DESCRIPTION (Verbatim from the applicant?s abstract) Transplantation is now a standard treatment for end stage heart failure. With the persistent lack of donors, however, xenotranplantation may be a future option. The previous barrier of hyperacute rejection associated with xenotransplantation has been gradually overcome with the combination of transgenic pigs expressing human complement regulatory proteins and new immunosuppressive regimens. To date, no one has systematically studied the activation status of nitric oxide (NO) in any xenotransplantation model. We propose to examine the role of NO in the phenomenon of delayed xenograft rejection. Specifically, in the pig-to-baboon cardiac transplantation model, we will be examining expression of NOS 2 (inducible NO synthase) via Northern and Western blotting, immunohistochemistry and by measuring the stable end-products of NO in serum and in urine. NO donors and NO synthase inhibitors will be administered to xenotransplanted animals and the transplanted heart will be examined. With a better understanding of the activation status of NO synthase, it is hoped to uncover potential novel therapies for transplant rejection.