© 2002 SAGE Publications
The Impact of Donor Hypertension on Intragraft Changes in Chronic Rat Cardiac Allograft Rejection
Due to the declining number of suitable donors, organs from hypertensive donors are increasingly used. The purpose of this study was to investigate the effect of donor hypertension on graft performance in a model of chronic rat cardiac allograft rejection. Hypertension (HTN) was induced in F344 rats by narrowing the right renal artery. After 10 weeks, hearts from such animals were transplanted heterotopically into Lewis rats treated with cyclosporine. Hearts from sham-operated animals (SHAM), also engrafted after 10 weeks, served as controls. Hearts from SHAM were normal at explantation, whereas hearts from HTN donors exhibited some mild medial hypertrophy and medial vacuolization in elastic arteries. Thirty and 60 days after transplantation, hearts from HTN exhibited increased focal mononuclear cell infiltration, expression of IL-2R, production of cytokines (TGF-ß, PDGF), and interstitial fibrosis (each P < 0.01) as compared with SHAM grafts. After 90 and 120 days, HTN donor hearts showed widespread fibrosis with only small areas of residual myocardium. By contrast, SHAM hearts exhibited some subendocardial and subepicardial fibrosis, and the myocardium appeared still well preserved. Hearts from HTN donors appear to induce increased alloresponsiveness in the recipient. As a result, fibrosis develops more rapidly in such hearts, ultimately leading to a loss of myocardial integrity.
Key Words: donor hypertension chronic rejection fibrosis cytokines