Reversal of cardiac allograft rejection without immunotherapy: an animal model.

Abstract

Immunosuppressive agents used in organ transplantation, including corticosteroids and cyclosporine, may alter the physiology of normal and grafted organs, and may not reverse graft rejection once it is established in the rat model of heterotopic heart transplantation. For the purpose of studying the effects of allograft rejection and its reversal on 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 F1 (LBNF1) donors. Hearts explanted as early as 4 days after transplantation demonstrated lymphocytic infiltrates and evidence of myocyte necrosis. In the present experiments, five LBNF1 cardiac grafts were transplanted into Lewis rats. After 4 days, the hearts were explanted and reimplanted into syngeneic LBNF1 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 allograft rejection by retransplantation is possible in the rat model without the use of immunosuppression, permitting the investigator to study intracellular processes that otherwise might be influenced by immune suppression.