IMPROVED METHODS FOR TRANSPLANTING SPLIT-HEART NEONATAL CARDIAC GRAFTS INTO THE EAR PINNA OF MICE AND RATS

The rodent heterotopic ear-heart transplant method is a useful alterna tive to the more technically demanding vascularized graft technique. W e modified the procedure to improve efficiency and used it in mice and rats to determine the survival times of both isologous and allogeneic grafts and compare reference immunosuppressants. Bisected rat and mou se cardiac (split-heart) isografts were uniformly viable up to 4 weeks postimplant; however, by 24 weeks only 90% of Lewis rat or C3H mouse split-heart isografts retained electrocardiographic activity, regressi ng to 81% by 60 weeks for the Lewis rat and to less than 50% for the C 3H mouse by 43 weeks post-implant. The potency of tacrolimus, sirolimu s, and cyclosporine for prevention of allograft rejection was comparab le whether using split-hearts or whole hearts in the Balb/C to C3H mou se model. The maximally effective doses at 2 weeks postimplant for int raperitoneally administered tacrolimus, sirolimus, cyclosporine, and o ral leflunomide with Brown-Norway (BN) to Lewis rat ear-split-heart al lografts (0.3, 0.1, 3.0, 10, mg/kg/day, respectively) agreed extremely well with published data for the rat primary vascularized heterotopic heart model. This reproducible and efficient transplantation model wa s improved by using split-hearts to double available donor tissue? a g onadotropin-enhanced breeding strategy that enables routine use of low -fecundity inbred rats as donors, implantation devices that speed and simplify the procedure, and defined electrocardiographic evaluation cr iteria to maximize sensitivity and provide an objective endpoint for d efining rejection. (C) 1998 Elsevier Science Inc.