INHIBITION OF INTIMAL HYPERPLASIA IN RAT AORTIC ALLOGRAFTS WITH CYCLOSPORINE

The rat aortic transplant model of chronic rejection was used to study the effect of cyclosporine (CsA) on the development of intimal hyperp lasia, ACI and Lewis rat strains were used to create isograft and allo graft CsA nontreated and treated groups, After orthotopic abdominal ao rtic transplantation, recipients received either no treatment, CsA 2.5 mg/kg/day, CsA 5 mg/kg/day, or CsA 10 mg/kg/day by gavage, Treated gr afts were harvested at 3 and 6 months after transplantation, and compu ter image digital analysis was used to measure intimal and medial area s of graft cross-sections, At 3 months, the reduction in percent intim a was 62% (P=0.005), 74% (P=0.002), and 97% (P<0.0001) for the 2.5-, 5 -, and 10-mg/kg allograft groups, respectively. There was a 93% (P<0.0 001) reduction in percent intima at 6 months in the 10-mg/kg allograft group, CsA treatment also preserved the aortic media, In comparison t o nontreated isografts, medial area in nontreated allografts was decre ased by 37% at 3 months after transplantation, In contrast, medial are a was not significantly changed in CsA-treated recipients (10 mg/kg/da y) in comparison to nontreated isografts, More importantly, medial nuc lear density was preserved in the CsA-treated recipients in comparison to nontreated allografts and was similar to treated or nontreated iso grafts. In conclusion, daily high dose CsA treatment was found to mark edly inhibit intimal hyperplasia in rat aortic allografts up to 6 mont hs after transplantation, which suggests that CsA at an adequate dosag e can suppress chronic rejection.