Objective: Vein graft disease after aorto-coronary bypass is characterized by massive neointimal
and smooth muscle cell proliferation of the vessel presumably due to pressure trauma
and endothelin-1 (ET-1) synthesis in the vessel wall. This alteration is induced at
the level of transcription of the pre-pro-endothelin-1 (ppET-1) gene. Decoy oligodesoxynucleotide
(dODN) and the ACE inhibitor Quinapril (QP) are capable of suppressing deformation-induced
gene expression in the vessel wall in vivo.
Material and Methods: In a carotid artery bypass model in rabbits we performed 48 end-to side jugular vein
grafts in different treatment groups: (1) 8 grafts were peri-procedually treated with
AP-1 consensus dODN, (2) 8 with mutated dODN, (3) 8 with QP, (4) 10 with QP and N(G)-nitro-L-arginine
(5) 8 with QP and B (2) receptor antagonist Icatibant, and 6 were untreated controls
(6). No anticoagulation was used. Bypass harvest was performed after 28 days. Data
were collected by histomorphometric evaluation and statistical analysis with Kruskal-Wallis-Test
and post hoc Mann-Whitney U-Test.
Results: Intimal thickness of treatment groups (median): (1) 28.3mm, (2) 48.4mm, (3) 91.8mm,
(4) 60.5mm, (5) 164.3mm, (6) 71.1mm. All groups were of final equal size (QP: n=5).
25 animals had to be excluded due to bypass thrombosis. DODN treatment resulted in
a significant reduction of neointimal formation (p=0.029) vs. control and (p=0.016)
vs. Quinapril treatment.
Conclusions: Results indicate that in this model neointimal proliferation could be reduced with
consensus dODN. Quinapril was not equal efficient. The results encourage the use of
dODN in coronary artery surgery for prevention of venous graft disease.
