INHIBITION OF INTIMAL HYPERPLASIA IN RAT AORTIC ALLOGRAFTS WITH CYCLOSPORINE

Abstract

The rat aortic transplant model of chronic rejection was used to study the effect of cyclosporine (CsA) on the development of intimal hyperplasia. ACI and Lewis rat strains were used to create isograft and allograft CsA nontreated and treated groups. After orthotopic abdominal aortic 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 grafts were harvested at 3 and 6 months after transplantation, and computer image digital analysis was used to measure intimal and medial areas of graft cross-sections. At 3 months, the reduction in percent intima 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 < 0.0001) reduction in percent intima at 6 months in the 10-mg/kg allograft group. CsA treatment also preserved the aortic media. In comparison to nontreated isografts, medial area in nontreated allografts was decreased by 37% at 3 months after transplantation. In contrast, medial area was not significantly changed in CsA-treated recipients (10 mg/kg/day) in comparison to nontreated isografts. More importantly, medial nuclear density was preserved in the CsA-treated recipients in comparison to nontreated allografts and was similar to treated or nontreated isografts. In conclusion, daily high dose CsA treatment was found to markedly inhibit intimal hyperplasia in rat aortic allografts up to 6 months after transplantation, which suggests that CsA at an adequate dosage can suppress chronic rejection.