Endovascular model of rabbit hindlimb ischemia: A platform to evaluate therapeutic angiogenesis

Robert Liddell, Tarak H. Patel, Clifford Weiss, David S. Lee, Toshio Matsuhashi, P. Rand Brown, Kathleen L Gabrielson, E. Rene Rodriguez, John Eng, Hideo Kimura, Lawrence V. Hofmann

Research output: Contribution to journalArticle

Abstract

PURPOSE: 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. MATERIALS AND 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 μm ± 240; endovascular, 345 μm ± 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 dumber 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). CONCLUSION: 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.

Original languageEnglish (US)
Pages (from-to)991-998
Number of pages8
JournalJournal of Vascular and Interventional Radiology
Volume16
Issue number7
DOIs
StatePublished - Jul 2005

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Hindlimb
Anatomic Models
Ischemia
Rabbits
Femoral Artery
Inflammation
Ligation
Perfusion
Blood Pressure
Therapeutics
Muscular Atrophy
Arterioles
Microspheres
Paralysis
Wound Healing
Atherosclerosis
Angiography
Arteries

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

Cite this

Endovascular model of rabbit hindlimb ischemia : A platform to evaluate therapeutic angiogenesis. / Liddell, Robert; Patel, Tarak H.; Weiss, Clifford; Lee, David S.; Matsuhashi, Toshio; Brown, P. Rand; Gabrielson, Kathleen L; Rodriguez, E. Rene; Eng, John; Kimura, Hideo; Hofmann, Lawrence V.

In: Journal of Vascular and Interventional Radiology, Vol. 16, No. 7, 07.2005, p. 991-998.

Research output: Contribution to journalArticle

Liddell, Robert ; Patel, Tarak H. ; Weiss, Clifford ; Lee, David S. ; Matsuhashi, Toshio ; Brown, P. Rand ; Gabrielson, Kathleen L ; Rodriguez, E. Rene ; Eng, John ; Kimura, Hideo ; Hofmann, Lawrence V. / Endovascular model of rabbit hindlimb ischemia : A platform to evaluate therapeutic angiogenesis. In: Journal of Vascular and Interventional Radiology. 2005 ; Vol. 16, No. 7. pp. 991-998.
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abstract = "PURPOSE: 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. MATERIALS AND 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 μm ± 240; endovascular, 345 μm ± 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 dumber 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). CONCLUSION: 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.",
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T1 - Endovascular model of rabbit hindlimb ischemia

T2 - A platform to evaluate therapeutic angiogenesis

AU - Liddell, Robert

AU - Patel, Tarak H.

AU - Weiss, Clifford

AU - Lee, David S.

AU - Matsuhashi, Toshio

AU - Brown, P. Rand

AU - Gabrielson, Kathleen L

AU - Rodriguez, E. Rene

AU - Eng, John

AU - Kimura, Hideo

AU - Hofmann, Lawrence V.

PY - 2005/7

Y1 - 2005/7

N2 - PURPOSE: 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. MATERIALS AND 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 μm ± 240; endovascular, 345 μm ± 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 dumber 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). CONCLUSION: 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.

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