REVERSAL OF CARDIAC ALLOGRAFT-REJECTION WITHOUT IMMUNOTHERAPY - AN ANIMAL-MODEL

Immunosuppressive agents used in organ transplantation, including cort icosteroids and cyclosporine, may alter the physiology of normal and g rafted organs, and may not reverse graft rejection once it is establis hed in the rat model of heterotopic heart transplantation. For the pur pose of studying the effects of allograft rejection and its reversal o n the molecular basis of contractile dysfunction in cardiac myocytes, we developed a reversible model of cardiac allograft rejection in the rat that does not use immunomodulating agents. In control experiments, 38 Lewis rats underwent heterotopic heart transplantation using Lewis x Brown-Norway F-1 (LBNF(1)) donors. Hearts explanted as early as 4 d ays after transplantation demonstrated lymphocytic infiltrates and evi dence of myocyte necrosis. In the present experiments, five LBNF(1) ca rdiac grafts were transplanted into Lewis rats. After 4 days, the hear ts were explanted and reimplanted into syngeneic LBNF(1) rats. Hearts were removed for histologic examination after 2 days. Four of the five hearts showed complete resolution of the lymphocytic infiltrate. One heart had a sparse residual infiltrate. Five control isografts (Lewis/ Lewis) were also explanted and reimplanted into Lewis rats. Histologic examination after 2 days showed normal morphology. Reversal of allogr aft rejection by retransplantation is possible in the rat model withou t the use of immunosuppression, permitting the investigator to study i nh acellular processes that otherwise might be influenced by immune su ppression.