Endovascular model of rabbit hindlimb ischemia: a platform to evaluate therapeutic angiogenesis.
OBJECTIVE
Current animal hindlimb ischemia models involve surgical ligation of the femoral artery and delivery of therapeutic angiogenic agents into the adductor compartment. The authors hypothesize that an endovascular model of hindlimb ischemia would be a more appropriate platform, closely resembling atherosclerosis by occluding the vessel from within, causing less inflammation, wound healing and subsequent collateralization.


METHODS
The left superficial femoral artery in 17 rabbits was occluded by endovascular coil embolization (n=9) or surgical ligation (n=8). Animals (n=3; in each group) were sacrificed on day 3 to determine the arteriolar luminal area, number of arterioles, microsphere determined perfusion, and degree of inflammation. On day 28, the remaining animals underwent calf blood pressure measurements and angiography to determine the number of collaterals and diameter of vessels supplying the hindlimb.


RESULTS
Immediate postprocedure (day 0) and presacrifice (day 3 or 28) occlusion rates were 89% (eight of nine rabbits) and 100% for the endovascular model; 100% and 100% for the surgical model, respectively. Hindlimb paralysis and muscle atrophy was found in one surgical animal. On day 3, there was an increase in hindlimb perfusion (surgery, 0.04+/-0.01; endovascular, 0.02+/-0.01; P=.02), an increase in arteriolar luminal area (surgery, 481 microm+/-240; endovascular, 345 microm+/-151; P=.04), and a trend toward more inflammation (surgery, 5.5+/-3.8; endovascular, 2.5+/-3.0; P=.08) in the surgical group. There was no difference in number of vessels between both groups. On day 28 there was no difference in the calf blood pressure ratios or in the number of collaterals. However, there was enlargement of the distal profunda femoris artery, the vessel closest to the surgical incision, in the surgical group (L/R ratio: immediate post-occlusion, 1.06+/-0.11; day 28, 1.27+/-0.08; P=.02).


CONCLUSIONS
The endovascular model was efficacious in providing occlusion of the superficial femoral artery, and induced less of an arteriogenic response compared with the surgical model. The authors believe that this endovascular model is a superior platform for studying therapeutic angiogenic agents.
Liddell
Robert P
RP
Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
Patel
Tarak H
TH
Weiss
Clifford R
CR
Lee
David S
DS
Matsuhashi
Toshio
T
Brown
P Rand
PR
Gabrielson
Kathleen L
KL
Rodriguez
E Rene
ER
Eng
John
J
Kimura
Hideo
H
Hofmann
Lawrence V
LV
D043925:Angiogenesis Inducing Agents / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D006614:Hindlimb / Q000098:blood supply*; D007150:Immunohistochemistry; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008863:Microspheres; D016491:Peripheral Vascular Diseases / Q000188:drug therapy; D011817:Rabbits
D043925:Angiogenesis Inducing Agents