Enhanced angiogenesis and growth of collaterals by in vivo administration of recombinant basic fibroblast growth factor in a rabbit model of acute lower limb ischemia: dose-response effect of basic fibroblast growth factor.
The purpose of this study was to evaluate the effects of exogenous recombinant basic fibroblast growth factor (bFGF) on angiogenesis in severely ischemic tissue beds. We used a two-stage procedure to produce severe ischemia of the hindlimb of 34 New Zealand rabbits. The ischemic hindlimb received intramuscular injection of saline (group A), 1 microgram bFGF (group B), or 3 micrograms bFGF (group C), daily for 2 weeks. Tissue perfusion, skeletal muscle infarction, angiogenesis, and collateral growth were assessed by angiography, transcutaneous oximetry (TcPO2), quantitative spectrophotometric assay of triphenyltetrazolium chloride reduction in muscle, capillary density (capillaries per square millimeter), and capillary per muscle fiber ratio. There were no significant differences in baseline TcPO2 among the three groups for both thigh and calf measurements. Angiography revealed extensive perfusion of the left hindlimb in all the assessed bFGF treated animals. Both thigh and calf TcPO2 values showed a significant increase in all groups over the 14 days ischemia was induced (p less than 0.0001), but the two treatment groups exhibited a much more rapid rise in TcPO2 than the control group (p less than 0.0001). The capillaries per square millimeter and capillaries per muscle fiber ratios were significantly increased in all posttreatment measurements for all animals that received bFGF. The treatment groups with bFGF had a significant (p = 0.025) increase in thigh muscle viability compared with controls based on triphenyltetrazolium chloride reduction. Whereas there was evidence of muscle infarction in both the thighs of groups A and B, there was none in group C.(ABSTRACT TRUNCATED AT 250 WORDS)
Baffour
R
R
Department of Surgery, Baystate Medical Center, Springfield, MA 01199.
Berman
J
J
Garb
J L
JL
Rhee
S W
SW
Kaufman
J
J
Friedmann
P
P
D000208:Acute Disease; D000704:Analysis of Variance; D000818:Animals; D001785:Blood Gas Monitoring, Transcutaneous; D003097:Collateral Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000627:therapeutic use*; D006614:Hindlimb / Q000098:blood supply* / Q000000981:diagnostic imaging; D007511:Ischemia / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D008026:Ligation; D008297:Male; D009389:Neovascularization, Pathologic / Q000139:chemically induced*; D011817:Rabbits; D011859:Radiography; D011994:Recombinant Proteins / Q000627:therapeutic use; D013053:Spectrophotometry; D013778:Tetrazolium Salts
D011994:Recombinant Proteins; D013778:Tetrazolium Salts; D016222:Fibroblast Growth Factor 2; C009591:triphenyltetrazolium