The impact of FK506 on graft coronary disease of rat cardiac allograft--a comparison with cyclosporine.

We studied the impact of FK506, a potent immunosuppressant, on graft coronary disease and graft-infiltrating lymphocyte subset after rat heart transplantation. Fisher rat heart grafts transplanted into Lewis rat recipients were divided into three groups: control (n = 7), rats treated with FK506 at a dose of 0.32 mg/kg/day intramuscularly (n = 7), and rats treated with cyclosporine at a dose of 10 mg/kg/day intramuscularly (n = 7). Grafts were removed on day 71 in the treated groups and on rejection in the control group. We blindly scored graft rejection and graft coronary disease on a scale of 0 to 4. Graft-infiltrating lymphocytes were investigated by flow-cytometric analysis with the following monoclonal antibodies: W3/25, anti-helper T lymphocyte; OX8, antisuppressor and cytotoxic T lymphocyte; and OX39, antiinterleukin-2 receptor. No difference of graft rejection was found between the two treated groups (FK506 1.66 +/- 0.49 versus cyclosporine 1.45 +/- 0.37), but the FK506 group showed severe graft coronary disease (FK506 2.14 +/- 0.82 versus cyclosporine 0.78 +/- 0.17; p less than 0.01) in this model. In flow-cytometric analysis, we found an increased proportion of OX8-positive lymphocytes (FK506 25.7 +/- 6.4 versus cyclosporine 4.9 +/- 2.4, p less than 0.01). These results suggest that suppression of cytotoxic T lymphocytes may be involved in graft coronary disease.