Xenogeneic and allogeneic canine heart transplantation: a model for cytologic and immunologic monitoring of rejection mechanisms.

In the model of heterotopic intrathoracic heart transplantation, rejections of the graft are not lethal for the recipient animal. Therefore it is possible to follow the immunologic rejection mechanism to the final stage. Allogeneic dog hearts (n = 6) and xenogeneic fox hearts (n = 6) were transplanted. Immunosuppression therapy included cyclosporine and methylprednisolone. Cytoimmunologic monitoring was done every second day. Due to fluctuations of lymphocyte subpopulations and their immature forms, endomyocardial biopsies were performed. The transplanted allogeneic hearts survived for 53.2 +/- 14.8 days if treated with cyclosporine (historical control group without immunosuppression 6.8 +/- 0.8 days). Xenogeneic fox hearts stopped beating after 20.2 +/- 4.1 days (historical control 8.4 +/- 1.9 days). The allogeneic grafts were all rejected in an acute cellular fashion, whereas xenogeneic transplanted hearts showed humoral and cellular rejection mechanisms. Monitoring of circulating inflammatory cells allowed differentiation between humoral and cellular rejection, which was confirmed by histology. Both types of rejection were accompanied by an increase of lymphocytes and their activated forms. Differentiation of lymphocyte subpopulations revealed a significant increase of surface IgG-positive B-lymphocytes under humoral rejection, whereas acute cellular rejection episodes showed a substantial increase of surface IgG-negative lymphocytes. Humoral rejection that developed even with cyclosporine administration was not influenced, whereas cellular rejections were controlled by increasing methylprednisolone to 250 mg/day for 3 days.