Assessment of mouse hind limb endothelial function by measuring femoral artery blood flow responses

Wang, Chao-Hung; Chen, Kuo-Ti; Mei, Hsiu-Fu; Lee, Ju-Fang; Cherng, Wen‐Jin; Lin, Shing‐Jong

doi:10.1016/j.jvs.2010.10.128

Cited by 12 publications

(8 citation statements)

References 24 publications

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“…5i) measured by NIR-II method was consistent with previous reports. 28,30,31 It was noteworthy that blood velocity in the ischemic animals was low and beyond the detection capability of ultrasonography. Clearly, the NIR-II imaging technique proved advantageous over ultrasound by providing a broader dynamic range of blood velocity measurements in vivo.…”

Section: Differentiation Of Arterial and Venous Vesselsmentioning

confidence: 99%

Multifunctional in vivo vascular imaging using near-infrared II fluorescence

Hong¹,

Lee²,

Robinson³

et al. 2012

Nat Med

892

688

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In vivo real-time epifluorescence imaging of mouse hindlimb vasculatures in the second near-infrared region (NIR-II, 1.1–1.4 µm) is performed using single-walled carbon nanotubes (SWNTs) as fluorophores. Both high spatial resolution (~30 µm) and temporal resolution (<200 ms/frame) for small vessel imaging are achieved 1~3 mm deep in the tissue owing to the beneficial NIR-II optical window that affords deep anatomical penetration and low scattering. This spatial resolution is unattainable by traditional NIR imaging (NIR-I, 0.75–0.9 µm) or microscopic computed tomography (micro-CT), while the temporal resolution far exceeds scanning microscopic imaging techniques. Arterial and venous vessels are unambiguously differentiated using a dynamic contrast-enhanced NIR-II imaging technique based on their distinct hemodynamics. Further, the deep tissue penetration, high spatial and temporal resolution of NIR-II imaging allow for precise quantifications of blood velocity in both normal and ischemic femoral arteries, which are beyond the capability of ultrasonography at lower blood velocity.

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Section: Differentiation Of Arterial and Venous Vesselsmentioning

confidence: 99%

Multifunctional in vivo vascular imaging using near-infrared II fluorescence

Hong¹,

Lee²,

Robinson³

et al. 2012

Nat Med

892

688

View full text Add to dashboard Cite

show abstract

“…For technical reasons related in part to vessel wall thickness, high-resolution fluorescence imaging of the hemostatic response in mouse models has primarily been limited to the microvasculature, usually in the cremaster muscle or the intestinal mesentery. The macrocirculation differs from the microcirculation significantly in vessel wall structure [13][14][15][16][17][18][19] and local hemodynamics [20][21][22]. These differences have been shown to affect the underlying molecular mechanisms driving platelet activation and thrombus formation in different vascular beds [23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Hierarchical organization of the hemostatic response to penetrating injuries in the mouse macrovasculature

Welsh

Poventud‐Fuentes

Sampietro

et al. 2017

Journal of Thrombosis and Haemostasis

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Summary Background Intravital studies performed in the mouse microcirculation show that hemostatic thrombi formed after penetrating injuries develop a characteristic architecture in which a core of fully-activated, densely-packed platelets is overlaid with a shell of less activated platelets. Objective Large differences in hemodynamics and vessel wall biology distinguish arteries from arterioles. Here we asked whether these differences affect the hemostatic response and alter the impact of anticoagulants and antiplatelet agents. Methods Approaches previously developed for intravital imaging in the mouse microcirculation were adapted to the femoral artery, enabling real time fluorescence imaging despite the markedly thicker vessel wall. Results Arterial thrombi initiated by penetrating injuries developed the core-and-shell architecture previously observed in the microcirculation. However, although platelet accumulation was greater in arterial thrombi, the kinetics of platelet activation were slower. Inhibiting platelet ADP P2Y12 receptors destabilized the shell and reduced thrombus size without affecting the core. Inhibiting thrombin with hirudin suppressed fibrin accumulation, but had little impact on thrombus size. Removing the platelet collagen receptor, glycoprotein VI, had no effect. Conclusions These results 1) demonstrate the feasibility of performing high speed fluorescence imaging in larger vessels and 2) highlight differences as well as similarities in the hemostatic response in the macro- and microcirculation. Similarities include the overall core-and-shell architecture. Differences include the slower kinetics of platelet activation and a smaller contribution from thrombin, which may be due in part to the greater thickness of the arterial wall and the correspondingly greater separation of tissue factor from the vessel lumen.

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“…However, the method is invasive and requires surgical training and experience to prevent complications including vascular injury. We did not experience complications and others have reported successful acute and chronic utilization of the miniature flow probes on the mouse artery(37–40). Our preliminary studies in the mouse (Figure 5) suggest that the venous outflow technique could be utilized in this species as well.…”

Section: Discussionmentioning

confidence: 89%

“…Sanne and Sivertsson in 1968 (35) utilized venous outflow assessed by an optical-drop method at rest and during maximal peripheral dilation to quantify vascular compensation to femoral artery ligation in the cat. Although not previously utilized for this purpose to our knowledge, the development and miniaturization of transit time ultrasound flow probes (36) has made it possible to perform similar venous outflow studies in the rat and mouse hindlimb(37–40). These probes have been shown to provide accurate measurements of volume flow on arteries and veins as determined by roller pumps and volume collections as well as microsphere and clearance techniques(36, 41–44).…”

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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Assessment of mouse hind limb endothelial function by measuring femoral artery blood flow responses

Abstract: This model can be widely used to analyze the in vivo endothelium-dependent vasodilatation function before and after a variety of therapeutic interventions on a mouse hind limb.

Cited by 12 publications

References 24 publications

Multifunctional in vivo vascular imaging using near-infrared II fluorescence

Multifunctional in vivo vascular imaging using near-infrared II fluorescence

Hierarchical organization of the hemostatic response to penetrating injuries in the mouse macrovasculature

Novel method to assess arterial insufficiency in rodent hind limb

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