© 2002 SAGE Publications
The Impact of Donor Brain Death on Graft Integrity after Transplantation: Insights from Chronic Rat Cardiac Allograft Rejection
In the present study, the effect of donor brain death on long-term intragraft changes was investigated in a model of chronic rat cardiac allograft rejection. Hearts of brain-dead (BD) LEW rats were transplanted heterotopically in F344 rats treated with cyclosporine; hearts from normal anesthetized LEW rats served as controls (CON). At the time of explantation, BD and CON hearts exhibited normal morphology. Fifteen days after transplantation, infiltration by CD4+ (P < 0.005) and CD8+ (P << 0.001) T cells, as well as by macrophages (P < 0.01) was significantly more intense in hearts from BD than in hearts from CON. The expression of IL-2R+ cells; the production of IL-2, IFN-, and TNF-; and the expression of profibrotic cytokines (TGF-ß, PDGF, FGF) was more pronounced in hearts from BD than in those from CON (each P < 0.01). By 90 days following engraftment, hearts from CON exhibited some fibrosis, predominately in the subendocardium and subepicardium. The myocardium, in general, was well preserved. In contrast, in hearts from BD, fibrosis was widespread throughout the graft (P < 0.001). The insult to the donor heart induced by brain death may trigger an increased host alloresponsiveness, which in the long term, ultimately results in fibrotic remodeling and loss of integrity.
Key Words: brain death chronic rejection fibrosis