Neomycin fixation followed by ethanol pretreatment leads to reduced buckling and inhibition of calcification in bioprosthetic valves.
Neomycin fixation followed by ethanol pretreatment leads to reduced buckling and inhibition of calcification in bioprosthetic valves.
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DOI：
10.1002/jbm.b.31503
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发表时间：
2010-01
影响因子：
3.4
通讯作者：
Vyavahare, Naren R.
中科院分区：
文献类型：
--
作者：
Raghavan, Devanathan;Shah, Sagar R.;Vyavahare, Naren R.
戊二醛交联人工生物心脏瓣膜（BHV）有两种失效模式：退化（由于基质失效导致瓣尖撕裂）和钙化。它们可以独立发生，也可以导致另一个导致共存。钙化失败之前已经被广泛研究，并且已经开发了几种抗钙化治疗方法;然而，很少有研究旨在了解瓣膜退行性变的机制。戊二醛固定的缺点之一是不能稳定组织中的所有细胞外基质成分。我们实验室之前的研究表明，新霉素可用作固定剂，以稳定瓣膜中存在的糖胺聚糖（GAG），从而改善基质性质。但新霉素固定并不能防止瓣尖钙化。在本研究中，我们希望通过乙醇预处理或硼氢化钠处理去除游离醛来增强新霉素固定瓣膜的抗钙化潜力。乙醇处理之前已被使用，并发现对瓣膜尖具有优异的抗钙化性能。本研究中的结果表明，新霉素后乙醇处理有效地保存GAG在体外以及在大鼠皮下植入后的体内。与戊二醛（GLUT）对照相比，用乙醇预处理的新霉素固定瓣尖抑制了体内钙化。硼氢化钠处理本身并不抑制钙化，也不稳定GAG对酶降解。BHV的乙醇处理后的新霉素固定可以防止两种失效模式，从而将这些生物假体的有效耐用性和寿命提高数倍。
Glutaraldehyde crosslinked bioprosthetic heart valves (BHVs) have two modalities of failure: degeneration (cuspal tear due to matrix failure) and calcification. They can occur independently as well as one can lead to the other causing co-existence. Calcific failure has been extensively studied before and several anticalcification treatments have been developed; however, little research is directed to understand mechanisms of valvular degeneration. One of the shortcomings of glutaraldehyde fixation is its inability to stabilize all extracellular matrix components in the tissue. Previous studies from our lab have demonstrated that neomycin could be used as a fixative to stabilize glycosaminoglycans (GAGs) present in the valve to improve matrix properties. But neomycin fixation did not prevent cuspal calcification. In the present study, we wanted to enhance the anti-calcification potential of neomycin fixed valves by pre-treating with ethanol or removing the free aldehydes by sodium borohydride treatment. Ethanol treatment has been previously used and found to have excellent anti-calcification properties for valve cusps. Results demonstrated in this study suggest that neomycin followed by ethanol treatment effectively preserves GAGs both in vitro as well as in vivo after subdermal implantation in rats. In vivo calcification was inhibited in neomycin fixed cusps pretreated with ethanol compared to glutaraldehyde (GLUT) control. Sodium borohydride treatment by itself did not inhibit calcification nor stabilized GAGs against enzymatic degradation. Neomycin fixation followed by ethanol treatment of BHVs could prevent both modalities of failure, thereby increasing the effective durability and lifetime of these bioprostheses several fold.
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影响因子：
14
作者：
Raghavan, Devanathan;Simionescu, Dan T.;Vyavahare, Naren R.
通讯作者：
Vyavahare, Naren R.
影响因子：
9.7
作者：
Raghavan, Devanathan;Starcher, Barry C.;Vyavahare, Naren R.
通讯作者：
Vyavahare, Naren R.
影响因子：
4.9
作者：
Simionescu, DT;Lovekamp, JJ;Vyavahare, NR
通讯作者：
Vyavahare, NR
影响因子：
14
作者：
Isenburg, JC;Simionescu, DT;Vyavahare, NR
通讯作者：
Vyavahare, NR
影响因子：
2.9
作者：
Eike, JH;Palmer, AF
通讯作者：
Palmer, AF