Circulation, Vol 88, 208-215, Copyright © 1993 by American Heart Association
LQ Pu, AD Sniderman, R Brassard, KJ Lachapelle, AM Graham, R Lisbona and JF Symes
BACKGROUND. This study tests the efficacy of an angiogenic growth factor,
endothelial cell growth factor, in a rabbit model of persistent hindlimb
ischemia. METHODS AND RESULTS. Ischemia was induced in the left hindlimb of
22 New Zealand White rabbits by ligation of the distal external iliac
artery and complete excision of the common and superficial femoral
arteries. Two groups of animals were studied: Group 1 consisted of 11
animals who for 10 days received daily intramuscular injections of 4 mg of
endothelial cell growth factor beginning on postoperative day 11, and group
2 consisted of 11 animals who underwent the same surgical ischemic
procedure but received only injections of saline daily for the same
postoperative period. Perfusion of the ischemic left limb was compared with
the normal right limb in each animal on postoperative days 10, 20, 30, and
40 using the calf blood pressure ratio, 99mTc macroaggregate radioisotopic
perfusion scans, and serial angiography. Neovascularization in the left
thigh at day 40 was quantified from the angiograms. Each technique
documented that animals in group 1 had significantly better perfusion than
animals in group 2; that is, the calf pressure ratio was higher in group 1
than in group 2 (0.56 versus 0.32 at day 20, 0.64 versus 0.44 at day 30,
and 0.70 versus 0.50, P < .0001), and the calf radioisotopic perfusion
ratio was also higher in group 1 than in group 2 (0.88 versus 0.74 at day
20, P < .02; 0.93 versus 0.76 at day 30, and 0.96 versus 0.79 at day 40,
P < .008). Angiographic studies correlated well with these results
demonstrating much earlier distal arterial reconstitution and enhanced
neovascularization (23.8 versus 9.0 vessels, P < .007). CONCLUSIONS. The
data clearly indicate that an angiogenic growth factor, endothelial cell
growth factor, promotes revascularization in this experimental ischemic
hindlimb model, raising the possibility that in the future such agents
might be of value in humans.
ARTICLES
Enhanced revascularization of the ischemic limb by angiogenic therapy
Department of Surgery, Royal Victoria Hospital, Montreal, Quebec, Canada.
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