The effects of immunosuppression and anticoagulation on fibrin deposition and swelling in rat cardiac allografts.
Rat cardiac allograft recipients were injected with radiolabeled human fibrinogen at intervals after transplantation. There was a progressive increase in tracer accumulation within graft ventricles, peaking at the time of rejection at about 30-fold that within syngeneic grafts. Protein extraction experiments indicated that ca. 90% of tracer was present as cross-linked fibrin at the time of rejection. Exudation within rejecting allografts was nearly threefold that in syngeneic grafts. The weight of allografts at different times after transplantation increased in close concordance with fibrin deposition. Pharmacologically immunosuppressed recipients showed negligible fibrin deposition and swelling whereas "B" rats and thoracic-duct-lymph-drained recipients showed moderate allograft swelling in the absence of significant fibrin deposition or rejection. The decreased fibrin deposition was not a result of depressed plasma clotting factor levels. B rats reconstituted with thoracic duct lymphocytes still had reduced allograft fibrin deposition in the presence of normal amounts of swelling and exudation. The anticoagulants warfarin and heparin greatly decreased allograft fibrin but were almost without effect on allograft swelling, exudation, and rejection. The possible participation of infiltrating macrophages in allograft fibrin deposition is discussed. Unlike cutaneous delayed hypersensitivity reactions, normal amounts of fibrin deposition appear not to be essential for full cardiac allograft rejection.
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D004487:Edema / Q000209:etiology / Q000378:metabolism; D005122:Exudates and Transudates; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D006084:Graft Rejection; D016027:Heart Transplantation; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008212:Lymphocyte Depletion; D008297:Male; D009929:Organ Size; D051381:Rats; D011919:Rats, Inbred Strains; D014184:Transplantation, Homologous
D000925:Anticoagulants; D007166:Immunosuppressive Agents; D005337:Fibrin; D005340:Fibrinogen