901-17 Extrinsic Coagulation Pathway Inhibition Using Inactivated Factor Vila Limits Restenosis in the Rabbit Atherosclerosis Model

• Published in: Journal of the American College of Cardiology 1995-02, Vol.25 (2), p.9A-9A
• Main Authors: Jang, Yangsoo, Guzman, Luis A., Lincoff, A. Michael, Gottsauner-Wolf, Michael, Forudi, Farhard, Hart, Charles E., Ellis, Stephen G., Topol, Eric J.
• Format: Article
• Language: English
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/0735-1097(95)91494-I

An inactivated factor Vila (DEGR-Vlla). which inhibits tissue factor initiation of the extrinsic coagulation pathway, has potential to block the response to vascular injury at the highest level of the coagulation cascade. We evaluated the effects of DEGR-Vlla on the restenosis process following balloon angioplasty (BA) in the rabbit. Focal femoral atherosclerosis was induced in 15 rabbits by air dessication method followed by 1% cholesterol diet for 28 days. BA of each femoral artery was then performed, using a 2.5 mm balloon with three inflations at 6 atm for 60 sec. Rabbits were randomized to two treatment groups: a control group (n=8). and a DEGR-Vlla group (n=7). In the control group, 150U/kg of heparin was injected intravenously to prevent thrombus formation during the procedure, followed by a 3 day intravenous infusion of saline. In the DEGR-Vlla group, 1mg/kg of DEGR-Vlla was injected intravenously as a bolus and 50μg/kg/hr of DEGR-Vlla was infused for 3 days. Angiograms were performed before (pre-BA). after (post-BA), and 21 days after BA (21 d) immediately prior to sacrifice. Femoral arteries (13 in control vs 10 in DEGR-Vlla treated groups) were pressure fixed in situ. Angiographic analysis of minimal luminal diameter (MLD, mm) at pre-BA. immediately post-BA, and 21 days post BA and planimetric analysis of cross-sectional area of neointima (%CSA) in histologic sections of the femoral arteries are shown below (mean±SD): [Display omitted] Thus, we have for the first time demonstrated that inhibition of the extrinsic coagulation pathway with DEGR-Vlla significantly limits the restenotic processes in this experimental model.