三缩水甘油胺交联结合乙醇可抑制生物人工心脏瓣膜钙化。
Triglycidyl amine crosslinking combined with ethanol inhibits bioprosthetic heart valve calcification.
机构信息
Division of Cardiology, The Children's Hospital of Philadelphia, and University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-4318, USA.
出版信息
Ann Thorac Surg. 2011 Sep;92(3):858-65. doi: 10.1016/j.athoracsur.2011.04.104.
BACKGROUND
One of the most important factors responsible for the calcific failure of bioprosthetic heart valves is glutaraldehyde crosslinking. Ethanol (EtOH) incubation after glutaraldehyde crosslinking has previously been reported to confer anticalcification efficacy for bioprostheses. The present studies investigated the anticalcification efficacy in vivo of the novel crosslinking agent, triglycidyl amine (TGA), with or without EtOH incubation, in comparison with glutaraldehyde.
METHODS
The TGA crosslinking (±EtOH) was used to prepare porcine aortic valves for both rat subdermal implants and sheep mitral valve replacements, for comparisons with glutaraldehyde-fixed controls. Thermal denaturation temperature, an index of crosslinking, cholesterol extraction, and hydrodynamic properties were quantified. Explant endpoints included quantitative and morphologic assessment of calcification.
RESULTS
Thermal denaturation temperatures after TGA were intermediate between unfixed and glutaraldehyde-fixed. EtOH incubation resulted in almost complete extraction of cholesterol from TGA or glutaraldehyde-fixed cusps. Rat subdermal explants (90 days) demonstrated that TGA-EtOH resulted in a significantly greater level of inhibition of calcification than other conditions. Thus, TGA-ethanol stent mounted porcine aortic valve bioprostheses were fabricated for comparisons with glutaraldehyde-pretreated controls. In hydrodynamic studies, TGA-EtOH bioprostheses had lower pressure gradients than glutaraldehyde-fixed. The TGA-ethanol bioprostheses used as mitral valve replacements in juvenile sheep (150 days) demonstrated significantly lower calcium levels in both explanted porcine aortic cusp and aortic wall samples compared with glutaraldehyde-fixed controls. However, TGA-EtOH sheep explants also demonstrated isolated calcific nodules and intracuspal hematomas.
CONCLUSIONS
The TGA-EtOH pretreatment of porcine aortic valves confers significant calcification resistance in both rat subdermal and sheep circulatory implants, but with associated structural instability.
背景
生物人工心脏瓣膜钙化失效的最重要因素之一是戊二醛交联。先前有报道称，戊二醛交联后进行乙醇（EtOH）孵育可赋予生物假体抗钙化功效。本研究调查了新型交联剂三缩水甘油基胺（TGA）在有或无EtOH孵育情况下与戊二醛相比的体内抗钙化功效。
方法
采用TGA交联（±EtOH）制备猪主动脉瓣，用于大鼠皮下植入和绵羊二尖瓣置换，与戊二醛固定的对照组进行比较。对交联指数热变性温度、胆固醇提取和流体动力学特性进行了量化。植入物终点包括钙化的定量和形态学评估。
结果
TGA处理后的热变性温度介于未固定和戊二醛固定之间。EtOH孵育导致TGA或戊二醛固定的瓣叶中胆固醇几乎完全提取。大鼠皮下植入物（90天）表明，TGA-EtOH导致的钙化抑制水平明显高于其他条件。因此，制备了TGA-乙醇支架安装的猪主动脉瓣生物假体，与戊二醛预处理的对照组进行比较。在流体动力学研究中，TGA-EtOH生物假体的压力梯度低于戊二醛固定的。在幼年绵羊（150天）中用作二尖瓣置换的TGA-乙醇生物假体显示，与戊二醛固定的对照组相比，移植的猪主动脉瓣叶和主动脉壁样本中的钙水平明显较低。然而，TGA-EtOH绵羊植入物也出现了孤立的钙化结节和瓣叶内血肿。
结论
猪主动脉瓣的TGA-EtOH预处理在大鼠皮下和绵羊循环植入物中均具有显著的抗钙化能力，但伴有相关的结构不稳定性。
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