Local administration of NF-kappa B decoy oligonucleotides to prevent restenosis after balloon angioplasty: an experimental study in New Zealand white rabbits.
OBJECTIVE
To evaluate the efficacy of NF-kappa B 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.


METHODS
In vitro, 8000 rabbit vascular smooth muscle cells (rVSMC) where transfected with a liposomal carrier (TfX50) 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 mug: n = 14; 10 mug: 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.


RESULTS
NF-kappa B decoy ODN but not scrambled ODN inhibited proliferation of rVSMC in vitro. 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 mm(2) using 1 mug NF-kappa B ODN compared to 0.98 mm(2) in the control group. The higher dose resulted in a neointimal area of 0.97 mm(2) compared to 1.07 mm(2) at the control side.


CONCLUSIONS
Local drug delivery of NF-kappa B ODN using the "channeled balloon" catheter could not reduce neointimal hyperplasia in stenostic rabbit iliac arteries. Application modalities have to be improved to enhance the effect of the local application to prevent restenosis after balloon angioplasty.
Kalinowski
Marc
M
Department of Diagnostic Radiology, Philipps University Hospital, Baldingerstrasse, 35033 Marburg, Germany. kalinows@mailer.uni-marburg.de
Viehofer
Kerstin
K
Hamann
Christine
C
Barry
James J
JJ
Kleb
Beate
B
Klose
Klaus Jochen
KJ
Wagner
Hans-Joachim
HJ
Alfke
Heiko
H
D000800:Angioplasty, Balloon; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D002404:Catheterization / Q000295:instrumentation; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003251:Constriction, Pathologic / Q000473:pathology / Q000517:prevention & control; D016503:Drug Delivery Systems; D006965:Hyperplasia; D007083:Iliac Artery / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D011817:Rabbits; D011897:Random Allocation; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
C468119:NF-kappaB decoy; D009838:Oligodeoxyribonucleotides