ALLOTRANSPLANTATION AND AUTOTRANSPLANTATION OF CAROTID-ARTERY - A NEWMODEL OF CHRONIC GRAFT VESSEL DISEASE - EVALUATION BY MAGNETIC-RESONANCE-IMAGING AND HISTOLOGY

Background. Graft vessel disease is a special form of accelerated arte riosclerosis. Because immunological and nonimmunological factors can c ontribute to graft vessel disease, we developed a model that enables t he study of both factors simultaneously. Methods. A carotid artery was allografted from DA to Lewis rats, with the excised native artery aut ografted on the contralateral side. Five groups of six to seven rats w ere treated for 8 weeks with vehicle (placebo) or cyclosporine (CsA) ( 0.3, 1, 3, and 10 mg kg(-1) day(-1)), which was administered using sub cutaneous osmotic minipumps. The carotid lumen area was estimated in v ivo at 2, 4, and 8 weeks by magnetic resonance imaging (MRI); CsA bloo d levels were determined twice. Carotid neointimal thickening and medi al and luminal area were measured with histological techniques. Result s. MRI showed bulging of the allografts but not autografts. Bulging di sappeared over time with narrowing of the allograft lumina estimated b y both MRI and histology. Histologically, vehicle-treated animals deve loped a massive neointima, which was inhibited in a dose-dependent man ner by CsA. Autografts remained normal except for minimal subintimal t hickening of two of four arteries in the group given the highest dose of CsA. Cellular rejection was detected in the allografts of all but t he highest-dose group. The CsA blood levels were similar to those used in man at the two lower doses and about 10-fold higher at the highest dose. Conclusions. Subintimal thickening did not correlate with in vi vo lumen size, a phenomenon that we have previously described for ball oon catheter-induced lesions. CsA blood concentrations similar to thos e used in patients suppressed neointima formation in part, and 10-fold higher concentrations almost completely suppressed neointima formatio n.