Vyavahare N R, Jones P L, Hirsch D, Schoen F J, Levy R J
Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, USA.
J Heart Valve Dis. 2000 Jul;9(4):561-6.
Calcification is a major cause of failure of bioprosthetic heart valves derived from glutaraldehyde-crosslinked bovine pericardium or porcine aortic valve (PAV) cusps. Recently, we have shown that ethanol pretreatment of PAV cusps prevents calcification in animal models.
In this study we showed that ethanol pretreatment was equally effective in preventing calcification of glutaraldehyde-crosslinked bovine pericardium (control Ca2+ = 121.16+/-7.49 microg/mg tissue; ethanol-pretreated Ca2+ = 2.95+/-0.78 microg/mg). Furthermore, other low-molecular weight alcohols such as methanol and isopropanol were also effective in mitigating calcification of PAV cusps. Storage of ethanol-pretreated cusps in glutaraldehyde before implantation allowed partial return of calcification, suggesting a role for ethanol-glutaraldehyde interactions in preventing calcification. However, when ethanol-pretreated cusps were stored in ethanolic glutaraldehyde up to one month, the anti-calcification effect of ethanol persisted. The conditions whereby PAV cusps were crosslinked in pure, non-aqueous, alcoholic glutaraldehyde solutions were also examined. The crosslinking was equivalent to the standard aqueous glutaraldehyde crosslinking as indicated by thermal denaturation temperatures (Td) obtained by differential scanning calorimetry (DSC) and resistance to collagenase digestion. However, these cusps had lower water content and showed a marked decrease in spin-lattice relaxation times (T1) obtained by solid-state proton nuclear magnetic resonance (NMR). Moreover, these cusps calcified heavily in the 21-day rat subdermal implants. Thus, alcohol treatment during glutaraldehyde crosslinking was not useful.
Glutaraldehyde storage after ethanol pretreatment aggravates calcification; moreover, alcoholic-glutaraldehyde crosslinking solutions are not beneficial for anti-calcification. Ethanol pretreatment of glutaraldehyde-pretreated bovine pericardium prevents its calcification.
钙化是戊二醛交联牛心包或猪主动脉瓣（PAV）瓣叶生物心脏瓣膜失效的主要原因。最近，我们已表明乙醇预处理PAV瓣叶可防止动物模型中的钙化。
在本研究中，我们表明乙醇预处理在防止戊二醛交联牛心包钙化方面同样有效（对照Ca2+ = 121.16±7.49μg/mg组织；乙醇预处理Ca2+ = 2.95±0.78μg/mg）。此外，其他低分子量醇类如甲醇和异丙醇在减轻PAV瓣叶钙化方面也有效。植入前将乙醇预处理的瓣叶储存在戊二醛中会使钙化部分恢复，这表明乙醇 - 戊二醛相互作用在防止钙化中起作用。然而，当乙醇预处理的瓣叶在乙醇戊二醛中储存长达一个月时，乙醇的抗钙化作用仍然存在。还研究了PAV瓣叶在纯的、非水的、含酒精的戊二醛溶液中交联的条件。通过差示扫描量热法（DSC）获得的热变性温度（Td）和对胶原酶消化的抗性表明，这种交联等同于标准的水性戊二醛交联。然而，这些瓣叶含水量较低，并且通过固态质子核磁共振（NMR）获得的自旋 - 晶格弛豫时间（T1）显著降低。此外，这些瓣叶在21天大鼠皮下植入物中严重钙化。因此，戊二醛交联期间的酒精处理并无益处。
乙醇预处理后储存戊二醛会加重钙化；此外，含酒精的戊二醛交联溶液对抗钙化无益。乙醇预处理戊二醛处理过的牛心包可防止其钙化。
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