Research on biological and mechanical heart valves: experimental studies in chronic animal models

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.