Low-Dose Basic Fibroblast Growth Factor and Vascular Endothelial Growth Factor for Angiogenesis in Canine Acute Hindlimb Insufficiency

Abstract

Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have shown strong angiogenetic effects in ischemic animals; however, whether such a beneficial effect could be achieved using low doses remains to be determined. The effects of identical low-level doses of these substances on the creation of collateral circulation in canine acute hind limb insufficiency were evaluated. Anesthetized dogs that had undergone left femoral artery occlusion received 20 microg (2 microg/kg) intravenous boluses of either bFGF or VEGF 3 times at 2-day intervals for the first week only, animals on vehicle saline injection served as controls. All groups, control (n=8), bFGF-treated (n=8), and VEGF-treated (n=6) underwent angiography, blood flow measurement (in ml/min) on the day of ligation (day 0), and at 7, 14 and 28 days, then underwent ischemic limb muscle biopsy at 28 days. Angiogenic-treated groups showed remarkable enhanced collateral circulation at 7 days, which was maintained up to 28 days, and the main collateral source artery of the angiogenic-treated groups dilated by 14 days. Many neovascularized arterioles in specimens of the angiogenic groups were recognized without any tissue edema or necrosis. Even low doses of bFGF or VEGF were enough to augment collateral circulation with no side-effects, and short treatment after acute ischemia was effective. Low-dose bFGF or VEGF may be therapeutical effective options in patients with acute lower limb vascular disease.