A CRUCIAL EFFECT OF SPLENECTOMY ON PROLONGING CARDIAC XENOGRAFT SURVIVAL IN COMBINATION WITH CYCLOSPORINE

  • 1 April 1989
    • journal article
    • research article
    • Vol. 105  (4) , 535-542
Abstract
In this study we investigated the effect of splenectomy in combination with cyclosporine (CsA) on survival of heterotopic cardiac xenografts from hamster to rat. A 12-fold prolongation of mean cardiac xenograft survival, to 41 days, was accomplished with the combined therapy. In both untreated control and CsA-treated recipients rejection occurred in 3 days. Splenectomy by itself prolonged xenograft function to 5 days. Evidence of humoral-mediated rejection in this cross-species combination was given for the extensive thrombosis and hemorrhage in teh subepicardial area, the appearance of lymphocytotoxic titers just before graft function ceased, and the presence of IgM deposits in subepicardial vessels of the xenograft. CsA by itself could not modify this pattern of rejection. Splenectomy decreased antibody formation significantly and rejection became more cellular in nature. The regimen of splenectomy in association with CsA suppressed antibody titre and produced a CsA dose-dependent prolongation of xenograft survival. Thus, a complementary or synergistic effect is the result of the immuno suppressive regimen of splenectomy and CsA in hamster-to-rat cardiac xenografts. In this study the effect of splenectomy in controlling the humoral response in concordant xenografts and its role in future clinical xenografting is emphasized.