In spite of improved technical methods, restenosis following stent implantation remains a central problem in interventional cardiology, especially in diabetic patients. Eminent for the development of restenosis are the proliferation of smooth muscle cells, the production of extracelluar matrix and inflammatory processes. Recently, a number of studies using drug-eluting stents have been performed, since the local and sustained application of antiproliferativ drugs can achieve a decrease in restenosis rates. Tacrolimus, a Rapamycin-derivative, owns, as an immunsuppressiv drug, antiinflammatoric as well as antiprolifative features. Aim of this study was to evaluate a Tacrolimus-eluting stent regarding restenosis in a diabetic animal model. Tacrolimus-eluting stents (TES) with a dosage of 173µg and Bare Metal Stents (BMS) were implanted biiliacal in alloxan-treated diabetic rabbits as well as non-diabetic rabbits. At the RWTH Aachen, an appropriate diabetic rabbit model was successfully established. The animals were partly sacrified after two weeks, and partly after 8 ± 1 weeks. 12 TES and 14 BMS could be analysed in the diabetic and 13 TES and 14 BMS in the non-diabetic group. Histomorphometric and immunhistochemical analyses and gene expression studies were performed. The procentual restenosis was lower with the BMS than with the TES (22 ± 6% vs. 31 ± 10%, p=0,05). The average rate of neointimal formation tended to be lower in the BMS group in comparism to the TES group (0,88 ± 0,32mm² vs. 1,13 ± 0,31mm², p=0,11). The average number of macrophages in the neointima was significantly decreased in the TES as compared to the BMS group (16,81± 5,55 vs. 24,31 ± 5,88, p=0,01). The relative VCAM 1 - expression was also decreased by the TES (1,9x 10-3 ± 3 *10-4 vs. 8x10-4 ± 6 *10-4 , p=0,05). Consequently, the inflammatory reaction was successfully suppressed by the TES, but the neointimal proliferation could not been positively influenced by this stent. Therfore, clinical evaluation of the TES in its current form, seems not justified yet in diabetic patients. Tacrolimus is offering a promising onset in the prevention of restenosis after stent implantation, which should be investigated further more
