EXPERIMENTAL CARDIAC ALLOGRAFT VASCULOPATHY IN MICE

Cardiac allograft vasculopathy is the most common cause of death in he art transplant recipients after the first postoperative year. The path ogenesis of cardiac allograft vasculopathy is not clearly defined. To better study this disease, a genetically well-defined and reproducible animal model such as the mouse is needed. We performed heterotopic, i ntraabdominal heart transplantation between two inbred strains of mice . The B10.A strain served as donors, and the B10.BR strain served as r ecipients. No immunosuppressive therapy was administered. The allograf ts in groups I (n = 6) and II (n = 6) were harvested at 30 and 50 days after operation, respectively. All allografts had palpable contractio ns at the time of harvest. The cardiac allografts from both groups sho wed mild to moderate acute cellular rejection. In groups I and II, 55% +/- 26% and 60% +/- 18% of arteries showed intimal thickening, respec tively. Pathologically, the vascular lesions were characterized with v arying degrees of intimal thickening, subendothelial mononuclear cell infiltration and fibrosis, frequent disruption of the internal elastic lamina, and perivascular inflammation. These findings are characteris tic of cardiac allograft vasculopathy seen clinically. Isografts (n = 6) showed no vascular lesions. The heterotopic transplantation of B10. A-strain hearts into B10.BR recipients provides a useful murine model for future studies in the pathogenesis and treatment of cardiac allogr aft vasculopathy.