Does cyclosporin a have any effect on accelerated atherosclerosis in absence of graft rejection? Pathologic and morphometric evaluation in an experimental model

Background: The effects of cyclosporin A on accelerated atherosclerosis were studied in an experimental model of aortic isotransplantation. Methods: Seventy-six Lewis rats were studied. Forty-one abdominal aortic isografts were performed and divided into five groups: 2-day isografts and 15- and 100-day isografts with and without cyclosporin treatment. The remaining rats were divided into seven groups: 15- and 100-day sham-operated, with and without cyclosporin administration; 15- and 100-day animals with cyclosporin treatment only; and normal controls. Cyclosporin was injected subcutaneously in doses of 10 mg/kg daily for the first 15 days and afterward every other day. Longitudinal sections of the proximal anastomosis and cross sections of the midgraft region were measured with a semiautomatic image-analyzer. Results: Histologic analysis showed that accelerated atherosclerosis was not observed either in NT2 rats or in nontransplanted animals. In the 15-day isografts, accelerated atherosclerosis was present in the perianastomotic tract of the recipient aorta in nine of nine NT15 rats, whereas it was found only in three of nine T15 animals (p < 0.02). Histomorphometric analysis showed that accelerated atherosclerosis was less pronounced in the T100 isografts than in the NT100 ones, this difference being significant at the recipient anastomotic side only (p < 0.0005). Conclusions: The present results support the hypothesis that cyclosporin, at immunosuppressant and nontoxic doses, can delay the onset and progression of accelerated atherosclerosis and that its effects are more significant at the recipient side of the anastomosis where accelerated atherosclerosis begins to develop.