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Cardiovascular Research 2003 59(4):997-1005; doi:10.1016/S0008-6363(03)00522-4
© 2003 by European Society of Cardiology
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Copyright © 2003, European Society of Cardiology

Enhanced hindlimb collateralization induced by acidic fibroblast growth factor is dependent upon femoral artery extraction

James C Hersheya,*, Halea A Corcorana, Elizabeth P Baskina, David B Gilbertob, Xianzhi Maoc, Kenneth A Thomasc and Jacquelynn J Cooka

aDepartment of Pharmacology, Merck Research Laboratories, West Point, PA 19454, USA
bLaboratory Animal Resources, Merck Research Laboratories, West Point, PA 19454, USA
cCancer Research, Merck Research Laboratories, West Point, PA 19454, USA

james_hershey{at}merck.com

* Corresponding author. Tel.: +1-215-652-9943; fax: +1-610-652-3811.

Recent investigations have established the feasibility of using exogenously delivered angiogenic growth factors to increase collateral artery development in animal models of myocardial and hindlimb ischemia. Objective: Our aim was to evaluate the ability of a stabilized form of acidic fibroblast growth factor (aFGF-S117) to stimulate collateralization and arteriogenesis in the rabbit hindlimb following the surgical induction of ischemia by femoral artery extraction. A secondary objective was to examine angiogenic and arteriogenic effects of aFGF-S117 in the absence of a peripheral blood flow deficit. Methods and results: Five days after femoral artery removal, aFGF-S117 (1, 3, or 30 µg/kg) was intramuscularly delivered into the hindlimb, three times per week for 2 consecutive weeks. End-point measurements performed on day 20 found that hindlimb reserve blood flow was significantly improved in rabbits that received 3 or 30 µg/kg of aFGF-S117, with no difference in efficacy between these two doses. These hemodynamic results were supported by angiographic evidence showing enhanced density of collateral vessels in the medial thigh region and histological findings of increased capillary density within the gastrocnemius muscle from rabbits treated with aFGF-S117. When an efficacious dose of 3 µg/kg of aFGF-S117 was administered to sham-operated rabbits with intact femoral arteries, there was no change in any of the blood flow, angiographic or histological parameters measured. Conclusions: These findings demonstrate that a stabilized form of aFGF stimulated the development of functional collateral arteries in the rabbit hindlimb, an effect which was dependent upon removal of the femoral artery. These results suggest that aFGF-S117 may have therapeutic potential for the treatment of arterial occlusive disorders.

KEYWORDS Angiogenesis; Growth factors; Collateral circulation; Arteries; Blood flow


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