Local gene delivery within the media of rabbit iliac arteries by using the infiltrator intramural delivery device.
Percutaneous transluminal angioplasty continues to be limited by restenosis. Prevention of restenosis is now focusing on local delivery of therapeutic agents, such as proliferation-inhibiting genes, directly to the site of arterial injury. We evaluated use of the Infiltrator catheter (IVT, San Diego, CA. U.S.A.) for gene delivery within the arterial media. The goals of our study were to evaluate the histologic effects of the injection and the suitability of the Infiltrator catheter for local delivery of viral therapy. We injected the femoral arteries of 21 New Zealand White rabbits. Six animals were used for an evaluation of the intramural distribution of dextran/rhodamine injected via the Infiltrator catheter. In seven animals, injection site histology and in vitro vasoreactivity were studied after an injection of saline. In the remaining eight animals, a replication-deficient adenovirus encoding for the firefly luciferase gene (Ad RSVLuc) was injected, and luciferase activity was quantified 3 and 8 days later. After injection via the Infiltrator catheter, the fluorescent tracer was distributed throughout the entire circumference and width of the arteries. Histologic examination showed minimal damage with partial endothelial abrasion and disruption of the internal elastic lamina confined to the penetration sites. In vitro endothelium-dependent vasodilation was present at a reduced level after injection via the Infiltrator (maximal endothelium-dependent acetylcholine-induced relaxation, 51.5 +/- 7.4% vs. 23.8 +/- 14.6%; p < 0.05). Significant luciferase expression was found in all the arteries, with a significant increase from day 3 to day 8 (5,392.5 +/- 2,300 vs. 2,012 +/- 471 cpm/mg; p < 0.05). These data obtained in a rabbit iliac artery model show that the Infiltrator catheter is an efficient and safe local intramural delivery device that provides significant transgene expression in the arterial wall without causing significant structural damage.
Teiger
E
E
INSERM U 492, Hôpital Henri Mondor, Créteil, France.
Deprez
I
I
Dupouy
P
P
Sitbon
M
M
Adnot
S
S
Dubois-Rande
J L
JL
D000256:Adenoviridae / Q000235:genetics; D015906:Angioplasty, Balloon, Coronary / Q000295:instrumentation*; D000818:Animals; D003911:Dextrans; D005456:Fluorescent Dyes; D018014:Gene Transfer Techniques; D007083:Iliac Artery / Q000201:enzymology / Q000473:pathology*; D008156:Luciferases / Q000378:metabolism; D008297:Male; D011817:Rabbits; D012235:Rhodamines
D003911:Dextrans; D005456:Fluorescent Dyes; D012235:Rhodamines; D008156:Luciferases