scholarly journals In Vivo Matrigel Plug Assay as a Potent Method to Investigate Specific Individual Contribution of Angiogenesis to Blood Flow Recovery in Mice

2021 ◽  
Vol 22 (16) ◽  
pp. 8909
Author(s):  
Zeen Aref ◽  
Paul H. A. Quax
Keyword(s):  
Blood Flow ◽  
Limb Ischemia ◽  
Arterial Disease ◽  
Matrigel Plug ◽  
Peripheral Arterial ◽  
The Sacrifice ◽  
Deficient Mice ◽  
Specific Contribution

Neovascularization restores blood flow recovery after ischemia in peripheral arterial disease. The main two components of neovascularization are angiogenesis and arteriogenesis. Both of these processes contribute to functional improvements of blood flow after occlusion. However, discriminating between the specific contribution of each process is difficult. A frequently used model for investigating neovascularization is the murine hind limb ischemia model (HLI). With this model, it is difficult to determine the role of angiogenesis, because usually the timing for the sacrifice of the mice is chosen to be optimal for the analysis of arteriogenesis. More importantly, the occurring angiogenesis in the distal calf muscles is probably affected by the proximally occurring arteriogenesis. Therefore, to understand and subsequently intervene in the process of angiogenesis, a model is needed which investigates angiogenesis without the influence of arteriogenesis. In this study we evaluated the in vivo Matrigel plug assay in genetic deficient mice to investigate angiogenesis. Mice deficient for interferon regulatory factor (IRF)3, IRF7, RadioProtective 105 (RP105), Chemokine CC receptor CCR7, and p300/CBP-associated factor (PCAF) underwent the in vivo Matrigel model. Histological analysis of the Matrigel plugs showed an increased angiogenesis in mice deficient of IRF3, IRF7, and RP105, and a decreased angiogenesis in PCAF deficient mice. Our results also suggest an involvement of CCR7 in angiogenesis. Comparing our results with results of the HLI model found in the literature suggests that the in vivo Matrigel plug assay is superior in evaluating the angiogenic response after ischemia.

The Role of Duplex Ultrasound in the Detection of Upper Extremity Artery Pathology, and Post Endovascular Complications

2018 ◽  
Vol 42 (1) ◽  
pp. 26-29
Author(s):  
Jason Roberts ◽  
Vaqar Ali ◽  
Mian Ahmed Hasan
Keyword(s):  
Upper Extremity ◽  
Fibromuscular Dysplasia ◽  
Duplex Ultrasound ◽  
Limb Ischemia ◽  
Arterial Disease ◽  
Upper Extremities ◽  
Peripheral Arterial ◽  
The Relationship ◽  
Abnormal Pathology

Upper extremity pathology is uncommon and generally involves the brachial artery in about 12% of the cases. Of chronic upper limb ischemia, trauma, fibromuscular dysplasia, giant cell arteritis, and atherosclerosis are among the most reported cases. After a thorough review of the literature, there is agreement with duplex ultrasound sensitivity and specificity for predicting >70% stenosis in the subclavian arteries with a sensitivity of >82% and specificity of >90%. This article not only correlates the relationship between duplex ultrasound and severe peripheral arterial disease, but it also proves with 100% accuracy the ability to detect latent and abnormal pathology of the upper extremities post endovascular intervention.

scholarly journals 2D-Perfusion Angiography Using Carbon Dioxide (CO2): A Feasible Tool to Monitor Immediate Treatment Response to Endovascular Therapy of Peripheral Arterial Disease?

2020 ◽  
Author(s):  
Cornelia L. A. Dewald ◽  
Lena S. Becker ◽  
Sabine K. Maschke ◽  
Timo C. Meine ◽  
Bernhard C. Meyer ◽  
...  
Keyword(s):  
Blood Flow ◽  
Peripheral Arterial Disease ◽  
Contrast Agent ◽  
Treatment Response ◽  
Endovascular Therapy ◽  
Negative Contrast ◽  
Limb Ischemia ◽  
Arterial Disease ◽  
Iodinated Contrast ◽  
Peripheral Arterial

Abstract Purpose Patients with peripheral arterial disease (PAD) or critical limb ischemia (CLI) require revascularization. Traditionally, endovascular therapy (EVT) is performed with iodinated contrast agent (ICM), which can provoke potential deterioration in renal function. CO2 is a safe negative contrast agent to guide vascular procedures, but interpretation of CO2 angiography is challenging. Changes in blood flow following iodine-aided EVT are assessable with 2D-perfusion angiography (2D-PA). The aim of this study was to evaluate 2D-PA as a tool to monitor blood flow changes during CO2-aided EVT. Material and Methods 2D-PA was performed before and after ten EVTs (nine stents; one endoprosthesis; 10/2012–02/2020) in nine patients (six men; 65 ± 10y) with Fontaine stage IIb (n = 8) and IV (n = 1). A reference ROI (ROIINFLOW) was placed in the artery before the targeted obstruction and a target ROI (ROIOUTFLOW) distally. Corresponding ROIs were used pre- and post-EVT. Time to peak (TTP), peak density (PD) and area under the curve (AUC) were computed. The reference/target ROI ratios (TTPOUTFLOW/TTPINFLOW; PDOUTFLOW/PDINFLOW; AUCOUTFLOW/AUCINFLOW) were calculated. Results 2D-PA was technically feasible in all cases. A significant increase of 82% in PDOUTFLOW/PDINFLOW (0.44 ± 0.4 to 0.8 ± 0.63; p = 0.002) and of 132% in AUCOUTFLOW/AUCINFLOW (0.34 ± 0.22 to 0.79 ± 0.59; p = 0.002) was seen. A trend for a decrease in TTPOUTFLOW/TTPINFLOW was observed (− 24%; 5.57 ± 3.66 s–4.25 ± 1.64 s; p = 0.6). Conclusion The presented 2D-PA technique facilitates the assessment of arterial flow in CO2-aided EVTs and has the potential to simplify the assessment of immediate treatment response.

scholarly journals Role of Vascular Smooth Muscle Cell Phenotype Switching in Arteriogenesis

2021 ◽  
Vol 22 (19) ◽  
pp. 10585
Author(s):  
Jasni Viralippurath Ashraf ◽  
Ayman Al Haj Zen
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Peripheral Arterial Disease ◽  
Vascular Smooth Muscle ◽  
Arterial Occlusion ◽  
Arterial Disease ◽  
Phenotypic Switching ◽  
Phenotype Switching ◽  
Peripheral Arterial

Arteriogenesis is one of the primary physiological means by which the circulatory collateral system restores blood flow after significant arterial occlusion in peripheral arterial disease patients. Vascular smooth muscle cells (VSMCs) are the predominant cell type in collateral arteries and respond to altered blood flow and inflammatory conditions after an arterial occlusion by switching their phenotype between quiescent contractile and proliferative synthetic states. Maintaining the contractile state of VSMC is required for collateral vascular function to regulate blood vessel tone and blood flow during arteriogenesis, whereas synthetic SMCs are crucial in the growth and remodeling of the collateral media layer to establish more stable conduit arteries. Timely VSMC phenotype switching requires a set of coordinated actions of molecular and cellular mediators to result in an expansive remodeling of collaterals that restores the blood flow effectively into downstream ischemic tissues. This review overviews the role of VSMC phenotypic switching in the physiological arteriogenesis process and how the VSMC phenotype is affected by the primary triggers of arteriogenesis such as blood flow hemodynamic forces and inflammation. Better understanding the role of VSMC phenotype switching during arteriogenesis can identify novel therapeutic strategies to enhance revascularization in peripheral arterial disease.

Abstract 216: Angiogenic Factor AGGF1 Promotes Therapeutic Angiogenesis in a Mouse Limb Ischemia Model for Peripheral Arterial Disease

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Qing Wang ◽  
Qiulun Lu ◽  
Xin Tu ◽  
Qing Wang
Keyword(s):  
Blood Flow ◽  
Limb Ischemia ◽  
Arterial Disease ◽  
Therapeutic Angiogenesis ◽  
Angiogenic Factor ◽  
Control Group ◽  
Hindlimb Ischemia ◽  
Empty Vector ◽  
Muscle Tissues ◽  
Peripheral Arterial

Introduction: Peripheral arterial disease (PAD) is caused by atherosclerosis. PAD is a common disease that affects 12% of the adult population and causes significant morbidity and mortality. The existing treatments for PAD, including pharmacological, interventional and surgical procedures, are not sufficient and many patients are opt for limb amputation. Therapeutic angiogenesis using angiogenic factors has been considered to be a potential treatment option for PAD patients. Hypothesis: In this study, we assessed the potential of a new angiogenic factor AGGF1 for therapeutic angiogenesis in a critical limb ischemia model in mice for PAD. Methods and Results: We generated a unilateral hindlimb ischemia model in mice by ligation of the right common iliac artery and femoral artery. Ischemic mice with intrasmuscular administration of DNA for an expression plasmid for human AGGF1 ( AGGF1 group) resulted in increased expression of both AGGF1 mRNA and protein after the administration compared with control mice of hindlimb ischemia with injection of the empty vector (control group). The blood flow in ischemic hindlimbs was significantly increased in the AGGF1 group compared to control mice at time points of 7, 14, and 28 days after DNA administration. Four weeks after the injection of DNA, the blood flow was approximately 2.19 fold higher in AGGF1 group than that in control. With the increased blood flow in the AGGF1 group, ambulatory impairement were inhibited compared with the control group. Increased AGGF1 expression decreased necrosis in muscle tissues injected with AGGF1 DNA compared with the control tissue injected with the empty vector. CD31-positive capillary vessel density was significantly higher in AGGF1 -injected limbs than in empty vector-injected limbs. Conclusions: These data establish that plasmid DNA-based gene transfer of AGGF1 into mouse skeletal muscles is efficient in increase the expression levels of AGGF1 mRNA and protein. Increased AGGF1 expression increases blood flow by increasing density of CD31-positive vessels and by decreasing necrosis in muscle tissues. These findings suggest that AGGF1 may be used as a candidate therapeutic agent for therapeutic angiogenesis to treat PAD.

scholarly journals Functioning of an arteriovenous fistula requires heme oxygenase-2

2013 ◽  
Vol 305 (4) ◽  
pp. F545-F552 ◽  
Author(s):  
Lu Kang ◽  
Joseph P. Grande ◽  
Gianrico Farrugia ◽  
Anthony J. Croatt ◽  
Zvonimir S. Katusic ◽  
...  
Keyword(s):  
Blood Flow ◽  
Carotid Artery ◽  
Heme Oxygenase ◽  
Jugular Vein ◽  
Arteriovenous Fistulas ◽  
Vascular Segment ◽  
And Function ◽  
Deficient Mice

Heme oxygenase-2 (HO-2), the constitutive isoform of the heme-degrading enzyme heme oxygenase, may serve as an anti-inflammatory vasorelaxant, in part, by generating carbon monoxide. Arteriovenous fistulas (AVFs) are employed as hemodialysis vascular accesses because they provide an accessible, high-blood-flow vascular segment. We examined the role of vascular expression of HO-2 in AVF function. An AVF was created in mice by anastomosing the carotid artery to the jugular vein. HO-2 expression was detected by immunohistochemistry in the intact carotid artery, mainly in endothelial cells and smooth muscle cells; expression of HO-2 protein and mRNA was modestly increased in the artery of the AVF. Creating an AVF in HO-2−/− mice compared with an AVF in HO-2+/+ mice led to markedly reduced AVF blood flow and increased numbers of nonfunctioning AVFs. The impairment of AVF function in the setting of HO-2 deficiency could not be ascribed to either preexisting intrinsic abnormalities in endothelium-dependent and endothelium-independent relaxation of the carotid artery in HO-2-deficient mice or to impaired vasorelaxant responses in the intact carotid artery in vivo. HO-1 mRNA was comparably induced in the AVF in HO-2+/+ and HO-2−/− mice, whereas the AVF in HO-2−/− mice compared with that in HO-2+/+ mice exhibited exaggerated induction of matrix metalloproteinase (MMP)-9 but similar induction of MMP-2. HO-2 deficiency also led to lower AVF blood flow when AVFs were created in uremia, the latter induced by subtotal nephrectomy. We conclude that HO-2 critically contributes to the adequacy of AVF blood flow and function.

The Feasibility of Using Millimeter Wave Heating for Non-Invasive Measurement of Skin Blood Flow in Humans

2013 ◽  
Author(s):  
D. A. Nelson ◽  
S. J. Leavesley ◽  
G. T. Hamlin ◽  
J. M. Downey
Keyword(s):  
Blood Flow ◽  
Skin Blood Flow ◽  
Limb Ischemia ◽  
Arterial Disease ◽  
Diagnosis And Management ◽  
Non Invasive ◽  
Wave Heating ◽  
Peripheral Arterial ◽  
Clinical Conditions ◽  
Revascularization Surgery

A non-contacting method to measure skin blood flow (SkBF) in human extremities that is both simple and accurate could be invaluable in the diagnosis and management of several clinical conditions. For excample, measurement of SkBF in the digit(s) can be useful in the diagnosis and management of Peripheral Arterial Disease, often associated with Type 2 diabetes (Petrofsky et al., 2008). Skin blood flow in the foot can be an indicator of successful infrainguinal revascularization surgery in patients with lower limb ischemia (Saucy et al., 2006; Yamada et al., 2008). Assessment of peripheral perfusion can be useful in determining hemodynamic stability of patients suffering from acute circulatory shock (Lima et al., 2009) or circulatory failure (Lima and Bakker, 2005).

scholarly journals In Vivo Confirmation of the Role of Statins in Reducing Nitric Oxide and C-Reactive Protein Levels in Peripheral Arterial Disease

2009 ◽  
Vol 37 (4) ◽  
pp. 443-447 ◽  
Author(s):  
E. Martínez Aguilar ◽  
J. De Haro Miralles ◽  
A. Flórez González ◽  
C. Varela Casariego ◽  
S. Bleda Moreno ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Peripheral Arterial Disease ◽  
Arterial Disease ◽  
C Reactive Protein ◽  
Protein Levels ◽  
Reactive Protein ◽  
Peripheral Arterial

scholarly journals Hallucal thenar index: A new index to detect peripheral arterial disease using laser speckle flowgraphy

Vascular ◽  
2020 ◽  
pp. 170853812093893
Author(s):  
Kazuhiro Tsunekawa ◽  
Fumio Nagai ◽  
Tamon Kato ◽  
Ikkei Takashimizu ◽  
Daisuke Yanagisawa ◽  
...  
Keyword(s):  
Blood Flow ◽  
Peripheral Arterial Disease ◽  
Operating Characteristic ◽  
Ankle Brachial Index ◽  
Arterial Disease ◽  
Laser Speckle ◽  
Laser Speckle Flowgraphy ◽  
Skin Perfusion ◽  
Peripheral Arterial ◽  
Cutaneous Blood

Objectives Laser speckle flowgraphy is a technology using reflected scattered light for visualization of blood distribution, which can be used to measure relative velocity of blood flow easily without contact with the skin within a short time. It was hypothesized that laser speckle flowgraphy may be able to identify foot ischemia. This study was performed to determine whether laser speckle flowgraphy could distinguish between subjects with and without peripheral arterial disease. Materials and methods All subjects were classified based on clinical observations using the Rutherford classification: non-peripheral arterial disease, class 0; peripheral arterial disease group, class 2–5. Rutherford class 6 was one of the exclusion criteria. Laser speckle flowgraphy measured the beat strength of skin perfusion as an indicator of average dynamic cutaneous blood flow change synchronized with the heartbeat. The beat strength of skin perfusion indicates the strength of the heartbeat on the skin, and the heartbeat strength calculator in laser speckle flowgraphy uses the blood flow data to perform a Fourier transform to convert the temporal changes in blood flow to a power spectrum. A total of 33 subjects with peripheral arterial disease and 40 subjects without peripheral arterial disease at a single center were prospectively examined. Laser speckle flowgraphy was used to measure hallucal and thenar cutaneous blood flow, and the measurements were repeated three times. The hallucal and thenar index was defined as the ratio of beat strength of skin perfusion value on hallux/beat strength of skin perfusion value on ipsilateral thenar eminence. The Mann–Whitney U-test was used to compare the median values of hallucal and thenar index and ankle brachial index between the two groups. A receiver operating characteristic curve for hallucal and thenar index of beat strength of skin perfusion was plotted, and a cutoff point was set. The correlation between hallucal and thenar index of beat strength of skin perfusion and ankle brachial index was explored in all subjects, the hemodialysis group, and the non-hemodialysis (non-hemodialysis) group. Results The median value of the hallucal and thenar index of beat strength of skin perfusion was significantly different between subjects with and without peripheral arterial disease (0.27 vs. 0.87, respectively; P <  0.001). The median value of ankle brachial index was significantly different between subjects with and without peripheral arterial disease (0.8 vs. 1.1, respectively; P <  0.001). Based on the receiver operating characteristic of hallucal and thenar index, the cutoff was 0.4416 and the sensitivity, specificity, positive predictive value, and negative predictive value were 68.7%, 95%, 91.7%, and 77.6%, respectively. The correlation coefficients of all subjects, the hemodialysis group, and the non-hemodialysis group were 0.486, 0.102, and 0.743, respectively. Conclusions Laser speckle flowgraphy is a noninvasive, rapid, and widely applicable method. Laser speckle flowgraphy using hallucal and thenar index would be helpful to determine the differences between subjects with and without peripheral arterial disease. The correlation between hallucal and thenar index of beat strength of skin perfusion and ankle brachial index indicated that this index was especially useful in the non-hemodialysis group.

scholarly journals What Is Currently the Role of TcPO2 in the Choice of the Amputation Level of Lower Limbs? A Comprehensive Review

2021 ◽  
Vol 10 (7) ◽  
pp. 1413
Author(s):  
Judith Catella ◽  
Anne Long ◽  
Lucia Mazzolai
Keyword(s):  
Arterial Disease ◽  
Major Amputation ◽  
Lower Limbs ◽  
Limb Amputation ◽  
Quality Of Data ◽  
Amputation Level ◽  
Increased Risk ◽  
Transcutaneous Oximetry ◽  
Peripheral Arterial

Some patients still require major amputation for lower extremity peripheral arterial disease treatment. The purpose of pre-operative amputation level selection is to determine the most distal amputation site with the highest healing probability without re-amputation. Transcutaneous oximetry (TcPO2) can detect viable tissue with the highest probability of healing. Several factors affect the accuracy of TcPO2; nevertheless, surgeons rely on TcPO2 values to determine the optimal amputation level. Background about the development of TcPO2, methods of measurement, consequences of lower limb amputation level, and the place of TcPO2 in the choice of the amputation level are reviewed herein. Most of the retrospective studies indicated that calf TcPO2 values greater than 40 mmHg were associated with a high percentage of successful wound healing after below-knee-amputation, whereas values lower than 20 mmHg indicated an increased risk of unsuccessful healing. However, a consensus on the precise cut-off value of TcPO2 necessary to assure healing is missing. Ways of improvement for TcPO2 performance applied to the optimization of the amputation-level are reported herein. Further prospective data are needed to better approach a TcPO2 value that will promise an acceptable risk of re-amputation. Standardized TcPO2 measurement is crucial to ensure quality of data.

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