Critical ischemia of the limbs or myocardium is frequently accompanied by d
iffuse distal vascular disease making it unapproachable by conventional rev
ascularization techniques. Pharmacological treatment is available for coron
ary artery disease but there has been no effective medical therapy for adva
nced ischemia of the limbs. In the search for alternative treatments for pa
tients with diffuse distal disease, recent developments in vascular biology
have directed attention towards use of Vascular growth factors. Therapeuti
c angiogenesis has shown promising results in early clinical studies as sho
wn by improved clinical status and in some cases angiographic studies. We e
mployed an angiogenic strategy that utilizes enhanced vascular endothelial
growth factor (VEGF) in a fibrin network, in two patients with critical lim
b ischemia. Objectively, we were able to demonstrate angiographically the g
rowth of new blood vessels after administration of VEGF and fibrin composit
e. Fibrin glue provides for the slow release of and prolongs the availabili
ty of VEGF, thereby sustaining angiogenesis resulting in improved oxygenati
on of ischemic tissue. Further investigations are warranted to validate if
angiogenesis may increase blood flow in patients with advanced vascular dis
ease.