Document Type
Thesis
Publication Date
January 1997
Abstract
At present the main question is whether homograft failure is due to rejection or mechanical degeneration. The use of cardiac valve transplants between syngeneic and allogeneic strains of rats permits investigations into the role of immune mediated rejection of these grafts. We expanded an already developed microsurgical rat model for aortic interposition allografts to include the aortic valve. Aortic valves were harvested from donor rats and then heterotopically transplanted into the abdominal aorta of a recipient rat using inbred strains. All recipient rats were Lewis and donor rats were either Lewis (syngeneic) or Brown Norway (allogeneic). Grafts were transplanted either fresh or cryopreserved, thus giving four experimental groups: fresh syngeneic, fresh allogeneic, cryopreserved syngeneic, and cryopreserved allogeneic. The valves were then explanted at different time points and histologically examined by two pathologists in a blinded fashion. A total of almost 100 transplants were performed. After 56 days, syngeneic grafts had preserved leaflets while allogeneic grafts were completely destroyed. Cryopreservation did not alter this process. This suggests that rejection plays a role in the failure of allograft valves. Histological features of rejection were observed.This new model of cryopreserved aortic valve allograft transplantation has been used to demonstrate histological features of acute and chronic rejection in allogeneic rat grafts. Should homografts be indeed immunogenic, then this model could be used to investigate the role of immunosuppression of the recipient or treatment of the graft in allograft survival. This will have important clinical implications for patients with valvular heart disease, particularly children.