| Abstract: | Whether InfusaSleeve(IS) catheter can deliver antisense oligodeoxynucleotide (ODNs)
following arterial denuation is unknown. We evaluate the feasibility of local endoluminal
delivery of Cmyc ODNs to the site of arterial denudation by using IS catheter and to determine
the biological importance of these effects. IS catheter was introduced into right side of iliac
artery of 21 rabbits after angioplasty of iliac artery. Animals were randomized to the control
group (n=6) receiving saline injection and the treated group receiving cmyc antisense (n=15, 1
mg ODNs per vessel). In two weeks and 40 days following the operation, angiography was
performed. Morphometric analyses were carried out in balloondenuded iliac arteries. The
expression of cmyc protein was detected by using a mouse monoclonal antibody to cmyc.
Morphometric analyses carried out at 40 days after transcatheter cmyc antisense oligomer
administration. The results showed that maximal neointimal area was reduced from 76637(105
m2) in the control group (n=6) to 404102(105 m2) in the antisense treated group (n=6, P<005).
These changes in vascular remodeling following denuding injury resulted in an increase in
residual luman from 2050% in the control group to 7090% in the antisensetreated group. Cmyc
protein expression was virtually undetectable at baseline in locally ODNsdelivered arteries and
detectable in control denuded arteries. The results show that: Single IS transcatheter
administration allowed endoluminal delivery of ODNs to the site of arterial injury; cmyc
antisense oligomer reduced the formation of neointime in denuded arteries, implying a
therapeutic potential of this approach. |
