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Updated: Jul 4, 2026
Preclinical Model of Hind Limb Ischemia in Diabetic Rabbits
Published on: June 2, 2019
Vascular effects of FGF-2 and VEGF-B in rabbits with bilateral hind limb ischemia
Rafif Wafai1, Elizabeth M Tudor, James A Angus
1Department of Pharmacology, Cardiovascular Therapeutics Unit, The University of Melbourne, Melbourne, Vic, Australia.
Aims:
To assess fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor-B (VEGF-B) effects on flow reserve and morphological adaptation in the rabbit ischemic hind limb.
Methods:
Following bilateral femoral artery ligation, calf blood pressure (C(BP)), flow reserve, collateral artery numbers and capillary numbers were assessed. Treatment consisted of rabbit serum albumin (RSA), FGF-2, VEGF-B or FGF-2 + VEGF-B.
Results:
Ligation decreased C(BP); on day 14, a 48% deficit remained in the RSA group compared with a deficit of only 22% in FGF-2 and VEGF-B groups. On day 3, flow reserve was attenuated 60%, but recovered by day 14 (with no treatment effects). Collateral artery numbers increased with RSA (+28%), FGF-2 (+53%), VEGF-B (+47%) and FGF-2 + VEGF-B (+59%). Rectus femoris muscle total capillary profiles and fibers per cross-section were alike across groups. Tibialis anterior muscle cross-sectional area was lower with ligation and total capillary number was less in RSA and FGF-2 groups, providing evidence for angiogenesis with VEGF-B. Capillary/muscle fiber ratio was similar in each group.
Conclusions:
FGF-2 and VEGF-B enhanced lower limb perfusion as indicated by improved C(BP) and combined treatment increased collateral artery number. Flow reserve recovery was not enhanced by cytokine treatment. VEGF-B, but not FGF-2, caused angiogenesis in the tibialis anterior muscle. Overall, VEGF-B may have advantages over FGF-2 in this setting; however, their combination may further improve arteriogenesis.
