INHIBITION OF CHRONIC VASCULAR REJECTION IN PRIMATE CARDIAC XENOGRAFTS USING MYCOPHENOLATE MOFETIL

Similar to human allografts, cardiac xenografts also appear susceptibl e to chronic vascular rejection. The study described here evaluated th e influence of mycophenolate mofetil on the incidence and severity of vascular rejection in a primate model of heart xenotransplantation. Ni ne baboons received heterotopic cardiac xenografts from donor cynomolg us monkeys. All baboons were placed on a cyclosporine and methylpredni solone-based immunosuppressive regimen. In addition, group 1 baboons r eceived azathioprine (4 mg.kg(-1).day(-1)) and group 2 baboons receive d 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, we re reviewed. Histologic evidence of vascular rejection was present in 16 of the 29 biopsy specimens from the group 1 animals and in only 2 o f the 21 specimens from the group 2 animals (p < 0.005). The mean graf t survival was 3 months in group 1 versus 10 months in group 2. At 1-y ear follow-up, profound intimal proliferation in the coronary vasculat ure was noted in the biopsy specimens from group 1, whereas the corona ry vessels were found to be normal in the specimens from group 2. The use of mycophenolate mofetil, in combination with cyclosporine and ste roids, resulted in reduced vascular rejection and prolonged xenograft survival.