Rapidly proliferative arteriopathy in cyclosporin-induced permanently surviving rat cardiac allografts simulating chronic vascular rejection

Abstract

SUMMARY In an attempt to create a model of chronic rejection in rat, cardiac allograft transplantation was performed of hearts from PVG rats to DA rats treated with cyclosporin, 20 mg/kg body weight per day for 14 days and thereafter no immunosuppressive therapy. Experiments were made in 83 rats fed on a normal diet and in 24 rats fed on a diet containing an additional 0·5% cholesterol. Rats on the normal diet showed moderate signs of acute rejection during the first 20–40 days and grafts were lost in acute rejection during this period of time. However, after 2–3 months no signs of acute rejection were present. On the contrary, excessive proliferative changes of the vascular intima and endocardium along with fibrosis and fibrin deposition appeared and was progressive until 6 months post-transplantation. These morphological changes are similar to those found in chronically rejected organs like heart and kidney. In rats fed on a cholesterol diet after cessation of cyclosporin, development of the vascular and endocardial proliferative changes appeared three to four times as fast and were on average fully developed within 4–6 weeks post cessation of cyclosporin treatment. The recipients’ own hearts showed no signs of vascular or endocardial damage. It is thus concluded that two models of vascular and endocardial proliferative changes in cardiac allografts have been developed showing distinct similarities to chronic vascular rejections seen in the clinical transplantation and with apparent similarities to severe arteriosclerosis. The models could be useful in the investigation of pathogenesis and therapeutical means for preventing chronic vascular damage in transplanted organs and arteriosclerosis.