Prolongation of rat cardiac allograft survival by donor pretreatment. Impact of dose and timing of drug administration.
We investigated the effect of two variables, the time interval between drug administration and transplant removal and the dosage of the drug, on the prolongation of rat heart allograft survival via donor pretreatment. A maximal or near-maximal survival-prolonging effect was recorded when the drug was given at least 6 hours before removal of the transplant; extension of pretreatment beyond that time had relatively little effect on the outcome of the graft. A maximal survival prolonging effect was obtained with all of the test drugs, cyclophosphamide, methotrexate, hydroxyurea, busulfan and procarbazine, in doses of LD-50. The therapeutical margin was small, however, as doses of 0.5 x LD-50 and 2 X LD-50 were clearly inferior in their effect.
D000818:Animals; D002066:Busulfan / Q000008:administration & dosage*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D006085:Graft Survival / Q000187:drug effects*; D006321:Heart / Q000187:drug effects; D016027:Heart Transplantation; D006918:Hydroxyurea / Q000008:administration & dosage*; D007928:Lethal Dose 50; D008727:Methotrexate / Q000008:administration & dosage*; D011344:Procarbazine / Q000008:administration & dosage*; D051381:Rats; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous
D011344:Procarbazine; D003520:Cyclophosphamide; D002066:Busulfan; D006918:Hydroxyurea; D008727:Methotrexate