LONG-TERM PROLONGATION OF CARDIAC ALLOGRAFTS BY SUBTHERAPEUTIC LEVELS OF CYCLOSPORINE IN RATS CONDITIONED WITH PRETRANSPLANT BLOOD TRANSFUSIONS AND CYCLOSPORINE

  • 1 January 1985
    • journal article
    • research article
    • Vol. 39  (1) , 1-5
Abstract
This study was aimed at ascertaining whether long-term graft survival was achievable with short-term cyclosporine (CsA) therapy or with subtherapeutic doses of CsA in rats conditioned with blood transfusion (BT) combined with CsA. Previous studies had shown that donor-specific transfusions combined with a short course of CsA interacted synergistically, resulting in considerable prolongations of ACI and BUF grafts in LEW hosts receiving no postoperative treatment. The donor-specific depression of alloreactivity was confirmed by showing a depression of mixed-lymphocyte reaction (MLR) reactivity as well as of humoral antidonor responses in BT-CsA conditioned rats. The effects of postoperative CsA were then studied in recipients conditioned with BT-CsA or BT alone. ACI and BUF cardiac graft survival in LEW hosts conditioned with BT and treated with a 5 day postoperative course of CsA (20 mg/kg per day) were indistinguishable from graft survival in untransfused hosts (ACI: 35.6 .+-. 15.5 vs. 38.8 .+-. 7.4; BUF: 58.4 .+-. 39.8 vs. 48.0 .+-. 21.7) indicating no interaction between BT and CsA under these conditions. In contrasts, the effect of a postoperative 5 day course of CsA (10 mg/kg per day) was extended by conditioning the recipients with donor-specific BT and CsA (ACI: 41.7 .+-. 7.0 vs. 27.4 .+-. 11.6; P < 0.05). More remarkably, a 30 day course of subtherapeutic doses of CsA (2.5 mg/kg per day) resulted in long-term prolongation (> 100 days) of ACI grafts in a large proportion of hosts conditioned with donor-specific BT and CsA, while the majority of controls conditioned with nonspecific BT and CsA or CsA alone rejected their grafts within 3 wk (P < 0.01). The possible mechanisms of this phenomenon are discussed.

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