Vyavahare N, Hirsch D, Lerner E, Baskin J Z, Schoen F J, Bianco R, Kruth H S, Zand R, Levy R J
Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor 48109-0576, USA.
Circulation. 1997 Jan 21;95(2):479-88. doi: 10.1161/01.cir.95.2.479.
Calcification of the cusps of bioprosthetic heart valves fabricated from either glutaraldehyde cross-linked porcine aortic valves or bovine pericardium frequently causes the clinical failure of these devices. Our investigations studied ethanol pretreatment of glutaraldehyde cross-linked porcine aortic valves as a new approach to prevent cuspal calcification. The hypothesis governing this approach holds that ethanol pretreatment inhibits calcification resulting from protein structural alterations and lipid extraction.
Results demonstrated complete inhibition of calcification of glutaraldehyde-pretreated porcine bioprosthetic aortic valve cusps by 80.0% ethanol in rat subdermal implants (60-day ethanol-pretreated calcium level, 1.87 +/- 0.29 micrograms/mg tissue compared with control calcium level, 236.00 +/- 6.10 micrograms/mg tissue) and in sheep mitral valve replacements (ethanol-pretreated calcium level, 5.22 +/- 2.94 micrograms/mg tissue; control calcium level, 32.50 +/- 11.50 micrograms/mg tissue). The mechanism of ethanol inhibition may be explained by several observations: ethanol pretreatment resulted in an irreversible alteration in the amide I band noted in the infrared spectra for both purified type I collagen and glutaraldehyde cross-linked porcine aortic leaflets. Ethanol pretreatment also resulted in nearly complete extraction of leaflet cholesterol and phospholipid.
Ethanol pretreatment of glutaraldehyde cross-linked porcine aortic valve bioprostheses represents a highly efficacious and mechanistically based approach and may prevent calcific bioprosthetic heart valve failure.
由戊二醛交联的猪主动脉瓣或牛心包制成的生物人工心脏瓣膜尖钙化常常导致这些装置出现临床故障。我们的研究将戊二醛交联的猪主动脉瓣乙醇预处理作为预防瓣尖钙化的一种新方法进行研究。该方法所依据的假设是乙醇预处理可抑制因蛋白质结构改变和脂质提取导致的钙化。
结果表明，在大鼠皮下植入物中，80.0%的乙醇可完全抑制戊二醛预处理的猪生物人工主动脉瓣尖钙化（乙醇预处理60天后的钙水平为1.87±0.29微克/毫克组织，而对照钙水平为236.00±6.10微克/毫克组织），在绵羊二尖瓣置换术中也是如此（乙醇预处理的钙水平为5.22±2.94微克/毫克组织；对照钙水平为32.50±11.50微克/毫克组织）。乙醇抑制的机制可通过以下几点观察结果来解释：乙醇预处理导致纯化的I型胶原蛋白和戊二醛交联的猪主动脉瓣叶的红外光谱中酰胺I带发生不可逆改变。乙醇预处理还导致瓣叶胆固醇和磷脂几乎完全被提取。
戊二醛交联的猪主动脉瓣生物假体的乙醇预处理是一种高效且基于机制的方法，可能预防生物人工心脏瓣膜钙化失败。
