CYCLOSPORINE-A DELAYS THE PRESENTATION OF INTIMAL HYPERPLASIA IN AN EXPERIMENTAL-MODEL OF ARTERIAL AUTOGRAFT

A study was made of the effect of cyclosporin A on intimal hyperplasia in an experimental model of arterial autograft. Fifty female Sprague- Dawley rats weighing 250-300 g were employed. Using a microsurgical te chnique, an arterial autograft measuring approximately 5 mm in length was implanted in right common iliac artery. Two groups were establishe d: group I (control), consisting of 25 animals subjected only to arter ial autograft, and group II (preoperative cyclosporin A), also consist ing of 25 animals, which received a daily subcutaneous dose of 5 mg/kg cyclosporin A (Sandimmun(R), Sandoz) for 4 days before the surgical p rocedure. The animals were sacrificed on postoperative days 7, 14, 21, 30 or 50. Specimens were studied by optical microscopy, transmission and scanning electron microscopy, autoradiography, and morphometry. En dothelialization of the graft zone was slow in the cyclosporin-treated group. Hyperplasia was delayed notably, but at 30 days the hyperplast ic process had improved and at 50 days it was similar to that of the c ontrol group. In the cyclosporin-treated group, thymidine was not take n up by the medial layer, the absence of medial thymidine uptake corre lated with ultra; structural evidence of medial degeneration with lipi d vacuolization of the smooth muscle cells and the presence of macroph ages. These results suggest that cyclosporin A does not inhibit intima l hyperplasia but instead delays its occurrence, probably because of t he drug's toxicity for smooth muscle cells.