Ta. Fey et al., IMPROVED METHODS FOR TRANSPLANTING SPLIT-HEART NEONATAL CARDIAC GRAFTS INTO THE EAR PINNA OF MICE AND RATS, Journal of pharmacological and toxicological methods, 39(1), 1998, pp. 9-17
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.