Use of Synchrotron Radiation Microangiography to Assess Development of Small Collateral Arteries in a Rat Model of Hindlimb Ischemia

Takeshita, Satoshi; Isshiki, Takaaki; Mori, Hiromu; Tanaka, Etsuro; Eto, Koji; Miyazawa, Yasuyuki; Tanaka, Akira; Shinozaki, Yoshiro; Hyodo, Kazuyuki; Ando, Masami; Kubota, Minoru; Tanioka, Kenkichi; Umetani, Keiji; Ochiai, Masahiko; Sato, Tomohide; Miyashita, Hideo

doi:10.1161/01.cir.95.4.805

Cited by 73 publications

(47 citation statements)

References 6 publications

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“…We have documented recently, by SR microangiography, that tortuous collaterals exist in ischemic but not in normal limbs. 7 It is possible that linear collaterals result from the functional opening and/or dilation of preexisting vessels, whereas tortuous microvessels result from remodeling of preexisting vessels or are newly formed and thus possess functionally different endothelial cells that have a smaller vasodilatory response to ACh.…”

Section: Discussionmentioning

confidence: 99%

“…6,7 Male Wistar rats weighing 300 to 350 g (Charles River Japan) were anesthetized with an injection of sodium pentobarbital 40 mg/kg IP, after which the left femoral artery was surgically excised to induce limb ischemia. Rats were then transfected with either VEGF (nϭ17) or ␤-galactosidase (nϭ18) plasmid.…”

Section: Direct Transfection Of Limb Musclesmentioning

confidence: 99%

“…Four weeks after transfection, 10 VEGF-treated and 12 control animals were reanesthetized, and angiographic assessment was performed with synchrotron radiation (SR) microangiography with a spatial resolution of 30 m. 7 After obtaining a baseline angiogram, we allowed a 10-minute interval to reestablish basal hindlimb blood flow. ACh (Sigma) prepared in saline (final volume of 0.4 mL) was then infused over 2 minutes (0.2 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ), after which a second angiogram was recorded.…”

Section: Microangiographic Assessmentmentioning

confidence: 99%

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Endothelium-Dependent Relaxation of Collateral Microvessels After Intramuscular Gene Transfer of Vascular Endothelial Growth Factor in a Rat Model of Hindlimb Ischemia

et al. 1998

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Background —Recent investigations have demonstrated the ability of vascular endothelial growth factor (VEGF) to augment the development of collateral arteries in vivo. In vitro studies have suggested that the use of VEGF also improves the endothelium-dependent relaxation of collaterals at the microvascular level. The purpose of this study was to determine in vivo the extent to which vasomotor responses of collateral microvessels are altered after VEGF treatment. Methods and Results —Ischemia was induced in the hindlimb of 35 rats by excision of the femoral artery. Immediately thereafter, 400 μg of a plasmid encoding VEGF or β-galactosidase (control) was transfected into limb muscles. Four weeks later, synchrotron radiation microangiography, with a spatial resolution of 30 μm, was performed to document the reactivity of collateral microvessels. Administration of the endothelium-dependent vasodilator acetylcholine failed to induce dilation of collateral microvessels in control animals. By contrast, profound dilation of collaterals was observed after acetylcholine in VEGF-treated animals. This response was evident in vessels with a linear appearance but not in those with an undulating appearance. The resulting blood flow in the ischemic limb after administration of acetylcholine in the control animals was only 64.6±17.0% of that of the contralateral normal limb, whereas blood flow was augmented to 106.1±8.4% in VEGF-treated animals ( P <0.05). Conclusions —These results demonstrate in vivo that the use of VEGF restores impaired vasomotor responses in some types of collateral microvessels, which may help to provide a basis for understanding the microcirculation after therapeutic angiogenesis with VEGF.

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Section: Discussionmentioning

confidence: 99%

Section: Direct Transfection Of Limb Musclesmentioning

confidence: 99%

Section: Microangiographic Assessmentmentioning

confidence: 99%

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Endothelium-Dependent Relaxation of Collateral Microvessels After Intramuscular Gene Transfer of Vascular Endothelial Growth Factor in a Rat Model of Hindlimb Ischemia

et al. 1998

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“…Six weeks after surgery, 6 rabbits from each experimental group were reanesthetized, and angiographic assessment was performed with synchrotron radiation microangiography with a spatial resolution of 30 m. 18 Contrast material containing 37% nonionic iodine (Iopamidol, Nihon Shering Co, Ltd, Osaka, Japan) was injected using an automated injector (Autoenhance A30-200, Nemoto Kyourindo Co, Ltd, Tokyo, Japan) at a rate of 1.25 ml/s via a 4F catheter placed immediately above the aortic bifurcation. Quantitative angiographic analysis of collateral vessel visualization was performed using a composite of 5×5 mm grids.…”

Section: Microangiographic Assessmentmentioning

confidence: 99%

Combined Treatment of Sustained-Release Basic Fibroblast Growth Factor and Sarpogrelate Enhances Collateral Blood Flow Effectively in Rabbit Hindlimb Ischemia

Hirose

Fujita

Marui

et al. 2006

Circ J

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Background The effectiveness of sustained-release basic fibroblast growth factor (bFGF) in potentiating arteriogenesis and angiogenesis was evaluated, as well as determining whether chronic oral administration of sarpogrelate, a serotonin blocker, would further increase collateral blood flow in the rabbit hindlimb following surgical induction of ischemia by femoral artery extraction. Methods and ResultsTwo weeks after femoral artery removal, the rabbits were assigned to 1 of 4 experimental groups and treated for 4 weeks: group A, no treatment; group B, supplemented with diet containing sarpogrelate; group C, single intramuscular injection of sustained-release form of bFGF microspheres; group D: combined treatment with sustained-release bFGF and sarpogrelate. Endpoint measurements performed at 6 weeks found that the ischemic hindlimb blood flow was significantly improved in the rabbits that received sustained-release bFGF, with a further significant improvement in those with the additional administration of sarpogrelate. Angiographic assessment revealed augmented density of collateral vessels in the medial thigh region in the rabbits given the combined treatment. Conclusions The findings demonstrate that sustained-release bFGF stimulated the development of collateral vessels, and additional administration of sarpogrelate produced a further improvement in hindlimb blood flow in the rabbit hindlimb ischemia model. (Circ J 2006; 70: 1190 -1194

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“…Furthermore, standard radiographic images have a limited resolution and are not suitable for visualizing medium-and smaller-sized vessels in rats. Recent advances in technology have increased the resolution, but require highly specialized equipment [11]. Corrosion casting allows visualization of small arteries b100 Am in diameter [8,12], but the casts are vulnerable and many of the smaller vessels are lost in the procedure.…”

Section: Discussionmentioning

confidence: 99%

A study of neovascularization in the rat ischemic hindlimb using Araldite casting and Spalteholtz tissue clearing

Westerweel

Rookmaaker

Zonneveld

et al. 2005

Cardiovascular Pathology

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Introduction: Understanding neovascularization is an important prerequisite for therapeutic advances aimed at the salvation of ischemic tissues. We explored an alternative strategy to corrosion casting for visualizing neovascularization in a rat hindlimb ischemia model. Methods: Rats were subjected to hindlimb ischemia by femoral artery ligation. Directly after femoral artery occlusion and at 7, 14, 21 and 28 days postsurgery, rats were sacrificed, and neovascularization was evaluated by vascular casting with Araldite plastic and subsequent Spalteholtz tissue clearing. Results: Semitransparent preparations were obtained, in which the casted arteries could be directly and three-dimensionally visualized in detail and in relation to the surrounding tissue. In the vascular casts, collateral formation and recanalization of previously thrombosed arteries were demonstrated. Conclusions: We describe an alternative approach to study neovascularization in animal models. This method, which combines Araldite plastic vascular casting with Spalteholtz tissue clearing, preserves all vasculature as well as the surrounding tissue. In a small time series in rat ischemic hindlimbs, we show that restoration of blood flow after ischemia not only involves newly formed collaterals, but also recanalization of previously thrombosed arterial segments. D

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Use of Synchrotron Radiation Microangiography to Assess Development of Small Collateral Arteries in a Rat Model of Hindlimb Ischemia

Cited by 73 publications

References 6 publications

Endothelium-Dependent Relaxation of Collateral Microvessels After Intramuscular Gene Transfer of Vascular Endothelial Growth Factor in a Rat Model of Hindlimb Ischemia

Endothelium-Dependent Relaxation of Collateral Microvessels After Intramuscular Gene Transfer of Vascular Endothelial Growth Factor in a Rat Model of Hindlimb Ischemia

Combined Treatment of Sustained-Release Basic Fibroblast Growth Factor and Sarpogrelate Enhances Collateral Blood Flow Effectively in Rabbit Hindlimb Ischemia

A study of neovascularization in the rat ischemic hindlimb using Araldite casting and Spalteholtz tissue clearing

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