Lokale Pharmakotherapie mit NF-kB "decoy"-Oligonukleotiden zur Prophylaxe der Restenose nach PTA

The purpose of this study was to evaluate the efficacy of NF-kB oligonucleotides (ODN) administered by local administration with the channeled balloon catheter to prevent restenosis after balloon angioplasty in restenotic iliac arteries of New Zealand white rabbits. In vitro, 8000 rabbit vascular smooth muscle cells (rVSMC) where transfected with a liposomal carrier (Tfx-50) with 100 ng of decoy and scrambled ODN. Inhibition of proliferation was measured using a MTT assay after 24 hours in comparison to control. In vivo, 22 male New Zealand White rabbits were fed a 1% cholesterol diet and received denudation of both common iliac arteries with a 3 mm balloon catheter to induce an arterial stenosis. Four weeks after stenosis induction, local application of NF-kappa B in two different concentrations (1 µg: n = 14; 10 µg: n = 8) was performed randomly on one common iliac artery. Scrambled oligonucleotides without specific binding capacities were injected into the contralateral side. The channeled balloon catheter allows simultaneous balloon dilation (8 atm) of the stenosis and local application of a drug solution (2 atm). Four weeks after local drug delivery the animals were killed and the vessels were excised and computerized morphometric measurements were performed. With the in vitro expemiments we could show that NF-kappa B decoy ODN but not scrambled ODN inhibited proliferation of rVSMC. Following local ODN application in the animals no acute vascular complications were seen. NF-kappa B ODN resulted in a statistically non significant reduction of neointimal area compared to the control group. The neointimal area was 0,97 mm² using 1 µg NF-kappa B ODN compared to 0,98 mm² in the control group. The higher dose resulted in a neointimal area of 0,97 mm² compared to 1,07 mm² at the control side. The results of the in vitro experiments could not be confirmed in vivo. Local drug delivery of NF-kappa B ODN using the "channeled balloon" catheter could not reduce neointimal hyperplasia in stenotic rabbit iliac arteries. Application modalities have to be improved to enhance the effect of the local application to prevent restenosis after balloon angioplasty.