Complete vascular healing and sustained suppression of neointimal thickening after local delivery of advanced c-myc antisense at six months follow-up in a rabbit balloon injury model.
BACKGROUND
Neointimal hyperplasia following percutaneous transluminal coronary angioplasty (PTCA) is one of the major components of the process of restenosis. We evaluated the long-term impact of local delivery of c-myc neutrally charged antisense oligonucleotides (Resten-NG) upon neointimal formation following PTCA in a rabbit model.


METHODS
PTCA was performed in the iliac arteries of 10 New Zealand white rabbits at 8 atm for 30 s, three times. An infusion of 500 micro g Resten-NG (n=6) or saline (n=4) was delivered to the site at 2 atm via the outer balloon pores of the transport catheter over 2 min. The diet was supplemented with 0.25% cholesterol for 10 days before and 6 months following PTCA.


RESULTS
After 6 months, animals were sacrificed and vessels were fixed in formalin, processed and stained with hematoxylin, eosin, and movat. Histological analysis revealed complete vascular healing in both groups of animals. Planimetry showed that intimal areas were 1.71+/-0.25 and 0.65+/-0.36 mm2 in the control and antisense delivery groups, respectively (P<.05).


CONCLUSIONS
We conclude that local delivery of Resten-NG significantly inhibited neointimal thickening following PTCA in a rabbit for up to 6 months.
Kipshidze
Nicholas
N
Lenox Hill Heart and Vascular Institute and Cardiovascular Research Foundation, New York, NY 10021, USA. nkipshidze@lenoxhill.net
Iversen
Patrick
P
Keane
Eamon
E
Stein
David
D
Chawla
Paramjith
P
Skrinska
Victor
V
Shankar
Latha Raja
LR
Mehran
Roxana
R
Chekanov
Valerie
V
Dangas
George
G
Komorowski
Richard
R
Haudenschild
Christian
C
Khanna
Ashwani
A
Leon
Martin
M
Keelan
Michael H
MH
Moses
Jeffrey
J
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005109:Extracellular Matrix / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D005500:Follow-Up Studies; D007083:Iliac Artery / Q000293:injuries / Q000378:metabolism / Q000601:surgery; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009336:Necrosis; D020319:Oligodeoxyribonucleotides, Antisense / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000627:therapeutic use*; D011817:Rabbits; D012720:Severity of Illness Index; D013995:Time; D016896:Treatment Outcome; D017539:Tunica Intima / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*; D014652:Vascular Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D020319:Oligodeoxyribonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc; D005337:Fibrin