REGULATION OF NEW BLOOD-VESSEL GROWTH INTO ISCHEMIC SKELETAL-MUSCLE

Purpose: In a rabbit model, transposition of a muscle pedicle nap to a n ischemic hind limb has been shown to result in the development of ne w blood vessels that connect the arterial circulation of the flap to t he circulation of the limb. The hypothesis that exogenous recombinant basic fibroblast growth factor (bFGF) would enhance the development of this new blood supply was examined and the regulation of bFGF in this process was investigated. Methods: The right common iliac artery was Ligated in 12 male New Zealand white rabbits. An abdominal wall muscle flap based on the left inferior epigastric artery was transposed to t he right thigh, bFGF in phosphate-buffered saline (PBS) at 3 ng/h (n = 6), or PBS alone (n = 6), was infused for 7 days via mini-osmotic pum ps with an infusion catheter positioned at the flap-muscle interface. The flap-muscle interface was immunostained with anti-alpha-actin anti body to determine blood vessel density (number of vessels/mm) and with anti-bFGF antibody to evaluate bFGE distribution. RNA was isolated fr om these sections, and polymerase chain reaction (PCR) was used to exa mine endogenous bFGF messenger RNA (mRNA) expression. Results: Blood v essel density was significantly increased in animals receiving exogeno us bEGF (22.0 +/- 10.6 vessels/mm vs. 10.7 +/- 8.8 vessels/mm, P = .00 9). In the controls, neovessels were arranged in clusters with endogen ous bFGF concentrated around these clusters. In bPGP-treated animals, vessels were diffusely scattered throughout the flap-limb interface, c orresponding to the distribution pattern of infused bFGE. There was no difference in bPGF mRNA expression between the control and the bPGP-t reated groups. Conclusion: Exogenous bFGF infusion significantly augme nted new blood vessel development at the flap-limb interface. Endogeno us bFGF was up-regulated around the newly developed microvessels in co ntrol animals, and vessel growth correlated with the diffuse distribut ion of exogenous bFGF,implicating bFGF as an important factor in angio genesis. Exogenous bEGF did not affect bFGE mRNA expression, suggestin g that the regulation of bFGF is not under autocrine control.