Vascular effects of FGF-2 and VEGF-B in rabbits with bilateral hind limb ischemia.

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.

Adaptation of hindquarter vascular reactivity to femoral artery ligation and hypercholesterolemia in the rabbit.

AIMS: The effects of ischemia and hypercholesterolemia on the function and morphological adaptation of the rabbit hindlimb were assessed. METHODS: In rabbits on normal or cholesterol diet, experiments were performed on days 0-28 following bilateral femoral artery ligation. Calf blood pressure (C(BP)), exercise tolerance, flow reserve, agonist vasodilatation, angiography and capillary density were examined and modeled. RESULTS: C(BP) decreased markedly post-ligation and returned to 41 and 68% of baseline by days 7 and 28. Exercise tolerance was attenuated 40% and flow reserve 50-60% on day 7, with recovery by day 28. Ligation caused decreases in 5-hydroxytryptamine-induced dilatation, while adenosine and acetylcholine responses were unaffected. Hypercholesterolemia attenuated acetylcholine-elicited dilatation. There was marked loss of adenosine dilatation on days 7-14 in the ligation plus hypercholesterolemia group. Ligation caused a doubling in the number of medium-sized collateral arteries. Hypercholesterolemia, either alone or combined with ligation, greatly augmented small vessel density. Capillary density was unaltered by any treatment. CONCLUSIONS: The rabbit hindlimb shows a remarkable ability to recover its muscle function through vascular adaptation and remodeling 4 weeks following ligation, with or without hypercholesterolemia. Exercise tolerance, flow reserve and vascular reactivity were mainly restored 28 days post-ligation.