Therapeutic angiogenesis for patients with limb ischemia by utilization of fibrin meshwork. Pilot randomized controlled study.
OBJECTIVE
The aim of this paper is to assess the feasibility and efficacy of fibrin in inducing neovascularization as an angiogenic substance and/or carrier for vascular endothelial growth factor (VEGF) in patients with limb ischemia.


METHODS
Twenty-three patients with limb ischemia and referred for below the knee amputations were randomized for treatment: group 1, 7 patients received only a saline injection; group 2, 9 received intramuscular injection of fibrin and group 3, 7 received the fibrin composition with deferoxamine and added VEGF(165). The fibrin meshwork was introduced into the popliteal area of the diseased limbs using a dual syringe system (1 contained thrombin solution [1 mg, 5000 U] and 1 contained fibrinogen [1 mg, Baxter Hyland Immuno] solution). In group 3, Deferoxamine (100 microg) and 500 microg of VEGF(165) were added to the fibrinogen solution.


RESULTS
In the control group 5 patients had undergone below the knee amputation at the 3-6 month follow-up. Only 1 patient from Group 2 had below the knee amputation 5 months following Fibrin only administration. Clinical improvement was noted in all 8 patients following fibrin administration and in all 7 patients injected with the fibrin meshwork, deferoxamine and VEGF combination.


CONCLUSIONS
IM injection of fibrin is safe and appears to be an efficient method to treat limb ischemia. These findings indicate that use of fibrin may be a novel and simple method for inducing therapeutic angiogenesis.
Kipshidze
N
N
Lenox Hill Heart and Vascular Institute, Cardiovascular Research Foundation, New York, NY 10021, USA. nkipshidze@lenoxhill.it
Kipiani
K
K
Beridze
N
N
Roubin
G
G
Tsapenko
M
M
Shehzad
M Z
MZ
Moses
J
J
Kipshidze
N N
NN
D000328:Adult; D003676:Deferoxamine / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005337:Fibrin / Q000008:administration & dosage*; D005340:Fibrinogen / Q000008:administration & dosage*; D006801:Humans; D007273:Injections, Intramuscular; D007511:Ischemia / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010865:Pilot Projects; D042442:Vascular Endothelial Growth Factors / Q000008:administration & dosage*
D042442:Vascular Endothelial Growth Factors; D005337:Fibrin; D005340:Fibrinogen; D003676:Deferoxamine