或牛心包)制成的生物假体瓣膜受到限制,原因是与钙化相关的失效问题。生物假体瓣膜钙化的机制相当复杂,有多种决定因素,包括宿主因素、组织固定条件和机械效应。目前,在临床环境中尚无有效的预防钙化的疗法。本文综述了正在先进动物模型或临床试验中研究的多种抗钙化策略。双膦酸盐,如依替膦酸二钠(EHBP),可抑制磷酸钙晶体形成。然而,由于其全身毒性,它们被用作组织处理或聚合物位点特异性递送系统。去污剂处理,如十二烷基硫酸钠(SDS),可从生物假体心脏瓣膜尖组织中提取几乎所有的磷脂。诸如氨基油酸预处理等程序可抑制钙摄取。作为生物假体或机械瓣膜假体替代品进行研究的聚氨酯三叶瓣膜会发生内在的和与血栓相关的钙化及降解。我们实验室通过独特的多环氧化化学方法将EHBP或肝素(整体或表面)共价连接合成的抗钙化和抗血栓聚氨酯是进一步研究的有吸引力的候选材料。组织工程心脏瓣膜在未来可能会占据重要地位。