A Rat Model for Severe Limb Ischemia at Rest

Lundberg, Göran; Luo, Fuwen; Blegen, Harald; Kalin, Bo; Wahlberg, Eric

doi:10.1159/000072228

Cited by 16 publications

(16 citation statements)

References 12 publications

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“…They have been successfully used in rat hindlimb models of arterial insufficiency, represent an outstanding method to assess muscle perfusion(16), and can be utilized in unanesthetized animals during treadmill running(60). However, the microsphere technique also has limitations(16), including: processing time, potential loss and variability, and difficulties with the technique related to consistency and interpretation of results when applied to a rat hindlimb model of ischemia(61). It also is invasive, technically challenging(55), and does not permit real time or longitudinal studies.…”

Section: Discussionmentioning

confidence: 99%

Novel method to assess arterial insufficiency in rodent hind limb

Ziegler

Distasi

Miller

et al. 2016

Journal of Surgical Research

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Background Lack of techniques to assess maximal blood flow capacity thwarts the use of rodent models of arterial insufficiency to evaluate therapies for intermittent claudication. We evaluated femoral vein outflow (VO) in combination with stimulated muscle contraction as a potential method to assess functional hindlimb arterial reserve and therapeutic efficacy in a rodent model of subcritical limb ischemia. Materials and methods VO was measured with perivascular flow probes at rest and during stimulated calf muscle contraction in young healthy rats (Wistar Kyoto, WKY; lean Zucker, LZR) and rats with cardiovascular risk factors (Spontaneously Hypertensive, SHR; Obese Zucker, OZR) with acute and/or chronic femoral arterial occlusion. Therapeutic efficacy was assessed by administration of Ramipril or Losartan to SHR after femoral artery excision. Results VO measurement in WKY demonstrated the utility of this method to assess hindlimb perfusion at rest and during calf muscle contraction. While application to diseased models (OZR, SHR) demonstrated normal resting perfusion compared to contralateral limbs, a significant reduction in reserve capacity was uncovered with muscle stimulation. Administration of Ramipril and Losartan demonstrated significant improvement in functional arterial reserve. Conclusion The results demonstrate that this novel method to assess distal limb perfusion in small rodents with subcritical limb ischemia is sufficient to unmask perfusion deficits not apparent at rest, detect impaired compensation in diseased animal models with risk factors, and assess therapeutic efficacy. The approach provides a significant advance in methods to investigate potential mechanisms and novel therapies for subcritical limb ischemia in pre-clinical rodent models.

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Section: Discussionmentioning

confidence: 99%

Novel method to assess arterial insufficiency in rodent hind limb

Ziegler

Distasi

Miller

et al. 2016

Journal of Surgical Research

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“…Before surgery, rats were anesthetized with a mixture of oxygen and halothane (2.5%), sodium pentobarbital (intra-peritoneally, i.p., 50 mg/Kg) and sodium heparin (1000 U/Kg). The common right iliac-femoral artery was ligated according to reported methods [2], [24]. The overlying skin was closed.…”

Section: Methodsmentioning

confidence: 99%

“…Animal models using femoral artery ligation were developed to mimic unilateral lower limb ischemia, permitting the assessment of concurrent morphologic and metabolic processes [2].…”

Section: Introductionmentioning

confidence: 99%

MR Angiography, MR Imaging and Proton MR Spectroscopy In-Vivo Assessment of Skeletal Muscle Ischemia in Diabetic Rats

et al. 2012

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To prospectively evaluate the feasibility of using magnetic resonance (MR) techniques for in-vivo assessing a rat diabetic model of limb ischemia. Unilateral hind limb ischemia was induced by ligation of the iliac-femoral artery in male streptozotocin-treated and non-diabetic control rats. Four weeks after ligation, rats underwent MR Angiography (MRA), T1-weighted and Short Time Inversion Recovery (STIR) sequences and muscle Proton MR Spectroscopy (1H-MRS) on both hind limbs. After MR examinations, immunoblotting and immunofluorescence analysis were performed. MRA showed a signal void due to flow discontinuation distal to the artery ligation. T1-weighted and STIR images showed, respectively, the presence of tissue swelling (p = 0.018 for non-diabetic; p = 0.027 for diabetic rats) and signal hyperintensity in tissue affected by occlusion. Mean total creatine/water for the occluded limb was significantly lower than for the non-occluded limbs in both non-diabetic (5.46×10−4 vs 1.14×10−3, p = 0.028) and diabetic rats (1.37×10−4 vs 1.10×10−3; p = 0.018). MR Imaging and 1H-MRS changes were more pronounced in diabetic than in non-diabetic occluded limbs (p = 0.032). MR findings were confirmed by using histological findings. Combined MR techniques can be used to demonstrate the presence of structural and metabolic changes produced by iliac-femoral artery occlusion in rat diabetic model of limb ischemia.

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“…An excellent model to study and manipulate the growth of blood vessels and in particular arteries in response to tissue hypoxia is the hind limb ischemia model, which can be performed in either mice or rats. In this model, all arteries supplying highly oxygenated blood to one of the back limbs of the animal are ligated in two steps, resulting in near-zero blood flow in the entire limb (Lundberg et al, 2002.) (Fig.…”

Section: Rat Ischemic Hind Limb Modelmentioning

confidence: 99%