Human aortic valve allografts are increasingly popular in the treatment of aortic valve disease. Many clinicians prefer aortic valve allografts to mechanical prostheses and to bovine or porcine bioprostheses because allografts have a low incidence of thromboembolic complications, have a low incidence of infection, do not require anticoagulation, do not undergo accelerated calcification in young patients, and are quite durable. Despite the considerable successes with clinical use of allografts, the ultimate cellular fate of these valves and optimum conditions for their use is uncertain. The importance of antigenicity and cellular viability of these grafts to long-term performance is unclear. Whether antigenicity and cellular viability are important to calcium deposition, and important cause of graft failure, is also unresolved. This study proposes to define the antigenicity of aortic valve allografts and the ability to modify this antigenicity. It would use a rat model of aortic valve transplantation and determine sensitization by examining skin grafts from rats syngeneic with the valve donor. It would also use monoclonal antibodies to detect immunologic qualities of the valve. Further experiments would attempt to modify the antigenicity of the valve using cryopreservation, prolonged storage, and immunosuppressive agents. The second objective of this project would address the cellular viability of the allograft valve and how it can be optimized. This phase of the study would use uptake of radiolabelled proline to determine the viability of fibroblasts in the allograft, while tissue culture would determine valve cusp viability. Alcian blue dye exclusion would determine the viability of aortic wall endothelium. The final objective of these investigations would determine what factors influence calcium deposition in the allograft valve.
