Effect of dose of cyclosporine or FK506 and antithrombotic agents on cardiac allograft vascular disease in heterotopically transplanted hearts in rats

Background: We compared the severity of cardiac allograft vascular disease in rats treated with cyclosporine or FK06 and studied the effect of antithrombotic agents on cardiac allograft vascular disease. Methods: One group each was treated with 2 and 5 mg/kg/day of cyclosporine. Two other groups were injected with heparin and dipyridamole, respectively, in addition to cyclosporine. Four other groups were similarly divided by dose of FK506 (0.1 or 0.25 mg/kg/day) and concomitant anticoagulant treatment. Results: Grade of rejection and percentage stenosis of coronary arteries were lower in groups with high doses of immunosuppressive agents or with heparin. Major histocompatibility class II antigens were expressed by the endothelium of grafted hearts, and IgM and C3 were deposited in the intimal and medial layers in all groups except those administered the higher doses of immunosuppressive drugs. However, no remarkable differences in density of major histocompatibility class II antigens were found between groups demonstrating expression of these antigens. On the other hand, the intensity of IgM or C3 expression grew significantly as coronary stenosis increased in severity. Conclusions: A significant difference in severity of cardiac allograft vascular disease was not found between the groups treated with cyclosporine and FK506, and cardiac allograft vascular disease was almost entirely suppressed when doses of cyclosporine and FK506 sufficient to suppress graft rejection were administered. Our findings also showed that concomitant heparin administration reduced the extent of allograft rejection and the incidence of cardiac allograft vascular disease