Lovekamp Joshua J, Simionescu Dan T, Mercuri Jeremy J, Zubiate Brett, Sacks Michael S, Vyavahare Narendra R
Cardiovascular Implant Research Laboratory, Department of Bioengineering, Clemson University, 501 Rhodes Engineering Research Center, Clemson, SC 29634, USA.
Biomaterials. 2006 Mar;27(8):1507-18. doi: 10.1016/j.biomaterials.2005.08.003. Epub 2005 Sep 6.
Glycosaminoglycans (GAGs) are important structural and functional components in native aortic heart valves and in glutaraldehyde (Glut)-fixed bioprosthetic heart valves (BHVs). However, very little is known about the fate of GAGs within the extracellular matrix of BHVs and their contribution to BHV longevity. BHVs used in heart valve replacement surgery have limited durability due to mechanical failure and pathologic calcification. In the present study we bring evidence for the dramatic loss of GAGs from within the BHV cusp structure during storage in saline and both short- and long-term Glut fixation. In order to gain insight into role of GAGs, we compared properties of fresh and Glut-fixed porcine heart valve cusps before and after complete GAG removal. GAG removal resulted in significant morphological and functional tissue alterations, including decreases in cuspal thickness, reduction of water content and diminution of rehydration capacity. By virtue of this diminished hydration, loss of GAGs also greatly increased the "with-curvature" flexural rigidity of cuspal tissue. However, removal of GAGs did not alter calcification potential of BHV cups when implanted in the rat subdermal model. Controlling the extent of pre-implantation GAG degradation in BHVs and development of improved GAG crosslinking techniques are expected to improve the mechanical durability of future cardiovascular bioprostheses.
糖胺聚糖（GAGs）是天然主动脉心脏瓣膜和戊二醛（Glut）固定的生物人工心脏瓣膜（BHVs）中重要的结构和功能成分。然而，关于BHVs细胞外基质中GAGs的命运及其对BHV寿命的贡献，人们知之甚少。用于心脏瓣膜置换手术的BHVs由于机械故障和病理性钙化，耐久性有限。在本研究中，我们提供证据表明，在盐水储存以及短期和长期Glut固定过程中，BHV瓣叶结构内的GAGs会大量流失。为了深入了解GAGs的作用，我们比较了完全去除GAGs前后新鲜和Glut固定的猪心脏瓣膜瓣叶的特性。去除GAGs导致了显著的形态和功能组织改变，包括瓣叶厚度减小、含水量降低和再水化能力减弱。由于这种水合作用的减弱，GAGs的流失也大大增加了瓣叶组织的“带曲率”弯曲刚度。然而，在大鼠皮下模型中植入时，去除GAGs并没有改变BHV瓣杯的钙化潜力。控制BHVs植入前GAGs的降解程度以及开发改进的GAG交联技术有望提高未来心血管生物假体的机械耐久性。
