Inhibition of chronic vascular rejection in primate cardiac xenografts using mycophenolate mofetil

Abstract

Similar to human allografts, cardiac xenografts also appear susceptible to chronic vascular rejection. The study described here evaluated the influence of mycophenolate mofetil on the incidence and severity of vascular rejection in a primate model of heart xenotransplantation. Nine baboons received heterotopic cardiac xenografts from donor cynomolgus monkeys. All baboons were placed on a cyclosporine and methylprednisolone-based immunosuppressive regimen. In addition, group 1 baboons received azathioprine (4 mg · kg −1 · day −1) and group 2 baboons received mycophenolate mofetil (70 mg · kg −1 · day −1). Biopsy specimens were obtained at regular intervals and reviewed blindly by a pathologist. A total of 50 biopsy specimens, 29 from group 1 and 21 from group 2, were reviewed. Histologic evidence of vascular rejection was present in 16 of the 29 biopsy specimens from the group 1 animals and in only 2 of the 21 specimens from the group 2 animals ( p < 0.005). The mean graft survival was 3 months in group 1 versus 10 months in group 2. At 1-year follow-up, profound intimal proliferation in the coronary vasculature was noted in the biopsy specimens from group 1, whereas the coronary vessels were found to be normal in the specimens from group 2. The use of mycophenolate mofetil, in combination with cyclosporine and steroids, resulted in reduced vascular rejection and prolonged xenograft survival.