Cardiac Transplantation in the Rat

Abstract

The development of arteriosclerosis is the most serious and common complication in long-term survivors of cardiac transplantation. We have used a variety of inbred rat strains with selected histocompatibility differences to examine the influence of prolonged, mild rejection reactions on the development of pathological changes in long-term cardiac allografts. Heterotopic cardiac allografts were exchanged between rat strains that differed for MHC class I (RT1.A and/or RT1.E) antigens or groups of minor, non-MHC antigens in MHC-compatible congenic combinations. Our results demonstrate that in strain combinations in which the allograft reaction is mild and prolonged, the donor hearts exhibit pathological changes that include a diffuse, interstitial myocardial fibrosis, perivascular fibrosis, and intimal proliferation in arteries of the graft myocardium. The lesions were less prominent in animals with more active rejection and infrequent in strains that differ for class I histocompatibility antigens or syngeneic controls. These results suggest that the comparable pathological changes seen in long-term human cardiac survivors may reflect low-level, persistent allograft reactions rather than factors associated with graft anoxia or effects of immunotherapy to prevent graft rejection.

Coronary Arteries from Human Cardiac Allografts with Chronic Rejection Contain Oligoclonal T Cells: Persistence of Identical Clonally Expanded TCR Transcripts from the Early Post-Transplantation Period (Endomyocardial Biopsies) to Chronic Rejection (Coronary Arteries)

“…The development of GA can be enhanced in rats with cardiac allografts by prior sensitization of recipient animals to donor splenic lymphocytes (11). In contrast, rats transplanted with cardiac allografts from syngeneic animals did not develope GA (12). These results suggest the involvement of an alloantigen-driven T cell response in the pathogenesis of chronic rejection.…”

Detection of primary direct and indirect human anti‐porcine T cell responses using a porcine dendritic cell population

“…It has been argued that the indirect pathway may contribute to the process of chronic rejection [61] which is notoriously difficult to treat, as might be expected if it is driven by effective antigen presentation.…”

Pharmacotherapy of Hyperlipidemia in Pediatric Heart Transplant Recipients

“…[1,4,39,40] the graft and stimulating a proliferative intimal reaction. [20] The Statins have been shown to reduce GCAD incidence and proneointima of arteries allografted in hypercholesterolemic mice gression among adult heart transplant recipients. [31][32][33] Furthercontain large numbers of nuclei.…”