© 2002 SAGE Publications
Chronic Rejection in the Rat Liver Transplantation Model
In the liver, as in other organs, chronic graft failure is induced not only by a rejection reactionto the graft but also by nonimmunological factors, such as ischemia or viral infections.In the rat, inbred strain combinations provide defined immunological differences,on the one hand. On the other hand, nonimmunological factors can be excludedunder experimental conditions. However, the morphological criteria of chronic liver rejectionin the rat are not yet defined. Thus, the authors induced chronic liver allograft rejectionin the rat model and defined its histomorphological criteria. As an immunosuppressant,tacrolimus (FK506) was applied intramuscularly in different dosages (0.1,0.05, 0.035, and 0.025 mg/kg/day) from days 0 to 13 postoperatively. On days 10, 30,100, and 120, biopsies were obtained for histological analyses. A stepwise tapering ofFK506 from 0.1 mg/kg/d to 0.025 mg/kg/d reduced the long-term survival rate. All animalsdied at an FK506 dosage of 0.025 mg/kg/d. Two forms of chronic rejection followingorthotopic rat liver transplantation can be defined in the inbred Dark Agouti-to-Lewis model: a more common ductoproliferative form with proliferation and periductal fibrosisof bile ducts and a less common ductopenic form paralleling the human situation.The fact that inbred rats show morphologically different forms of chronic graft hepatopathymay be indirect evidence of yet unknown nonimmunologic factors in the evolutionof this phenomenon. Both forms, however, evolve from persistent cellular "acute"rejection and can be prevented by selective immunosuppression.
Key Words: orthotopic rat liver transplantation chronic rejection FK 506 histomorphological criteria of chronic liver rejection