Prevention of calcification of glutaraldehyde-crosslinked porcine aortic cusps by ethanol preincubation: Mechanistic studies of protein structure and water-biomaterial relationships
Prevention of calcification of glutaraldehyde-crosslinked porcine aortic cusps by ethanol preincubation: Mechanistic studies of protein structure and water-biomaterial relationships
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DOI：
10.1002/(sici)1097-4636(19980615)40:4
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发表时间：
1998-06-15
期刊：
影响因子：
--
通讯作者：
Levy, RJ
中科院分区：
文献类型：
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作者：
Vyavahare, NR;Hirsch, D;Levy, RJ
由戊二醛预处理的猪主动脉瓣制成的生物人工心脏瓣膜（BPHV）的临床使用由于钙化相关的失败而受到限制。我们以前曾报道过一种高效的乙醇预处理BPHV预防瓣尖钙化。本研究的目的是扩大我们的理解所带来的物质变化和这些物质的影响乙醇预处理抗钙化机制的关系。使用固态质子NMR研究了戊二醛去交联猪主动脉瓣尖（对照和乙醇预处理）对组织含水量和自旋-晶格弛豫时间（T1）的影响。通过ATR-FTIR光谱法研究瓣尖样品因乙醇引起的蛋白质构象变化。还研究了瓣尖组织-胆固醇（体外）相互作用的变化。根据残留戊二醛含量和胶原酶降解评估瓣尖材料稳定性。由于乙醇预处理，瓣尖样品的含水量显著降低。即使在大鼠皮下植入瓣尖样品7天后，乙醇预处理引起的瓣尖胶原蛋白构象变化（根据红外光谱）仍持续存在。乙醇预处理的结果是瓣尖的体外胆固醇摄取大大降低。瓣尖的乙醇预处理也导致对胶原酶消化的抵抗力增加。乙醇预处理对瓣尖戊二醛含量无影响。我们的结论是，乙醇预处理的生物心脏瓣膜尖引起的组织/材料和大分子特性的多组分效应，这可能部分解释乙醇预处理的抗钙化机制。(C)John Wiley & Sons，Inc.
Clinical usage of bioprosthetic heart valves (BPHVs) fabricated from glutaraldehyde-pretreated porcine aortic valves is restricted due to calcification-related failure. We previously reported a highly efficacious ethanol pretreatment of BPHVs for the prevention of cuspal calcification. The aim of the present study is to extend our understanding of the material changes brought about by ethanol and the relationship of these material effects to the ethanol pretreatment anticalcification mechanism. Glutaraldehyde-crosslinked porcine aortic valve cusps (control and ethanol-pretreated) were studied for the effects of ethanol on tissue water content and for spin-lattice relaxation times (T1) using solid state proton NMR. Cusp samples were studied for protein conformational changes due to ethanol by ATR-FTIR spectroscopy. The changes in cuspal tissue-cholesterol (in vitro) interactions also were studied. Cusp material stability was assessed in terms of residual glutaraldehyde content and collagenase degradation. Water content of the cusp samples was decreased significantly due to ethanol pretreatment. The cuspal collagen conformational changes (per infrared spectroscopy) brought about by ethanol pretreatment were persistent even after rat subdermal implantation of cusp samples for 7 days. In vitro cholesterol uptake by cusps was greatly reduced as a result of ethanol pretreatment. Ethanol pretreatment of cusps also resulted in increased resistance to collagenase digestion. Cuspal glutaraldehyde content was not changed by ethanol pretreatment. We conclude that ethanol pretreatment of bioprosthetic heart valve cusps causes multi-component effects on the tissue/material and macromolecular characteristics, which partly may explain the ethanol-pretreatment anticalcification mechanism. (C) 1998 John Wiley & Sons, Inc.