Simionescu Dan T, Lovekamp Joshua J, Vyavahare Narendra R
Cardiovascular Implant Research Laboratory, Department of Bioengineering, Clemson University, Clemson, South Carolina 29634, USA.
J Heart Valve Dis. 2003 Mar;12(2):226-34.
Chronic tissue degeneration is a major factor in the failure of porcine bioprosthetic heart valves. Stabilization with glutaraldehyde (GA) has become the standard in preparation of bioprosthetic heart valves, but there is increasing evidence that GA does not effectively stabilize all tissue structures, specifically glycosaminoglycans (GAGs). The study aim was to establish the status of GAGs in bioprosthetic heart valves and to ascertain whether degeneration of the extracellular matrix (ECM) is initiated during preparation of porcine tissues for use as bioprosthetic heart valves.
Stentless porcine bioprosthetic heart valves were prepared by tissue harvesting, 24 h of storage in cold saline, and 14 days' fixation in buffered 0.6% GA. Tissue samples obtained from fresh and fixed aortic cusps and wall conduit were analyzed for ECM integrity and GAG localization by transmission electron microscopy combined with toluidine blue staining.
Major degenerative changes occurred in the ECM ultrastructure of both porcine cusp and wall during tissue preparation for use as bioprosthetic heart valves. Modifications in the aortic cusp included loss of GAGs from the interfibrillary space and from the surface of the collagen fibers. In the aortic wall, GAGs were lost from the interfibrillary space and from the surface of collagen fibers. In addition, the surface of wall elastic fibers exhibited marked paucity of GAGs and elastin-associated microfibrils.
The typical steps involved in the preparation of porcine aortic bioprosthetic heart valves induce, or cannot fully prevent, degeneration of some components of the ECM. Controlling the extent of this pre-implantation deterioration will open new gateways for improvement of the quality and durability of future cardiovascular bioprostheses.
慢性组织退变是猪生物人工心脏瓣膜失效的主要因素。用戊二醛（GA）进行稳定处理已成为生物人工心脏瓣膜制备的标准方法，但越来越多的证据表明，GA并不能有效稳定所有组织结构，特别是糖胺聚糖（GAGs）。本研究的目的是确定生物人工心脏瓣膜中GAGs的状态，并确定在将猪组织制备成生物人工心脏瓣膜的过程中，细胞外基质（ECM）的退变是否开始。
通过组织采集、在冷盐水中储存24小时以及在0.6%的缓冲GA中固定14天来制备无支架猪生物人工心脏瓣膜。通过透射电子显微镜结合甲苯胺蓝染色，对从新鲜和固定的主动脉瓣叶及壁导管获取的组织样本进行ECM完整性和GAG定位分析。
在将猪瓣叶和壁制备成生物人工心脏瓣膜的组织过程中，ECM超微结构发生了主要的退变变化。主动脉瓣叶的改变包括GAGs从纤维间间隙和胶原纤维表面丢失。在主动脉壁中，GAGs从纤维间间隙和胶原纤维表面丢失。此外，壁弹性纤维表面的GAGs和弹性蛋白相关微原纤维明显缺乏。
猪主动脉生物人工心脏瓣膜制备过程中涉及的典型步骤会引发或无法完全防止ECM某些成分的退变。控制这种植入前退变的程度将为提高未来心血管生物假体的质量和耐久性开辟新途径。
