Combined treatment of sustained-release basic fibroblast growth factor and sarpogrelate enhances collateral blood flow effectively in rabbit hindlimb ischemia.
BACKGROUND
The effectiveness of sustained-release basic fibroblast growth factor (bFGF) in potentiating arteriogenesis and angiogenesis was evaluated, as well as determining whether chronic oral administration of sarpogrelate, a serotonin blocker, would further increase collateral blood flow in the rabbit hindlimb following surgical induction of ischemia by femoral artery extraction.


RESULTS
Two weeks after femoral artery removal, the rabbits were assigned to 1 of 4 experimental groups and treated for 4 weeks: group A, no treatment; group B, supplemented with diet containing sarpogrelate; group C, single intramuscular injection of sustained-release form of bFGF microspheres; group D: combined treatment with sustained-release bFGF and sarpogrelate. Endpoint measurements performed at 6 weeks found that the ischemic hindlimb blood flow was significantly improved in the rabbits that received sustained-release bFGF, with a further significant improvement in those with the additional administration of sarpogrelate. Angiographic assessment revealed augmented density of collateral vessels in the medial thigh region in the rabbits given the combined treatment.


CONCLUSIONS
The findings demonstrate that sustained-release bFGF stimulated the development of collateral vessels, and additional administration of sarpogrelate produced a further improvement in hindlimb blood flow in the rabbit hindlimb ischemia model.
Hirose
Keiichi
K
Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Japan.
Fujita
Masatoshi
M
Marui
Akira
A
Arai
Yoshio
Y
Sakaguchi
Hisashi
H
Huang
Yuhong
Y
Chandra
Shyamal
S
Tabata
Yasuhiko
Y
Komeda
Masashi
M
D000818:Animals; D003097:Collateral Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D004338:Drug Combinations; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000188:drug therapy*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011817:Rabbits; D013386:Succinates / Q000008:administration & dosage*; D013997:Time Factors
D004338:Drug Combinations; D005343:Fibrinolytic Agents; D013386:Succinates; D016222:Fibroblast Growth Factor 2; C064294:sarpogrelate