CARDIAC ALLOGRAFT ATHEROSCLEROSIS IN THE RAT - THE EFFECT OF HISTOCOMPATIBILITY FACTORS, CYCLOSPORINE, AND AN ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR

Cardiac transplant atherosclerosis is thought to result from immune-me diated vessel wall injury. The present experiments were designed to te st whether CsA alone or in combination with the ACE-inhibitor cilazapr il has any effect on graft atherosclerosis in a rat cardiac transplant model. Cardiac grafts were transplanted heterotopically into either s yngeneic or allogeneic recipients and followed by daily palpation; lon g-surviving grafts were removed after 100 days and the extent and degr ee of atherosclerosis was assessed using computerized morphometry. Ath erosclerosis was more extensive in grafts removed from untreated allog eneic recipients compared with syngeneic recipients; CsA treatment inc reased the extent of atherosclerosis in syngeneic transplants. The ext ent and degree of vascular occlusion in allogeneic grafts from recipie nts treated with 15 mg/kg of CsA every other day was not different fro m that in grafts removed from recipients that received initially highe r CsA doses. Cilazapril had no effect on the extent of graft atheroscl erosis but decreased the degree of luminal narrowing in grafts from Cs A-treated recipients significantly. Some grafts showed neovascularizat ion in the subendocardial region adjacent to organized intraventricula r clots, suggesting the release of angiogenic factors from such clots; such growth factors may contribute to the atherosclerotic vessel wall reaction in this model. We conclude that CsA promotes the development of graft atherosclerosis in heterotopically transplanted syngeneic ca rdiac grafts in the rat. We furthermore found that cilazapril has a be neficial effect on the degree of atherosclerosis in CsA-treated recipi ents.