Korean J Radiol.  2013 Dec;14(6):923-930. 10.3348/kjr.2013.14.6.923.

Rat Model of Hindlimb Ischemia Induced via Embolization with Polyvinyl Alcohol and N-Butyl Cyanoacrylate

Affiliations
  • 1Department of Radiology, Seoul National University Hospital, Seoul 110-744, Korea. angiointervention@gmail.com
  • 2Institute of Radiation Medicine, Seoul National University Medical Research Center (SNUMRC), Seoul 110-799, Korea.
  • 3Department of Pathology, Seoul National University Hospital, Seoul 110-744, Korea.

Abstract


OBJECTIVE
To investigate the feasibility of a rat model on hindlimb ischemia induced by embolization from the administration of polyvinyl alcohol (PVA) particles or N-butyl cyanoacrylate (NBCA).
MATERIALS AND METHODS
Unilateral hindlimb ischemia was induced by embolization with NBCA (n = 4), PVA (n = 4) or surgical excision (n = 4) in a total of 12 Sprague-Dawley rats. On days 0, 7 and 14, the time-of-flight magnetic resonance angiography (TOF-MRA) and enhanced MRI were obtained as scheduled by using a 3T-MR scanner. The clinical ischemic index, volume change and degree of muscle necrosis observed on the enhanced MRI in the ischemic hindlimb were being compared among three groups using the analysis of variance. Vascular patency on TOF-MRA was evaluated and correlated with angiographic findings when using an inter-rater agreement test.
RESULTS
There was a technical success rate of 100% for both the embolization and surgery groups. The clinical ischemic index did not significantly differ. On day 7, the ratios of the muscular infarctions were 0.436, 0.173 and 0 at thigh levels and 0.503, 0.337 and 0 at calf levels for the NBCA, PVA and surgery groups, respectively. In addition, the embolization group presented increased volume and then decreased volume on days 7 and 14, respectively. The surgery group presented a gradual volume decrease. Good correlation was shown between the TOF-MRA and angiographic findings (kappa value of 0.795).
CONCLUSION
The examined hindlimb ischemia model using embolization with NBCA and PVA particles in rats is a feasible model for further research, and muscle necrosis was evident as compared with the surgical model.

Keyword

Hindlimb ischemia; Embolization; Enhanced MR; TOF-MRA

MeSH Terms

Animals
*Disease Models, Animal
Embolization, Therapeutic/*adverse effects
Enbucrilate/administration & dosage/*toxicity
Feasibility Studies
Hindlimb/*blood supply
Injections, Intra-Arterial
Ischemia/*chemically induced/diagnosis
Magnetic Resonance Angiography/*methods
Male
Polyvinyl Alcohol/administration & dosage/*toxicity
Rats
Rats, Sprague-Dawley
Tissue Adhesives/administration & dosage/toxicity
Enbucrilate
Polyvinyl Alcohol
Tissue Adhesives

Figure

  • Fig. 1 Typical cases of three groups with gross picture (upper column) and enhanced MR of calf on day 14 (lower column). A. Rats in NBCA group presented edema of distal toe and larger area of muscular infarction (*) than PVA group (B, lower column) with surrounding enhancements. B. Rat in PVA group presented distal toe necrosis and mild muscle atrophy with tiny necrotic foci (arrowhead) surrounded by large area of enhancement. C. Rat in surgery group presented foot necrosis and marked atrophic change of calf but no definite muscular necrosis. NBCA = N-butyl cyanoacrylate, PVA = polyvinyl alcohol

  • Fig. 2 Ratio of infarcted muscle in thigh (A) and calf level (B). Both NBCA and PVA induced muscle infarction at both thigh and calf level. Infarct ratio was higher in NBCA group than in PVA group, but difference did not show statistical difference. Excision of external iliac artery did not result in muscular infarction. NBCA = N-butyl cyanoacrylate, PVA = polyvinyl alcohol

  • Fig. 3 Volume changes of calf in ischemic limb is compared with contralateral normal limb. NBCA and PVA groups presented volume increase on day 7, and then decrease on day 14, but surgery group presented gradual decrease. NBCA = N-butyl cyanoacrylate, PVA = polyvinyl alcohol

  • Fig. 4 Example of angiogram (A) and TOF-MRA (B) on day 14 of PVA group. Left common iliac artery (curved arrows), left internal iliac artery (empty arrows), right popliteal artery (straight arrows), and right saphenous artery (arrowheads) are well correlated on both angiograms and TOF-MRAs. Note that small vessels are in left hindlimb, which are subcutaneous superficial arteries. TOF-MRA = time-of-flight magnetic resonance angiography, PVA = polyvinyl alcohol

  • Fig. 5 Representative photomicrographs of hematoxylin and eosin staining of calf muscles. A. In rat of NBCA group, short transition zone (arrowheads) was noted between infarcted (I) and normal tissues (N) (4 ×). B. In rat of PVA group, many leukocytes (empty errows) infiltrated around infarcted tissues (I), with smaller diameter of muscle cells suggesting ischemic changes (4 ×). C. In rat of surgery group, no infarcted tissues were noted, but multifocal small diameter of muscle fibers (arrow) was visible (10 ×). NBCA = N-butyl cyanoacrylate, PVA = polyvinyl alcohol


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