Meuris B
Dept. of Cardiac Surgery, KULeuven, Center for Experimental Surgery and Anaesthesiology, C. E. H. A., Provisorium I, Minderbroedersstraat 17, B-3000 Leuven.
Verh K Acad Geneeskd Belg. 2002;64(4):287-302.
In the total pre-clinical evaluation of new heart valve substitutes, there is an absolute need for chronic experimental valve testing in different animal models. Also fundamental research towards mechanisms of calcification, tissue degeneration and valve thrombosis requires standardized and well-controlled animal models. Possible clinical use of a new experimental valve type and/or future developments and improvements in prosthetic heart valves, all depend on such research activities. Our recent studies concerning prosthetic heart valves resulted in following conclusions. 1. Photo-oxidation, a new tissue treatment, seems to have many possible advantages over currently existing valve fixation techniques (glutaraldehyde-fixation). The stentless porcine photo-fixed valve shows, in contrast to standard stentless valves, no aortic wall mineralization together with a good preservation of cuspal function. 2. For clinical right-sided valve implantations, the presence of a stent, together with the fixation pressure of the valve, can have its influence on the long-term behaviour of the valves in this low-pressure environment. Both stented valves, as valves fixed under pressure, seem to suffer more from fibrous tissue overgrowth 3. Mechanical stress is an important factor in the degeneration and calcification of biological valve tissue, mainly when an unfavourable stress pattern is present. Not all currently used animal models are equally reliable for valve testing and evaluation. 4. Implantation of aortic wall samples in the jugular vein of juvenile sheep is a simple, reliable and cost-effective model of aortic wall calcification. Calcification of glutaraldehyde-fixed aortic wall tissue is initiated at the level of cellular remnants, with little or no contribution from elastic fibers. Acellularization can avoid this cell-mediated calcification, but an additional treatment will be necessary to avoid the inflammation leading to elastolysis and consequent calcification of elastic fibers. 5. Mechanical valve implantation in pulmonary position delivers a reliable and reproducible test of mechanical valve thrombosis. The model allows us to compare the thrombogenic potential of different mechanical valve types, while it can also serve as a test for new therapeutic or diagnostic tools for mechanical valve thrombosis.
在新型心脏瓣膜替代品的全面临床前评估中，绝对需要在不同动物模型中进行慢性实验性瓣膜测试。此外，针对钙化、组织退化和瓣膜血栓形成机制的基础研究也需要标准化且严格控制的动物模型。新型实验性瓣膜类型的可能临床应用以及人工心脏瓣膜未来的发展与改进，都依赖于此类研究活动。我们近期关于人工心脏瓣膜的研究得出了以下结论。1. 光氧化作为一种新的组织处理方法，相较于目前现有的瓣膜固定技术（戊二醛固定）似乎具有许多潜在优势。与标准无支架瓣膜相比，无支架猪光固定瓣膜未出现主动脉壁矿化，同时瓣叶功能得到良好保留。2. 对于临床右侧瓣膜植入，支架的存在以及瓣膜的固定压力会对瓣膜在这种低压环境下的长期性能产生影响。有支架瓣膜以及在压力下固定的瓣膜，似乎更容易出现纤维组织过度生长。3. 机械应力是生物瓣膜组织退化和钙化的重要因素，主要是在存在不利应力模式时。并非所有目前使用的动物模型在瓣膜测试和评估方面都同样可靠。4. 将主动脉壁样本植入幼年绵羊颈静脉是一种简单、可靠且经济高效的主动脉壁钙化模型。戊二醛固定的主动脉壁组织钙化始于细胞残余物水平，弹性纤维几乎没有或没有贡献。脱细胞处理可以避免这种细胞介导的钙化，但需要额外的处理来避免导致弹性纤维溶解和随后钙化的炎症。5. 将机械瓣膜植入肺动脉位置可提供对机械瓣膜血栓形成的可靠且可重复的测试。该模型使我们能够比较不同机械瓣膜类型的血栓形成潜力，同时它也可作为机械瓣膜血栓形成新治疗或诊断工具的测试。
