AORTA TRANSPLANTATION AS A MODEL TO STUDY HYPERACUTE, ACUTE, AND CHRONIC REJECTION OF XENOGRAFTS

To explore the mechanism of rejection of vascularized xenografts, we p erformed discordant and concordant transplantation of aortic grafts. F orty-one guinea pig-to-rat and 50 hamster-to-rat aortic transplantatio ns were performed successfully. Recipient rats were either untreated o r treated three times per week with 10 mg/kg of cyclosporine (CsA) sta rting the day before transplantation. Recipients were sacrificed at va rious timepoints after transplantation and the grafts were processed f or histology and immunohistochemistry. Guinea pig aortic grafts were r ejected hyperacutely in both the control and CsA treated group. Four h ours after transplantation all endothelial cells and some of the media l smooth muscle cells had disappeared. Seven days after transplantatio n the media were totally acellular, whereas the adventitia was enlarge d due to infiltrating cells, consisting mainly of macrophages. At day 56, only traces of the original graft could be identified. Hamster aor tic grafts developed signs of chronic rejection. In control rats, the intimal lesions could already be demonstrated in 17% of the rats at da y 14, and in all rats from day 28. CsA treatment inhibited the develop ment of the intimal lesions. At days 56 and 84 the difference in intim al thickness between the control group and the CsA treated group was s tatistically significant. The cellularity of the media of the hamster grafts remained constant during the first 21 days in both groups but d eclined sharply thereafter as a consequence of migration or necrosis o f myocytes. The thickness of the adventitia in both groups increased a fter transplantation, due to infiltrating macrophages and T cells, rea ching a peak at day 14. In conclusion, the aorta transplantation model provides useful information with regard to the development of chronic rejection in concordant grafts. Discordant aortic grafts are rejected hyperacutely just like discordant heart grafts.