Sato Masataka, Hiramatsu Yuji, Matsushita Shonosuke, Sato Shoko, Watanabe Yasunori, Sakakibara Yuzuru
Department of Cardiovascular Surgery, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan.
J Artif Organs. 2014 Sep;17(3):265-71. doi: 10.1007/s10047-014-0768-y. Epub 2014 May 4.
Since bioprosthetic valve dysfunction may arise due to histological calcification in the crosslinking process by glutaraldehyde (GA), non-GA crosslinking reagents have been investigated. We compared the efficacy of triglycidylamine (TGA), a newly synthesized epoxy compound, and GA as crosslinking reagents for the treatment of autologous tissues. We assessed the strength of crosslinked tissues using shrinkage temperature (Ts) measured by differential scanning calorimetry. We also conducted subdermal allografting of the crosslinked pericardium and thoracic aorta in rats, and verified the anti-calcification efficacy of TGA by histological evaluations with von Kossa stain, and immunological evaluations using tenascin-C (TN-C) or matrix metalloproteinase-9 (MMP-9). TGA treatment resulted in slower increases in Ts of the pericardium, and it required 9-12 h to reach Ts achieved by GA. In subdermal implantation of rat tissues, calcium content was lower in the TGA group than in the GA groups (p < 0.005). The expression site of TN-C and MMP-9 differed from the primary location of calcium deposition in the thoracic aorta treated with TGA suggesting a different underlying mechanism in calcification between GA and TGA crosslinking. In conclusion, TGA crosslinking in the allograft showed superior anti-calcification effect as compared to brief treatment by GA, although TGA crosslinking process was slow.
由于生物假体瓣膜功能障碍可能因戊二醛(GA)交联过程中的组织学钙化而出现,因此人们对非GA交联试剂进行了研究。我们比较了新合成的环氧化合物三缩水甘油胺(TGA)和GA作为自体组织交联试剂的效果。我们使用差示扫描量热法测量的收缩温度(Ts)评估交联组织的强度。我们还在大鼠中对交联的心包和胸主动脉进行了皮下同种异体移植,并通过冯·科萨染色的组织学评估以及使用腱生蛋白-C(TN-C)或基质金属蛋白酶-9(MMP-9)的免疫学评估来验证TGA的抗钙化效果。TGA处理导致心包Ts升高较慢,达到GA所达到的Ts需要9至12小时。在大鼠组织的皮下植入中,TGA组的钙含量低于GA组(p < 0.005)。TN-C和MMP-9的表达部位与TGA处理的胸主动脉中钙沉积的主要位置不同,这表明GA和TGA交联在钙化方面存在不同的潜在机制。总之,同种异体移植中的TGA交联与GA的短暂处理相比显示出更好的抗钙化效果,尽管TGA交联过程较慢。