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  1. Microvascular rarefaction

    PubMed Central

    2010-01-01

    The goals of this presentation are twofold: (1) to briefly sketch the field of vascular rarefaction as a key component of various fibrotic diseases and (2) to illustrate it with four vignettes depicting diverse mechanisms of microvascular rarefaction. Specifically, I shall describe migratory and angiogenic incompetence of endothelial cells under conditions of reduced bioavailability of nitric oxide, role of endothelial-to-mesenchymal cell and mesenchymal stem cell-to-endothelial reprogramming, and potential role of antiangiogenic peptides in the development of graft vascular disease as exemplified by chronic allograft nephropathy PMID:20592859

  2. Hemorheology and Microvascular Disorders

    PubMed Central

    Cho, Daniel J

    2011-01-01

    The present review presents basic concepts of blood rheology related to vascular diseases. Blood flow in large arteries is dominated by inertial forces exhibited at high flow velocities, while viscous forces (i.e., blood rheology) play an almost negligible role. When high flow velocity is compromised by sudden deceleration as at a bifurcation, endothelial cell dysfunction can occur along the outer wall of the bifurcation, initiating inflammatory gene expression and, through mechanotransduction, the cascade of events associated with atherosclerosis. In sharp contrast, the flow of blood in microvessels is dominated by viscous shear forces since the inertial forces are negligible due to low flow velocities. Shear stress is a critical parameter in microvascular flow, and a force-balance approach is proposed for determining microvascular shear stress, accounting for the low Reynolds numbers and the dominance of viscous forces over inertial forces. Accordingly, when the attractive forces between erythrocytes (represented by the yield stress of blood) are greater than the shear force produced by microvascular flow, tissue perfusion itself cannot be sustained, leading to capillary loss. The yield stress parameter is presented as a diagnostic candidate for future clinical research, specifically, as a fluid dynamic biomarker for microvascular disorders. The relation between the yield stress and diastolic blood viscosity (DBV) is described using the Casson model for viscosity, from which one may be able determine thresholds of DBV where the risk of microvascular disorders is high. PMID:21779279

  3. What Causes Coronary Microvascular Disease?

    MedlinePlus

    ... Living With Clinical Trials Links Related Topics Angina Atherosclerosis Coronary Heart Disease Coronary Heart Disease Risk Factors ... Microvascular Disease? The same risk factors that cause atherosclerosis may cause coronary microvascular disease. Atherosclerosis is a ...

  4. Microvascular invasion in hepatocellular carcinoma

    PubMed Central

    Ünal, Emre; İdilman, İlkay Sedakat; Akata, Deniz; Özmen, Mustafa Nasuh; Karçaaltıncaba, Muşturay

    2016-01-01

    Microvascular invasion is a crucial histopathologic prognostic factor for hepatocellular carcinoma. We reviewed the literature and aimed to draw attention to clinicopathologic and imaging findings that may predict the presence of microvascular invasion in hepatocellular carcinoma. Imaging findings suggesting microvascular invasion are disruption of capsule, irregular tumor margin, peritumoral enhancement, multifocal tumor, increased tumor size, and increased glucose metabolism on positron emission tomography-computed tomography. In the presence of typical findings, microvascular invasion may be predicted. PMID:26782155

  5. Líneas UV como indicadores de temperatura y densidad

    NASA Astrophysics Data System (ADS)

    Brusasco, M. A.; Cidale, L. S.

    In order to investigate the behavior of Fe II lines in Be stars, we carry out a statistical analysis over a sample of IUE images. We found that only 4 of the 39 studied stars (with spectral types B2, B5 and B8) show Fe II lines. Synthetic spectra of Fe II lines were computed by means of a rigorous treatment of the line transfer equation for moving flows, considering different effective temperature, velocity and temperature structure. Preliminary results show that the shape of the profiles depends mainly on the velocity structure, while the intensity changes with both the temperature and the density structure.

  6. Microvascular decompression for intractable singultus.

    PubMed

    Saito, Atsushi; Hatayama, Toru; Kon, Hiroyuki; Nakamura, Taigen; Sasaki, Tatsuya

    2016-10-01

    Intractable singultus due to cerebrovascular disease is very rare. We report a case of intractable singultus that improved after microvascular decompression and present a literature review. The patient was a 58-year-old man with a 30-year history of persistent singultus. Its frequency and duration gradually increased and it was resistant to multiple medical treatments. Microvascular decompression to relieve pressure on the anterolateral surface of the lower medulla oblongata from the vertebral artery resulted in the resolution of singultus. Patients with intractable idiopathic singultus who fail to respond to medical therapy need to be considered for the evaluation of cerebrovascular diseases and microvascular decompression. PMID:27335312

  7. A history of vascular and microvascular surgery.

    PubMed

    Rickard, Rory F; Hudson, Donald A

    2014-10-01

    The history of microvascular surgery is intimately linked to that of vascular surgery. Microvascular techniques, developed mainly in China, Japan, Australia, and the United States of America, built on the principles of vascular anastomosis established by pioneers in France, Germany, Italy, and the United States of America. We present a history of the technique here.

  8. Coronary microvascular obstruction in acute myocardial infarction.

    PubMed

    Niccoli, Giampaolo; Scalone, Giancarla; Lerman, Amir; Crea, Filippo

    2016-04-01

    The success of a primary percutaneous intervention (PCI) in the setting of ST elevation myocardial infarction depends on the functional and structural integrity of coronary microcirculation. Coronary microvascular dysfunction and obstruction (CMVO) occurs in up to half of patients submitted to apparently successful primary PCI and is associated to a much worse outcome. The current review summarizes the complex mechanisms responsible for CMVO, including pre-existing coronary microvascular dysfunction, and highlights the current limitations in the assessment of microvascular function. More importantly, at the light of the substantial failure of trials hitherto published on the treatment of CMVO, this review proposes a novel integrated therapeutic approach, which should overcome the limitations of previous studies.

  9. Roles of LOX-1 in microvascular dysfunction.

    PubMed

    Lubrano, Valter; Balzan, Silvana

    2016-05-01

    Studies from human and animal models with metabolic disease and hypertension highlight atrophic remodeling, reduced lumen size and thinner vascular walls of microvessels with profound density reduction. This impaired vascular response limits the perfusion of peripheral tissues inducing organ damage. These conditions are strongly associated with oxidative stress and in particular with the up-regulation of lectin-like oxidized low density lipoprotein receptor-1 (LOX-1). Several factors such as cytokines, shear stress, and advanced glycation end-products, especially oxLDL, can up-regulate LOX-1. The activation of this receptor induces the production of adhesion molecules, cytokines and the release of reactive oxygen species via NADPH oxidase. LOX-1 is considered a potent mediator of endothelial dysfunction and it is significantly associated with reduced microvascular endothelium NO-dependent vasodilation in hypercholesterolemia and hypertension. Microvascular endothelial cells increased the expression of IL-6 in association with the increased concentration of LDL and its degree of oxidation. Moreover, increased IL-6 levels are associated with up-regulation of LOX-1 in a dose-dependent manner. Another consequence of microvascular inflammation is the generation of small amounts of ROS, similar to those induced by low concentration of oxLDL (<5 μg/mL) which induces capillary tube formation of endothelial cells, through LOX-1 up-regulation. In light of its central role, LOX-1 represents an attractive therapeutic target for the treatment of human atherosclerotic diseases and microvascular disorders. PMID:26907636

  10. Microvascular dysfunction in the context of diabetic neuropathy.

    PubMed

    Stirban, Alin

    2014-01-01

    Microvascular dysfunction in diabetes plays a crucial role in the development of diabetic complications. The skin, as one of the most accessible organs, serves as a model for the investigation of microvascular dysfunction. Several non-invasive, mostly laser-Doppler-based methods have been developed lately to assess microvascular function in the skin. Microvascular functional changes occur even in the prediabetic state and become more complex with overt diabetes, being exacerbated by the presence of peripheral and/or autonomic diabetic neuropathy. The present article aims at shedding light on the implication of endothelial and neurovascular dysfunction in microvascular changes in diabetes, highlighting the contribution of different forms of diabetic neuropathy.

  11. Treatment of hemimasticatory spasm with microvascular decompression.

    PubMed

    Wang, Yong-Nan; Dou, Ning-Ning; Zhou, Qiu-Meng; Jiao, Wei; Zhu, Jin; Zhong, Jun; Li, Shi-Ting

    2013-01-01

    Hemimasticatory spasm is a rare disorder characterized by paroxysmal involuntary contraction of the jaw-closing muscles. As the ideology and pathogenesis of the disease are still unclear, there has been no treatment that could give rise to a good outcome so far. Herein, we tried to use surgical management to cure the disease. Six patients with the disease were included in this study. These patients underwent microvascular decompression of the motor fibers of the trigeminal root. After the operation, all faces of the patients felt relaxed at varied degrees, except for 1 patient. Our study showed that microvascular decompression of the trigeminal nerve could lead to a better outcome. However, a control study with a large sample is needed before this technique is widely used.

  12. Predictors of Microvascular Invasion in Hepatocellular Carcinoma.

    PubMed

    Yamashita, Yo-Ichi; Shirabe, Ken; Aishima, Shinichi; Maehara, Yoshihiko

    2015-09-01

    This chapter covers a range of important topics in the evaluation of the microvascular invasion (MVI) in hepatocellular carcinoma (HCC) before treatment. The malignant potential of HCC is reflected by the types of MVI such as portal venous (vp), hepatic vein (vv) or bile duct (b) infiltration. The identification of the type of MVI in HCC has a key role in decisions regarding the effective treatment of HCC. Here, we describe the possible and important predictors of MVI in HCC. PMID:26398341

  13. Fabrication of 3-dimensional multicellular microvascular structures

    PubMed Central

    Barreto-Ortiz, Sebastian F.; Fradkin, Jamie; Eoh, Joon; Trivero, Jacqueline; Davenport, Matthew; Ginn, Brian; Mao, Hai-Quan; Gerecht, Sharon

    2015-01-01

    Despite current advances in engineering blood vessels over 1 mm in diameter and the existing wealth of knowledge regarding capillary bed formation, studies for the development of microvasculature, the connecting bridge between them, have been extremely limited so far. Here, we evaluate the use of 3-dimensional (3D) microfibers fabricated by hydrogel electrospinning as templates for microvascular structure formation. We hypothesize that 3D microfibers improve extracellular matrix (ECM) deposition from vascular cells, enabling the formation of freestanding luminal multicellular microvasculature. Compared to 2-dimensional cultures, we demonstrate with confocal microscopy and RT-PCR that fibrin microfibers induce an increased ECM protein deposition by vascular cells, specifically endothelial colony-forming cells, pericytes, and vascular smooth muscle cells. These ECM proteins comprise different layers of the vascular wall including collagen types I, III, and IV, as well as elastin, fibronectin, and laminin. We further demonstrate the achievement of multicellular microvascular structures with an organized endothelium and a robust multicellular perivascular tunica media. This, along with the increased ECM deposition, allowed for the creation of self-supporting multilayered microvasculature with a distinct circular lumen following fibrin microfiber core removal. This approach presents an advancement toward the development of human microvasculature for basic and translational studies.—Barreto-Ortiz, S. F., Fradkin, J., Eoh, J., Trivero, J., Davenport, M., Ginn, B., Mao, H.-Q., Gerecht, S. Fabrication of 3-dimensional multicellular microvascular structures. PMID:25900808

  14. Hypertension Management and Microvascular Insulin Resistance in Diabetes

    PubMed Central

    Ko, Seung-Hyun; Cao, Wenhong; Liu, Zhenqi

    2011-01-01

    Type 2 diabetes is in essence a vascular disease and is frequently associated with hypertension, macrovascular events, and microvascular complications. Microvascular dysfunction, including impaired recruitment and capillary rarefaction, has been implicated in the pathogenesis of diabetic complications. Microvascular insulin resistance and renin-angiotensin system upregulation are present in diabetes, and each contributes to the development of hypertension and microvascular dysfunction. In the insulin-sensitive state, insulin increases microvascular perfusion by increasing endothelial nitric oxide production, but this effect is abolished by insulin resistance. Angiotensin II, acting via the type 1 receptors, induces inflammation and oxidative stress, leading to impaired insulin signaling, reduced nitric oxide availability, and vasoconstriction. Conversely, it acts on the type 2 receptors to cause vasodilatation. Because substrate and hormonal exchanges occur in the microvasculature, antihypertensive agents targeted to improve microvascular insulin sensitivity and function may have beneficial effects beyond their capacity to lower blood pressure in patients with diabetes. PMID:20582734

  15. Skin microvascular endothelial function as a biomarker in cardiovascular diseases?

    PubMed

    Hellmann, Marcin; Roustit, Matthieu; Cracowski, Jean-Luc

    2015-08-01

    Skin microvascular endothelial function is impaired in many cardiovascular diseases, and could be therefore considered as a representative vascular bed. However, today, available evidence allows considering skin microvascular endothelial function neither as a diagnostic biomarker nor as a prognostic biomarker in cardiovascular diseases. Large follow-up studies using standardized methods should now be conducted to assess the potential predictive value of skin microvascular function in cardiovascular diseases.

  16. Modelo semi-empírico de protuberancia solar a partir del diagnóstico de densidades

    NASA Astrophysics Data System (ADS)

    Cirigliano, D.; Vial, J. C.; Rovira, M.

    A partir de la observación del espectro del quintuplete de C III alrededor de 1175 Å, se ha realizado el diagnóstico de la densidad y presión electrónica, basado en el cálculo del cociente de las intensidades observadas. Una vez establecida la densidad electrónica, y con el cálculo de las velocidades Doppler, hemos investigado el flujo de masa en la protuberancia en función de la temperatura. Estableciendo como hipótesis la conservación del número de partículas que ingresan y salen del cuerpo de la protuberancia, se investiga la variación del área de un tubo de flujo semi-empírico en función de la temperatura. A partir de dicho diagnóstico, se examina el comportamiento del radio del tubo magnético en función de la temperatura, los que dan cuenta de la abertura de las líneas de campo magnético que confinan el plasma y de la divergencia del campo magnético en diferentes alturas de la atmósfera solar.

  17. Direct ink writing of microvascular networks

    NASA Astrophysics Data System (ADS)

    Wu, Willie

    Nature is replete with examples of embedded microvascular systems that enable efficient fluid flow and distribution for autonomic healing, cooling, and energy harvesting. The ability to incorporate microvascular networks in functional materials systems is therefore both scientifically and technologically important. In this PhD thesis, the direct-write assembly of planar and 3D biomimetic microvascular networks within polymer and hydrogel matrices is demonstrated. In addition, the influence of network design of fluid transport efficiency is characterized. Planar microvascular networks composed of periodic lattices of uniformal microchannels and hierarchical, branching architectures are constructed by direct-write assembly of a fugitive organic ink. Several advancements are required to facilitate their patterning, including pressure valving, dual ink printing, and dynamic pressure variation to allow tunable control of ink deposition. The hydraulic conductance is measured using a high pressure flow meter as a function of network design. For a constant vascular volume and areal coverage, 2- and 4-generation branched architectures that obey Murray's Law exhibited the highest hydraulic conductivity. These experimental observations are in good agreement with predictions made by analytic models. 3D microvascular networks are fabricated by omnidirectional printing a fugitive organic ink into a photopolymerizable hydrogel matrix that is capped with fluid filler of nearly identical composition. Using this approach, 3D networks of arbitrary design can be patterned. After ink deposition is complete, the matrix and fluid filler are chemically cross-linked via UV irradiation, and the ink is removed by liquefication. Aqueous solutions composed of a triblock copolymer of polyethylene oxide (PEO)-polypropylene oxide (PPO)-PEO constitute the materials system of choice due to their thermal- and concentration-dependent phase behavior. Specifically, the fugitive ink consists of a 23 w

  18. Listeriolysin O mediates cytotoxicity against human brain microvascular

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Penetration of the brain microvascular endothelial layer is one of the routes L. monocytogenes use to breach the blood-brain barrier. Because host factors in the blood severely limit direct invasion of human brain microvascular endothelial cells (HBMECs) by L. monocytogenes, alternative mechanisms m...

  19. Rapid homogeneous endothelialization of high aspect ratio microvascular networks.

    PubMed

    Naik, Nisarga; Hanjaya-Putra, Donny; Haller, Carolyn A; Allen, Mark G; Chaikof, Elliot L

    2015-08-01

    Microvascularization of an engineered tissue construct is necessary to ensure the nourishment and viability of the hosted cells. Microvascular constructs can be created by seeding the luminal surfaces of microfluidic channel arrays with endothelial cells. However, in a conventional flow-based system, the uniformity of endothelialization of such an engineered microvascular network is constrained by mass transfer of the cells through high length-to-diameter (L/D) aspect ratio microchannels. Moreover, given the inherent limitations of the initial seeding process to generate a uniform cell coating, the large surface-area-to-volume ratio of microfluidic systems demands long culture periods for the formation of confluent cellular microconduits. In this report, we describe the design of polydimethylsiloxane (PDMS) and poly(glycerol sebacate) (PGS) microvascular constructs with reentrant microchannels that facilitates rapid, spatially homogeneous endothelial cell seeding of a high L/D (2 cm/35 μm; > 550:1) aspect ratio microchannels. MEMS technology was employed for the fabrication of a monolithic, elastomeric, reentrant microvascular construct. Isotropic etching and PDMS micromolding yielded a near-cylindrical microvascular channel array. A 'stretch - seed - seal' operation was implemented for uniform incorporation of endothelial cells along the entire microvascular area of the construct yielding endothelialized microvascular networks in less than 24 h. The feasibility of this endothelialization strategy and the uniformity of cellularization were established using confocal microscope imaging. PMID:26227213

  20. Rapid homogeneous endothelialization of high aspect ratio microvascular networks.

    PubMed

    Naik, Nisarga; Hanjaya-Putra, Donny; Haller, Carolyn A; Allen, Mark G; Chaikof, Elliot L

    2015-08-01

    Microvascularization of an engineered tissue construct is necessary to ensure the nourishment and viability of the hosted cells. Microvascular constructs can be created by seeding the luminal surfaces of microfluidic channel arrays with endothelial cells. However, in a conventional flow-based system, the uniformity of endothelialization of such an engineered microvascular network is constrained by mass transfer of the cells through high length-to-diameter (L/D) aspect ratio microchannels. Moreover, given the inherent limitations of the initial seeding process to generate a uniform cell coating, the large surface-area-to-volume ratio of microfluidic systems demands long culture periods for the formation of confluent cellular microconduits. In this report, we describe the design of polydimethylsiloxane (PDMS) and poly(glycerol sebacate) (PGS) microvascular constructs with reentrant microchannels that facilitates rapid, spatially homogeneous endothelial cell seeding of a high L/D (2 cm/35 μm; > 550:1) aspect ratio microchannels. MEMS technology was employed for the fabrication of a monolithic, elastomeric, reentrant microvascular construct. Isotropic etching and PDMS micromolding yielded a near-cylindrical microvascular channel array. A 'stretch - seed - seal' operation was implemented for uniform incorporation of endothelial cells along the entire microvascular area of the construct yielding endothelialized microvascular networks in less than 24 h. The feasibility of this endothelialization strategy and the uniformity of cellularization were established using confocal microscope imaging.

  1. Current Diagnostic and Therapeutic Strategies in Microvascular Angina

    PubMed Central

    Mumma, Bryn; Flacke, Nathalie

    2014-01-01

    Microvascular angina is common among patients with signs and symptoms of acute coronary syndrome and is associated with an increased risk of cardiovascular and cerebrovascular events. Unfortunately, microvascular is often under-recognized in clinical settings. The diagnosis of microvascular angina relies on assessment of the functional status of the coronary microvasculature. Invasive strategies include acetylcholine provocation, intracoronary Doppler ultrasound, and intracoronary thermodilution; noninvasive strategies include cardiac positron emission tomography (PET), cardiac magnetic resonance, and Doppler echocardiography. Once the diagnosis of microvascular angina is established, treatment is focused on improving symptoms and reducing future risk of cardiovascular and cerebrovascular events. Pharmacologic options and lifestyle modifications for patients with microvascular angina are similar to those for patients with coronary artery disease. PMID:25685641

  2. Myocardial perfusion echocardiography and coronary microvascular dysfunction

    PubMed Central

    Barletta, Giuseppe; Del Bene, Maria Riccarda

    2015-01-01

    Our understanding of coronary syndromes has evolved in the last two decades out of the obstructive atherosclerosis of epicardial coronary arteries paradigm to include anatomo-functional abnormalities of coronary microcirculation. No current diagnostic technique allows direct visualization of coronary microcirculation, but functional assessments of this circulation are possible. This represents a challenge in cardiology. Myocardial contrast echocardiography (MCE) was a breakthrough in echocardiography several years ago that claimed the capability to detect myocardial perfusion abnormalities and quantify coronary blood flow. Research demonstrated that the integration of quantitative MCE and fractional flow reserve improved the definition of ischemic burden and the relative contribution of collaterals in non-critical coronary stenosis. MCE identified no-reflow and low-flow within and around myocardial infarction, respectively, and predicted the potential functional recovery of stunned myocardium using appropriate interventions. MCE exhibited diagnostic performances that were comparable to positron emission tomography in microvascular reserve and microvascular dysfunction in angina patients. Overall, MCE improved echocardiographic evaluations of ischemic heart disease in daily clinical practice, but the approval of regulatory authorities is lacking. PMID:26730291

  3. Microvascular Repair: Post-Angiogenesis Vascular Dynamics

    PubMed Central

    LeBlanc, Amanda J.; Krishnan, Laxminarayanan; Sullivan, Christopher J.; Williams, Stuart K.; Hoying, James B.

    2013-01-01

    Vascular compromise and the accompanying perfusion deficits cause or complicate a large array of disease conditions and treatment failures. This has prompted the exploration of therapeutic strategies to repair or regenerate vasculatures thereby establishing more competent microcirculatory beds. Growing evidence indicates that an increase in vessel numbers within a tissue does not necessarily promote an increase in tissue perfusion. Effective regeneration of a microcirculation entails the integration of new stable microvessel segments into the network via neovascularization. Beginning with angiogenesis, neovascularization entails an integrated series of vascular activities leading to the formation of a new mature microcirculation and includes vascular guidance and inosculation, vessel maturation, pruning, arterio-venous specification, network patterning, structural adaptation, intussusception, and microvascular stabilization. While the generation of new vessel segments is necessary to expand a network, without the concomitant neovessel remodeling and adaptation processes intrinsic to microvascular network formation, these additional vessel segments give rise to a dysfunctional microcirculation. While many of the mechanisms regulating angiogenesis have been detailed, a thorough understanding of the mechanisms driving post-angiogenesis activities specific to neovascularization has yet to be fully realized, but is necessary in order to develop effective therapeutic strategies for repairing compromised microcirculations as a means to treat disease. PMID:22734666

  4. Effects of radiation therapy in microvascular anastomoses

    SciTech Connect

    Fried, M.P.

    1985-07-01

    The otolaryngologist, as a head and neck surgeon, commonly cares for patients with upper aerodigestive tract malignancies. Therapy of these neoplasms often requires wide excision. One standard reconstructive procedure utilizes pedicled regional flaps, both dermal and myodermal which have some disadvantages. The shortcomings of these pedicled regional flaps have led to the use of the vascularized free flap in certain cases. The occasional case may lead to catastrophe if microanastomoses fail when combined with radiation. Notwithstanding, many surgical series have reported success when radiation has been given. The present investigation was undertaken to assess the effects of radiation therapy on microvascular anastomoses when radiation is administered pre- or postoperatively or when nonradiated tissue is transferred to an irradiated recipient site. These effects were observed serially in an experimental rat model using a tubed superficial epigastric flap that adequately reflected tissue viability and vascular patency. The histologic changes were then noted over a three month period after completion of both radiation and surgery. This study adds credence to the observation of the lack of deleterious effects of radiation on experimental microvascular anastomotic patency whether the radiation is given before or after surgery or if radiated tissue is approximated to nonradiated vessels.

  5. Acute Alcohol Intoxication-Induced Microvascular Leakage

    PubMed Central

    Doggett, Travis M.; Breslin, Jerome W.

    2014-01-01

    Background Alcohol intoxication can increase inflammation and worsen injury, yet the mechanisms involved are not clear. We investigated whether acute alcohol intoxication elevates microvascular permeability, and investigated potential signaling mechanisms in endothelial cells that may be involved. Methods Conscious rats received a 2.5 g/kg alcohol bolus via gastric catheters to produce acute intoxication. Microvascular leakage of intravenously administered FITC-albumin from the mesenteric microcirculation was assessed by intravital microscopy. Endothelial-specific mechanisms were studied using cultured endothelial cell monolayers. Transendothelial electrical resistance (TER) served as an index of barrier function, before and after treatment with alcohol or its metabolite acetaldehyde. Pharmacologic agents were used to test the roles of alcohol metabolism, oxidative stress, p38 mitogen-activated protein (MAP) kinase, myosin light chain kinase (MLCK), rho kinase (ROCK), and exchange protein activated by cAMP (Epac). VE-cadherin localization was investigated to assess junctional integrity. Rac1 and RhoA activation were assessed by ELISA assays. Results Alcohol significantly increased FITC-albumin extravasation from the mesenteric microcirculation. Alcohol also significantly decreased TER and disrupted VE-cadherin organization at junctions. Acetaldehyde significantly decreased TER, but inhibition of ADH or application of a superoxide dismutase mimetic failed to prevent alcohol-induced decreases in TER. Inhibition of p38 MAP kinase, but not MLCK or ROCK, significantly attenuated the alcohol-induced barrier dysfunction. Alcohol rapidly decreased GTP-bound Rac1 but not RhoA during the drop in TER. Activation of Epac increased TER, but did not prevent alcohol from decreasing TER. However, activation of Epac after initiation of alcohol-induced barrier dysfunction quickly resolved TER to baseline levels. Conclusions Our results suggest that alcohol intoxication increases

  6. Differentiation state determines neural effects on microvascular endothelial cells

    SciTech Connect

    Muffley, Lara A.; Pan, Shin-Chen; Smith, Andria N.; Ga, Maricar; Hocking, Anne M.; Gibran, Nicole S.

    2012-10-01

    Growing evidence indicates that nerves and capillaries interact paracrinely in uninjured skin and cutaneous wounds. Although mature neurons are the predominant neural cell in the skin, neural progenitor cells have also been detected in uninjured adult skin. The aim of this study was to characterize differential paracrine effects of neural progenitor cells and mature sensory neurons on dermal microvascular endothelial cells. Our results suggest that neural progenitor cells and mature sensory neurons have unique secretory profiles and distinct effects on dermal microvascular endothelial cell proliferation, migration, and nitric oxide production. Neural progenitor cells and dorsal root ganglion neurons secrete different proteins related to angiogenesis. Specific to neural progenitor cells were dipeptidyl peptidase-4, IGFBP-2, pentraxin-3, serpin f1, TIMP-1, TIMP-4 and VEGF. In contrast, endostatin, FGF-1, MCP-1 and thrombospondin-2 were specific to dorsal root ganglion neurons. Microvascular endothelial cell proliferation was inhibited by dorsal root ganglion neurons but unaffected by neural progenitor cells. In contrast, microvascular endothelial cell migration in a scratch wound assay was inhibited by neural progenitor cells and unaffected by dorsal root ganglion neurons. In addition, nitric oxide production by microvascular endothelial cells was increased by dorsal root ganglion neurons but unaffected by neural progenitor cells. -- Highlights: Black-Right-Pointing-Pointer Dorsal root ganglion neurons, not neural progenitor cells, regulate microvascular endothelial cell proliferation. Black-Right-Pointing-Pointer Neural progenitor cells, not dorsal root ganglion neurons, regulate microvascular endothelial cell migration. Black-Right-Pointing-Pointer Neural progenitor cells and dorsal root ganglion neurons do not effect microvascular endothelial tube formation. Black-Right-Pointing-Pointer Dorsal root ganglion neurons, not neural progenitor cells, regulate

  7. Microvascularization on collared peccary placenta: a microvascular cast study [corrected] in late pregnancy.

    PubMed

    Santos, Tatiana Carlesso; Oliveira, Moacir Franco; Dantzer, Vibeke; Miglino, Maria Angélica

    2012-07-01

    The microvascularization of the collared peccary (Tayassu tajacu) placenta was studied by vascular casts and immunolocalization of α-smooth muscle actin and vimentin, to identify the three dimensional organization and vascular flow interrelation in the microvasculature between the maternal and fetal compartments of the placentae. The immunolocalization of vimentin in the vascular endothelium and in the smooth muscle cells of blood vessels showed indented capillaries along the uterine epithelium and the trophoblast at the sides of complementary maternal and fetal microfolds, or rugae. This confers the three-dimensional structure observed in vascular casts. On the maternal side, casts demonstrated uterine folds coated by with primary and secondary ridges, and by areolae dispersed between these ridges. The arteriole runs through the center/middle of ridges, branching at the top into a microvascular network wall in a basket-like fashion. At the base of these baskets venules were formed. On the fetal side, arterioles branched centrally in the fetal rugae into a capillary network in a bulbous form, complementary to the opposite maternal depressions forming the baskets. At the base of the bulbous protrusions, the fetal venules arise. The blood vessel orientation in the materno-fetal interface of the placentae of collared peccaries suggests a blood flow pattern of the type countercurrent to cross current. The same pattern has been reported in domestic swine demonstrating that, even after 38 million years, the Tayassuidae and Suidae families exhibit similar placental morphology, which is here characterized at the microvascular level.

  8. Self-healing materials with microvascular networks.

    PubMed

    Toohey, Kathleen S; Sottos, Nancy R; Lewis, Jennifer A; Moore, Jeffrey S; White, Scott R

    2007-08-01

    Self-healing polymers composed of microencapsulated healing agents exhibit remarkable mechanical performance and regenerative ability, but are limited to autonomic repair of a single damage event in a given location. Self-healing is triggered by crack-induced rupture of the embedded capsules; thus, once a localized region is depleted of healing agent, further repair is precluded. Re-mendable polymers can achieve multiple healing cycles, but require external intervention in the form of heat treatment and applied pressure. Here, we report a self-healing system capable of autonomously repairing repeated damage events. Our bio-inspired coating-substrate design delivers healing agent to cracks in a polymer coating via a three-dimensional microvascular network embedded in the substrate. Crack damage in the epoxy coating is healed repeatedly. This approach opens new avenues for continuous delivery of healing agents for self-repair as well as other active species for additional functionality.

  9. Phase transition of the microvascular network architecture in human pathologies.

    PubMed

    Bianciardi, Giorgio; Traversi, Claudio; Cattaneo, Ruggero; De Felice, Claudia; Monaco, Annalisa; Tosi, Gianmarco; Parrini, Stefano; Latini, Giuseppe

    2012-01-01

    We have investigated the microvascular pattern in acquired or genetic diseases in humans. The lower gingival and vestibular oral mucosa, as well as the optic nerve head, was chosen to characterize the vascular pattern complexity due to the simple accessibility and visibility Local fractal dimensions, fractal dimension of the minimum path and Lempel-Ziv complexity have been used as operational numerical tools to characterize the microvascular networks. In the normal healthy subjects microvascular networks show nonlinear values corresponding to the complexity of a diffusion limited aggregation (DLA) model, while in several acquired or genetic diseases they are approaching the ones of an invasion percolation model. PMID:23193796

  10. Microvascular temporalis fascia transfer for penile girth enhancement.

    PubMed

    Küçükçelebi, A; Ertaş, N M; Aydin, A; Eroğlu, A; Ozmen, E; Velidedeoğlu, H

    2001-07-01

    The authors report a 44-year-old man with inadequate penile girth that caused psychological problems. Using microvascular temporalis fascia transfer, they achieved satisfactory penile girth enhancement based on reliable vascularity in a single stage. PMID:11756810

  11. Protein osmotic pressure gradients and microvascular reflection coefficients.

    PubMed

    Drake, R E; Dhother, S; Teague, R A; Gabel, J C

    1997-08-01

    Microvascular membranes are heteroporous, so the mean osmotic reflection coefficient for a microvascular membrane (sigma d) is a function of the reflection coefficient for each pore. Investigators have derived equations for sigma d based on the assumption that the protein osmotic pressure gradient across the membrane (delta II) does not vary from pore to pore. However, for most microvascular membranes, delta II probably does vary from pore to pore. In this study, we derived a new equation for sigma d. According to our equation, pore-to-pore differences in delta II increase the effect of small pores and decrease the effect of large pores on the overall membrane osmotic reflection coefficient. Thus sigma d for a heteroporous membrane may be much higher than previously derived equations indicate. Furthermore, pore-to-pore delta II differences increase the effect of plasma protein osmotic pressure to oppose microvascular fluid filtration. PMID:9277520

  12. Microvascular Plasticity: Angiogenesis in Health and Disease--Preface.

    PubMed

    Secomb, Timothy W; Pries, Axel R

    2016-02-01

    This Special Topic Issue is concerned with the mechanisms that determine the structure of microvascular networks. The vast number of vessels and the highly plastic character of the microcirculation give evidence that microvascular network structures emerge as a result of responses of individual vessels and cells to the local stimuli that they experience, through a combination of angiogenesis, remodeling and pruning. The articles in this issue of Microcirculation address a range of cellular and molecular mechanisms involved in these processes. PMID:26639099

  13. Microvascular complications and diabetic retinopathy: recent advances and future implications.

    PubMed

    Barot, Megha; Gokulgandhi, Mitan R; Patel, Sulabh; Mitra, Ashim K

    2013-03-01

    Retinal microvascular alterations have been observed during diabetic retinopathy (DR) due to the retinal susceptibility towards subtle pathological alterations. Therefore, retinal microvascular pathology is essential to understand the nature of retinal degenerations during DR. In this review, the role of retinal microvasculature complications during progression of DR, along with recent efforts to normalize such alterations for better therapeutic outcome, will be underlined. In addition, current therapeutics and future directions for advancement of standard treatment for DR patients will be discussed. PMID:23464520

  14. Scalp reconstruction by microvascular free tissue transfer

    SciTech Connect

    Furnas, H.; Lineaweaver, W.C.; Alpert, B.S. )

    1990-05-01

    We report on a series of patients with scalp defects who have been treated with a variety of free flaps, spanning the era of microvascular free tissue transfer from its incipient stages to the present. Between 1971 and 1987, 18 patients underwent scalp reconstruction with 21 free flaps: 11 latissimus dorsi, 3 scalp transfers between identical twins, 3 groin, one combined latissimus dorsi and serratus anterior, two serratus anterior, and one omentum. These flaps were used to cover scalp defects resulting from burns, trauma, radiation, and tumors in patients ranging from 7 to 79 years of age. Follow-up has ranged from 3 weeks to 7 years. All of our flaps survived and covered complex defects, many of which had failed more conservative attempts at cover. One patient received radiation therapy to his flap without unfavorable sequelae. This experience began with a pioneering omental flap and includes cutaneous and muscle flaps. The latissimus dorsi is our first choice for free flap reconstruction of extensive, complicated scalp wounds because of its large size, predictable blood supply, ease of harvesting, and provision of excellent vascularity to compromised beds.

  15. Influence of silicone sheets on microvascular anastomosis.

    PubMed

    Hoang Nguyen, The; Kloeppel, Marcus; Hoehnke, Christoph; Staudenmaier, Rainer

    2008-12-01

    The use of silicone products combined with free flap transfer is well established in reconstructive surgery. We determined the risk of thrombosis as a result of direct contact between the silicone sheet and the point of microanastomosis. We performed microvascular surgery in 24 female Chinchilla Bastard rabbits weighing 3500 to 4000 g using two groups: Group 1 (n = 12), microanastomosis directly in contact with silicone sheets; and Group 2 (n = 12), microanastomosis protected by a 2 x 3 x 1-cm muscle cuff before being placed in contact with the silicone. We assessed flow-through of the microanastomosis by selective microangiography and histology at 1 and 3 weeks. All microanastomoses in Group 1 were occluded by postoperative thromboses, whereas all microanastomoses in Group 2 had adequate flow-through. Histologic analysis revealed thromboses in Group 1 formed from collagenous bundles of fiber securely attached to the intraluminal wall of the vessel. Three weeks after the procedure, these thromboses were canalized by varying small vessels. In Group 2, a slight luminal stenosis with evidence of infiltration of inflammatory cells at the microanastomosis line was observed histologically in all cases. Prefabricated flaps using silicone sheets and muscular cuffs placed around the anastomoses appear to reduce the risk of thrombosis and enhance neovascularization. PMID:18636304

  16. Systemic Microvascular Dysfunction and Inflammation after Pulmonary Particulate Matter Exposure

    PubMed Central

    Nurkiewicz, Timothy R.; Porter, Dale W.; Barger, Mark; Millecchia, Lyndell; Rao, K. Murali K.; Marvar, Paul J.; Hubbs, Ann F.; Castranova, Vincent; Boegehold, Matthew A.

    2006-01-01

    The epidemiologic association between pulmonary exposure to ambient particulate matter (PM) and cardiovascular dysfunction is well known, but the systemic mechanisms that drive this effect remain unclear. We have previously shown that acute pulmonary exposure to PM impairs or abolishes endothelium-dependent arteriolar dilation in the rat spinotrapezius muscle. The purpose of this study was to further characterize the effect of pulmonary PM exposure on systemic microvascular function and to identify local inflammatory events that may contribute to these effects. Rats were intratracheally instilled with residual oil fly ash (ROFA) or titanium dioxide at 0.1 or 0.25 mg/rat 24 hr before measurement of pulmonary and systemic microvascular responses. In vivo microscopy of the spinotrapezius muscle was used to study systemic arteriolar responses to intraluminal infusion of the Ca2+ ionophore A23187 or iontophoretic abluminal application of the adrenergic agonist phenylephrine (PHE). Leukocyte rolling and adhesion were quantified in venules paired with the studied arterioles. Histologic techniques were used to assess pulmonary inflammation, characterize the adherence of leukocytes to systemic venules, verify the presence of myeloperoxidase (MPO) in the systemic microvascular wall, and quantify systemic microvascular oxidative stress. In the lungs of rats exposed to ROFA or TiO2, changes in some bronchoalveolar lavage markers of inflammation were noted, but an indication of cellular damage was not found. In rats exposed to 0.1 mg ROFA, focal alveolitis was evident, particularly at sites of particle deposition. Exposure to either ROFA or TiO2 caused a dose-dependent impairment of endothelium-dependent arteriolar dilation. However, exposure to these particles did not affect microvascular constriction in response to PHE. ROFA and TiO2 exposure significantly increased leukocyte rolling and adhesion in paired venules, and these cells were positively identified as

  17. Systemic microvascular dysfunction and inflammation after pulmonary particulate matter exposure.

    PubMed

    Nurkiewicz, Timothy R; Porter, Dale W; Barger, Mark; Millecchia, Lyndell; Rao, K Murali K; Marvar, Paul J; Hubbs, Ann F; Castranova, Vincent; Boegehold, Matthew A

    2006-03-01

    The epidemiologic association between pulmonary exposure to ambient particulate matter (PM) and cardiovascular dysfunction is well known, but the systemic mechanisms that drive this effect remain unclear. We have previously shown that acute pulmonary exposure to PM impairs or abolishes endothelium-dependent arteriolar dilation in the rat spinotrapezius muscle. The purpose of this study was to further characterize the effect of pulmonary PM exposure on systemic microvascular function and to identify local inflammatory events that may contribute to these effects. Rats were intratracheally instilled with residual oil fly ash (ROFA) or titanium dioxide at 0.1 or 0.25 mg/rat 24 hr before measurement of pulmonary and systemic microvascular responses. In vivo microscopy of the spinotrapezius muscle was used to study systemic arteriolar responses to intraluminal infusion of the Ca2+ ionophore A23187 or iontophoretic abluminal application of the adrenergic agonist phenylephrine (PHE). Leukocyte rolling and adhesion were quantified in venules paired with the studied arterioles. Histologic techniques were used to assess pulmonary inflammation, characterize the adherence of leukocytes to systemic venules, verify the presence of myeloperoxidase (MPO) in the systemic microvascular wall, and quantify systemic microvascular oxidative stress. In the lungs of rats exposed to ROFA or TiO2, changes in some bronchoalveolar lavage markers of inflammation were noted, but an indication of cellular damage was not found. In rats exposed to 0.1 mg ROFA, focal alveolitis was evident, particularly at sites of particle deposition. Exposure to either ROFA or TiO2 caused a dose-dependent impairment of endothelium-dependent arteriolar dilation. However, exposure to these particles did not affect microvascular constriction in response to PHE. ROFA and TiO2 exposure significantly increased leukocyte rolling and adhesion in paired venules, and these cells were positively identified as

  18. Computational design of microvascular biomimetic materials

    NASA Astrophysics Data System (ADS)

    Aragon, Alejandro Marcos

    Biomimetic microvascular materials are increasingly considered for a variety of autonomic healing, cooling and sensing applications. The microvascular material of interest in this work consists of a network of hollow microchannels, with diameters as small as 10 mum, embedded in a polymeric matrix. Recent advances in the manufacturing of this new class of materials have allowed for the creation of very complex 2D and 3D structures. The computational design of such network structures, which is the focus of this work, involves a set of particular challenges, including a large number of design variables (e.g., topology of the network, number of diameters to consider and their sizes) that define the network, and a large number of multidisciplinary objective functions and constraints that drive the optimization process. The computational design tool to be developed must be capable of capturing the trade-off between the different objective and constraint functions, as, for example, networks designed for flow efficiency are likely to have a topology that is very different from those designed for structural integrity or thermal control. In this work, we propose to design these materials using Genetic Algorithms (GAs), the most common methodology within a broader category of Evolutionary Algorithms (EAs). GAs can be combined with a Pareto-selection mechanism to create Multi-Objective Genetic Algorithms (MOGAs), which enable the optimization of an arbitrary number of objective functions. As a result, a Pareto-optimal front is obtained, where all candidates are optimal solutions to the optimization problem. Adding a procedure to deal with constraints results in a powerful tool for multi-objective constrained optimization. The method allows the use of discrete variable problems and it does not require any a priori knowledge of the optimal solution. Furthermore, GAs search the entire decision space so the optimal solutions found are likely to be global. The

  19. Bariatric surgery and microvascular complications of type 2 diabetes mellitus.

    PubMed

    Jackson, Sabrina; le Roux, Carel W; Docherty, Neil G

    2014-11-01

    Metabolic dysregulation is the defining characteristic of type 2 diabetes mellitus (T2DM) and can give rise to microvascular complications, specifically retinopathy, nephropathy and neuropathy. Pharmacological targeting of risk factors for microvascular complications can yield therapeutic gains, particularly in relation to retinopathy and nephropathy. Bariatric surgery is superior to intensified pharmacotherapy in relation to glycaemic control and can remediate dyslipidaemia and hypertension. Consequently, evidence of the effect of bariatric surgery on microvascular complications is now emerging in the literature. Examination of the recent published evidence base (covering the period 2011-2014) on the effects of bariatric surgery on microvascular complications reveals further evidence supportive of the efficacy of bariatric surgery in preventing the incidence and progression of albuminuria and arresting renal functional decline. Data on retinopathy are more ambivalent potentially representing the potential in some cases for a degree of surgery associated reactive hypoglycaemia to detract from the benefits of amelioration of hyperglycaemia. A significant gap in the literature remains in relation to the effects of surgery on diabetic neuropathy. Overall, there is a pressing need for prospective randomised controlled trials examining long-term microvascular outcomes following bariatric surgery in patients with T2DM.

  20. Brain microvascular function during cardiopulmonary bypass

    SciTech Connect

    Sorensen, H.R.; Husum, B.; Waaben, J.; Andersen, K.; Andersen, L.I.; Gefke, K.; Kaarsen, A.L.; Gjedde, A.

    1987-11-01

    Emboli in the brain microvasculature may inhibit brain activity during cardiopulmonary bypass. Such hypothetical blockade, if confirmed, may be responsible for the reduction of cerebral metabolic rate for glucose observed in animals subjected to cardiopulmonary bypass. In previous studies of cerebral blood flow during bypass, brain microcirculation was not evaluated. In the present study in animals (pigs), reduction of the number of perfused capillaries was estimated by measurements of the capillary diffusion capacity for hydrophilic tracers of low permeability. Capillary diffusion capacity, cerebral blood flow, and cerebral metabolic rate for glucose were measured simultaneously by the integral method, different tracers being used with different circulation times. In eight animals subjected to normothermic cardiopulmonary bypass, and seven subjected to hypothermic bypass, cerebral blood flow, cerebral metabolic rate for glucose, and capillary diffusion capacity decreased significantly: cerebral blood flow from 63 to 43 ml/100 gm/min in normothermia and to 34 ml/100 gm/min in hypothermia and cerebral metabolic rate for glucose from 43.0 to 23.0 mumol/100 gm/min in normothermia and to 14.1 mumol/100 gm/min in hypothermia. The capillary diffusion capacity declined markedly from 0.15 to 0.03 ml/100 gm/min in normothermia but only to 0.08 ml/100 gm/min in hypothermia. We conclude that the decrease of cerebral metabolic rate for glucose during normothermic cardiopulmonary bypass is caused by interruption of blood flow through a part of the capillary bed, possibly by microemboli, and that cerebral blood flow is an inadequate indicator of capillary blood flow. Further studies must clarify why normal microvascular function appears to be preserved during hypothermic cardiopulmonary bypass.

  1. Hypercholesterolemia and microvascular dysfunction: interventional strategies.

    PubMed

    Stapleton, Phoebe A; Goodwill, Adam G; James, Milinda E; Brock, Robert W; Frisbee, Jefferson C

    2010-01-01

    Hypercholesterolemia is defined as excessively high plasma cholesterol levels, and is a strong risk factor for many negative cardiovascular events. Total cholesterol levels above 200 mg/dl have repeatedly been correlated as an independent risk factor for development of peripheral vascular (PVD) and coronary artery disease (CAD), and considerable attention has been directed toward evaluating mechanisms by which hypercholesterolemia may impact vascular outcomes; these include both results of direct cholesterol lowering therapies and alternative interventions for improving vascular function. With specific relevance to the microcirculation, it has been clearly demonstrated that evolution of hypercholesterolemia is associated with endothelial cell dysfunction, a near-complete abrogation in vascular nitric oxide bioavailability, elevated oxidant stress, and the creation of a strongly pro-inflammatory condition; symptoms which can culminate in profound impairments/alterations to vascular reactivity. Effective interventional treatments can be challenging as certain genetic risk factors simply cannot be ignored. However, some hypercholesterolemia treatment options that have become widely used, including pharmaceutical therapies which can decrease circulating cholesterol by preventing either its formation in the liver or its absorption in the intestine, also have pleiotropic effects with can directly improve peripheral vascular outcomes. While physical activity is known to decrease PVD/CAD risk factors, including obesity, psychological stress, impaired glycemic control, and hypertension, this will also increase circulating levels of high density lipoprotein and improving both cardiac and vascular function. This review will provide an overview of the mechanistic consequences of the predominant pharmaceutical interventions and chronic exercise to treat hypercholesterolemia through their impacts on chronic sub-acute inflammation, oxidative stress, and microvascular structure

  2. Free and microvascular bone grafting in the irradiated dog mandible

    SciTech Connect

    Altobelli, D.E.; Lorente, C.A.; Handren, J.H. Jr.; Young, J.; Donoff, R.B.; May, J.W. Jr.

    1987-01-01

    Microvascular and free rib grafts were placed in 4.5 cm defects in an edentate mandibular body defect 18 to 28 days after completion of 50 Gy of irradiation from a /sup 60/Co source. The animals were sacrificed from two to forty weeks postoperatively and evaluated clinically, radiographically, and histologically. There was a marked difference in the alveolar mucosal viability with the two grafts. Mucosal dehiscence was not observed over any of the microvascular grafts, but was present in seven-eighths of the free grafts. Union of the microvascular bone graft to the host bone occurred within six weeks. In contrast, after six weeks the free graft was sequestered in all the animals. An unexpected finding with both types of graft was the marked subperiosteal bone formation. This bone appeared to be derived from the host bed, stabilizing and bridging the defects bilaterally. The results suggest that radiated periosteum may play an important role in osteogenesis.

  3. Regional cutaneous microvascular flow responses during gravitational and LBNP stresses

    NASA Technical Reports Server (NTRS)

    Breit, Gregory A.; Watenpaugh, Donald E.; Ballard, Richard E.; Murthy, Gita; Hargens, Alan R.

    1993-01-01

    Due to the regional variability of local hydrostatic pressures, microvascular flow responses to gravitational stress probably vary along the length of the body. Although these differences in local autoregulation have been observed previously during whole-body tilting, they have not been investigated during application of artificial gravitational stresses, such as lower body negative pressure or high gravity centrifugation. Although these stresses can create equivalent G-levels at the feet, they result in distinct distributions of vascular transmural pressure along the length of the body, and should consequently elicit different magnitudes and distributions of microvascular response. In the present study, the effects of whole-body tilting and lower body negative pressure on the level and distribution of microvascular flows within skin along the length of the body were compared.

  4. Vascular grafts in microvascular surgery. An experimental study

    SciTech Connect

    Marrangoni, A.G.; Marcelli, G.; Culig, M.; Simone, S.T.

    1988-02-01

    The patency of microvascular grafts depends on the luminal diameter, which is determined by the amount of fibrin and platelets deposited on the intraluminal surface and the anastomotic site, and the extent of pseudointimal formation. An experimental microvascular model in rats has been developed in our laboratory using Indium-111-labeled platelets to measure the amount of deposition on grafts inserted into the infrarenal aorta. This study was designed to assess the patency rates in these grafts and the pathologic maturation as determined by light and electron microscopy. Our study suggests that substantial patency rates can be achieved in aspirin-treated rats, although there was little influence on the pathologic maturation. Indium-111 oxine-labeled platelets can be used to document platelet aggregation, and the technique can be a valuable adjunct in the study of microvascular grafts.

  5. Thermal provocation to evaluate microvascular reactivity in human skin

    PubMed Central

    2010-01-01

    With increased interest in predictive medicine, development of a relatively noninvasive technique that can improve prediction of major clinical outcomes has gained considerable attention. Current tests that are the target of critical evaluation, such as flow-mediated vasodilation of the brachial artery and pulse-wave velocity, are specific to the larger conduit vessels. However, evidence is mounting that functional changes in the microcirculation may be an early sign of globalized microvascular dysfunction. Thus development of a test of microvascular reactivity that could be used to evaluate cardiovascular risk or response to treatment is an exciting area of innovation. This mini-review is focused on tests of microvascular reactivity to thermal stimuli in the cutaneous circulation. The skin may prove to be an ideal site for evaluation of microvascular dysfunction due to its ease of access and growing evidence that changes in skin vascular reactivity may precede overt clinical signs of disease. Evaluation of the skin blood flow response to locally applied heat has already demonstrated prognostic utility, and the response to local cooling holds promise in patients in whom cutaneous disorders are present. Whether either of these tests can be used to predict cardiovascular morbidity or mortality in a clinical setting requires further evaluation. PMID:20507974

  6. Xenobiotic Particle Exposure and Microvascular Endpoints: A Call to Arms

    PubMed Central

    Stapleton, Phoebe A.; Minarchick, Valerie C.; McCawley, Michael; Knuckles, Travis L.; Nurkiewicz, Timothy R.

    2011-01-01

    Xenobiotic particles can be considered in two genres: air pollution particulate matter and engineered nanoparticles. Particle exposures can occur in the greater environment, the workplace, and our homes. The majority of research in this field has, justifiably, focused on pulmonary reactions and outcomes. More recent investigations indicate that cardiovascular effects are capable of correlating with established mortality and morbidity epidemiological data following particle exposures. While the preliminary and general cardiovascular toxicology has been defined, the mechanisms behind these effects, specifically within the microcirculation, are largely unexplored. Therefore, the purpose of this review is several fold: first, a historical background on toxicological aspects of particle research is presented. Second, essential definitions, terminology, and techniques that may be unfamiliar to the microvascular scientist will be discussed. Third, the most current concepts and hypotheses driving cardiovascular research in this field will be reviewed. Lastly, potential future directions for the microvascular scientist will be suggested. Collectively speaking, microvascular research in the particle exposure field represents far more than a “niche”. The immediate demand for basic, translational, and clinical studies is high and diverse. Microvascular scientists at all career stages are strongly encouraged to expand their research interests to include investigations associated with particle exposures. PMID:21951337

  7. Targeting brain microvascular endothelial cells: a therapeutic approach to neuroprotection against stroke

    PubMed Central

    Yu, Qi-jin; Tao, Hong; Wang, Xin; Li, Ming-chang

    2015-01-01

    Brain microvascular endothelial cells form the interface between nervous tissue and circulating blood, and regulate central nervous system homeostasis. Brain microvascular endothelial cells differ from peripheral endothelial cells with regards expression of specific ion transporters and receptors, and contain fewer fenestrations and pinocytotic vesicles. Brain microvascular endothelial cells also synthesize several factors that influence blood vessel function. This review describes the morphological characteristics and functions of brain microvascular endothelial cells, and summarizes current knowledge regarding changes in brain microvascular endothelial cells during stroke progression and therapies. Future studies should focus on identifying mechanisms underlying such changes and developing possible neuroprotective therapeutic interventions. PMID:26807131

  8. A Novel Microvascular Flow Technique: Initial Results in Thyroids.

    PubMed

    Machado, Priscilla; Segal, Sharon; Lyshchik, Andrej; Forsberg, Flemming

    2016-03-01

    To evaluate the flow imaging capabilities of a new prototype ultrasound (US) image processing technique (superb micro-vascular imaging [SMI]; Toshiba Medical Systems, Tokyo, Japan) for depiction of microvascular flow in normal thyroid tissue and thyroid nodules compared with standard color and power Doppler US imaging.Ten healthy volunteers and 22 patients, with a total of 25 thyroid nodules, scheduled for US-guided fine needle aspiration were enrolled in this prospective study. Subjects underwent US examination consisting of grayscale, color and power Doppler imaging (CDI and PDI) followed by color and monochrome SMI and pulsed Doppler. SMI is a novel, microvascular flow imaging mode implemented on the Aplio 500 US system (Toshiba). SMI uses advanced clutter suppression to extract flow signals from large to small vessels and depicts this information at high frame rates as a color overlay image or as a monochrome map of flow. Two radiologists independently scored still images and digital clips for overall flow detection, vessel branching details and noise on a visual-analog scale of 1 (worst) to 10 (best).For the volunteers SMI visualized microvasculature with significantly lower velocity than CDI and PDI (P < 0.012). In all thyroid nodules, SMI demonstrated microvascular flow with significantly higher image scores and provided better depiction of the vessel branching details compared with CDI and PDI (P < 0.0001). Clutter noise was significantly higher in monochrome SMI mode than in the other modes, including color SMI (P < 0.001).The novel SMI mode consistently improved the depiction of thyroid microvascular flow compared with standard CDI and PDI.

  9. A Novel Microvascular Flow Technique: Initial Results in Thyroids.

    PubMed

    Machado, Priscilla; Segal, Sharon; Lyshchik, Andrej; Forsberg, Flemming

    2016-03-01

    To evaluate the flow imaging capabilities of a new prototype ultrasound (US) image processing technique (superb micro-vascular imaging [SMI]; Toshiba Medical Systems, Tokyo, Japan) for depiction of microvascular flow in normal thyroid tissue and thyroid nodules compared with standard color and power Doppler US imaging.Ten healthy volunteers and 22 patients, with a total of 25 thyroid nodules, scheduled for US-guided fine needle aspiration were enrolled in this prospective study. Subjects underwent US examination consisting of grayscale, color and power Doppler imaging (CDI and PDI) followed by color and monochrome SMI and pulsed Doppler. SMI is a novel, microvascular flow imaging mode implemented on the Aplio 500 US system (Toshiba). SMI uses advanced clutter suppression to extract flow signals from large to small vessels and depicts this information at high frame rates as a color overlay image or as a monochrome map of flow. Two radiologists independently scored still images and digital clips for overall flow detection, vessel branching details and noise on a visual-analog scale of 1 (worst) to 10 (best).For the volunteers SMI visualized microvasculature with significantly lower velocity than CDI and PDI (P < 0.012). In all thyroid nodules, SMI demonstrated microvascular flow with significantly higher image scores and provided better depiction of the vessel branching details compared with CDI and PDI (P < 0.0001). Clutter noise was significantly higher in monochrome SMI mode than in the other modes, including color SMI (P < 0.001).The novel SMI mode consistently improved the depiction of thyroid microvascular flow compared with standard CDI and PDI. PMID:25900162

  10. Coronary Microvascular Dysfunction and Microvascular Angina: A Systematic Review of Therapies

    PubMed Central

    Marinescu, Mark A; Löffler, Adrián I.; Ouellette, Michelle; Smith, Lavone; Kramer, Christopher M.; Bourque, Jamieson

    2015-01-01

    Angina without coronary artery disease (CAD) has substantial morbidity and is present in 10–30% of patients undergoing angiography. Coronary microvascular dysfunction (CMD) is present in 50–65% of these patients. The optimal treatment of this cohort is undefined. We performed a systematic review to evaluate treatment strategies for objectively defined CMD in the absence of CAD. We included studies assessing therapy in human subjects with angina and coronary flow reserve (CFR) or myocardial perfusion reserve (MPR) <2.5 by positron emission tomography (PET), cardiac magnetic resonance imaging (CMR), dilution methods, or intracoronary Doppler in the absence of coronary artery stenosis ≥50% or structural heart disease. Only 8 articles met strict inclusion criteria. The articles were heterogeneous, using different treatments, end-points, and definitions of CMD. Small sample sizes severely limit the power of these studies, with an average of 11 patients per analysis. Studies evaluating, sildenafil, quinapril, estrogen, and transcutaneous electrical nerve stimulation (TENS) application demonstrated benefits in their respective endpoints. No benefit was found with L-arginine, doxazosin, pravastatin, and diltiazem. Our systematic review highlights that there is little data to support therapies for CMD. We assess the data meeting rigorous inclusion criteria and review the related but excluded literature. We additionally describe the next steps needed to address this research gap, including a standardized definition of CMD, routine assessment of CMD in studies of chest pain without obstructive CAD, and specific therapy assessment in the population with confirmed CMD. PMID:25677893

  11. Regional cutaneous microvascular flow responses during gravitational and LBNP stresses.

    PubMed

    Breit, G A; Watenpaugh, D E; Ballard, R E; Murthy, G; Hargens, A R

    1993-01-01

    The most significant cardiovascular event during the transition to microgravity is the redistribution of vascular transmural pressures that results from the loss of hydrostatic gradients along the length of the body. The well-documented effects of this redistribution include facial venous engorgement, headache, and a significant decrease in leg volume. These effects predominantly represent bulk fluid volume shifts, especially in the venous macro- and microcirculation, where volume is a direct function of pressure, related by the mechanical compliance of the vascular compartment. When considering the effect of gravitational pressure alterations on microcirculatory blood flow and volume, however, this direct monotonic relationship no longer applies. Regional microvascular perfusion is largely a function of local arteriolar tone, which is subject to a variety of central and local controls. Lower body venous pooling during application of footward gravitational stress unloads arterial and cardiopulmonary baroreceptors, increasing sympathetic arteriolar tone to elicit vasoconstriction and a general decrease in microvascular perfusion. The same stimulus also triggers an increase in the levels of circulating vasoactive hormones, such as norepinephrine and angiotensin II, further augmenting arteriolar tone. Vasomotor tone is also mediated by local mechanisms such as myogenic autoregulation and veno-arteriolar reflexes, which enhance microvascular tone in response to elevated local arteriolar and venular pressure, respectively. Due to the regional variability of local hydrostatic pressures, microvascular flow responses to gravitational stress probably vary along the length of the body. Although these differences in local autoregulation have been observed previously during whole-body tilting, they have not been investigated during application of artificial gravitational stresses, such as lower body negative pressure (LBNP) or +Gz centrifugation. Although these stresses can

  12. Photoacoustic microscopy of microvascular responses to cortical electrical stimulation

    NASA Astrophysics Data System (ADS)

    Tsytsarev, Vassiliy; Hu, Song; Yao, Junjie; Maslov, Konstantin; Barbour, Dennis L.; Wang, Lihong V.

    2011-07-01

    Advances in the functional imaging of cortical hemodynamics have greatly facilitated the understanding of neurovascular coupling. In this study, label-free optical-resolution photoacoustic microscopy (OR-PAM) was used to monitor microvascular responses to direct electrical stimulations of the mouse somatosensory cortex through a cranial opening. The responses appeared in two forms: vasoconstriction and vasodilatation. The transition between these two forms of response was observed in single vessels by varying the stimulation intensity. Marked correlation was found between the current-dependent responses of two daughter vessels bifurcating from the same parent vessel. Statistical analysis of twenty-seven vessels from three different animals further characterized the spatial-temporal features and the current dependence of the microvascular response. Our results demonstrate that OR-PAM is a valuable tool to study neurovascular coupling at the microscopic level.

  13. Multiple equilibrium states for blood flow in microvascular networks

    NASA Astrophysics Data System (ADS)

    Pollock-Muskin, Halley; Diehl, Cecilia; Mohamed, Nora; Karst, Nathan; Geddes, John; Storey, Brian

    2015-11-01

    When blood flows through a vessel bifurcation at the microvascular scale, the hematocrits in the downstream daughter vessels are generally not equal. This phenomenon, known as plasma skimming, can cause heterogeneity in the distribution of red blood cells inside a vessel network. Using established models for plasma skimming, we investigate the equilibrium states in a microvascular network with simple topologies. We find that even simple networks can have multiple equilibrium states for the flow rates and distributions of red blood cells inside the network for fixed inlet conditions. In a ladder network, we find that for certain inlet conditions the network can have 2N observable equilibrium states where N is the number of rungs in the ladder. For ladders with even just a few rungs, the complex equilibrium curves make it seemingly impossible to set the internal state of the network by controlling the inlet flows. Microfluidic experiments are being used to confirm the model predictions.

  14. Treatment of Angina Pectoris Associated with Coronary Microvascular Dysfunction.

    PubMed

    Ong, Peter; Athanasiadis, Anastasios; Sechtem, Udo

    2016-08-01

    Treatment of angina pectoris associated with coronary microvascular dysfunction is challenging as the underlying mechanisms are often diverse and overlapping. Patients with type 1 coronary microvascular dysfunction (i.e. absence of epicardial coronary artery disease and myocardial disease) should receive strict control of their cardiovascular risk factors and thus receive statins and ACE-inhibitors in most cases. Antianginal medication consists of ß-blockers and/or calcium channel blockers. Second line drugs are ranolazine and nicorandil with limited evidence. Despite individually titrated combinations of these drugs up to 30 % of patients have refractory angina. Rho-kinase inhibitors and endothelin-receptor antagonists represent potential drugs that may prove useful in these patients in the future.

  15. Impact of simulated microgravity on microvascular endothelial cell apoptosis.

    PubMed

    Kang, Chun-Yan; Zou, Lin; Yuan, Ming; Wang, Yang; Li, Tian-Zhi; Zhang, Ye; Wang, Jun-Feng; Li, Yan; Deng, Xiao-Wei; Liu, Chang-Ting

    2011-09-01

    Cardiovascular deconditioning is known to occur in astronauts exposed to microgravity. Endothelial dysfunction at microcirculatory sites might contribute to cardiovascular deconditioning induced by weightlessness. Recent studies have reported changes in the morphology and gene expression of endothelial cells exposed to conditions of simulated microgravity. The present study was aimed at examining the effects of microgravity on the apoptosis of microvascular endothelial cells and the mechanism underlying these effects. We simulated a microgravity environment and found that microgravity induced microvascular endothelial cell apoptosis and that this effect was correlated with the downregulation of the PI3K/Akt pathway, increased expression of NF-κB, and depolymerization of F-actin. These findings may provide important insights into the origin of the adverse physiological changes occurring due to exposure to microgravity conditions. PMID:21287193

  16. Impact of simulated microgravity on microvascular endothelial cell apoptosis.

    PubMed

    Kang, Chun-Yan; Zou, Lin; Yuan, Ming; Wang, Yang; Li, Tian-Zhi; Zhang, Ye; Wang, Jun-Feng; Li, Yan; Deng, Xiao-Wei; Liu, Chang-Ting

    2011-09-01

    Cardiovascular deconditioning is known to occur in astronauts exposed to microgravity. Endothelial dysfunction at microcirculatory sites might contribute to cardiovascular deconditioning induced by weightlessness. Recent studies have reported changes in the morphology and gene expression of endothelial cells exposed to conditions of simulated microgravity. The present study was aimed at examining the effects of microgravity on the apoptosis of microvascular endothelial cells and the mechanism underlying these effects. We simulated a microgravity environment and found that microgravity induced microvascular endothelial cell apoptosis and that this effect was correlated with the downregulation of the PI3K/Akt pathway, increased expression of NF-κB, and depolymerization of F-actin. These findings may provide important insights into the origin of the adverse physiological changes occurring due to exposure to microgravity conditions.

  17. Microvascular endothelium and pericytes: high yield, low passage cultures.

    PubMed

    Carson, M P; Haudenschild, C C

    1986-06-01

    Cultured microvascular endothelial cells (MEC) have become a valuable model for studies of microvascular physiology and pathology. Most current techniques involve manual removal of undesirable cell types or cloning, require one to several months, and yield high population doubling level cultures derived from a relatively small sample of the original population. We have devised a technique to more rapidly produce larger numbers of MEC. This method provided primary cultures consisting predominantly of MEC within 1 wk. The technique involves selective aspiration of gray matter from the bovine cerebral cortex followed by homogenization, sieving, enzymatic dissociation, and then dense plating (10(4) to 10(5) vessel fragments/cm2) onto gelatin- or fibronectin-coated plastic. Typical yields were 0.1 to 0.5 X 10(6) fragments/g of aspirated gray matter. The optimal culture medium for these cells was 15% equine plasma derived serum, 20% conditioned medium, 2% retinal extract, 60% fresh medium, and 500 micrograms/ml heparin. Cells attached within 24 h, well-spread colonies were present within 1 to 2 d, and cultures approached confluence within 2 to 3 d. Alkaline phosphatase staining confirmed the microvascular origin of the material plated. Morphology, Factor VIII-related antigen staining and 1,1'-dioctacecyl-3,3,3'3,-tetramethyl-indocarbocyanine perchlorate acetylated low density lipoprotein uptake suggested that MEC predominated. Cultures could be passaged and additionally purified by sequential exposure to pancreatin and trypsin-EDTA. Pancreatin selectively removed MEC colonies leaving a relatively homogeneous pericyte population. The relative ease with which such cultures can be produced should facilitate the in vitro study of brain microvascular function and may also provide insights useful for growing MEC from other vascular beds.

  18. Preventing microvascular complications in type 1 diabetes mellitus.

    PubMed

    Viswanathan, Vijay

    2015-04-01

    Patients with complications of diabetes such as retinopathy, nephropathy, and cardiovascular complications have increased hospital stay with greater economic burden. Prevention of complications should be started before the onset of type 1 diabetes mellitus (T1DM) by working on risk factors and thereafter by intervention upon confirmatory diagnosis which can prevent further damage to β-cells. The actual risk of getting microvascular complications like microalbuminuria and retinopathy progression starts at glycated hemoglobin (HbA1c) level of 7%. As per the American Diabetes Association, a new pediatric glycemic control target of HbA1c <7.5% across all ages replaces previous guidelines that had called for different targets by age. Evidence shows that prevalence of microvascular complications is greater in patients with age >20 years as compared to patients <10 years of age. Screening of these complications should be done regularly, and appropriate preventive strategies should be followed. Angiotensin converting enzyme inhibitors and angiotensin II receptor blocker reduce progression from microalbuminuria to macroalbuminuria and increase the regression rate to normoalbuminuria. Diabetic microvascular complications can be controlled with tight glycemic therapy, dyslipidemia management and blood pressure control along with renal function monitoring, lifestyle changes, including smoking cessation and low-protein diet. An integrated and personalized care would reduce the risk of development of microvascular complications in T1DM patients. The child with diabetes who receives limited care is more likely to develop long-term complications at an earlier age. Screening for subclinical complications and early interventions with intensive therapy is the need of the hour.

  19. Hemimasticatory spasm treated with microvascular decompression of the trigeminal nerve.

    PubMed

    Chon, Kyu-Hyon; Lee, Jong-Myong; Koh, Eun-Jeong; Choi, Ha-Young

    2012-09-01

    Hemimasticatory spasm is a very rare disorder of the trigeminal nerve characterized by paroxysmal involuntary contraction of the jaw-closing muscles. The mechanisms leading to hemimasticatory spasm are still unclear. Recently, injection of botulinum toxin has become the treatment of choice due to its excellent results. We report a case of a successful treatment of hemimasticatory spasm via microvascular decompression of the motor branch of the trigeminal nerve.

  20. Patterns and Variations in Microvascular Decompression for Trigeminal Neuralgia

    PubMed Central

    TODA, Hiroki; GOTO, Masanori; IWASAKI, Koichi

    2015-01-01

    Microvascular decompression (MVD) is a highly effective surgical treatment for trigeminal neuralgia (TN). Although there is little prospective clinical evidence, accumulated observational studies have demonstrated the benefits of MVD for refractory TN. In the current surgical practice of MVD for TN, there have been recognized patterns and variations in surgical anatomy and various decompression techniques. Here we provide a stepwise description of surgical procedures and relevant anatomical characteristics, as well as procedural options. PMID:25925756

  1. Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability.

    PubMed

    Salmon, Andrew H J; Satchell, Simon C

    2012-03-01

    Appreciation of the glomerular microcirculation as a specialized microcirculatory bed, rather than as an entirely separate entity, affords important insights into both glomerular and systemic microvascular pathophysiology. In this review we compare regulation of permeability in systemic and glomerular microcirculations, focusing particularly on the role of the endothelial glycocalyx, and consider the implications for disease processes. The luminal surface of vascular endothelium throughout the body is covered with endothelial glycocalyx, comprising surface-anchored proteoglycans, supplemented with adsorbed soluble proteoglycans, glycosaminoglycans and plasma constituents. In both continuous and fenestrated microvessels, this endothelial glycocalyx provides resistance to the transcapillary escape of water and macromolecules, acting as an integral component of the multilayered barrier provided by the walls of these microvessels (ie acting in concert with clefts or fenestrae across endothelial cell layers, basement membranes and pericytes). Dysfunction of any of these capillary wall components, including the endothelial glycocalyx, can disrupt normal microvascular permeability. Because of its ubiquitous nature, damage to the endothelial glycocalyx alters the permeability of multiple capillary beds: in the glomerulus this is clinically apparent as albuminuria. Generalized damage to the endothelial glycocalyx can therefore manifest as both albuminuria and increased systemic microvascular permeability. This triad of altered endothelial glycocalyx, albuminuria and increased systemic microvascular permeability occurs in a number of important diseases, such as diabetes, with accumulating evidence for a similar phenomenon in ischaemia-reperfusion injury and infectious disease. The detection of albuminuria therefore has implications for the function of the microcirculation as a whole. The importance of the endothelial glycocalyx for other aspects of vascular function

  2. Evaluation of intraoperative anticoagulants in microvascular free-flap surgery.

    PubMed Central

    Pugh, C. M.; Dennis, R. H.; Massac, E. A.

    1996-01-01

    This retrospective study evaluated anticoagulants used during surgery to determine efficacy and associated complications. The patient population was comprised of 15 patients who underwent microvascular free-flap surgery for wound coverage of the lower one third of the leg. Results indicated that the use of heparin in conjunction with other anticoagulants was associated with the development of more hematomas compared with the use of aspirin and dextran, both separately and together. PMID:8918071

  3. Reversibility of retinal microvascular changes in severe falciparum malaria.

    PubMed

    Maude, Richard J; Kingston, Hugh W F; Joshi, Sonia; Mohanty, Sanjib; Mishra, Saroj K; White, Nicholas J; Dondorp, Arjen M

    2014-09-01

    Malarial retinopathy allows detailed study of central nervous system vascular pathology in living patients with severe malaria. An adult with cerebral malaria is described who had prominent retinal whitening with corresponding retinal microvascular obstruction, vessel dilatation, increased vascular tortuosity, and blood retinal barrier leakage with decreased visual acuity, all of which resolved on recovery. Additional study of these features and their potential role in elucidating the pathogenesis of cerebral malaria is warranted.

  4. Microvascular Transport and Tumor Cell Adhesion in the Microcirculation

    PubMed Central

    Fu, Bingmei M.; Liu, Yang

    2016-01-01

    One critical step in tumor metastasis is tumor cell adhesion to the endothelium forming the microvessel wall. Understanding this step may lead to new therapeutic concepts for tumor metastasis. Vascular endothelium forming the microvessel wall and the glycocalyx layer at its surface are the principal barriers to, and regulators of the material exchange between circulating blood and body tissues. The cleft between adjacent ECs (interendothelial cleft) is the principal pathway for water and solutes transport through the microvessel wall in health. It is also suggested to be the pathway for high molecular weight plasma proteins, leukocytes and tumor cells across microvessel walls in disease. Thus the first part of the review introduced the mathematical models for water and solutes transport through the interendothelial cleft. These models, combined with the experimental results from in vivo animal studies and electron microscopic observations, are used to evaluate the role of the endothelial surface glycocalyx, the junction strand geometry in the interendothelial cleft, and the surrounding extracellular matrix and tissue cells, as the determinants of microvascular transport. The second part of the review demonstrated how the microvascular permeability, hydrodynamic factors, microvascular geometry and cell adhesion molecules affect tumor cell adhesion in the microcirculation. PMID:22476895

  5. Obesity Related Coronary Microvascular Dysfunction: From Basic to Clinical Practice

    PubMed Central

    Selthofer-Relatić, K.; Bošnjak, I.; Kibel, A.

    2016-01-01

    Obesity related coronary microvascular disease is a medical entity which is not yet fully elucidated. The pathophysiological basis of coronary microcirculatory dysfunction consists of a heterogeneous group of disorders with individual morphologic/functional/clinical presentation and prognosis. Coronary microcirculatory changes include mechanisms connected with vascular dysfunction, as well as extravascular and vasostructural changes in responses to neural, mechanical, and metabolic factors. Cardiometabolic changes that include obesity, dyslipidemia, diabetes mellitus type II, and hypertension are associated with atherosclerosis of epicardial coronary arteries and/or microvascular coronary dysfunction, with incompletely understood underlying mechanisms. In obesity, microvascular disease is mediated via adipokines/cytokines causing chronic, subclinical inflammation with (a) reduced NO-mediated dilatation, (b) changed endothelial- and smooth muscle-dependent vasoregulating mechanisms, (c) altered vasomotor control with increased sympathetic activity, and (d) obesity related hypertension with cardiomyocytes hypertrophy and impaired cardiac vascular adaptation to metabolic needs. From a clinical point of view it can present itself in acute or chronic form with different prognosis, as a practice problem for real-life diagnosis and treatment. PMID:27092288

  6. Microvascular Abnormality in Schizophrenia as Shown by Retinal Imaging

    PubMed Central

    Meier, Madeline H.; Shalev, Idan; Moffitt, Terrie E.; Kapur, Shitij; Keefe, Richard S.E.; Wong, Tien; Belsky, Daniel W.; Harrington, HonaLee; Hogan, Sean; Houts, Renate; Caspi, Avshalom; Poulton, Richie

    2013-01-01

    Objective Retinal and cerebral microvessels are structurally and functionally homologous, but, unlike cerebral microvessels, retinal microvessels can be noninvasively measured in vivo via retinal imaging. Here we test the hypothesis that individuals with schizophrenia show microvascular abnormality and evaluate the utility of retinal imaging as a tool for future schizophrenia research. Methods Participants were members of the Dunedin Study, a population-representative cohort followed from birth with 95% retention. Study members underwent retinal imaging at age 38 years. We assessed retinal arteriolar and venular caliber for all members of the cohort, including individuals who developed schizophrenia. Results Study members who developed schizophrenia were distinguished by wider retinal venules, suggesting microvascular abnormality reflective of insufficient brain oxygen supply. Analyses that controlled for confounding health conditions suggested that wider retinal venules are not simply an artifact of co-occurring health problems in schizophrenia patients. Wider venules were also associated with a dimensional measure of adult psychosis symptoms and with psychosis symptoms reported in childhood. Conclusions Findings provide initial support for the hypothesis that individuals with schizophrenia show microvascular abnormality. Moreover, results suggest that the same vascular mechanisms underlie subthreshold symptoms and clinical disorder and that these associations may begin early in life. These findings highlight the promise of retinal imaging as a tool for understanding the pathogenesis of schizophrenia. PMID:24030514

  7. Evaluation of gravimetric techniques to estimate the microvascular filtration coefficient.

    PubMed

    Dongaonkar, R M; Laine, G A; Stewart, R H; Quick, C M

    2011-06-01

    Microvascular permeability to water is characterized by the microvascular filtration coefficient (K(f)). Conventional gravimetric techniques to estimate K(f) rely on data obtained from either transient or steady-state increases in organ weight in response to increases in microvascular pressure. Both techniques result in considerably different estimates and neither account for interstitial fluid storage and lymphatic return. We therefore developed a theoretical framework to evaluate K(f) estimation techniques by 1) comparing conventional techniques to a novel technique that includes effects of interstitial fluid storage and lymphatic return, 2) evaluating the ability of conventional techniques to reproduce K(f) from simulated gravimetric data generated by a realistic interstitial fluid balance model, 3) analyzing new data collected from rat intestine, and 4) analyzing previously reported data. These approaches revealed that the steady-state gravimetric technique yields estimates that are not directly related to K(f) and are in some cases directly proportional to interstitial compliance. However, the transient gravimetric technique yields accurate estimates in some organs, because the typical experimental duration minimizes the effects of interstitial fluid storage and lymphatic return. Furthermore, our analytical framework reveals that the supposed requirement of tying off all draining lymphatic vessels for the transient technique is unnecessary. Finally, our numerical simulations indicate that our comprehensive technique accurately reproduces the value of K(f) in all organs, is not confounded by interstitial storage and lymphatic return, and provides corroboration of the estimate from the transient technique.

  8. Delayed, bilateral, non-microvascular ear replantation after violent amputation.

    PubMed

    García-Murray, E; Adán-Rivas, O; Salcido-Calzadilla, H

    2009-06-01

    Amputation of any body part is undoubtedly a traumatic experience leaving a terrible deformity, especially when the part or parts involved are visible and constitute an essential component of someone's facial whole. Bilateral ear amputation and successful subsequent replantation has been reported historically, but not in the modern surgical literature. We report the case of a 27-year-old female who was abducted and suffered a bilateral ear amputation at the hands of one of her captors to speed delivery of ransom money; the severed parts were sent to the parents approximately 2 hours after the amputation had taken place, and the girl was released some 48 hours after the ears were delivered. Microvascular replantation was attempted immediately after admission to the hospital some 2 hours after her release, but failed, and so a non-microvascular replantation was performed and was successful, after approximately 54 hours of ischaemia time. We consider this the first report of a complete bilateral, delayed, non-microvascular, successful ear replantation in a human being in the modern literature. PMID:18083644

  9. Inflammatory pathways and microvascular responses in the lung.

    PubMed

    Kuebler, Wolfgang M

    2005-01-01

    Neutrophil granulocytes constitute an important host defense mechanism, but may at the same time damage functional tissue and propagate acute organ failure. This balance is particularly vulnerable in the lung which provides a large surface area for invading pathogens and microorganisms, and simultaneously harbors a large pool of physiologically marginated neutrophils within its microvascular bed. Pathophysiological stimuli further amplify this accumulation of blood cells and promote the emigration of neutrophils into the pulmonary interstitium and the airspaces by different mechanisms depending on the pathophysiological stimulus, its route of entry into or site of production in the lung, and the time course of its action. Importantly, the pulmonary microvascular endothelium plays a key role in regulating not only sequestration and emigration of neutrophils, but by initiating the inflammatory response to a variety of diverse stimuli many of which do not directly target the circulating neutrophil, but elicit microvascular reactions by primarily acting on the endothelium. This review highlights the inflammatory process in the pulmonary microvasculature with special emphasis on the role of the pulmonary endothelium.

  10. Microvascular architecture of the filiform papillae in primates and insectivores.

    PubMed

    Okada, S; Ohta, Y; Matsukawa, N; Sugioka, S

    1993-03-01

    The microvascular architecture of filiform papillae was investigated under a scanning electron microscope in man, Japanese monkeys, common squirrel monkeys, common marmosets, common tree shrews, large Japanese moles and dwarf shrews utilizing microvascular corrosion casts. Filiform papillae were circularly arranged in primates, and each of them was supplied by a hairpin capillary loop. These papillae sometimes were aggregated. The filiform papillae of Japanese monkeys exhibited markedly locational differences on the lingual dorsum and were supplied by circularly arranged capillary loops or by an intrapapillary capillary network. Small filiform papillae were located on an epithelial eminence in the lingual radix, each of them supplied by a low and simple hairpin capillary loop. The aggregated filiform papillae of common squirrel monkeys were less frequent without any locational differences. Low filiform papillae of common marmosets and tree shrews were simpler in form, being arranged in a circle and supplied by a simple hairpin capillary loop. The filiform papillae of insectivores were not arranged in a circle. The filiform papillae of dwarf shrews were supplied by an incomplete capillary ring without a loop. With respect to species differences, the circularly arranged capillary loops in man were most complicated and highly developed. Microvascular architecture of the filiform papillae of insectivores was much simpler, different from those observed in primates.

  11. Evaluation of gravimetric techniques to estimate the microvascular filtration coefficient.

    PubMed

    Dongaonkar, R M; Laine, G A; Stewart, R H; Quick, C M

    2011-06-01

    Microvascular permeability to water is characterized by the microvascular filtration coefficient (K(f)). Conventional gravimetric techniques to estimate K(f) rely on data obtained from either transient or steady-state increases in organ weight in response to increases in microvascular pressure. Both techniques result in considerably different estimates and neither account for interstitial fluid storage and lymphatic return. We therefore developed a theoretical framework to evaluate K(f) estimation techniques by 1) comparing conventional techniques to a novel technique that includes effects of interstitial fluid storage and lymphatic return, 2) evaluating the ability of conventional techniques to reproduce K(f) from simulated gravimetric data generated by a realistic interstitial fluid balance model, 3) analyzing new data collected from rat intestine, and 4) analyzing previously reported data. These approaches revealed that the steady-state gravimetric technique yields estimates that are not directly related to K(f) and are in some cases directly proportional to interstitial compliance. However, the transient gravimetric technique yields accurate estimates in some organs, because the typical experimental duration minimizes the effects of interstitial fluid storage and lymphatic return. Furthermore, our analytical framework reveals that the supposed requirement of tying off all draining lymphatic vessels for the transient technique is unnecessary. Finally, our numerical simulations indicate that our comprehensive technique accurately reproduces the value of K(f) in all organs, is not confounded by interstitial storage and lymphatic return, and provides corroboration of the estimate from the transient technique. PMID:21346245

  12. Microfabrication of cylindrical microfluidic channel networks for microvascular research.

    PubMed

    Huang, Zhouchun; Li, Xiang; Martins-Green, Manuela; Liu, Yuxin

    2012-10-01

    Current methods for formation of microvascular channel scaffolds are limited with non-circular channel cross-sections, complicated fabrication, and less flexibility in microchannel network design. To address current limitations in the creation of engineered microvascular channels with complex three-dimensional (3-D) geometries in the shape of microvessels, we have developed a reproducible, cost-effective, and flexible micromanufacturing process combined with photolithographic reflowable photoresist and soft lithography techniques to fabricate cylindrical microchannel and networks. A positive reflowable photoresist AZ P4620 was used to fabricate a master microchannel mold with semi-circular cross-sections. By the alignment and bonding of two polydimethylsiloxane (PDMS) microchannels replicated from the master mold together, a cylindrical microchannel or microchannel network was created. Further examination of the channel dimensions and surface profiles at different branching levels showed that the shape of the microfluidic channel was well approximated by a semi-circular surface, and a multi-level, multi-depth channel network was created. In addition, a computational fluidic dynamics (CFD) model was used to simulate shear flows and corresponding pressure distributions inside of the microchannel and channel network based on the dimensions of the fabricated channels. The fabricated multi-depth cylindrical microchannel network can provide platforms for the investigation of microvascular cells growing inside of cylindrical channels under shear flows and lumen pressures, and work as scaffolds for the investigation of morphogenesis and tubulogenesis. PMID:22729782

  13. Microfabrication of cylindrical microfluidic channel networks for microvascular research.

    PubMed

    Huang, Zhouchun; Li, Xiang; Martins-Green, Manuela; Liu, Yuxin

    2012-10-01

    Current methods for formation of microvascular channel scaffolds are limited with non-circular channel cross-sections, complicated fabrication, and less flexibility in microchannel network design. To address current limitations in the creation of engineered microvascular channels with complex three-dimensional (3-D) geometries in the shape of microvessels, we have developed a reproducible, cost-effective, and flexible micromanufacturing process combined with photolithographic reflowable photoresist and soft lithography techniques to fabricate cylindrical microchannel and networks. A positive reflowable photoresist AZ P4620 was used to fabricate a master microchannel mold with semi-circular cross-sections. By the alignment and bonding of two polydimethylsiloxane (PDMS) microchannels replicated from the master mold together, a cylindrical microchannel or microchannel network was created. Further examination of the channel dimensions and surface profiles at different branching levels showed that the shape of the microfluidic channel was well approximated by a semi-circular surface, and a multi-level, multi-depth channel network was created. In addition, a computational fluidic dynamics (CFD) model was used to simulate shear flows and corresponding pressure distributions inside of the microchannel and channel network based on the dimensions of the fabricated channels. The fabricated multi-depth cylindrical microchannel network can provide platforms for the investigation of microvascular cells growing inside of cylindrical channels under shear flows and lumen pressures, and work as scaffolds for the investigation of morphogenesis and tubulogenesis.

  14. Effect of Qi-regulating,Phlegm-resolving,and Blood-promoting Prescription on Rat Coronary Microvascular Thrombosis and Coronary Microvascular Occlusion.

    PubMed

    2016-06-10

    Objective To explore the effect of qi-regulating,phlegm-resolving,and blood-promoting prescription on coronary microvascular thrombosis and coronary microvascular occlusion in rat models. Methods Totally 125 healthy clean-grade male SD rats weighing (300±25) g were sequentially numbered and then randomly divided into treatment group (n=60),control group (n=60) and blank group (n=5).Rats in the treatment group and control group received apical left ventricular injection of sodium laurate to establish rat models of coronary microvascular thrombosis. Then,rats in the control group were given distilled water by gavage one day before operation and after surgery. In contrast,rats in the treatment group were given qi-regulating,phlegm-resolving,and blood-promoting prescription by gavage one day before operation and after surgery. Five rats from both treatment group and control group were killed at each of six time points (1 hour,24th hour,7th day,14th day,21th day,and 28th day),and the myocardium specimens were harvested. The 5 rats in the blank group did not receive any special treatment and were given normal feeding;in the 28th day,they were sacrificed to obtain the myocardial specimens. Pathological sections of rat myocardial tissues were made to observe and compare the degrees of coronary microvascular thrombosis and coronary microvascular obstruction. Results In the treatment group and the control group,coronary microvascular thrombosis occurred 1 hour after apical sodium laurate injection and reached the peak at the 24th hour. Compared with the blank group,the treatment group and the control group showed different degree of coronary microvascular obstruction. Comparison between the treatment group and the control group at each time point showed that the coronary microvascular thrombosis in the treatment group was significantly lower than that in the control group (P<0.05 or P<0.01).The severity of coronary

  15. TUBERCULOSIS COMO ENFERMEDAD OCUPACIONAL

    PubMed Central

    Mendoza-Ticona, Alberto

    2014-01-01

    Existe evidencia suficiente para declarar a la tuberculosis como enfermedad ocupacional en diversos profesionales especialmente entre los trabajadores de salud. En el Perú están normados y reglamentados los derechos laborales inherentes a la tuberculosis como enfermedad ocupacional, como la cobertura por discapacidad temporal o permanente. Sin embargo, estos derechos aún no han sido suficientemente socializados. En este trabajo se presenta información sobre el riesgo de adquirir tuberculosis en el lugar de trabajo, se revisan las evidencias para declarar a la tuberculosis como enfermedad ocupacional en trabajadores de salud y se presenta la legislación peruana vigente al respecto. PMID:22858771

  16. Dietary nitrite prevents hypercholesterolemic microvascular inflammation and reverses endothelial dysfunction.

    PubMed

    Stokes, Karen Y; Dugas, Tammy R; Tang, Yaoping; Garg, Harsha; Guidry, Eric; Bryan, Nathan S

    2009-05-01

    The nitrite anion is an endogenous product of mammalian nitric oxide (NO) metabolism, a key intermediate in the nitrogen cycle in plants, and a constituent of many foods. Research over the past 6 years has revealed surprising biological and cytoprotective activity of this anion. Hypercholesterolemia causes a proinflammatory phenotype in the microcirculation. This phenotype appears to result from a decline in NO bioavailability that results from a reduction in NO biosynthesis, inactivation of NO by superoxide, or both. Since nitrite has been shown to be potently cytoprotective and restore NO biochemical homeostasis, we investigated if supplemental nitrite could attenuate microvascular inflammation caused by a high cholesterol diet. C57Bl/6J mice were fed either a normal diet or a high cholesterol diet for 3 wk to induce microvascular inflammation. Mice on the high cholesterol diet received either nitrite-free drinking water or supplemental nitrite at 33 or 99 mg/l ad libitum in their drinking water. The results from this investigation reveal that mice fed a cholesterol-enriched diet exhibited significantly elevated leukocyte adhesion to and emigration through the venular endothelium as well as impaired endothelium-dependent relaxation in arterioles. Administration of nitrite in the drinking water inhibited the leukocyte adhesion and emigration and prevented the arteriolar dysfunction. This was associated with sparing of reduced tetrahydrobiopterin and decreased levels of C-reactive protein. These data reveal novel anti-inflammatory properties of nitrite and implicate the use of nitrite as a new natural therapy for microvascular inflammation and endothelial dysfunction associated with hypercholesterolemia.

  17. Skeletal muscle microvascular function in girls with Turner syndrome

    PubMed Central

    West, Sarah L.; O'Gorman, Clodagh S.; Elzibak, Alyaa H.; Caterini, Jessica; Noseworthy, Michael D.; Rayner, Tammy; Hamilton, Jill; Wells, Greg D.

    2014-01-01

    Background Exercise intolerance is prevalent in individuals with Turner Syndrome (TS). We recently demonstrated that girls with TS have normal aerobic but altered skeletal muscle anaerobic metabolism compared to healthy controls (HC). The purpose of this study was to compare peripheral skeletal muscle microvascular function in girls with TS to HC after exercise. We hypothesized that girls with TS would have similar muscle blood-oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) signal responses during recovery from exercise compared to HC. Methods Thirteen TS participants and 8 HC completed testing. BOLD MRI was used to measure skeletal muscle microvascular response during 60 second recovery, following 60 s of exercise at 65% of maximal workload. Exercise and recovery were repeated four times, and the BOLD signal time course was fit to a four-parameter sigmoid function. Results Participants were 13.7 ± 3.1 years old and weighed 47.9 ± 14.6 kg. The mean change in BOLD signal intensity following exercise at the end of recovery, the mean response time of the function/the washout of deoxyhemoglobin, and the mean half-time of recovery were similar between the TS and HC groups. Conclusions Our results demonstrate that compared to HC, peripheral skeletal muscle microvascular function following exercise in girls with TS is not impaired. General significance This study supports the idea that the aerobic energy pathway is not impaired in children with TS in response to submaximal exercise. Other mechanisms are likely responsible for exercise intolerance in TS; this needs to be further investigated. PMID:26676172

  18. Antiproliferative effect of elevated glucose in human microvascular endothelial cells

    NASA Technical Reports Server (NTRS)

    Kamal, K.; Du, W.; Mills, I.; Sumpio, B. E.

    1998-01-01

    Diabetic microangiopathy has been implicated as a fundamental feature of the pathological complications of diabetes including retinopathy, neuropathy, and diabetic foot ulceration. However, previous studies devoted to examining the deleterious effects of elevated glucose on the endothelium have been performed largely in primary cultured cells of macrovessel origin. Difficulty in the harvesting and maintenance of microvascular endothelial cells in culture have hindered the study of this relevant population. Therefore, the objective of this study was to characterize the effect of elevated glucose on the proliferation and involved signaling pathways of an immortalized human dermal microvascular endothelial cell line (HMEC-1) that possess similar characteristics to their in vivo counterparts. Human dermal microvascular endothelial cells (HMEC-1) were grown in the presence of normal (5 mM) or high D-glucose (20 mM) for 14 days. The proliferative response of HMEC-1 was compared under these conditions as well as the cAMP and PKC pathways by in vitro assays. Elevated glucose significantly inhibited (P < 0.05) HMEC-1 proliferation after 7, 10, and 14 days. This effect was not mimicked by 20 mM mannitol. The antiproliferative effect was more pronounced with longer exposure (1-14 days) to elevated glucose and was irreversible 4 days after a 10-day exposure. The antiproliferative effect was partially reversed in the presence of a PKA inhibitor, Rp-cAMP (10-50 microM), and/or a PKC inhibitor, Calphostin C (10 nM). HMEC-1 exposed to elevated glucose (20 mM) for 14 days caused an increase in cyclic AMP accumulation, PKA, and PKC activity but was not associated with the activation of downstream events such as CRE and AP-1 binding activity. These data support the hypothesis that HMEC-1 is a suitable model to study the deleterious effects of elevated glucose on microvascular endothelial cells. Continued studies with HMEC-1 may prove advantageous in delineation of the molecular

  19. Quantifying Therapeutic and Diagnostic Efficacy in 2D Microvascular Images

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, Patricia; Vickerman, Mary B.; Keith, Patricia A.

    2009-01-01

    VESGEN is a newly automated, user-interactive program that maps and quantifies the effects of vascular therapeutics and regulators on microvascular form and function. VESGEN analyzes two-dimensional, black and white vascular images by measuring important vessel morphology parameters. This software guides the user through each required step of the analysis process via a concise graphical user interface (GUI). Primary applications of the VESGEN code are 2D vascular images acquired as clinical diagnostic images of the human retina and as experimental studies of the effects of vascular regulators and therapeutics on vessel remodeling.

  20. Alternative venous outflow vessels in microvascular breast reconstruction.

    PubMed

    Mehrara, Babak J; Santoro, Timothy; Smith, Andrew; Arcilla, Eric A; Watson, James P; Shaw, William W; Da Lio, Andrew L

    2003-08-01

    The lack of adequate recipient vessels often complicates microvascular breast reconstruction in patients who have previously undergone mastectomy and irradiation. In addition, significant size mismatch, particularly in the outflow veins, is an important contributor to vessel thrombosis and flap failure. The purpose of this study was to review the authors' experience with alternative venous outflow vessels for microvascular breast reconstruction. In a retrospective analysis of 1278 microvascular breast reconstructions performed over a 10-year period, the authors identified all patients in whom the external jugular or cephalic veins were used as the outflow vessels. Patient demographics, flap choice, the reasons for the use of alternative venous drainage vessels, and the incidence of microsurgical complications were analyzed. The external jugular was used in 23 flaps performed in procedures with 22 patients. The superior gluteal and transverse rectus abdominis musculocutaneous (TRAM) flaps were used in the majority of the cases in which the external jugular vein was used (72 percent gluteal, 20 percent TRAM flap). The need for alternative venous outflow vessels was usually due to a significant vessel size mismatch between the superior gluteal and internal mammary veins (74 percent). For three of the external jugular vein flaps (13 percent), the vein was used for salvage after the primary draining vein thrombosed, and two of three flaps in these cases were eventually salvaged. In three patients, the external jugular vein thrombosed, resulting in two flap losses, while the third was salvaged using the cephalic vein. A total of two flaps were lost in the external jugular vein group. The cephalic vein was used in 11 flaps (TRAM, 64.3 percent; superior gluteal, 35.7 percent) performed in 11 patients. In five patients (54.5 percent), the cephalic vein was used to salvage a flap after the primary draining vein thrombosed; the procedure was successful in four cases. In three

  1. Microvascular alterations and the role of complement in dermatomyositis.

    PubMed

    Lahoria, Rajat; Selcen, Duygu; Engel, Andrew G

    2016-07-01

    Different mechanisms have been proposed to explain the pathological basis of perifascicular muscle fibre atrophy in dermatomyositis. These include ischaemia due to immune-mediated microvascular injury, enhanced expression of type 1 interferon-induced gene transcripts in perifascicular capillaries and muscle fibres, and occlusion of larger perimysial blood vessels. Microvascular complement deposition is a feature of dermatomyositis pathology but the trigger for complement activation, the predominant complement pathway involved, or its role in the pathogenesis of the disease, has not been clearly defined. In the first step of this study we examined the density of capillaries and transverse vessels and searched for occlusion or depletion of larger perimysial blood vessels in 10 patients with dermatomyositis. This revealed an invariable association of perifascicular atrophy with capillary and transverse vessel depletion. The capillary and transverse vessel densities in non-atrophic fibre regions were not significantly different from those in muscle specimens of 10 age-matched controls. Next, in the same 10, as well as in 40 additional dermatomyositis patients, we searched for vascular deposits of IgG, IgM, and the C5b-9 complement membrane attack complex. Thirty-one of 50 dermatomyositis specimens contained C5b-9 reactive endomysial microvessels but none of these or other vessels reacted for IgG. Ten of 50 specimens harboured IgM-positive capillaries but only a few of these reacted for C5b-9. Finally, we analysed and compared different pathways of complement activation in dermatomyositis, lupus nephritis, and necrotic muscle fibres in Duchenne dystrophy. In lupus nephritis, C5-b9 deposits co-localized with IgG, IgM, C1q, and C4d, consistent with immune complex dependent activation of the classical complement pathway. In both dermatomyositis and Duchenne dystrophy, C5-b9 deposits co-localized with C1q and C4d and rarely with IgM indicating activation of the classical

  2. Globular Adiponectin Enhances Muscle Insulin Action via Microvascular Recruitment and Increased Insulin Delivery

    PubMed Central

    Zhao, Lina; Chai, Weidong; Fu, Zhuo; Dong, Zhenhua; Aylor, Kevin W.; Barrett, Eugene J.; Cao, Wenhong; Liu, Zhenqi

    2014-01-01

    Rationale Adiponectin enhances insulin action and induces nitric oxide–dependent vasodilatation. Insulin delivery to muscle microcirculation and transendothelial transport are 2 discrete steps that limit insulin's action. We have shown that expansion of muscle microvascular surface area increases muscle insulin delivery and action. Objective To examine whether adiponectin modulates muscle microvascular recruitment thus insulin delivery and action in vivo. Methods and Results Overnight fasted adult male rats were studied. We determined the effects of adiponectin on muscle microvascular recruitment, using contrast-enhanced ultrasound, on insulin-mediated microvascular recruitment and whole-body glucose disposal, using contrast-enhanced ultrasound and insulin clamp, and on muscle insulin clearance and uptake with 125I-insulin. Globular adiponectin potently increased muscle microvascular blood volume without altering microvascular blood flow velocity, leading to a significantly increased microvascular blood flow. This was paralleled by a ≈30% to 40% increase in muscle insulin uptake and clearance, and ≈30% increase in insulin-stimulated whole-body glucose disposal. Inhibition of endothelial nitric oxide synthase abolished globular adiponectin-mediated muscle microvascular recruitment and insulin uptake. In cultured endothelial cells, globular adiponectin dose-dependently increased endothelial nitric oxide synthase phosphorylation but had no effect on endothelial cell internalization of insulin. Conclusions Globular adiponectin increases muscle insulin uptake by recruiting muscle microvasculature, which contributes to its insulin-sensitizing action. PMID:23459195

  3. Microvascular Perfusion and Intramuscular Temperature of the Calf During Cooling

    PubMed Central

    Selkow, Noelle M; Day, Carly; Liu, Zhenqi; Hart, Joseph M; Hertel, Jay; Saliba, Susan A

    2011-01-01

    Purpose To examine how the microvascularity of the gastrocnemius changed after a cryotherapy intervention based on subcutaneous tissue thickness. A secondary purpose was to compare intramuscular temperature change to subcutaneous tissue thickness. Methods This was a single-blinded crossover study; each subject received both conditions (cryotherapy or sham). Subjects had baseline measurements of blood flow, blood volume, and intramuscular temperature recorded at 1cm into the muscle belly of the medial gastrocnemius. The randomized condition was applied for 10, 25, 40, or 60min depending on subcutaneous tissue thickness. Immediate post treatment microvascular measures were taken. After a designated rewarm period, again based on subcutaneous tissue thickness, measurements were retaken. At least 48 hours separated the two conditions. Results There were significant condition by time interactions for blood flow (p=0.01), blood volume (p=0.022), and intramuscular temperature (p<0.001). For blood flow and volume, the cryotherapy condition maintained baseline levels, while the sham condition increased at immediate-post treatment and rewarm. For intramuscular temperature, the cryotherapy condition caused a decrease in intramuscular temperature from baseline compared to no change in the sham condition from baseline. Intramuscular temperature change was significantly correlated to subcutaneous tissue thickness (r=.49; p=0.05). Conclusions Cryotherapy did not decrease blood flow and blood volume from resting levels, even though the intramuscular temperature decreased. An intramuscular change of 7–9°C may not be cold enough to cause local vasoconstriction. PMID:21988932

  4. Mechanisms for microvascular damage induced by ultrasound-activated microbubbles

    NASA Astrophysics Data System (ADS)

    Chen, Hong; Brayman, Andrew A.; Evan, Andrew P.; Matula, Thomas J.

    2012-10-01

    To provide insight into the mechanisms of microvascular damage induced by ultrasound-activated microbubbles, experimental studies were performed to correlate microvascular damage to the dynamics of bubble-vessel interactions. High-speed photomicrography was used to record single microbubbles interacting with microvessels in ex vivo tissue, under the exposure of short ultrasound pulses with a center frequency of 1 MHz and peak negative pressures (PNP) ranging from 0.8-4 MPa. Vascular damage associated with observed bubble-vessel interactions was either indicated directly by microbubble extravasation or examined by transmission electron microscopy (TEM) analyses. As observed previously, the high-speed images revealed that ultrasound-activated microbubbles could cause distention and invagination of adjacent vessel walls, and could form liquid jets in microvessels. Vessel distention, invagination, and liquid jets were associated with the damage of microvessels whose diameters were smaller than those of maximally expanded microbubbles. However, vessel invagination appeared to be the dominant mechanism for the damage of relative large microvessels.

  5. Mechanisms for microvascular damage induced by ultrasound-activated microbubbles

    SciTech Connect

    Chen Hong; Brayman, Andrew A.; Evan, Andrew P.; Matula, Thomas J.

    2012-10-03

    To provide insight into the mechanisms of microvascular damage induced by ultrasound-activated microbubbles, experimental studies were performed to correlate microvascular damage to the dynamics of bubble-vessel interactions. High-speed photomicrography was used to record single microbubbles interacting with microvessels in ex vivo tissue, under the exposure of short ultrasound pulses with a center frequency of 1 MHz and peak negative pressures (PNP) ranging from 0.8-4 MPa. Vascular damage associated with observed bubble-vessel interactions was either indicated directly by microbubble extravasation or examined by transmission electron microscopy (TEM) analyses. As observed previously, the high-speed images revealed that ultrasound-activated microbubbles could cause distention and invagination of adjacent vessel walls, and could form liquid jets in microvessels. Vessel distention, invagination, and liquid jets were associated with the damage of microvessels whose diameters were smaller than those of maximally expanded microbubbles. However, vessel invagination appeared to be the dominant mechanism for the damage of relative large microvessels.

  6. Microvascular responsiveness in obesity: implications for therapeutic intervention

    PubMed Central

    Bagi, Zsolt; Feher, Attila; Cassuto, James

    2012-01-01

    Obesity has detrimental effects on the microcirculation. Functional changes in microvascular responsiveness may increase the risk of developing cardiovascular complications in obese patients. Emerging evidence indicates that selective therapeutic targeting of the microvessels may prevent life-threatening obesity-related vascular complications, such as ischaemic heart disease, heart failure and hypertension. It is also plausible that alterations in adipose tissue microcirculation contribute to the development of obesity. Therefore, targeting adipose tissue arterioles could represent a novel approach to reducing obesity. This review aims to examine recent studies that have been focused on vasomotor dysfunction of resistance arteries in obese humans and animal models of obesity. Particularly, findings in coronary resistance arteries are contrasted to those obtained in other vascular beds. We provide examples of therapeutic attempts, such as use of statins, ACE inhibitors and insulin sensitizers to prevent obesity-related microvascular complications. We further identify some of the important challenges and opportunities going forward. LINKED ARTICLES This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3 PMID:21797844

  7. Tissue viability imaging for assessment of microvascular events

    NASA Astrophysics Data System (ADS)

    O'Doherty, Jim; Nilsson, Gert E.; Henricson, Joakim; Sjoberg, Folke; Leahy, Martin J.

    2005-08-01

    A new technique for the investigation of microvascular tissue blood concentration is presented, based on the method of polarisation spectroscopy of blood in superficial skin tissue. Linearly polarised light incident on the skin is partly reflected by the surface layers, and partly backscattered from the dermal tissue. Use of orthogonal polarisation filters over both a light source and a CCD suppresses the reflections from the surface, and only the depolarised light backscattered from the dermal matrix reaches the CCD array. By separating the colour planes of an image acquired in this manner and applying a dedicated image processing algorithm, spectroscopic information about the amount of red blood cells (RBCs) in the underlying area of tissue can be discovered. The algorithm incorporates theory that utilises the differences in light absorption of RBCs and dermal tissue in the red and green wavelength regions. In vitro fluid models compare well to computer simulations in describing a linear relationship between output signal (called TiViindex) and RBC concentration in the physiological range of 0%-4%. In vivo evaluation of the technique via transepidermal application of acetylcholine by iontophoresis displayed a heterogeneity pattern of vasodilation, which is typical of the vasoactive agent. Extension of the technique to capture and process continuous real-time data creates a new possibility of online real-time image processing. Application of tissue viability (TiVi) imaging include skin care products and drug development, as well as investigations of microvascular angiogenesis.

  8. Effects of hyperoxia on microvascular cells in vitro

    SciTech Connect

    D'Amore, P.A.; Sweet, E.

    1987-02-01

    Microvascular cells are most vulnerable to direct oxygen damage. Using an in vitro model system we have investigated the effect of elevated oxygen on the proliferation, morphology, and integrity of microvascular endothelial cells (EC) and pericytes. Cultivation of these cells at oxygen concentrations of 40% for 1 wk resulted in the inhibition of EC proliferation but had no effect on the growth of the pericytes. Similarly, hyperoxia induced a dramatic change in the shape of the EC, increasing their spread area by close to six-fold. Under the same conditions, the spread area of the pericytes was unaffected. To understand the effect of the hyperoxic treatment on the cells, the integrity of various membrane systems was assessed. /sup 51/Cr release was used to monitor plasma membrane integrity. There was no difference in chromium release by EC and pericytes over the 7 d of growth under normoxic and hyperoxic conditions. Mitochondrial integrity was examined by staining the cells with Rhodamine 123, which is selectively accumulated by the mitochondria. The staining pattern of the mitochondria of both EC and pericytes was altered by growth in the elevated oxygen. Finally, the lysosomes were visualized using acridine orange. The acridine orange staining pattern revealed enlarged and perinuclear lysosomes in the EC but no change in the pericyte lysosomal staining pattern. Thus, the cells of the microvasculature seem to be differentially affected by hyperoxia, a fact that may be significant in the etiology of reperfusion injury, ischemic disease, and pathologies associated with prematurity.

  9. Modulation of cerebral microvascular permeability by endothelial nicotinic acetylcholine receptors.

    PubMed

    Hawkins, Brian T; Egleton, Richard D; Davis, Thomas P

    2005-07-01

    Nicotine increases the permeability of the blood-brain barrier in vivo. This implies a possible role for nicotinic acetylcholine receptors in the regulation of cerebral microvascular permeability. Expression of nicotinic acetylcholine receptor subunits in cerebral microvessels was investigated with immunofluorescence microscopy. Positive immunoreactivity was found for receptor subunits alpha3, alpha5, alpha7, and beta2, but not subunits alpha4, beta3, or beta4. Blood-brain barrier permeability was assessed via in situ brain perfusion with [14C]sucrose. Nicotine increased the rate of sucrose entry into the brain from 0.3 +/- 0.1 to 1.1 +/- 0.2 microl.g(-1).min(-1), as previously described. This nicotine-induced increase in blood-brain barrier permeability was significantly attenuated by both the blood-brain barrier-permeant nicotinic antagonist mecamylamine and the blood-brain barrier-impermeant nicotinic antagonist hexamethonium to 0.5 +/- 0.2 and 0.3 +/- 0.2 microl.g(-1).min(-1), respectively. These data suggest that nicotinic acetylcholine receptors expressed on the cerebral microvascular endothelium mediate nicotine-induced changes in blood-brain barrier permeability.

  10. Optically measured microvascular blood flow contrast of malignant breast tumors.

    PubMed

    Choe, Regine; Putt, Mary E; Carlile, Peter M; Durduran, Turgut; Giammarco, Joseph M; Busch, David R; Jung, Ki Won; Czerniecki, Brian J; Tchou, Julia; Feldman, Michael D; Mies, Carolyn; Rosen, Mark A; Schnall, Mitchell D; DeMichele, Angela; Yodh, Arjun G

    2014-01-01

    Microvascular blood flow contrast is an important hemodynamic and metabolic parameter with potential to enhance in vivo breast cancer detection and therapy monitoring. Here we report on non-invasive line-scan measurements of malignant breast tumors with a hand-held optical probe in the remission geometry. The probe employs diffuse correlation spectroscopy (DCS), a near-infrared optical method that quantifies deep tissue microvascular blood flow. Tumor-to-normal perfusion ratios are derived from thirty-two human subjects. Mean (95% confidence interval) tumor-to-normal ratio using surrounding normal tissue was 2.25 (1.92-2.63); tumor-to-normal ratio using normal tissues at the corresponding tumor location in the contralateral breast was 2.27 (1.94-2.66), and using normal tissue in the contralateral breast was 2.27 (1.90-2.70). Thus, the mean tumor-to-normal ratios were significantly different from unity irrespective of the normal tissue chosen, implying that tumors have significantly higher blood flow than normal tissues. Therefore, the study demonstrates existence of breast cancer contrast in blood flow measured by DCS. The new, optically accessible cancer contrast holds potential for cancer detection and therapy monitoring applications, and it is likely to be especially useful when combined with diffuse optical spectroscopy/tomography. PMID:24967878

  11. Angina pectoris in women: focus on microvascular disease.

    PubMed

    Zuchi, Cinzia; Tritto, Isabella; Ambrosio, Giuseppe

    2013-02-20

    Ischemic heart disease (IHD) is the leading cause of death among women in Western countries, and it is associated with higher morbidity and mortality than in men. Nevertheless, IHD in women remains underdiagnosed and undertreated, and the misperception that females are "protected" against cardiovascular disease leads to underestimation of their cardiovascular risk; instead, women with chest pain have a high risk of cardiovascular events. Women suffering from angina pectoris tend to have different characteristics compared to men, with a high prevalence of non-significant coronary artery disease. Angina in women is more commonly microvascular in origin than in men, and therefore standard diagnostic algorithms may be suboptimal for women. This different pathophysiology impacts clinical management of IHD in women. While response to medical therapy may differ in women, they are scarcely represented in clinical trials. Therefore, solid data in terms of gender efficacy of antianginal drugs are lacking, and particularly when angina is microvascular in origin women often continue to be symptomatic despite maximal therapy with classical antianginal drugs. Recently, new molecules have shown promising results in women. In conclusion, women with angina are a group of patients in whom it seems appropriate to concentrate efforts aimed at reducing morbidity and improving quality of life.

  12. Albumin microvascular leakage in brains with diabetes mellitus.

    PubMed

    Fujihara, Ryuji; Chiba, Yoichi; Nakagawa, Toshitaka; Nishi, Nozomu; Murakami, Ryuta; Matsumoto, Koichi; Kawauchi, Machi; Yamamoto, Tetsuji; Ueno, Masaki

    2016-09-01

    Their aim was to examine whether microvascular leakage of endogenous albumin, a representative marker for blood-brain barrier (BBB) damage, was induced in the periventricular area of diabetic db/db mice because periventricular white matter hyperintensity formation in magnetic resonance images was accelerating in elderly patients with diabetes mellitus. Using light and electron microscopes, and semi-quantitative analysis techniques, immunoreactivity of endogenous albumin, indicating vascular permeability, was examined in the periventricular area and spinal cord of db/db mice and db/+m control mice. Greater immunoreactivity of albumin was observed in the vessel wall of the periventricular area of db/db mice than in controls. Additionally, weak immunoreactivity was observed in the spinal cord of both db/db mice and controls. The number of gold particles, indicating immunoreactivity of albumin, in the perivascular area of db/db mice was significantly higher than that of control mice, but there was no significant difference in the number of particles in the spinal cord between db/db mice and controls. These findings suggest that albumin microvascular leakage, or BBB breakdown, is induced in the periventricular area of diabetic mice. Microsc. Res. Tech. 79:833-837, 2016. © 2016 Wiley Periodicals, Inc. PMID:27333535

  13. Directed assembly of three-dimensional microvascular networks

    NASA Astrophysics Data System (ADS)

    Therriault, Daniel

    Three-dimensional (3-D) microvascular networks with pervasive, interconnected channels less than 300 mum in diameter may find widespread application in microfluidic devices, biotechnology, sensors, and autonomic healing materials. Although microchannel arrays are readily constructed in two-dimensions by photolithographic or soft lithographic techniques, their construction in three-dimensions remains a challenging problem. The development of a microfabrication method to build 3-D microvascular networks based on direct-write assembly is described is this thesis. The method is based on the robotic deposition of a fugitive organic ink to form a free-standing scaffold structure. Secondary infiltration of a structural resin followed by setting of the matrix and removal of the scaffold yields an embedded pervasive network of smooth cylindrical channels (˜10--500 mum) with defined connectivity. Rheological and other material properties studies of fugitive organic ink were performed in order to identify the critical characteristics required for successful deposition of 3-D scaffolds by direct-write assembly. Guided by the results of these studies, several new ink formulations were screened for improved deposition performance. The most successful of these inks (40wt% microcrystalline wax, 60wt% petroleum jelly) showed excellent deposition and had an equilibrium modulus at room temperature (G 'eq ˜ 7.70 kPa 1 Hz) nearly two orders of magnitude higher than the original ink. The optimized ink was used to successfully build thick (i.e., ˜100 layers) scaffold structures at room temperature with negligible time-dependent deformation post-deposition. Secondary infiltration of the resin was accomplished at room temperature while maintaining the scaffold architecture. The optimized ink was also successfully extruded through small micronozzles (1 mum). The construction of 3-D microvascular networks enables microfluidic devices with unparallel geometric complexity. In one example, a

  14. Microvascular Injury in Ketamine-Induced Bladder Dysfunction

    PubMed Central

    Lin, Chih-Chieh; Lin, Alex Tong-Long; Yang, An-Hang; Chen, Kuang-Kuo

    2016-01-01

    The pathogenesis of ketamine-induced cystitis (KC) remains unclear. In this study, bladder microvascular injury was investigated as a possible contributing mechanism. A total of 36 KC patients with exposure to ketamine for more than 6 months, and 9 control subjects, were prospectively recruited. All participants completed questionnaires, including the O’Leary–Sant interstitial cystitis symptom index (ICSI) and the interstitial cystitis problem index (ICPI). All KC patients received a urodynamic study and radiological exams. Bladder tissues were obtained from cystoscopic biopsies in the control group and after hydrodistention in the KC group. Double-immunofluorescence staining of N-methyl-d-aspartate receptor subunit 1 (NMDAR1) and the endothelial marker, cluster of differentiation 31 (CD31), was performed to reveal the existence of NMDAR1 on the endothelium. Electron microscopy (EM) was applied to assess the microvascular change in the urinary bladder and to measure the thickening of the basement membrane (BM). A proximity ligation assay (PLA) was used to quantify the co-localization of the endothelial CD31 receptor and the mesenchymal marker [fibroblast-specific protein 1 (FSP-1)]. The Mann–Whitney U test and Spearman’s correlation coefficient were used for statistical analysis. The mean ICSI [14.38 (± 4.16)] and ICPI [12.67 (± 3.54)] scores of the KC group were significantly higher than those (0 and 0, respectively) of the control group (both p < 0.001). The KC patients had decreasing cystometric bladder capacity (CBC) with a mean volume of 65.38 (± 48.67) mL. NMDAR1 was expressed on endothelial cells in both groups under immunofluorescence staining. Moreover, KC patients had significant BM duplication of microvessels in the mucosa of the urinary bladder under EM. The co-expression of the endothelial marker CD31 and mesenchymal marker FSP1 was significantly stained and calculated under PLA. In conclusion, microvascular injury and mesenchymal phenotypic

  15. Intrinsic sex-specific differences in microvascular endothelial cell phosphodiesterases

    PubMed Central

    Bingaman, Susan; Huxley, Virginia H.

    2010-01-01

    The importance of gonadal hormones in the regulation of vascular function has been documented. An alternate and essential contribution of the sex chromosomes to sex differences in vascular function is poorly understood. We reported previously sex differences in microvessel permeability (Ps) responses to adenosine that were mediated by the cAMP signaling pathway (Wang J, PhD thesis, 2005; Wang J and Huxley V, Proceedings of the VIII World Congress of Microcirculation, 2007; Wang J and Huxley VH, Am J Physiol Heart Circ Physiol 291: H3094–H3105, 2006). The two cyclic nucleotides, cAMP and cGMP, central to the regulation of vascular barrier integrity, are hydrolyzed by phosphodiesterases (PDE). We hypothesized that microvascular endothelial cells (EC) would retain intrinsic and inheritable sexually dimorphic genes with respect to the PDEs modulating EC barrier function. Primary cultured microvascular EC from skeletal muscles isolated from male and female rats, respectively, were used. SRY (a sex-determining region Y gene) mRNA expression was observed exclusively in male, not female, cells. The predominant isoform among PDE1–5, present in both XY and XX EC, was PDE4. Expression mRNA levels of PDE1A (male > female) and PDE3B (male < female) were sex dependent; PDE2A, PDE4D, and PDE5A were sex independent. Barrier function, Ps, was determined from measures of albumin flux across confluent primary cultured microvessel XY and XX EC monolayers. Consistent with intact in situ microvessels, basal monolayer Ps did not differ between XY (1.7 ± 0.2 × 10−6 cm/s; n = 8) and XX (1.8 ± 0.1 × 10−6 cm/s; n = 10) EC. Cilostazol, a PDE3 inhibitor, reduced (11%, P < 0.05) Ps in XX, not XY, cells. These findings demonstrate the presence and maintenance of intrinsic sex-related differences in gene expression and cellular phenotype by microvascular EC in a gonadal-hormone-free environment. Furthermore, intrinsic cell-sex likely contributes significantly to sexual dimorphism in

  16. Microvascular Injury in Ketamine-Induced Bladder Dysfunction.

    PubMed

    Lin, Chih-Chieh; Lin, Alex Tong-Long; Yang, An-Hang; Chen, Kuang-Kuo

    2016-01-01

    The pathogenesis of ketamine-induced cystitis (KC) remains unclear. In this study, bladder microvascular injury was investigated as a possible contributing mechanism. A total of 36 KC patients with exposure to ketamine for more than 6 months, and 9 control subjects, were prospectively recruited. All participants completed questionnaires, including the O'Leary-Sant interstitial cystitis symptom index (ICSI) and the interstitial cystitis problem index (ICPI). All KC patients received a urodynamic study and radiological exams. Bladder tissues were obtained from cystoscopic biopsies in the control group and after hydrodistention in the KC group. Double-immunofluorescence staining of N-methyl-d-aspartate receptor subunit 1 (NMDAR1) and the endothelial marker, cluster of differentiation 31 (CD31), was performed to reveal the existence of NMDAR1 on the endothelium. Electron microscopy (EM) was applied to assess the microvascular change in the urinary bladder and to measure the thickening of the basement membrane (BM). A proximity ligation assay (PLA) was used to quantify the co-localization of the endothelial CD31 receptor and the mesenchymal marker [fibroblast-specific protein 1 (FSP-1)]. The Mann-Whitney U test and Spearman's correlation coefficient were used for statistical analysis. The mean ICSI [14.38 (± 4.16)] and ICPI [12.67 (± 3.54)] scores of the KC group were significantly higher than those (0 and 0, respectively) of the control group (both p < 0.001). The KC patients had decreasing cystometric bladder capacity (CBC) with a mean volume of 65.38 (± 48.67) mL. NMDAR1 was expressed on endothelial cells in both groups under immunofluorescence staining. Moreover, KC patients had significant BM duplication of microvessels in the mucosa of the urinary bladder under EM. The co-expression of the endothelial marker CD31 and mesenchymal marker FSP1 was significantly stained and calculated under PLA. In conclusion, microvascular injury and mesenchymal phenotypic

  17. New technique to quantitate regional pulmonary microvascular transit times from dynamic x-ray CT images

    NASA Astrophysics Data System (ADS)

    Tajik, Jehangir K.; Tran, Binh Q.; Hoffman, Eric A.

    1998-07-01

    Microvascular red blood cell mean transit time is a crucial parameter underlying basic pulmonary physiology. Dynamic x-ray CT imaging during bolus radiopaque tracer injection offers the ability to make functional measurements throughout the lungs, but is not able to resolve individual microvascular beds. We have implemented a model-free Fast Fourier Transform deconvolution algorithm to extract the microvascular transport characteristics from the acquired time-intensity data. The deconvolved feeding arterial bolus input curves and corresponding regional pulmonary parenchymal 'response' functions provide measures of regional pulmonary tracer residence times, allowing calculation of microvascular transit times for different spatial regions of the pulmonary system. The acquired feeding (main) pulmonary artery and regional pulmonary parenchyma time-intensity curves were fit to gamma variate functions which were then sampled with a temporal resolution of 0.1 seconds. Deconvolution of the feeding arterial and regional parenchymal curves consistently results in bimodal regional residue functions. The two modes consist of a relatively large, sharp, narrow peak approximating a delta function followed by a smaller more dispersed curve. The sharp, narrow peak appears to be due to small artery inclusion in the sampled parenchymal region (partial volume effects). The magnitude of the dominant arterial peak decreases as sampling locations are moved from the less expanded dependent to the more expanded non-dependent lung regions of supine dogs. Mathematical separation of the two modes allowed isolation of the arterial and microvascular components. The shape and transit times of the putative microvascular components agree well with results from similar measurements via microfocal angiography and in vivo microscopy. Reconvolving the microvascular component with the input curve results in a corrected parenchymal curve representing the regional microvascular transport characteristics

  18. Blood flow in microvascular networks: A study in nonlinear biology

    PubMed Central

    Geddes, John B.; Carr, Russell T.; Wu, Fan; Lao, Yingyi; Maher, Meaghan

    2010-01-01

    Plasma skimming and the Fahraeus–Lindqvist effect are well-known phenomena in blood rheology. By combining these peculiarities of blood flow in the microcirculation with simple topological models of microvascular networks, we have uncovered interesting nonlinear behavior regarding blood flow in networks. Nonlinearity manifests itself in the existence of multiple steady states. This is due to the nonlinear dependence of viscosity on blood cell concentration. Nonlinearity also appears in the form of spontaneous oscillations in limit cycles. These limit cycles arise from the fact that the physics of blood flow can be modeled in terms of state dependent delay equations with multiple interacting delay times. In this paper we extend our previous work on blood flow in a simple two node network and begin to explore how topological complexity influences the dynamics of network blood flow. In addition we present initial evidence that the nonlinear phenomena predicted by our model are observed experimentally. PMID:21198135

  19. Diabetic microvascular complications: possible targets for improved macrovascular outcomes

    PubMed Central

    D’Elia, John A; Bayliss, George; Roshan, Bijan; Maski, Manish; Gleason, Ray E; Weinrauch, Larry A

    2011-01-01

    The results of recent outcome trials challenge hypotheses that tight control of both glycohemoglobin and blood pressure diminishes macrovascular events and survival among type 2 diabetic patients. Relevant questions exist regarding the adequacy of glycohemoglobin alone as a measure of diabetes control. Are we ignoring mechanisms of vasculotoxicity (profibrosis, altered angiogenesis, hypertrophy, hyperplasia, and endothelial injury) inherent in current antihyperglycemic medications? Is the polypharmacy for lowering cholesterol, triglyceride, glucose, and systolic blood pressure producing drug interactions that are too complex to be clinically identified? We review angiotensin–aldosterone mechanisms of tissue injury that magnify microvascular damage caused by hyperglycemia and hypertension. Many studies describe interruption of these mechanisms, without hemodynamic consequence, in the preservation of function in type 1 diabetes. Possible interactions between the renin–angiotensin–aldosterone system and physiologic glycemic control (through pulsatile insulin release) suggest opportunities for further clinical investigation. PMID:21694944

  20. Diagnosis of coronary microvascular dysfunction – Present status

    PubMed Central

    Mittal, S.R.

    2015-01-01

    Definite clinical diagnosis of microvascular angina is not possible with the existing knowledge. Resting electrocardiogram may be normal, and exercise electrocardiogram may be unremarkable. Echocardiography usually does not show regional wall motion abnormalities. Transthoracic Doppler echocardiography can satisfactorily evaluate only left anterior descending coronary artery and that too in some patients. Radio-isotope imaging can detect only severe localized disease. Noninvasive diagnosis needs high index of suspicion. At present, definite diagnosis is based on documentation of normal epicardial coronaries, coronary flow reserve less than 2.5 on adenosine induced hyperemia, and absence of spasm of epicardial coronaries on acetylcholine provocation. Invasive evaluation is costly, needs sophisticated equipments and expertise. Therapeutic and prognostic implications of various parameters remains to be evaluated. At present invasive evaluation is recommended only for patients with intractable symptoms with unconfirmed diagnosis, requiring repeated hospitalization and evaluation with failure of empirical therapy. PMID:26702685

  1. Surgical variation of microvascular decompression for trigeminal neuralgia: A technical note and anatomical study

    PubMed Central

    da Silva, Otávio T.; de Almeida, César C.; Iglesio, Ricardo F.; de Navarro, Jessie M.; Teixeira, Manoel J.; Duarte, Kleber P.

    2016-01-01

    Background: In this article, the authors described their experience in microvascular decompression for trigeminal neuralgia. Methods: The microvascular decompression technique used in the authors’ institution is described in a step by step manner with some illustrative cases as well as a cadaver dissection to highlight the differences with other previously described techniques. Results: Since 2013, 107 patients were operated in the Neurosurgery Division of the University of São Paulo using the described technique, with a shorter operative time and avoiding cerebellar retractor compared with classic techniques. Conclusion: Our modified microvascular decompression technique for trigeminal neuralgia can be used with safety and efficiency for treating trigeminal neuralgia. PMID:27625893

  2. The Utility of Cardiopulmonary Exercise Testing in the Assessment of Suspected Microvascular Ischemia

    PubMed Central

    Chaudhry, Sundeep; Arena, Ross; Wasserman, Karlman; Hansen, James E.; Lewis, Gregory D.; Myers, Jonathan; Belardinelli, Romualdo; LaBudde, Brian; Menasco, Nicholas; Boden, William E.

    2010-01-01

    Evidence demonstrating the potential value of cardiopulmonary exercise testing (CPET) to accurately detect myocardial ischemia secondary to macro-vascular disease is beginning to emerge. Despite distinct mechanisms mediating ischemia in micro-vascular and macrovascular coronary artery disease (CAD), the net physiologic effect of exercise-induced left ventricular (LV) dysfunction is common to both. The abnormal physiologic response to CPET may, therefore, be similar in patients with macro- and micro-vascular ischemia. The following case report describes the CPET abnormalities in a patient with suspected microvascular CAD and the subsequent improvement in LV function following three weeks of medical therapy with the anti-ischemic drug ranolazine. PMID:19233492

  3. Surgical variation of microvascular decompression for trigeminal neuralgia: A technical note and anatomical study

    PubMed Central

    da Silva, Otávio T.; de Almeida, César C.; Iglesio, Ricardo F.; de Navarro, Jessie M.; Teixeira, Manoel J.; Duarte, Kleber P.

    2016-01-01

    Background: In this article, the authors described their experience in microvascular decompression for trigeminal neuralgia. Methods: The microvascular decompression technique used in the authors’ institution is described in a step by step manner with some illustrative cases as well as a cadaver dissection to highlight the differences with other previously described techniques. Results: Since 2013, 107 patients were operated in the Neurosurgery Division of the University of São Paulo using the described technique, with a shorter operative time and avoiding cerebellar retractor compared with classic techniques. Conclusion: Our modified microvascular decompression technique for trigeminal neuralgia can be used with safety and efficiency for treating trigeminal neuralgia.

  4. Microvascular dysfunction in schizophrenia: a case–control study

    PubMed Central

    Vetter, Martin W; Martin, Billie-Jean; Fung, Marinda; Pajevic, Milada; Anderson, Todd J; Raedler, Thomas J

    2015-01-01

    Background: Schizophrenia is a mental illness associated with cardiovascular disease at a younger age than in the general population. Endothelial dysfunction has predictive value for future cardiovascular events; however, the impact of a diagnosis of schizophrenia on this marker is unknown. Aims: We tested the hypothesis that subjects with schizophrenia have impaired endothelial function. Methods: A total of 102 subjects (34.5±7.5 years) participated in this study. This sample consisted of 51 subjects with a diagnosis of schizophrenia and 51 healthy subjects, who were matched for age (P=0.442), sex (P>0.999), and smoking status (P=0.842). Peripheral artery microvascular and conduit vessel endothelial function was measured using hyperemic velocity time integral (VTI), pulse arterial tonometry (PAT), and flow-mediated dilation (FMD). Results: Significantly lower values of VTI were noted in subjects with schizophrenia (104.9±33.0 vs. 129.1±33.8 cm, P<0.001), whereas FMD (P=0.933) and PAT (P=0.862) did not differ between the two groups. A multivariable-linear-regression analysis, built on data from univariate and partial correlations, showed that only schizophrenia, sex, lipid-lowering medications, antihypertensive medications, and low-density lipoprotein (LDL)-cholesterol were predictive of attenuated VTI, whereas age, ethnicity, family history of cardiovascular disease, smoking status, systolic blood pressure, waist circumference, HDL-cholesterol, triglycerides, C-reactive protein, and homeostatic model assessment-insulin resistance (HOMA-IR), antidiabetic medications, antidepressant medications, mood stabilizers, benzodiazepines, and anticholinergic medications did not predict VTI in this model (adjusted R 2=0.248). Conclusions: Our findings suggest that a diagnosis of schizophrenia is associated with impaired microvascular function as indicated by lower values of VTI, irrespective of many other clinical characteristics. It might be an early indicator of

  5. Oxidative stress modulates nucleobase transport in microvascular endothelial cells.

    PubMed

    Bone, Derek B J; Antic, Milica; Vilas, Gonzalo; Hammond, James R

    2014-09-01

    Purine nucleosides and nucleobases play key roles in the physiological response to vascular ischemia/reperfusion events. The intra- and extracellular concentrations of these compounds are controlled, in part, by equilibrative nucleoside transporter subtype 1 (ENT1; SLC29A1) and by equilibrative nucleobase transporter subtype 1 (ENBT1). These transporters are expressed at the membranes of numerous cell types including microvascular endothelial cells. We studied the impact of reactive oxygen species on the function of ENT1 and ENBT1 in primary (CMVEC) and immortalized (HMEC-1) human microvascular endothelial cells. Both cell types displayed similar transporter expression profiles, with the majority (>90%) of 2-chloro[(3)H]adenosine (nucleoside) uptake mediated by ENT1 and [(3)H]hypoxanthine (nucleobase) uptake mediated by ENBT1. An in vitro mineral oil-overlay model of ischemia/reperfusion had no effect on ENT1 function, but significantly reduced ENBT1 Vmax in both cell types. This decrease in transport function was mimicked by the intracellular superoxide generator menadione and could be reversed by the superoxide dismutase mimetic MnTMPyP. In contrast, neither the extracellular peroxide donor TBHP nor the extracellular peroxynitrite donor 3-morpholinosydnonimine (SIN-1) affected ENBT1-mediated [(3)H]hypoxanthine uptake. SIN-1 did, however, enhance ENT1-mediated 2-chloro[(3)H]adenosine uptake. Our data establish HMEC-1 as an appropriate model for study of purine transport in CMVEC. Additionally, these data suggest that the generation of intracellular superoxide in ischemia/reperfusion leads to the down-regulation of ENBT1 function. Modification of purine transport by oxidant stress may contribute to ischemia/reperfusion induced vascular damage and should be considered in the development of therapeutic strategies.

  6. Alteration of the sublingual microvascular glycocalyx in critically ill patients.

    PubMed

    Donati, Abele; Damiani, Elisa; Domizi, Roberta; Romano, Rocco; Adrario, Erica; Pelaia, Paolo; Ince, Can; Singer, Mervyn

    2013-11-01

    Glycocalyx degradation may contribute to microvascular dysfunction and tissue hypoperfusion during systemic inflammation and sepsis. In this observational study we evaluated the alteration of the sublingual microvascular glycocalyx in 16 healthy volunteers and 50 critically ill patients. Sidestream Dark Field images of the sublingual microcirculation were automatically analyzed by dedicated software. The Perfused Boundary Region (PBR) was calculated as the dimensions of the permeable part of the glycocalyx allowing the penetration of circulating red blood cells, providing an index of glycocalyx damage. The PBR was increased in ICU patients compared to healthy controls (2.7 [2.59-2.88] vs. 2.46 [2.37-2.59]μm, p<0.0001) and tended to be higher in the 32 septic patients compared to non-septics (2.77 [2.62-2.93] vs. 2.67 [2.55-2.75]μm, p=0.05), suggesting more severe glycocalyx alterations. A PBR of 2.76 showed the best discriminative ability towards the presence of sepsis (sensitivity: 50%, specificity: 83%; area under the receiver operating characteristic curve: 0.67, 95% CI 0.52-0.82, p=0.05). A weak positive correlation was found between PBR and heart rate (r=0.3, p=0.03). In 17 septic patients, a correlation was found between PBR and number of rolling leukocytes in post-capillary venules (RL/venule) (r=0.55, p=0.02), confirming that glycocalyx shedding enhances leukocyte-endothelium interaction.

  7. Evaluation of Microvascular Perfusion and Resuscitation after Severe Injury.

    PubMed

    Lee, Yann-Leei L; Simmons, Jon D; Gillespie, Mark N; Alvarez, Diego F; Gonzalez, Richard P; Brevard, Sidney B; Frotan, Mohammad A; Schneider, Andrew M; Richards, William O

    2015-12-01

    Achieving adequate perfusion is a key goal of treatment in severe trauma; however, tissue perfusion has classically been measured by indirect means. Direct visualization of capillary flow has been applied in sepsis, but application of this technology to the trauma population has been limited. The purpose of this investigation was to compare the efficacy of standard indirect measures of perfusion to direct imaging of the sublingual microcirculatory flow during trauma resuscitation. Patients with injury severity scores >15 were serially examined using a handheld sidestream dark-field video microscope. In addition, measurements were also made from healthy volunteers. The De Backer score, a morphometric capillary density score, and total vessel density (TVD) as cumulative vessel area within the image, were calculated using Automated Vascular Analysis (AVA3.0) software. These indices were compared against clinical and laboratory parameters of organ function and systemic metabolic status as well as mortality. Twenty severely injured patients had lower TVD (X = 14.6 ± 0.22 vs 17.66 ± 0.51) and De Backer scores (X = 9.62 ± 0.16 vs 11.55 ± 0.37) compared with healthy controls. These scores best correlated with serum lactate (TVD R(2) = 0.525, De Backer R(2) = 0.576, P < 0.05). Mean arterial pressure, heart rate, oxygen saturation, pH, bicarbonate, base deficit, hematocrit, and coagulation parameters correlated poorly with both TVD and De Backer score. Direct measurement of sublingual microvascular perfusion is technically feasible in trauma patients, and seems to provide real-time assessment of microcirculatory perfusion. This study suggests that in severe trauma, many indirect measurements of perfusion do not correlate with microvascular perfusion. However, visualized perfusion deficiencies do reflect a shift toward anaerobic metabolism. PMID:26736167

  8. Autonomic dysfunction and microvascular damage in systemic sclerosis.

    PubMed

    Di Franco, Manuela; Paradiso, Michele; Riccieri, Valeria; Basili, Stefania; Mammarella, Antonio; Valesini, Guido

    2007-08-01

    Systemic sclerosis (SSc) is a connective tissue disease characterized by vascular damage and interstizial fibrosis of many organs. Our interest was focused on the evaluation of cardiac autonomic function by measurements of heart rate variability (HRV) and microvascular damage detected by nailfold capillaroscopy (NC) in SSc patients. We examined 25 consecutive outpatients affected by systemic sclerosis and 25 healthy controls. Exclusion criteria were the presence of cardiac disease, hypertension, diabetes mellitus, or neurological diseases. All subjects underwent 24-h ambulatory ECG Holter recording and NC examination. Heart rate variability was evaluated in the time domain, using appropriate software, computing the time series of all normal-to-normal (NN) QRS intervals throughout the 24-h recording period. A semiquantitative rating scale was adopted to score the NC abnormalities, as well as a rating system for avascular areas and morphological NC patterns. In SSc patients, HRV analysis showed significantly lower values of SDNN (standard deviation of all NN intervals) (p=0.009), SDANN (standard deviation of the averages of NN intervals in all 5-min segments of the entire recording) (p=0.01), and pNN50 (the percentage of adjacent NN intervals that differed by more than 50 ms) (p=0.02), compared to the control group. These parameters in SSc patients significantly decreased with the worsening of semiquantitative capillaroscopy score. In conclusion, an abnormal autonomic nervous control of the heart might contribute to identify subclinical cardiac involvement in SSc patients. The coexistence of autonomic dysfunction with a more severe microvascular damage could be considered a potential prognostic tool in the identification of those patients particularly at risk for cardiac mortality.

  9. Long noncoding RNA-MEG3 is involved in diabetes mellitus-related microvascular dysfunction.

    PubMed

    Qiu, Gui-Zhen; Tian, Wei; Fu, Hai-Tao; Li, Chao-Peng; Liu, Ban

    2016-02-26

    Microvascular dysfunction is an important characteristic of diabetic retinopathy. Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes. In this study, we investigated the role of lncRNA-MEG3 in diabetes-related microvascular dysfunction. We show that MEG3 expression level is significantly down-regulated in the retinas of STZ-induced diabetic mice, and endothelial cells upon high glucose and oxidative stress. MEG3 knockdown aggravates retinal vessel dysfunction in vivo, as shown by serious capillary degeneration, and increased microvascular leakage and inflammation. MEG3 knockdown also regulates retinal endothelial cell proliferation, migration, and tube formation in vitro. The role of MEG3 in endothelial cell function is mainly mediated by the activation of PI3k/Akt signaling. MEG3 up-regulation may serve as a therapeutic strategy for treating diabetes-related microvascular complications. PMID:26845358

  10. SPONTANEOUSLY HYPERTENSIVE RATS ARE SUSCEPTIBLE TO MICROVASCULAR THROMBOSIS IN RESPONSE TO PARTICULATE MATTER EXPOSURE

    EPA Science Inventory

    SPONTANEOUSLY HYPERTENSIVE RATS ARE SUSCEPTIBLE TO MICROVASCULAR THROMBOSIS IN RESPONSE TO PARTICULATE MATTER EXPOSURE.
    PS Gilmour, MC Schladweiler, AD Ledbetter, and UP Kodavanti. US EPA, ORD, NHEERL, ETD, PTB, Research Triangle Park, NC USA.
    Environmental particles (PM...

  11. Genetic Studies on Diabetic Microvascular Complications: Focusing on Genome-Wide Association Studies

    PubMed Central

    Kwak, Soo Heon

    2015-01-01

    Diabetes is a common metabolic disorder with a worldwide prevalence of 8.3% and is the leading cause of visual loss, end-stage renal disease and amputation. Recently, genome-wide association studies (GWASs) have identified genetic risk factors for diabetic microvascular complications of retinopathy, nephropathy, and neuropathy. We summarized the recent findings of GWASs on diabetic microvascular complications and highlighted the challenges and our opinion on future directives. Five GWASs were conducted on diabetic retinopathy, nine on nephropathy, and one on neuropathic pain. The majority of recent GWASs were underpowered and heterogeneous in terms of study design, inclusion criteria and phenotype definition. Therefore, few reached the genome-wide significance threshold and the findings were inconsistent across the studies. Recent GWASs provided novel information on genetic risk factors and the possible pathophysiology of diabetic microvascular complications. However, further collaborative efforts to standardize phenotype definition and increase sample size are necessary for successful genetic studies on diabetic microvascular complications. PMID:26194074

  12. Interactions of the Gasotransmitters Contribute to Microvascular Tone (Dys)regulation in the Preterm Neonate

    PubMed Central

    Dyson, Rebecca M.; Palliser, Hannah K.; Latter, Joanna L.; Kelly, Megan A.; Chwatko, Grazyna; Glowacki, Rafal; Wright, Ian M. R.

    2015-01-01

    Background & Aims Hydrogen sulphide (H2S), nitric oxide (NO), and carbon monoxide (CO) are involved in transitional microvascular tone dysregulation in the preterm infant; however there is conflicting evidence on the interaction of these gasotransmitters, and their overall contribution to the microcirculation in newborns is not known. The aim of this study was to measure the levels of all 3 gasotransmitters, characterise their interrelationships and elucidate their combined effects on microvascular blood flow. Methods 90 preterm neonates were studied at 24h postnatal age. Microvascular studies were performed by laser Doppler. Arterial COHb levels (a measure of CO) were determined through co-oximetry. NO was measured as nitrate and nitrite in urine. H2S was measured as thiosulphate by liquid chromatography. Relationships between levels of the gasotransmitters and microvascular blood flow were assessed through partial correlation controlling for the influence of gestational age. Structural equation modelling was used to examine the combination of these effects on microvascular blood flow and derive a theoretical model of their interactions. Results No relationship was observed between NO and CO (p = 0.18, r = 0.18). A positive relationship between NO and H2S (p = 0.008, r = 0.28) and an inverse relationship between CO and H2S (p = 0.01, r = -0.33) exists. Structural equation modelling was used to examine the combination of these effects on microvascular blood flow. The model with the best fit is presented. Conclusions The relationships between NO and H2S, and CO and H2S may be of importance in the preterm newborn, particularly as NO levels in males are associated with higher H2S levels and higher microvascular blood flow and CO in females appears to convey protection against vascular dysregulation. Here we present a theoretical model of these interactions and their overall effects on microvascular flow in the preterm newborn, upon which future mechanistic studies may

  13. Visualization of microvascularity in glioblastoma multiforme with 8-T high-spatial-resolution MR imaging.

    PubMed

    Christoforidis, Gregory A; Grecula, John C; Newton, Herbert B; Kangarlu, Allahyar; Abduljalil, Amir M; Schmalbrock, Petra; Chakeres, Donald W

    2002-10-01

    We used 8-T high-spatial-resolution gradient-echo MR imaging to directly visualize microvascularity in pathologically proved glioblastoma multiforme. Images were compared with 1.5-T high-spatial-resolution fast spin-echo T2-weighted images and digital subtraction angiograms. Preliminary data indicate that 8-T high-spatial-resolution MR imaging may enable the identification of areas of abnormal microvascularity in glioblastoma multiforme that are not visible with other routine clinical techniques.

  14. [THE AGING OF MICROVASCULAR NETWORK FORMED IN CORTEX FOLLOWING INTRACEREBRAL TRANSPLANTATION OF MESENCHYMAL STEM CELLS].

    PubMed

    Sokolova, I B; Anisimov, S V; Puzanov, M V; Sergeev, I V; Dvoretskiĭ, D P

    2015-01-01

    Using a TV device to study microcirculation in brain we found that intracerebral transplantation of mesenchymal stem cells to 12-months old rats led to a significant increase (circa 1,5-fold times) of microvascular density in pia tissue and to increased constriction reactions of pia arterioles in response to noradrenalin application on a brain surface. Both microvascular density and pia arterioles reactivity was completely preserved in aging until 22-24 months. PMID:26390610

  15. Microvascular patterns in the blubber of shallow and deep diving odontocetes.

    PubMed

    McClelland, Sara J; Gay, Mark; Pabst, D Ann; Dillaman, Richard; Westgate, Andrew J; Koopman, Heather N

    2012-08-01

    Blubber, a specialized form of subdermal adipose tissue, surrounds marine mammal bodies. Typically, adipose tissue is perfused by capillaries but information on blubber vascularization is lacking. This study's goals were to: 1) describe and compare the microvasculature (capillaries, microarterioles, and microvenules) of blubber across odontocete species; 2) compare microvasculature of blubber to adipose tissue; and 3) examine relationships between blubber's lipid composition and its microvasculature. Percent microvascularity, distribution, branching pattern, and diameter of microvessels were determined from images of histochemically stained blubber sections from shallow-diving bottlenose dolphins (Tursiops truncatus), deeper-diving pygmy sperm whales (Kogia breviceps), deep-diving beaked whales (Mesoplodon densirostris; Ziphius cavirostris), and the subdermal adipose tissue of domestic pigs (Sus scrofa). Tursiops blubber showed significant stratification in percent microvascularity among the superficial, middle, and deep layers and had a significantly higher percent microvascularity than all other animals analyzed, in which the microvasculature was more uniformly distributed. The percent microvasculature of Kogia blubber was lower than that of Tursiops but higher than that of beaked whales and the subdermal adipose tissue of domestic pigs. Tursiops had the most microvascular branching. Microvessel diameter was relatively uniform in all species. There were no clear patterns associating microvascular and lipid characteristics. The microvascular characteristics of the superficial layer of blubber resembled the adipose tissue of terrestrial mammals, suggesting some conservation of microvascular patterns in mammalian adipose tissue. The middle and deep layers of blubber, particularly in Tursiops, showed the greatest departure from typical mammalian microvascular arrangement. Factors such as metabolics or thermoregulation may be influencing the microvasculature in these

  16. Deeper Penetration of Erythrocytes into the Endothelial Glycocalyx Is Associated with Impaired Microvascular Perfusion

    PubMed Central

    Lee, Dae Hyun; Dane, Martijn J. C.; van den Berg, Bernard M.; Boels, Margien G. S.; van Teeffelen, Jurgen W.; de Mutsert, Renée; den Heijer, Martin; Rosendaal, Frits R.; van der Vlag, Johan; van Zonneveld, Anton Jan; Vink, Hans; Rabelink, Ton J.

    2014-01-01

    Changes in endothelial glycocalyx are one of the earliest changes in development of cardiovascular disease. The endothelial glycocalyx is both an important biological modifier of interactions between flowing blood and the vessel wall, and a determinant of organ perfusion. We hypothesize that deeper penetration of erythrocytes into the glycocalyx is associated with reduced microvascular perfusion. The population-based prospective cohort study (the Netherlands Epidemiology of Obesity [NEO] study) includes 6,673 middle-aged individuals (oversampling of overweight and obese individuals). Within this cohort, we have imaged the sublingual microvasculature of 915 participants using sidestream darkfield (SDF) imaging together with a recently developed automated acquisition and analysis approach. Presence of RBC (as a marker of microvascular perfusion) and perfused boundary region (PBR), a marker for endothelial glycocalyx barrier properties for RBC accessibility, were assessed in vessels between 5 and 25 µm RBC column width. A wide range of variability in PBR measurements, with a mean PBR of 2.14 µm (range: 1.43–2.86 µm), was observed. Linear regression analysis showed a marked association between PBR and microvascular perfusion, reflected by RBC filling percentage (regression coefficient β: −0.034; 95% confidence interval: −0.037 to −0.031). We conclude that microvascular beds with a thick (“healthy”) glycocalyx (low PBR), reflects efficient perfusion of the microvascular bed. In contrast, a thin (“risk”) glycocalyx (high PBR) is associated with a less efficient and defective microvascular perfusion. PMID:24816787

  17. Drag-Reducing Polymer Enhances Microvascular Perfusion in the Traumatized Brain with Intracranial Hypertension.

    PubMed

    Bragin, Denis E; Thomson, Susan; Bragina, Olga; Statom, Gloria; Kameneva, Marina V; Nemoto, Edwin M

    2016-01-01

    Current treatments for traumatic brain injury (TBI) have not focused on improving microvascular perfusion. Drag-reducing polymers (DRP), linear, long-chain, blood-soluble, nontoxic macromolecules, may offer a new approach to improving cerebral perfusion by primary alteration of the fluid dynamic properties of blood. Nanomolar concentrations of DRP have been shown to improve hemodynamics in animal models of ischemic myocardium and ischemic limb, but have not yet been studied in the brain. We recently demonstrated that DRP improved microvascular perfusion and tissue oxygenation in a normal rat brain. We hypothesized that DRP could restore microvascular perfusion in hypertensive brain after TBI. Using in vivo two-photon laser scanning microscopy we examined the effect of DRP on microvascular blood flow and tissue oxygenation in hypertensive rat brains with and without TBI. DRP enhanced and restored capillary flow, decreased microvascular shunt flow, and, as a result, reduced tissue hypoxia in both nontraumatized and traumatized rat brains at high intracranial pressure. Our study suggests that DRP could constitute an effective treatment for improving microvascular flow in brain ischemia caused by high intracranial pressure after TBI. PMID:27165871

  18. Deeper penetration of erythrocytes into the endothelial glycocalyx is associated with impaired microvascular perfusion.

    PubMed

    Lee, Dae Hyun; Dane, Martijn J C; van den Berg, Bernard M; Boels, Margien G S; van Teeffelen, Jurgen W; de Mutsert, Renée; den Heijer, Martin; Rosendaal, Frits R; van der Vlag, Johan; van Zonneveld, Anton Jan; Vink, Hans; Rabelink, Ton J

    2014-01-01

    Changes in endothelial glycocalyx are one of the earliest changes in development of cardiovascular disease. The endothelial glycocalyx is both an important biological modifier of interactions between flowing blood and the vessel wall, and a determinant of organ perfusion. We hypothesize that deeper penetration of erythrocytes into the glycocalyx is associated with reduced microvascular perfusion. The population-based prospective cohort study (the Netherlands Epidemiology of Obesity [NEO] study) includes 6,673 middle-aged individuals (oversampling of overweight and obese individuals). Within this cohort, we have imaged the sublingual microvasculature of 915 participants using sidestream darkfield (SDF) imaging together with a recently developed automated acquisition and analysis approach. Presence of RBC (as a marker of microvascular perfusion) and perfused boundary region (PBR), a marker for endothelial glycocalyx barrier properties for RBC accessibility, were assessed in vessels between 5 and 25 µm RBC column width. A wide range of variability in PBR measurements, with a mean PBR of 2.14 µm (range: 1.43-2.86 µm), was observed. Linear regression analysis showed a marked association between PBR and microvascular perfusion, reflected by RBC filling percentage (regression coefficient β: -0.034; 95% confidence interval: -0.037 to -0.031). We conclude that microvascular beds with a thick ("healthy") glycocalyx (low PBR), reflects efficient perfusion of the microvascular bed. In contrast, a thin ("risk") glycocalyx (high PBR) is associated with a less efficient and defective microvascular perfusion.

  19. Drag-Reducing Polymer Enhances Microvascular Perfusion in the Traumatized Brain with Intracranial Hypertension.

    PubMed

    Bragin, Denis E; Thomson, Susan; Bragina, Olga; Statom, Gloria; Kameneva, Marina V; Nemoto, Edwin M

    2016-01-01

    Current treatments for traumatic brain injury (TBI) have not focused on improving microvascular perfusion. Drag-reducing polymers (DRP), linear, long-chain, blood-soluble, nontoxic macromolecules, may offer a new approach to improving cerebral perfusion by primary alteration of the fluid dynamic properties of blood. Nanomolar concentrations of DRP have been shown to improve hemodynamics in animal models of ischemic myocardium and ischemic limb, but have not yet been studied in the brain. We recently demonstrated that DRP improved microvascular perfusion and tissue oxygenation in a normal rat brain. We hypothesized that DRP could restore microvascular perfusion in hypertensive brain after TBI. Using in vivo two-photon laser scanning microscopy we examined the effect of DRP on microvascular blood flow and tissue oxygenation in hypertensive rat brains with and without TBI. DRP enhanced and restored capillary flow, decreased microvascular shunt flow, and, as a result, reduced tissue hypoxia in both nontraumatized and traumatized rat brains at high intracranial pressure. Our study suggests that DRP could constitute an effective treatment for improving microvascular flow in brain ischemia caused by high intracranial pressure after TBI.

  20. Thiel embalming technique: a valuable method for microvascular exercise and teaching of flap raising.

    PubMed

    Wolff, Klaus-D; Kesting, Marco; Mücke, Thomas; Rau, Andrea; Hölzle, Frank

    2008-01-01

    Because of its high requirements on dexterity and microsurgical skills and the need of complete understanding of flap anatomy, microvascular free flap transfer belongs to the most demanding surgical procedures. Therefore, courses for flap raising and microvascular exercise are considered a prerequisite to prepare for clinical practise. To achieve teaching conditions as realistic as possible we used a novel cadaver embalming method enabling tissue dissection comparable to the living body. Thirty cadavers which were offered to us by the Institute of Anatomy for the purpose of running flap raising courses were embalmed in the technique described by Thiel. On each cadaver, nine free flaps were dissected according to a structured protocol by each course participant and afterwards used for microvascular exercise. The conservation of fine vascular structures and the suitability of the embalmed tissue for microvascular suturing were observed and photographically documented. The Thiel embalming technique provided flap raising procedures to be performed under realistic conditions similar to the living body. Vessels and nerves could be exposed and dissected up to a diameter of 1 mm and allowed for microvascular suturing even after weeks like fresh specimens. The Thiel embalming method is a unique technique and ideally suited to teach flap raising and microvascular suturing on human material.

  1. Added Qualifications in Microsurgery: Consideration for Subspecialty Certification in Microvascular Surgery in Europe.

    PubMed

    Heidekrueger, Paul I; Tanna, Neil; Weichman, Katie E; Szpalski, Caroline; Tos, Pierluigi; Ninkovic, Milomir; Broer, P Niclas

    2016-07-01

    Background While implementation of subspecializations may increase expertise in a certain area of treatment, there also exist downsides. Aim of this study was, across several disciplines, to find out if the technique of microsurgery warrants the introduction of a "Certificate of Added Qualifications (CAQ) in microsurgery." Methods An anonymous, web-based survey was administered to directors of microsurgical departments in Europe (n = 205). Respondents were asked, among other questions, whether they had completed a 12-month microvascular surgery fellowship and whether they believed a CAQ in microvascular surgery should be instituted. Results The response rate was 57%, and 33% of the respondents had completed a 12-month microvascular surgery fellowship.A total of 61% of all surgeons supported a CAQ in microsurgery. Answers ranged from 47% of support to 100% of support, depending on the countries surveyed. Discussion This is one of the few reports to evaluate the potential role of subspecialty certification of microvascular surgery across several European countries. The data demonstrate that the majority of directors of microsurgical departments support such a certificate. There was significantly greater support for a CAQ in microsurgery among those who have completed a formal microvascular surgery fellowship themselves. Conclusion This study supports the notion that further discussion and consideration of subspecialty certification in microvascular surgery appears necessary. There are multiple concerns surrounding this issue. Similar to the evolution of hand surgery certification, an exploratory committee of executive members of the respective medical boards and official societies may be warranted.

  2. Atorvastatin reduces endotoxin-induced microvascular inflammation via NOSII.

    PubMed

    McGown, Caroline C; Brookes, Zoë L S; Hellewell, Paul G; Ross, Jonathan J; Brown, Nicola J

    2015-05-01

    In a lipopolysaccharide (LPS)-induced rat model of sepsis (endotoxaemia), we previously demonstrated that pravastatin reduced microvascular inflammation via increased endothelial nitric oxide synthase III (NOSIII). This study aimed to determine whether atorvastatin, the most commonly used statin for lowering cholesterol, exerted beneficial pleiotropic effects via a similar mechanism. The mesenteric microcirculation of anaesthetised male Wistar rats (308 ± 63 g, n = 54) was prepared for fluorescent intravital microscopy. Over 4 h, animals received intravenous (i.v.) administration of either saline, LPS (150 μg kg(-1) h(-1)) or LPS + atorvastatin (200 μg kg(-1) s.c., 18 and 3 h before LPS), with/without the non-specific NOS inhibitor L-NG-Nitroarginine Methyl Ester (L-NAME) (10 μg kg(-1) h(-1)) or NOSII-specific inhibitor 1400 W (20 μg kg(-1) min(-1)). LPS decreased mean arterial blood pressure (MAP) (4 h, control 113 ± 20 mmHg; LPS 70 ± 23 mmHg), being reversed by atorvastatin (105 ± 3 mmHg) (p < 0.05). LPS also increased macromolecular leak measured after 100 mg kg(-1) of i.v FITC-BSA (arbitrary grey level adjacent to venules), which again was attenuated by atorvastatin (control 1.9 ± 4.0; LPS 12.0 ± 2.4; LPS + atorvastatin 4.5 ± 2.2) (p < 0.05). Furthermore, immunohistochemistry identified that atorvastatin decreased LPS-induced upregulation of endothelial cell NOSII expression, but NOSIII was unchanged in all groups. Atorvastatin improved MAP and reduced microvascular inflammation during endotoxaemia, associated with a reduction of pro-inflammatory NOSII. This differs from previous studies, whereby pravastatin increased expression of NOSIII. Thus preoperative statins have beneficial anti-inflammatory effects during endotoxaemia, but careful consideration must be given to the specific statin being used. PMID:25678054

  3. Evaluation of coronary microvascular function in patients with vasospastic angina

    PubMed Central

    Teragawa, Hiroki; Mitsuba, Naoya; Ishibashi, Ken; Nishioka, Kenji; Kurisu, Satoshi; Kihara, Yasuki

    2013-01-01

    AIM: To investigate endothelium-dependent and -independent coronary microvascular functions in patients with vasospastic angina (VSA). METHODS: Thirty-six patients with VSA (30 men and 6 women; mean age, 58 years) were enrolled in this study. VSA was defined as ≥ 90% narrowing of the epicardial coronary arteries on angiography performed during a spasm provocation test, presence of chest pain, and/or ST-segment deviation on an electrocardiogram (ECG). Patients (n = 36) with negative spasm provocation test results and those matched for age and sex were enrolled as a control group (nonVSA group). Low-dose acetylcholine (ACh; 3 μg/min) was infused into the left coronary ostium for 2 min during the spasm provocation test. Following the spasm provocation test, nitroglycerin (0.2 mg) was administered intracoronally. Coronary blood flow (was calculated from quantitative angiography and Doppler flow velocity measurements, and the coronary flow reserve was calculated as the ratio of coronary flow velocity after injection of adenosine triphosphate (20 μg) to the baseline value. Changes in the coronary artery diameter in response to ACh and nitroglycerin infusion were expressed as percentage changes from baseline measurements. RESULTS: Body mass index was significantly lower in the VSA group than in the nonVSA group. The frequency of conventional coronary risk factors and the rate of statin use were similar between the 2 groups. The left ventricular ejection fraction as evaluated by echocardiography was similar between the 2 groups. The duration of angina was 9 ± 2 mo. The results of blood chemistry analysis were similar between the 2 groups. Low-dose ACh did not cause coronary spasms. The change in coronary artery diameter in response to ACh was lower in the VSA group (-1.4% ± 9.3%) than in the nonVSA group (3.1% ± 6.5%, P < 0.05), whereas nitroglycerin-induced coronary artery dilatation and coronary blood flow increase in response to ACh or coronary flow reserve did

  4. Brain microvascular endothelial cell transplantation ameliorates ischemic white matter damage.

    PubMed

    Puentes, Sandra; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Yoshimoto, Yuhei; Mikuni, Masahiko; Imai, Hideaki; Ishizaki, Yasuki

    2012-08-21

    Ischemic insults affecting the internal capsule result in sensory-motor disabilities which adversely affect the patient's life. Cerebral endothelial cells have been reported to exert a protective effect against brain damage, so the transplantation of healthy endothelial cells might have a beneficial effect on the outcome of ischemic brain damage. In this study, endothelin-1 (ET-1) was injected into the rat internal capsule to induce lacunar infarction. Seven days after ET-1 injection, microvascular endothelial cells (MVECs) were transplanted into the internal capsule. Meningeal cells or 0.2% bovine serum albumin-Hank's balanced salt solution were injected as controls. Two weeks later, the footprint test and histochemical analysis were performed. We found that MVEC transplantation improved the behavioral outcome based on recovery of hind-limb rotation angle (P<0.01) and induced remyelination (P<0.01) compared with the control groups. Also the inflammatory response was repressed by MVEC transplantation, judging from fewer ED-1-positive activated microglial cells in the MVEC-transplanted group than in the other groups. Elucidation of the mechanisms by which MVECs ameliorate ischemic damage of the white matter may provide important information for the development of effective therapies for white matter ischemia.

  5. Isolation and characterization of equine microvascular endothelial cells in vitro.

    PubMed

    Bochsler, P N; Slauson, D O; Chandler, S K; Suyemoto, M M

    1989-10-01

    The use of cultured tissue has not yet become widespread in research involving equine disease, and this may be attributable in part to the scarcity of published reports concerning tissue culture methods for this species. We report here the isolation of equine microvascular endothelium (EMVE) from fresh omental tissue of horses and ponies. Fresh donor tissue was minced, subjected to collagenase digestion, and filtered. Cells were layered on 5% bovine serum albumin for gravity sedimentation, the bottom layer was collected, and the cells were plated onto fibronectin-coated flasks. Medium consisted of Dulbecco modified Eagle medium with 10% whole fetal bovine serum (wFBS) and 20 micrograms of endothelial cell growth supplement/ml. The EMVE grew readily in culture, had the cobblestone morphologic feature at confluence, stained positively for factor VIII-related antigen, and metabolized acetylated low-density lipoprotein. Fibroblast and smooth muscle cell contamination was minimal in primary cell cultures, which were successfully passed and maintained in culture for 3 to 5 serial passages, using various media and substrates. Preliminary studies were undertaken to determine optimal growth conditions with a range of variables: serum concentration, extracellular matrix components, and growth factors, Optimal conditions were achieved with a minimum of 10% wFBS, and with either fibronectin or laminin as extracellular matrix substrates. The EMVE grew adequately in Dulbecco modified Eagle medium plus 10% wFBS, and the added growth factors or serum supplements did not appear necessary for growth of EMVE.

  6. Macro- and microvascular effects of nitrous oxide in the rat.

    PubMed Central

    Matheny, J. L.; Westphal, K. A.; Richardson, D. R.; Roth, G. I.

    1991-01-01

    The aims of this study were: (1) to determine the macro- and microvascular actions of nitrous oxide (N2O) in the rat, and (2) to determine whether the vascular actions of N2O involved specific interaction with alpha-adrenergic receptors or opioid receptors. Systolic blood pressure, heart rat, total tail blood flow, blood cell velocity in subepidermal capillaries of the tail, and percentage of capillaries exhibiting flow were monitored in conscious rats during the administration of N2O before and after administration of clonidine (an alpha 2-adrenergic agonist), prazosin (an alpha 1-adrenergic antagonist) or naloxone (an opioid antagonist). Total tail blood flow increased significantly in a dose-dependent manner with N2O at 20% and 40% with oxygen. This action of N2O was not blocked by clonidine, prazosin, or naloxone. Capillary flow velocity increased during 20% and 40% N2O compared to 100% O2, but the changes were not statistically significant nor did they correlate with the changes in tail blood flow. These data suggest that the peripheral vascular action of N2O does not involve specific actions at alpha-adrenergic receptors or opioid receptors and may be the result of direct actions on the peripheral vasculature. PMID:1667350

  7. Cardiac microvascular endothelial cells express a functional Ca+ -sensing receptor.

    PubMed

    Berra Romani, Roberto; Raqeeb, Abdul; Laforenza, Umberto; Scaffino, Manuela Federica; Moccia, Francesco; Avelino-Cruz, Josè Everardo; Oldani, Amanda; Coltrini, Daniela; Milesi, Veronica; Taglietti, Vanni; Tanzi, Franco

    2009-01-01

    The mechanism whereby extracellular Ca(2+) exerts the endothelium-dependent control of vascular tone is still unclear. In this study, we assessed whether cardiac microvascular endothelial cells (CMEC) express a functional extracellular Ca(2+)-sensing receptor (CaSR) using a variety of techniques. CaSR mRNA was detected using RT-PCR, and CaSR protein was identified by immunocytochemical analysis. In order to assess the functionality of the receptor, CMEC were loaded with the Ca(2+)-sensitive fluorochrome, Fura-2/AM. A number of CaSR agonists, such as spermine, Gd(3+), La(3+) and neomycin, elicited a heterogeneous intracellular Ca(2+) signal, which was abolished by disruption of inositol 1,4,5-trisphosphate (InsP(3)) signaling and by depletion of intracellular stores with cyclopiazonic acid. The inhibition of the Na(+)/Ca(2+) exchanger upon substitution of extracellular Na(+) unmasked the Ca(2+) signal triggered by an increase in extracellular Ca(2+) levels. Finally, aromatic amino acids, which function as allosteric activators of CaSR, potentiated the Ca(2+) response to the CaSR agonist La(3+). These data provide evidence that CMEC express CaSR, which is able to respond to physiological agonists by mobilizing Ca(2+) from intracellular InsP(3)-sensitive stores.

  8. Syndecan-2 downregulation impairs angiogenesis in human microvascular endothelial cells

    SciTech Connect

    Noguer, Oriol Villena, Joan; Lorita, Jordi; Vilaro, Senen; Reina, Manuel

    2009-03-10

    The formation of new blood vessels, or angiogenesis, is a necessary process during development but also for tumour growth and other pathologies. It is promoted by different growth factors that stimulate endothelial cells to proliferate, migrate, and generate new tubular structures. Syndecans, transmembrane heparan sulphate proteoglycans, bind such growth factors through their glycosaminoglycan chains and could transduce the signal to the cytoskeleton, thus regulating cell behaviour. We demonstrated that syndecan-2, the major syndecan expressed by human microvascular endothelial cells, is regulated by growth factors and extracellular matrix proteins, in both bidimensional and tridimensional culture conditions. The role of syndecan-2 in 'in vitro' tumour angiogenesis was also examined by inhibiting its core protein expression with antisense phosphorothioate oligonucleotides. Downregulation of syndecan-2 reduces spreading and adhesion of endothelial cells, enhances their migration, but also impairs the formation of capillary-like structures. These results suggest that syndecan-2 has an important function in some of the necessary steps that make up the angiogenic process. We therefore propose a pivotal role of this heparan sulphate proteoglycan in the formation of new blood vessels.

  9. Review: Cerebral microvascular pathology in aging and neurodegeneration

    PubMed Central

    Brown, William R.; Thore, Clara R.

    2010-01-01

    This review of age-related brain microvascular pathologies focuses on topics studied by this laboratory, including anatomy of the blood supply, tortuous vessels, venous collagenosis, capillary remnants, vascular density, and microembolic brain injury. Our studies feature thick sections, large blocks embedded in celloidin, and vascular staining by alkaline phosphatase (AP). This permits study of the vascular network in three dimensions, and the differentiation of afferent from efferent vessels. Current evidence suggests that there is decreased vascular density in aging, Alzheimer’s disease (AD), and leukoaraiosis (LA), and cerebrovascular dysfunction precedes and accompanies cognitive dysfunction and neurodegeneration. A decline in cerebrovascular angiogenesis may inhibit recovery from hypoxia-induced capillary loss. Cerebral blood flow (CBF) is inhibited by tortuous arterioles and deposition of excessive collagen in veins and venules. Misery perfusion due to capillary loss appears to occur before cell loss in LA, and CBF is also reduced in the normal-appearing white matter. Hypoperfusion occurs early in AD, inducing white matter lesions and correlating with dementia. In vascular dementia, cholinergic reductions are correlated with cognitive impairment, and cholinesterase inhibitors have some benefit. Most lipid microemboli from cardiac surgery pass through the brain in a few days, but some remain for weeks. They can cause what appears to be a type of vascular dementia years after surgery. Donepezil has shown some benefit. Emboli, such as clots, cholesterol crystals, and microspheres can be extruded through the walls of cerebral vessels, but there is no evidence yet that lipid emboli undergo such extravasation. PMID:20946471

  10. Brain microvascular endothelial cell transplantation ameliorates ischemic white matter damage.

    PubMed

    Puentes, Sandra; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Yoshimoto, Yuhei; Mikuni, Masahiko; Imai, Hideaki; Ishizaki, Yasuki

    2012-08-21

    Ischemic insults affecting the internal capsule result in sensory-motor disabilities which adversely affect the patient's life. Cerebral endothelial cells have been reported to exert a protective effect against brain damage, so the transplantation of healthy endothelial cells might have a beneficial effect on the outcome of ischemic brain damage. In this study, endothelin-1 (ET-1) was injected into the rat internal capsule to induce lacunar infarction. Seven days after ET-1 injection, microvascular endothelial cells (MVECs) were transplanted into the internal capsule. Meningeal cells or 0.2% bovine serum albumin-Hank's balanced salt solution were injected as controls. Two weeks later, the footprint test and histochemical analysis were performed. We found that MVEC transplantation improved the behavioral outcome based on recovery of hind-limb rotation angle (P<0.01) and induced remyelination (P<0.01) compared with the control groups. Also the inflammatory response was repressed by MVEC transplantation, judging from fewer ED-1-positive activated microglial cells in the MVEC-transplanted group than in the other groups. Elucidation of the mechanisms by which MVECs ameliorate ischemic damage of the white matter may provide important information for the development of effective therapies for white matter ischemia. PMID:22771710

  11. Holographic laser Doppler imaging of microvascular blood flow.

    PubMed

    Magnain, C; Castel, A; Boucneau, T; Simonutti, M; Ferezou, I; Rancillac, A; Vitalis, T; Sahel, J A; Paques, M; Atlan, M

    2014-12-01

    We report on local superficial blood flow monitoring in biological tissue from laser Doppler holographic imaging. In time-averaging recording conditions, holography acts as a narrowband bandpass filter, which, combined with a frequency-shifted reference beam, permits frequency-selective imaging in the radio frequency range. These Doppler images are acquired with an off-axis Mach-Zehnder interferometer. Microvascular hemodynamic components mapping is performed in the cerebral cortex of the mouse and the eye fundus of the rat with near-infrared laser light without any exogenous marker. These measures are made from a basic inverse-method analysis of local first-order optical fluctuation spectra at low radio frequencies, from 0 Hz to 100 kHz. Local quadratic velocity is derived from Doppler broadenings induced by fluid flows, with elementary diffusing wave spectroscopy formalism in backscattering configuration. We demonstrate quadratic mean velocity assessment in the 0.1-10 mm/s range in vitro and imaging of superficial blood perfusion with a spatial resolution of about 10 micrometers in rodent models of cortical and retinal blood flow.

  12. Normal Muscle Oxygen Consumption and Fatigability in Sickle Cell Patients Despite Reduced Microvascular Oxygenation and Hemorheological Abnormalities

    PubMed Central

    Waltz, Xavier; Pichon, Aurélien; Lemonne, Nathalie; Mougenel, Danièle; Lalanne-Mistrih, Marie-Laure; Lamarre, Yann; Tarer, Vanessa; Tressières, Benoit; Etienne-Julan, Maryse; Hardy-Dessources, Marie-Dominique; Hue, Olivier; Connes, Philippe

    2012-01-01

    Background/Aim Although it has been hypothesized that muscle metabolism and fatigability could be impaired in sickle cell patients, no study has addressed this issue. Methods We compared muscle metabolism and function (muscle microvascular oxygenation, microvascular blood flow, muscle oxygen consumption and muscle microvascular oxygenation variability, which reflects vasomotion activity, maximal muscle force and local muscle fatigability) and the hemorheological profile at rest between 16 healthy subjects (AA), 20 sickle cell-hemoglobin C disease (SC) patients and 16 sickle cell anemia (SS) patients. Results Muscle microvascular oxygenation was reduced in SS patients compared to the SC and AA groups and this reduction was not related to hemorhelogical abnormalities. No difference was observed between the three groups for oxygen consumption and vasomotion activity. Muscle microvascular blood flow was higher in SS patients compared to the AA group, and tended to be higher compared to the SC group. Multivariate analysis revealed that muscle oxygen consumption was independently associated with muscle microvascular blood flow in the two sickle cell groups (SC and SS). Finally, despite reduced muscle force in sickle cell patients, their local muscle fatigability was similar to that of the healthy subjects. Conclusions Sickle cell patients have normal resting muscle oxygen consumption and fatigability despite hemorheological alterations and, for SS patients only, reduced muscle microvascular oxygenation and increased microvascular blood flow. Two alternative mechanisms can be proposed for SS patients: 1) the increased muscle microvascular blood flow is a way to compensate for the lower muscle microvascular oxygenation to maintain muscle oxygen consumption to normal values or 2) the reduced microvascular oxygenation coupled with a normal resting muscle oxygen consumption could indicate that there is slight hypoxia within the muscle which is not sufficient to limit

  13. Early microvascular changes in the preterm neonate: a comparative study of the human and guinea pig

    PubMed Central

    Dyson, Rebecca M.; Palliser, Hannah K.; Lakkundi, Anil; de Waal, Koert; Latter, Joanna L.; Clifton, Vicki L.; Wright, Ian M. R.

    2014-01-01

    Abstract Dysfunction of the transition from fetal to neonatal circulatory systems may be a major contributor to poor outcome following preterm birth. Evidence exists in the human for both a period of low flow between 5 and 11 h and a later period of increased flow, suggesting a hypoperfusion–reperfusion cycle over the first 24 h following birth. Little is known about the regulation of peripheral blood flow during this time. The aim of this study was to conduct a comparative study between the human and guinea pig to characterize peripheral microvascular behavior during circulatory transition. Very preterm (≤28 weeks GA), preterm (29–36 weeks GA), and term (≥37 weeks GA) human neonates underwent laser Doppler analysis of skin microvascular blood flow at 6 and 24 h from birth. Guinea pig neonates were delivered prematurely (62 day GA) or at term (68–71 day GA) and laser Doppler analysis of skin microvascular blood flow was assessed every 2 h from birth. In human preterm neonates, there is a period of high microvascular flow at 24 h after birth. No period of low flow was observed at 6 h. In preterm animals, microvascular flow increased after birth, reaching a peak at 10 h postnatal age. Blood flow then steadily decreased, returning to delivery levels by 24 h. Preterm birth was associated with higher baseline microvascular flow throughout the study period in both human and guinea pig neonates. The findings do not support a hypoperfusion–reperfusion cycle in the microcirculation during circulatory transition. The guinea pig model of preterm birth will allow further investigation of the mechanisms underlying microvascular function and dysfunction during the initial extrauterine period. PMID:25350751

  14. Endurance, interval sprint, and resistance exercise training: impact on microvascular dysfunction in type 2 diabetes.

    PubMed

    Olver, T Dylan; Laughlin, M Harold

    2016-02-01

    Type 2 diabetes (T2D) alters capillary hemodynamics, causes capillary rarefaction in skeletal muscle, and alters endothelial and vascular smooth muscle cell phenotype, resulting in impaired vasodilatory responses. These changes contribute to altered blood flow responses to physiological stimuli, such as exercise and insulin secretion. T2D-induced microvascular dysfunction impairs glucose and insulin delivery to skeletal muscle (and other tissues such as skin and nervous), thereby reducing glucose uptake and perpetuating hyperglycemia and hyperinsulinemia. In patients with T2D, exercise training (EX) improves microvascular vasodilator and insulin signaling and attenuates capillary rarefaction in skeletal muscle. EX-induced changes subsequently augment glucose and insulin delivery as well as glucose uptake. If these adaptions occur in a sufficient amount of tissue, and skeletal muscle in particular, chronic exposure to hyperglycemia and hyperinsulinemia and the risk of microvascular complications in all vascular beds will decrease. We postulate that EX programs that engage as much skeletal muscle mass as possible and recruit as many muscle fibers within each muscle as possible will generate the greatest improvements in microvascular function, providing that the duration of the stimulus is sufficient. Primary improvements in microvascular function occur in tissues (skeletal muscle primarily) engaged during exercise, and secondary improvements in microvascular function throughout the body may result from improved blood glucose control. We propose that the added benefit of combined resistance and aerobic EX programs and of vigorous intensity EX programs is not simply "more is better." Rather, we believe the additional benefit is the result of EX-induced adaptations in and around more muscle fibers, resulting in more muscle mass and the associated microvasculature being changed. Thus, to acquire primary and secondary improvements in microvascular function and improved

  15. Methylene blue solder re-absorption in microvascular anastomoses

    NASA Astrophysics Data System (ADS)

    Birch, Jeremy F.; Hepplewhite, J.; Frier, Malcolm; Bell, Peter R. F.

    2003-06-01

    Soldered vascular anastomoses have been reported using several chromophores but little is known of the optimal conditions for microvascular anastomosis. There are some indications of the optimal protein contents of a solder, and the effects of methylene blue on anastomotic strength. The effects of varying laser power density in vivo have also been described, showing a high rate of thrombosis with laser power over 22.9Wcm-2. However no evidence exists to describe how long the solder remains at the site of the anastomosis. Oz et al reported that the fibrin used in their study had been almost completely removed by 90 days but without objective evidence of solder removal. In order to address the issue of solder re-absorption from the site of an anastomosis we used radio-labelled albumin (I-125) incorporated into methylene blue based solder. This was investigated in both the situation of the patent and thrombosed anastomosis with anastomoses formed at high and low power. Iodine-125 (half life: 60.2 days) was covalently bonded to porcine albumin and mixed with the solder solution. Radio-iodine has been used over many years to determine protein turnover using either I-125 or I-131. Iodine-125 labelled human albumin is regularly used as a radiopharmaceutical tool for the determination of plasma volume. Radio-iodine has the advantages of not affecting protein metabolism and the label is rapidly excreted after metabolic breakdown. Labelling with chromium (Cr-51) causes protein denaturation and is lost from the protein with time. Labelled albumin has been reported in human studies over a 21-day period, with similar results reported by Matthews. Most significantly McFarlane reported a different rate of catabolism of I-131 and I-125 over a 22-day period. The conclusion from this is that the rate of iodine clearance is a good indicator of protein catabolism. In parallel with the surgery a series of blank standards were prepared with a known mass of solder to correct for isotope

  16. Mst1 inhibits CMECs autophagy and participates in the development of diabetic coronary microvascular dysfunction

    PubMed Central

    Lin, Jie; Zhang, Lei; Zhang, Mingming; Hu, Jianqiang; Wang, Tingting; Duan, Yu; Man, Wanrong; Wu, Bin; Feng, Jiaxu; Sun, Lei; Li, Congye; Zhang, Rongqing; Wang, Haichang; Sun, Dongdong

    2016-01-01

    Cardiovascular complications account for a substantial proportion of morbidity and mortality in diabetic patients. Abnormalities of cardiac microvascular endothelial cells (CMECs) lead to impaired cardiac microvascular vessel integrity and subsequent cardiac dysfunction, underlining the importance of coronary microvascular dysfunction. In this study, experimental diabetes models were constructed using Mst1 transgenic, Mst1 knockout and sirt1 knockout mice. Diabetic Mst1 transgenic mice exhibited impaired cardiac microvessel integrity and decreased cardiac function. Mst1 overexpression deceased CMECs autophagy as evidenced by decreased LC3 expression and enhanced protein aggregation when subjected to high glucose culture. Mst1 knockout improved cardiac microvessel integrity and enhanced cardiac functions in diabetic mice. Mst1 knockdown up-regulated autophagy as indicated by more typical autophagosomes and increased LC3 expression in CMECs subjected to high glucose cultures. Mst1 knockdown also promoted autophagic flux in the presence of bafilomycin A1. Mst1 overexpression increased CMECs apoptosis, whereas Mst1 knockout decreased CMECs apoptosis. Sirt1 knockout abolished the effects of Mst1 overexpression in cardiac microvascular injury and cardiac dysfunction. In conclusion, Mst1 knockout preserved cardiac microvessel integrity and improved cardiac functions in diabetic mice. Mst1 decreased sirt1 activity, inhibited autophagy and enhanced apoptosis in CMECs, thus participating in the pathogenesis of diabetic coronary microvascular dysfunction. PMID:27680548

  17. Conditioned Media from Microvascular Endothelial Cells Cultured in Simulated Microgravity Inhibit Osteoblast Activity

    PubMed Central

    Cazzaniga, Alessandra; Castiglioni, Sara; Maier, Jeanette A. M.

    2014-01-01

    Background and Aims. Gravity contributes to the maintenance of bone integrity. Accordingly, weightlessness conditions during space flight accelerate bone loss and experimental models in real and simulated microgravity show decreased osteoblastic and increased osteoclastic activities. It is well known that the endothelium and bone cells cross-talk and this intercellular communication is vital to regulate bone homeostasis. Because microgravity promotes microvascular endothelial dysfunction, we anticipated that the molecular cross-talk between endothelial cells exposed to simulated microgravity and osteoblasts might be altered. Results. We cultured human microvascular endothelial cells in simulated microgravity using the rotating wall vessel device developed by NASA. Endothelial cells in microgravity show growth inhibition and release higher amounts of matrix metalloproteases type 2 and interleukin-6 than controls. Conditioned media collected from microvascular endothelial cells in simulated microgravity were used to culture human osteoblasts and were shown to retard osteoblast proliferation and inhibit their activity. Discussion. Microvascular endothelial cells in microgravity are growth retarded and release high amounts of matrix metalloproteases type 2 and interleukin-6, which might play a role in retarding the growth of osteoblasts and impairing their osteogenic activity. Conclusions. We demonstrate that since simulated microgravity modulates microvascular endothelial cell function, it indirectly impairs osteoblastic function. PMID:25210716

  18. [Coronary microvascular dysfunction : Clinical aspects, diagnosis and therapy].

    PubMed

    Ong, P; Sechtem, U

    2016-06-01

    Just as in epicardial coronary stenosis, coronary microvascular dysfunction (CMD) also leads to an imbalance of myocardial oxygen supply and demand. The dysfunction is located at the level of the coronary microcirculation with vessel diameters < 500 µm and structural as well as functional alterations have been described. The underlying mechanisms are diverse, frequently overlap and are still incompletely understood. Among others, conditions such as chronic inflammation, estrogen deficiency and a genetic familial predisposition have been reported. A common and often underdiagnosed clinical manifestation of CMD is found in patients who have symptoms of angina pectoris but no obstructive epicardial coronary artery disease or myocardial disease. The CMD can be diagnosed using non-invasive procedures, such as the combination of coronary computed tomography (CT) angiography and cardiac stress magnetic resonance imaging (MRI) or coronary CT and positron emission tomography (PET). In addition, invasive coronary vasomotor assessment is also suitable. Very little evidence is available regarding the effectiveness of pharmacological treatment of CMD. The current European Society of Cardiology (ESC) guidelines on the management of stable coronary artery disease from 2013 recommend using acetylsalicylic acid (ASS) and a statin as well as beta blockers and/or calcium channel blockers. Patients with CMD have an elevated risk for coronary events and death of approximately 1.7 % per year. Moreover, there is an increased morbidity with frequent presentations in practices and emergency admissions. Clinical research efforts should aim at a better characterization of the underlying mechanisms of CMD in order to develop targeted treatment approaches. PMID:27255117

  19. Novel Biomarkers of Arterial and Venous Ischemia in Microvascular Flaps

    PubMed Central

    Nguyen, Gerard K.; Monahan, John F. W.; Davis, Gabrielle B.; Lee, Yong Suk; Ragina, Neli P.; Wang, Charles; Zhou, Zhao Y.; Hong, Young Kwon; Spivak, Ryan M.; Wong, Alex K.

    2013-01-01

    both diagnose and successfully treat microvascular complications before irreversible tissue damage and flap loss occurs. PMID:23977093

  20. Microvascular coronary dysfunction and ischemic heart disease: where are we in 2014?

    PubMed

    Petersen, John W; Pepine, Carl J

    2015-02-01

    Many patients with angina and signs of myocardial ischemia on stress testing have no significant obstructive epicardial coronary disease. There are many potential coronary and non-coronary mechanisms for ischemia without obstructive epicardial coronary disease, and prominent among these is coronary microvascular and/or endothelial dysfunction. Patients with coronary microvascular and/or endothelial dysfunction are often at increased risk of adverse cardiovascular events, including ischemic events and heart failure despite preserved ventricular systolic function. In this article, we will review the diagnosis and treatment of coronary microvascular and endothelial dysfunction, discuss their potential contribution to heart failure with preserved ejection fraction, and highlight recent advances in the evaluation of atherosclerotic morphology in these patients, many of whom have non-obstructive epicardial disease.

  1. Monitoring the healing process of laser-induced microvascular lesions using optical-resolution photoacoustic microscopy

    NASA Astrophysics Data System (ADS)

    Hu, Song; Maslov, Konstantin I.; Wang, Lihong V.

    2009-02-01

    Optical resolution photoacoustic microscopy (OR-PAM) possesses optical resolution and reveals endogenous optical absorption contrast, promising to be a valuable tool for in vivo microvascular imaging. In laser dermatology, OR-PAM can provide fruitful structural and functional information about the targeted microvascular lesions, such as their threedimensional (3D) morphology, precise location inside the tissue, and blood oxygenation within single vessels, which will facilitate accurate diagnosis and proper treatment. More importantly, the advantages of noninvasiveness and measurement consistency also permit OR-PAM to monitor the healing process of the laser-surgical wound noninvasively. In this work, we employed OR-PAM to monitor the healing process of microvascular lesions induced by nanosecond-pulsed laser. Our results indicate that OR-PAM could be a very useful tool in laser dermatology and laser microsurgery.

  2. The prevention of diabetic microvascular complications of diabetes: is there a role for lipid lowering?

    PubMed

    Leiter, Lawrence A

    2005-06-01

    The role of hyperglycemia in the development of microvascular complications of diabetes, such as nephropathy, retinopathy and neuropathy, has been well documented. Evidence is accumulating to support the concept that dyslipidemia can also contribute to the development of these complications. Lipid-lowering agents, such as statins, have been shown to prevent cardiovascular events in patients with diabetes. However, in addition to preventing macrovascular diseases, statins may also be able to retard the progression of microvascular complications of diabetes. Indeed, in addition to reducing lipid levels, these agents can improve endothelial function and reduce oxidative stress, which can improve microvascular function. These findings would provide further support for the use of lipid-lowering agents in patients with diabetes.

  3. Microvascular Branching as a Determinant of Blood Flow by Intravital Particle Imaging Velocimetry

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, Patricia; McKay, Terri L.; Vickerman, Mary B.; Wernet, Mark P.; Myers, Jerry G.; Radhakrishnan, Krishnan

    2007-01-01

    The effects of microvascular branching on blood flow were investigated in vivo by microscopic particle imaging velocimetry (micro-PIV). We use micro-PIV to measure blood flow by tracking red blood cells (RBC) as the moving particles. Velocity flow fields, including flow pulsatility, were analyzed for the first four branching orders of capillaries, postcapillary venules and small veins of the microvascular network within the developing avian yolksac at embryonic day 5 (E5). Increasing volumetric flowrates were obtained from parabolic laminar flow profiles as a function of increasing vessel diameter and branching order. Maximum flow velocities increased approximately twenty-fold as the function of increasing vessel diameter and branching order compared to flow velocities of 100 - 150 micron/sec in the capillaries. Results from our study will be useful for the increased understanding of blood flow within anastomotic, heterogeneous microvascular networks.

  4. Applications of computational models to better understand microvascular remodelling: a focus on biomechanical integration across scales

    PubMed Central

    Murfee, Walter L.; Sweat, Richard S.; Tsubota, Ken-ichi; Gabhann, Feilim Mac; Khismatullin, Damir; Peirce, Shayn M.

    2015-01-01

    Microvascular network remodelling is a common denominator for multiple pathologies and involves both angiogenesis, defined as the sprouting of new capillaries, and network patterning associated with the organization and connectivity of existing vessels. Much of what we know about microvascular remodelling at the network, cellular and molecular scales has been derived from reductionist biological experiments, yet what happens when the experiments provide incomplete (or only qualitative) information? This review will emphasize the value of applying computational approaches to advance our understanding of the underlying mechanisms and effects of microvascular remodelling. Examples of individual computational models applied to each of the scales will highlight the potential of answering specific questions that cannot be answered using typical biological experimentation alone. Looking into the future, we will also identify the needs and challenges associated with integrating computational models across scales. PMID:25844149

  5. Effect of high altitude and exercise on microvascular parameters in acclimatized subjects.

    PubMed

    Bauer, Andreas; Demetz, Florian; Bruegger, Dirk; Schmoelz, Martin; Schroepfer, Sebastian; Martignoni, André; Baschnegger, Heiko; Hoelzl, Josef; Thiel, Manfred; Choukér, Alexander; Peter, Klaus; Gamble, John; Christ, Frank

    2006-02-01

    The role of microvascular fluid shifts in the adaptation to hypobaric hypoxia and its contribution to the pathophysiology of AMS (acute mountain sickness) is unresolved. In a systematic prospective study, we investigated the effects of hypobaric hypoxia and physical exercise alone, and in combination, on microvascular fluid exchange and related factors. We used computer-assisted VCP (venous congestion plethysmography) on the calves of ten altitude-acclimatized volunteers. We investigated the effects of: (i) actively climbing to an altitude of 3196 m, (ii) airlifting these subjects to the same altitude, and (iii) exercise at low altitude. CFC (capillary filtration capacity), Pvi (isovolumetric venous pressure) and Qa (calf blood flow) were assessed before and after each procedure and then repeated after an overnight rest. Measurements of CFC showed no evidence of increased microvascular permeability after any of the procedures. Pvi was significantly decreased (P<0.001) from 20.3+/-4.4 to 8.9+/-4.3 mmHg after active ascent, and was still significantly lower (P=0.009) after overnight rest at high altitude (13.6+/-5.9 mmHg). No such changes were observed after the passive ascent (16.7+/-4.0 mmHg at baseline; 17.3+/-4.5 mmHg after passive ascent; and 19.9+/-5.3 mmHg after overnight rest) or after exercise at low altitude. After the active ascent, Qa was significantly increased. We also found a significant correlation between Qa, Pvi and the number of circulating white blood cells. In conclusion, we found evidence to support the hypothesis that increased microvascular permeability associated with AMS does not occur in acclimatized subjects. We also observed that the microvascular equilibrium pressure (Pvi) fell in inverse relation to the increase in Qa, especially in hypoxic exercise. We hypothesize that this inverse relationship reflects the haemodynamic changes at the microvascular interface, possibly attributable to the flow-induced increases in endothelial surface

  6. Segmental resection of the anterior mandibular arch with fibular microvascular reconstruction.

    PubMed

    Dierks, E J; Karakourtis, M H

    1997-09-01

    Segmental mandibular resection should be undertaken if there is a demonstrable invasion by cancer or if such invasion is suspected. Before the advent of microvascular free flaps, immediate osseous reconstruction of the anterior mandible was technically demanding and unreliable. Mandibular reconstruction with microvascular free flaps is no longer a novelty, nor is it reserved for unusually large resections. It has become the method of choice for the immediate reconstruction of defects resulting from mandibular cancer. This technique is particularly well-suited for defects of the anterior mandibular arch.

  7. Decreased Endothelial Nitric Oxide Bioavailability, Impaired Microvascular Function, and Increased Tissue Oxygen Consumption in Children with Falciparum Malaria

    PubMed Central

    Yeo, Tsin W.; Lampah, Daniel A.; Kenangalem, Enny; Tjitra, Emiliana; Weinberg, J. Brice; Granger, Donald L.; Price, Ric N.; Anstey, Nicholas M.

    2014-01-01

    Endothelial nitric oxide (NO) bioavailability, microvascular function, and host oxygen consumption have not been assessed in pediatric malaria. We measured NO-dependent endothelial function by using peripheral artery tonometry to determine the reactive hyperemia index (RHI), and microvascular function and oxygen consumption (VO2) using near infrared resonance spectroscopy in 13 Indonesian children with severe falciparum malaria and 15 with moderately severe falciparum malaria. Compared with 19 controls, children with severe malaria and those with moderately severe malaria had lower RHIs (P = .03); 12% and 8% lower microvascular function, respectively (P = .03); and 29% and 25% higher VO2, respectively. RHIs correlated with microvascular function in all children with malaria (P < .001) and all with severe malaria (P < .001). Children with malaria have decreased endothelial and microvascular function and increased oxygen consumption, likely contributing to the pathogenesis of the disease. PMID:24879801

  8. Decreased endothelial nitric oxide bioavailability, impaired microvascular function, and increased tissue oxygen consumption in children with falciparum malaria.

    PubMed

    Yeo, Tsin W; Lampah, Daniel A; Kenangalem, Enny; Tjitra, Emiliana; Weinberg, J Brice; Granger, Donald L; Price, Ric N; Anstey, Nicholas M

    2014-11-15

    Endothelial nitric oxide (NO) bioavailability, microvascular function, and host oxygen consumption have not been assessed in pediatric malaria. We measured NO-dependent endothelial function by using peripheral artery tonometry to determine the reactive hyperemia index (RHI), and microvascular function and oxygen consumption (VO2) using near infrared resonance spectroscopy in 13 Indonesian children with severe falciparum malaria and 15 with moderately severe falciparum malaria. Compared with 19 controls, children with severe malaria and those with moderately severe malaria had lower RHIs (P = .03); 12% and 8% lower microvascular function, respectively (P = .03); and 29% and 25% higher VO2, respectively. RHIs correlated with microvascular function in all children with malaria (P < .001) and all with severe malaria (P < .001). Children with malaria have decreased endothelial and microvascular function and increased oxygen consumption, likely contributing to the pathogenesis of the disease.

  9. Intraoperative microvascular Doppler ultrasonography in cerebral aneurysm surgery

    PubMed Central

    Stendel, R.; Pietila, T.; Al, H; Schilling, A.; Brock, M.

    2000-01-01

    OBJECTIVES—Outcome of surgical treatment of cerebral aneurysms may be severely compromised by local cerebral ischaemia or infarction resulting from the inadvertent occlusion of an adjacent vessel by the aneurysm clip, or by incomplete aneurysm closure. It is therefore mandatory to optimise clip placement in situ to reduce the complication rate. The present study was performed to investigate the reliability of intraoperative microvascular Doppler ultrasonography (MDU) in cerebral aneurysm surgery, and to assess the impact of this method on the surgical procedure itself.
METHODS—Seventy five patients (19 men, 56 women, mean age 54.8 years, range 22-84 years) with 90 saccular cerebral aneurysms were evaluated. Blood flow velocities in the aneurysmal sac and in the adjacent vessels were determined by MDU before and after aneurysm clipping. The findings of MDU were analysed and compared with those of visual inspection of the surgical site and of postoperative angiography. Analysis was also made of the cases in which the clip was repositioned due to MDU findings.
RESULTS—A relevant stenosis of an adjacent vessel induced by clip positioning that had escaped detection by visual inspection was identified by Doppler ultrasonography in 17 out of 90 (18.9%) aneurysms. In addition, Doppler ultrasound demonstrated a primarily unoccluded aneurysm in 11 out of 90 (12.2%) patients. The aneurysm clip was repositioned on the basis of the MDU findings in 26 out of 90 (28.8%) cases. In middle cerebral artery (MCA) aneurysms, the MDU results were relevant to the surgical procedure in 17out of 44 (38.6%) cases. Whereas with aneurysms of the anterior cerebral artery significant findings occurred in only five of 32cases (15.6%; p<0.05). The clip was repositioned on the basis of the MDU results in 18 out of 50 (36%) aneurysms in patients with subarachnoid haemorrhage (SAH) grade I-V compared with only eight out of 40 (20%) aneurysms in patients without SAH (p<0.05).

  10. Sonothrombolysis with BR38 Microbubbles Improves Microvascular Patency in a Rat Model of Stroke

    PubMed Central

    Kampschulte, Marian; Hyvelin, Jean-Marc; Botteron, Catherine; Juenemann, Martin; Yeniguen, Mesut; Krombach, Gabriele A.; Kaps, Manfred; Spratt, Neil J.; Gerriets, Tibo; Nedelmann, Max

    2016-01-01

    Background Early recanalization of large cerebral vessels in ischemic stroke is associated with improved clinical outcome, however persisting hypoperfusion leads to poor clinical recovery despite large vessel recanalization. Limited experimental sonothrombolysis studies have shown that addition of microbubbles during treatment can improve microvascular patency. We aimed to determine the effect of two different microbubble formulations on microvascular patency in a rat stroke model. Methods We tested BR38 and SonoVue® microbubble-enhanced sonothrombolysis in Wistar rats submitted to 90-minute filament occlusion of the middle cerebral artery. Rats were randomized to treatment (n = 6/group): control, rt-PA, or rt-PA+3-MHz ultrasound insonation with BR38 or SonoVue® at full or 1/3 dose. Treatment duration was 60 minutes, beginning after withdrawal of the filament, and sacrifice was immediately after treatment. Vascular volumes were evaluated with microcomputed tomography. Results Total vascular volume of the ipsilateral hemisphere was reduced in control and rt-PA groups (p<0.05), but was not significantly different from the contralateral hemisphere in all microbubble-treated groups (p>0.1). Conclusions Microbubble-enhanced sonothrombolysis improves microvascular patency. This effect is not dose- or microbubble formulation-dependent suggesting a class effect of microbubbles promoting microvascular reopening. This study demonstrates that microbubble-enhanced sonothrombolysis may be a therapeutic strategy for patients with persistent hypoperfusion of the ischemic territory. PMID:27077372

  11. Circulation, bone scans, and tetracycline labeling in microvascularized and vascular bundle implanted rib grafts

    SciTech Connect

    Lalonde, D.H.; Williams, H.B.; Rosenthall, L.; Viloria, J.B.

    1984-11-01

    The circulation in microvascularized rib grafts has been compared with that in conventional rib grafts and in those augmented by a direct vascular bundle implantation into the bone grafts. A new experimental model has been designed to correlate vascular perfusion, bone scan patterns, tetracycline labeling, and histological findings in these bone grafts. Posterior microvascularized rib grafts were found to have a circulatory pattern identical to that of the normal rib. Failed microvascularized rib grafts were revascularized more slowly than conventional rib grafts. Vascular bundles implanted into rib grafts remained patent and increased the rate of revascularization. The stripping or preservation of periosteum had no observable effects on the rate or pattern of conventional rib graft revascularization. The circulation in rib grafts was accurately reflected in technetium 99 bone scans, as was the patency of the anastomoses of microvascularized rib grafts and of implanted vascular bundles. In contrast, tetracycline labeling was repeatedly observed in avascular areas of bone grafts and, therefore, is not a reliable indicator of bone graft circulation.

  12. High fat diet induces central obesity, insulin resistance and microvascular dysfunction in hamsters.

    PubMed

    Costa, Rute R S; Villela, Nivaldo Ribeiro; Souza, Maria das Graças C; Boa, Beatriz C S; Cyrino, Fátima Z G A; Silva, Simone V; Lisboa, Patricia C; Moura, Egberto G; Barja-Fidalgo, Thereza Christina; Bouskela, Eliete

    2011-11-01

    Microvascular dysfunction is an early finding in obesity possibly related to co-morbidities like diabetes and hypertension. Therefore we have investigated changes on microvascular function, body composition, glucose and insulin tolerance tests (GTT and ITT) on male hamsters fed either with high fat (HFD, n=20) or standard (Control, n=21) diet during 16 weeks. Total body fat and protein content were determined by carcass analysis, aorta eNOS and iNOS expression by immunoblotting assay and mean blood pressure (MAP) and heart rate (HR) by an arterial catheter. Microvascular reactivity in response to acetylcholine and sodium nitroprusside, functional capillary density (FCD), capillary recruitment induced by a hyperinsulinemic status and macromolecular permeability after 30 min ischemia was assessed on either cheek pouch or cremaster muscle preparations. Compared to Control, HFD animals have shown increased visceral fat (6.0 ± 0.8 vs. 13.8 ± 0.6g/100g BW), impaired endothelial dependent vasodilatation, decreased FCD (11.3 ± 1.3 vs. 6.8 ± 1.2/field) and capillary recruitment during hyperinsulinemia and increased macromolecular permeability after ischemia/reperfusion (86.4 ± 5.2 vs.105.2 ± 5.1 leaks/cm(2)), iNOS expression and insulin resistance. MAP, HR, endothelial independent vasodilatation and eNOS expression were not different between groups. Our results have shown that HFD elicits an increase on visceral fat deposition, microvascular dysfunction and insulin resistance in hamsters.

  13. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity.

    PubMed

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-12-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chronic inflammation engenders both. In the present study, we investigate the temporal relationship between vascular insulin resistance and metabolic insulin resistance. We assessed insulin responses in all arterial segments, including aorta, distal saphenous artery and the microvasculature, as well as the metabolic insulin responses in muscle in rats fed on a high-fat diet (HFD) for various durations ranging from 3 days to 4 weeks with or without sodium salicylate treatment. Compared with controls, HFD feeding significantly blunted insulin-mediated Akt (protein kinase B) and eNOS [endothelial nitric oxide (NO) synthase] phosphorylation in aorta in 1 week, blunted vasodilatory response in small resistance vessel in 4 weeks and microvascular recruitment in as early as 3 days. Insulin-stimulated whole body glucose disposal did not begin to progressively decrease until after 1 week. Salicylate treatment fully inhibited vascular inflammation, prevented microvascular insulin resistance and significantly improved muscle metabolic responses to insulin. We conclude that microvascular insulin resistance is an early event in diet-induced obesity and insulin resistance and inflammation plays an essential role in this process. Our data suggest microvascular insulin resistance contributes to the development of metabolic insulin resistance in muscle and muscle microvasculature is a potential therapeutic target in the prevention and treatment of diabetes and its related complications.

  14. Usefulness of Microvascular Ultrasonography in Differentiating Metastatic Lymphadenopathy from Tuberculous Lymphadenitis.

    PubMed

    Ryoo, Inseon; Suh, Sangil; You, Sung-Hye; Seol, Hae Young

    2016-09-01

    This study was undertaken to evaluate the usefulness of vascular pattern analysis on microvascular ultrasonography in distinguishing metastatic lymphadenopathy from tuberculous lymphadenitis, compared with conventional power Doppler ultrasonography, and to evaluate inter-observer agreement for microvascular ultrasonography. Thirty-four patients with metastatic lymphadenopathy and 27 patients with tuberculous lymphadenitis were included. The level of inter-observer agreement was excellent or good for all aspects of vascular pattern analysis on both ultrasonographic examinations. Vascular distribution, internal vascularity and internal vascular features of lymph nodes on microvascular ultrasonography differed significantly different (p ≤ 0.002) between metastatic lymphadenopathy and tuberculous lymphadenitis. A central vascular pattern with displacement was prevalent in metastasis, and an avascular pattern was more frequent in tuberculosis. Internal vascularity of metastasis was higher than that of tuberculosis. Vascular patterns on power Doppler ultrasonography did not differ significantly. Vascular pattern analysis using microvascular ultrasonography can be helpful in differentiating metastatic lymphadenopathy from tuberculous lymphadenitis with good inter-observer agreement.

  15. Integration of Self-Assembled Microvascular Networks with Microfabricated PEG-Based Hydrogels

    PubMed Central

    Cuchiara, Michael P.; Gould, Daniel J.; McHale, Melissa K.; Dickinson, Mary E.

    2013-01-01

    Despite tremendous efforts, tissue engineered constructs are restricted to thin, simple tissues sustained only by diffusion. The most significant barrier in tissue engineering is insufficient vascularization to deliver nutrients and metabolites during development in vitro and to facilitate rapid vascular integration in vivo. Tissue engineered constructs can be greatly improved by developing perfusable microvascular networks in vitro in order to provide transport that mimics native vascular organization and function. Here a microfluidic hydrogel is integrated with a self-assembling pro-vasculogenic co-culture in a strategy to perfuse microvascular networks in vitro. This approach allows for control over microvascular network self-assembly and employs an anastomotic interface for integration of self-assembled micro-vascular networks with fabricated microchannels. As a result, transport within the system shifts from simple diffusion to vessel supported convective transport and extra-vessel diffusion, thus improving overall mass transport properties. This work impacts the development of perfusable prevascularized tissues in vitro and ultimately tissue engineering applications in vivo. PMID:23536744

  16. Angiotensin AT1 and AT2 Receptors Regulate Basal Skeletal Muscle Microvascular Volume and Glucose Utilization

    PubMed Central

    Chai, Weidong; Wang, Wenhui; Liu, Jia; Barrett, Eugene J.; Carey, Robert M.; Cao, Wenhong; Liu, Zhenqi

    2010-01-01

    Angiotensin II causes vasoconstriction via the type 1 receptor (AT1R) and vasodilatation through the type 2 receptor (AT2R). Both are expressed in muscle microvasculature where substrate exchanges occur. Whether they modulate basal muscle microvascular perfusion and substrate metabolism is not known. We measured microvascular blood volume (MBV), a measure of microvascular surface area and perfusion, in rats during systemic infusion of angiotensin II at either 1 or 100 ng/kg/min. Each caused a significant increase in muscle MBV. Likewise, administration of AT1R blocker losartan increased muscle MBV by >3-fold (p<0.001). Hindleg glucose extraction and muscle interstitial oxygen saturation simultaneously increased by 2–3-fold. By contrast, infusing AT2R antagonist PD123319 significantly decreased muscle MBV by up to 80% (p<0.001). This was associated with a significant decrease in hindleg glucose extraction and muscle oxygen saturation. AT2R antagonism and inhibition of nitric oxide synthase each blocked the losartan-induced increase in muscle MBV and glucose uptake. In conclusion, angiotensin II acts on both AT1R and AT2R to regulate basal muscle microvascular perfusion. Basal AT1R tone restricts muscle MBV and glucose extraction while basal AT2R activity increases muscle MBV and glucose uptake. Pharmacologic manipulation of the balance of AT1R and AT2R activity affords the potential to improve glucose metabolism. PMID:19996061

  17. Early Systemic Microvascular Damage in Pigs with Atherogenic Diabetes Mellitus Coincides with Renal Angiopoietin Dysbalance

    PubMed Central

    Khairoun, Meriem; van den Heuvel, Mieke; van den Berg, Bernard M.; Sorop, Oana; de Boer, Rients; van Ditzhuijzen, Nienke S.; Bajema, Ingeborg M.; Baelde, Hans J.; Zandbergen, Malu; Duncker, Dirk J.; Rabelink, Ton J.; Reinders, Marlies E. J.; Rotmans, Joris I.

    2015-01-01

    Background Diabetes mellitus (DM) is associated with a range of microvascular complications including diabetic nephropathy (DN). Microvascular abnormalities in the kidneys are common histopathologic findings in DN, which represent one manifestation of ongoing systemic microvascular damage. Recently, sidestream dark-field (SDF) imaging has emerged as a noninvasive tool that enables one to visualize the microcirculation. In this study, we investigated whether changes in the systemic microvasculature induced by DM and an atherogenic diet correlated spatiotemporally with renal damage. Methods Atherosclerotic lesion development was triggered in streptozotocin-induced DM pigs (140 mg/kg body weight) by administering an atherogenic diet for approximately 11 months. Fifteen months following induction of DM, microvascular morphology was visualized in control pigs (n = 7), non-diabetic pigs fed an atherogenic diet (ATH, n = 5), and DM pigs fed an atherogenic diet (DM+ATH, n = 5) using SDF imaging of oral mucosal tissue. Subsequently, kidneys were harvested from anethesized pigs and the expression levels of well-established markers for microvascular integrity, such as Angiopoietin-1 (Angpt1) and Angiopoietin-2 (Angpt2) were determined immunohistochemically, while endothelial cell (EC) abundance was determined by immunostaining for von Willebrand factor (vWF). Results Our study revealed an increase in the capillary tortuosity index in DM+ATH pigs (2.31±0.17) as compared to the control groups (Controls 0.89±0.08 and ATH 1.55±0.11; p<0.05). Kidney biopsies showed marked glomerular lesions consisting of mesangial expansion and podocyte lesions. Furthermore, we observed a disturbed Angpt2/ Angpt1balance in the cortex of the kidney, as evidenced by increased expression of Angpt2 in DM+ATH pigs as compared to Control pigs (p<0.05). Conclusion In the setting of DM, atherogenesis leads to the augmentation of mucosal capillary tortuosity, indicative of systemic microvascular damage

  18. Cardiopulmonary bypass increases pulmonary microvascular permeability through the Src kinase pathway: Involvement of caveolin-1 and vascular endothelial cadherin

    PubMed Central

    ZHANG, JUNWEN; JIANG, ZHAOLEI; BAO, CHUNRONG; MEI, JU; ZHU, JIAQUAN

    2016-01-01

    Changes in pulmonary microvascular permeability following cardiopulmonary bypass (CPB) and the underlying mechanisms have not yet been established. Therefore, the aim of the present study was to elucidate the alterations in pulmonary microvascular permeability following CPB and the underlying mechanism. The pulmonary microvascular permeability was measured using Evans Blue dye (EBD) exclusion, and the neutrophil infiltration and proinflammatory cytokine secretion was investigated. In addition, the activation of Src kinase and the phosphorylation of caveolin-1 and vascular endothelial cadherin (VE-cadherin) was examined. The results revealed that CPB increased pulmonary microvascular leakage, neutrophil count and proinflammatory cytokines in the bronchoalveolar lavage fluid, and activated Src kinase. The administration of PP2, an inhibitor of Src kinase, decreased the activation of Src kinase and attenuated the increase in pulmonary microvascular permeability observed following CPB. Two important proteins associated with vascular permeability, caveolin-1 and VE-cadherin, were significantly activated at 24 h in the lung tissues following CPB, which correlated with the alterations in pulmonary microvascular permeability and Src kinase. PP2 administration inhibited their activation, suggesting that they are downstream factors of Src kinase activation. The data indicated that the Src kinase pathway increased pulmonary microvascular permeability following CPB, and the activation of caveolin-1 and VE-cadherin may be involved. Inhibition of this pathway may provide a potential therapy for acute lung injury following cardiac surgery. PMID:26847917

  19. Heparin-binding EGF-like Growth Factor Increases Intestinal Microvascular Blood Flow in Necrotizing Enterocolitis

    PubMed Central

    Yu, Xiaoyi; Radulescu, Andrei; Zorko, Nicholas; Besner, Gail E.

    2009-01-01

    Background & Aims Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in neonates. Although the exact etiology remains unknown, decreased intestinal blood flow is thought to play a critical role. We have shown that heparin-binding EGF-like growth factor (HB-EGF) protects the intestines from injury in a rodent model of NEC. Our current goal was to assess the effect of HB-EGF on intestinal microvascular blood flow and intestinal injury in rat pups subjected to experimental NEC. Methods Newborn rat pups were subjected to stress by exposure to hypoxia, hypothermia, hypertonic feedings and lipopolysaccharide, with some pups receiving HB-EGF (800 μg/kg/dose) added to the feeds. Control animals received breast milk. Intestinal injury was graded using a standard histologic injury scoring system. Microvascular blood flow was assessed by FITC-dextran angiography with fluorescent images subjected to quantification, and by scanning electron microscopy. Results Intestinal microvascular blood flow (defined as the extent of vascular filling with FITC-dextran) was significantly decreased in pups subjected to stress compared to breast fed pups. Stressed pups treated with HB-EGF had significantly increased microvascular blood flow. The changes in villous microvasculature correlated with histologic injury scores, with stressed pups treated with HB-EGF showing decreased histologic injury. Conclusions HB-EGF significantly preserved intestinal microvascular blood flow in pups subjected to experimental NEC, indicating that HB-EGF may play a critical role in the therapy of various diseases manifested by decreased intestinal blood flow, including NEC. PMID:19361505

  20. The mechanisms of gastric mucosal injury: focus on microvascular endothelium as a key target.

    PubMed

    Tarnawski, A S; Ahluwalia, A; Jones, M K

    2012-01-01

    This paper reviews and updates current views on gastric mucosal injury with a focus on the microvascular endothelium as the key target and the role of the anti-apoptosis protein survivin. Under normal conditions, mucosal integrity is maintained by well structured and mutually amplifying defense mechanisms, which include pre-epithelial "barrier"--the first line of defense; and, an epithelial "barrier". Other important defense mechanisms of gastric mucosa include: continuous epithelial cell renewal, blood flow through mucosal microvessels (providing oxygen and nutrients), an endothelial microvascular "barrier," sensory innervation, and generation of PGs, nitric oxide and hydrogen sulfide. The microvascular endothelium lining gastric mucosal blood microvessels severs not only as a barrier but is a biologically active tissue involved in many synthetic and metabolic functions. It allows transport of oxygen and nutrients, and produces prostaglandins and leukotriens, procoagulant factors, nitric oxide, endothelin, ghrelin, HSP, growth factors such VEGF, bFGF, angiopoietin 2 and others, specific types of collagen, plasminogen activator, and can also actively contract. Accumulating evidence indicates that the gastric microvascular endothelium is a critical target for injury by ethanol, NSAIDs, free radicals, ischemia-reperfusion and other damaging factors. The injury--microvessel rupture, plasma and erythrocyte extravasation, platelet aggregation and fibrin deposition caused by these damaging factors--occurs early (1-5 min), precedes glandular epithelial cell injury and results in cessation of blood flow, ischemia, hypoxia and impaired oxygen and nutrient transport. As a consequence, mucosal necrosis develops. One of the main reasons for the increased susceptibility of gastric microvascular endothelial (vs. epithelial) cells to injury is reduced expression levels of survivin, an anti-apoptosis protein, which is a regulator of both proliferation and cell survival. PMID

  1. Muscle endothelial-dependent microvascular dysfunction in adulthood due to early postnatal overnutrition.

    PubMed

    Leite, Richard Diego; Kraemer-Aguiar, Luiz Guilherme; Boa, Beatriz Costa da Silva; Cyrino, Fatima Z G A; Nivoit, Pierre; Bouskela, Eliete

    2012-07-01

    The aims of our study were to investigate effects of postnatal overnutrition, obtained by restricting the number of pups per litter, on microcirculatory reactivity, fat depots, its total percentage and lipid profile. Microvascular reactivity was evaluated in the cremaster muscle of 24 hamsters divided into four groups, with 6 animals in each one: normal (NL) and restricted (RL) litter groups, both at 6th and 21st weeks of age. The NL group had 8-9 pups and the RL 3 pups per litter and to avoid the litter effect, only one animal was used per litter. The results have shown that the RL group had higher velocity of weight, body mass and fat gain compared to the NL one at weeks 6 and 21. Significant differences were also observed on urogenital fat depot, total cholesterol and low density lipoprotein between groups. At the lowest concentration of Ach, the RL group showed smaller arteriolar dilatation at the 21st than at the 6th week [5(3-13) vs 19(8-40)%, p<0.01] while the NL one did not show any difference within the group. The highest concentration of Ach at the 21th week pointed to endothelial-dependent microvascular dysfunction in RL compared to NL [3(8-26) vs. 13(8-26)%, p<0.05]. Endothelial-independent microvascular reactivity was similar between groups. Our data suggest that postnatal overnutrition is associated to muscle endothelial-dependent microvascular dysfunction, greater body mass and total percentage of fat and impaired the lipid profile. In conclusion, the imprinting promoted by this experimental model of obesity was able to influence microvascular reactivity later in life.

  2. Microvascular resistance of the culprit coronary artery in acute ST-elevation myocardial infarction

    PubMed Central

    Carrick, David; Haig, Caroline; Carberry, Jaclyn; McCartney, Peter; Welsh, Paul; Ahmed, Nadeem; McEntegart, Margaret; Petrie, Mark C.; Eteiba, Hany; Lindsay, Mitchell; Hood, Stuart; Watkins, Stuart; Rauhalammi, Samuli M.O.; Mordi, Ify; Ford, Ian; Radjenovic, Aleksandra; Sattar, Naveed; Oldroyd, Keith G.

    2016-01-01

    BACKGROUND. Failed myocardial reperfusion is common and prognostically important after acute ST-elevation myocardial infarction (STEMI). The purpose of this study was to investigate coronary flow reserve (CFR), a measure of vasodilator capacity, and the index of microvascular resistance (IMR; mmHg × s) in the culprit artery of STEMI survivors. METHODS. IMR (n = 288) and CFR (n = 283; mean age [SD], 60 [12] years) were measured acutely using guide wire–based thermodilution. Cardiac MRI disclosed left ventricular pathology, function, and volumes at 2 days (n = 281) and 6 months after STEMI (n = 264). All-cause death or first heart failure hospitalization was independently adjudicated (median follow-up 845 days). RESULTS. Myocardial hemorrhage and microvascular obstruction occurred in 89 (42%) and 114 (54%) patients with evaluable T2*-MRI maps. IMR and CFR were associated with microvascular pathology (none vs. microvascular obstruction only vs. microvascular obstruction and myocardial hemorrhage) (median [interquartile range], IMR: 17 [12.0–33.0] vs. 17 [13.0–39.0] vs. 37 [21.0–63.0], P < 0.001; CFR: 1.7 [1.4–2.5] vs. 1.5 [1.1–1.8] vs. 1.4 [1.0–1.8], P < 0.001), whereas thrombolysis in myocardial infarction blush grade was not. IMR was a multivariable associate of changes in left ventricular end-diastolic volume (regression coefficient [95% CI] 0.13 [0.01, 0.24]; P = 0.036), whereas CFR was not (P = 0.160). IMR (5 units) was a multivariable associate of all-cause death or heart failure hospitalization (n = 30 events; hazard ratio [95% CI], 1.09 [1.04, 1.14]; P < 0.001), whereas CFR (P = 0.124) and thrombolysis in myocardial infarction blush grade (P = 0.613) were not. IMR had similar prognostic value for these outcomes as <50% ST-segment resolution on the ECG. CONCLUSIONS. IMR is more closely associated with microvascular pathology, left ventricular remodeling, and health outcomes than the angiogram or CFR. TRIAL REGISTRATION. NCT02072850. FUNDING. A

  3. Microvascular resistance of the culprit coronary artery in acute ST-elevation myocardial infarction

    PubMed Central

    Carrick, David; Haig, Caroline; Carberry, Jaclyn; McCartney, Peter; Welsh, Paul; Ahmed, Nadeem; McEntegart, Margaret; Petrie, Mark C.; Eteiba, Hany; Lindsay, Mitchell; Hood, Stuart; Watkins, Stuart; Rauhalammi, Samuli M.O.; Mordi, Ify; Ford, Ian; Radjenovic, Aleksandra; Sattar, Naveed; Oldroyd, Keith G.

    2016-01-01

    BACKGROUND. Failed myocardial reperfusion is common and prognostically important after acute ST-elevation myocardial infarction (STEMI). The purpose of this study was to investigate coronary flow reserve (CFR), a measure of vasodilator capacity, and the index of microvascular resistance (IMR; mmHg × s) in the culprit artery of STEMI survivors. METHODS. IMR (n = 288) and CFR (n = 283; mean age [SD], 60 [12] years) were measured acutely using guide wire–based thermodilution. Cardiac MRI disclosed left ventricular pathology, function, and volumes at 2 days (n = 281) and 6 months after STEMI (n = 264). All-cause death or first heart failure hospitalization was independently adjudicated (median follow-up 845 days). RESULTS. Myocardial hemorrhage and microvascular obstruction occurred in 89 (42%) and 114 (54%) patients with evaluable T2*-MRI maps. IMR and CFR were associated with microvascular pathology (none vs. microvascular obstruction only vs. microvascular obstruction and myocardial hemorrhage) (median [interquartile range], IMR: 17 [12.0–33.0] vs. 17 [13.0–39.0] vs. 37 [21.0–63.0], P < 0.001; CFR: 1.7 [1.4–2.5] vs. 1.5 [1.1–1.8] vs. 1.4 [1.0–1.8], P < 0.001), whereas thrombolysis in myocardial infarction blush grade was not. IMR was a multivariable associate of changes in left ventricular end-diastolic volume (regression coefficient [95% CI] 0.13 [0.01, 0.24]; P = 0.036), whereas CFR was not (P = 0.160). IMR (5 units) was a multivariable associate of all-cause death or heart failure hospitalization (n = 30 events; hazard ratio [95% CI], 1.09 [1.04, 1.14]; P < 0.001), whereas CFR (P = 0.124) and thrombolysis in myocardial infarction blush grade (P = 0.613) were not. IMR had similar prognostic value for these outcomes as <50% ST-segment resolution on the ECG. CONCLUSIONS. IMR is more closely associated with microvascular pathology, left ventricular remodeling, and health outcomes than the angiogram or CFR. TRIAL REGISTRATION. NCT02072850. FUNDING. A

  4. Microvascular dysfunction in the course of metabolic syndrome induced by high-fat diet

    PubMed Central

    2014-01-01

    Background Metabolic syndrome (MetS) is associated with increased risk of cardiovascular disease (CVD). One important feature underlying the pathophysiology of many types of CVD is microvascular dysfunction. Although components of MetS are themselves CVD risk factors, the risk is increased when the syndrome is considered as one entity. We aimed to characterize microvascular function and some of its influencing factors in the course of MetS development. Methods Development of MetS in C57BL/6 mice on a high-fat diet (HFD, 51% of energy from fat) was studied. The initial phase of MetS (I-MetS) was defined as the first 2 weeks of HFD feeding, with the fully developed phase occurring after 8 weeks of HFD. We characterized these phases by assessing changes in adiposity, blood pressure, and microvascular function. All data are presented as mean ± standard error (SEM). Differences between cumulative dose–response curves of myograph experiments were calculated using non-linear regression analysis. In other experiments, comparisons between two groups were made with Student’s t-test. Comparisons between more than two groups were made using one-way ANOVA with Tukey post-hoc test. A probability value <0.05 was considered statistically significant. Results I-MetS mice presented with weight gain, blood pressure elevation, and microvascular dysfunction characterized by augmented vasoconstriction. This finding, contrary to those in mice with fully developed MetS, was not associated with endothelial dysfunction, insulin resistance, or systemic inflammation. In the initial phase, perivascular adipose tissue showed no sign of inflammation and had no influence on the pattern of vasoconstriction. These findings suggest that the onset of hypertension in MetS is strongly influenced by vascular smooth muscle cell dysfunction and independent of important factors known to influence microvascular function and consequently blood pressure levels. Conclusion We identified in I

  5. Analysis of microvascular density in early gastric carcinoma using magnifying endoscopy with narrow-band imaging

    PubMed Central

    Kawamura, Masashi; Naganuma, Hiroshi; Shibuya, Rie; Kikuchi, Tatsuya; Sakai, Yoshitaka; Nagasaki, Futoshi; Nomura, Eiki; Suzuki, Noriaki; Saito, Eri

    2016-01-01

    Background and study aims: Intramucosal vascular density differs between differentiated and undifferentiated type gastric carcinomas. This study aimed to evaluate the microvascular density characteristics of these two types of carcinoma using magnifying endoscopy with narrow-band imaging (ME-NBI). Patients and methods: In total, 42 differentiated and 10 undifferentiated types were evaluated. The microvessels observed using ME-NBI were extracted from stored still images and the microvascular density in the two carcinoma types was analyzed. Histological vascular density in resected specimens was also evaluated using CD34 immunostaining. Results: There were significant differences between the microvascular density in the differentiated and undifferentiated types of carcinoma (10.02 ± 4.72 % vs 4.02 ± 0.40 %; P < 0.001) using ME-NBI. Vascular density assessed histologically also differed significantly between differentiated and undifferentiated types in both the whole mucosal (5.81 ± 3.17 % vs 3.25 ± 1.21 %) and the superficial mucosal layers (0 – 100 μm) (6.38 ± 3.73 % vs 3.66 ± 1.46 %). However, the vascular density in the surrounding non-carcinomatous mucosa assessed using ME-NBI and histologically, was significantly lower in the differentiated than in the undifferentiated types (P < 0.001). There was good agreement between ME-NBI and histologically assessed microvascular density in both the whole (r = 0.740; P < 0.001) and superficial mucosal layers (r = 0.764; P < 0.001). White opaque substance (WOS) was seen in eight patients who had the differentiated type carcinoma. In almost all cases with WOS, the appearance of the carcinoma was discolored. Conclusions: There was a close relationship between ME-NBI assessed microvascular density and histologically assessed vascular density in the mucosal layer. Microvascular density differed significantly between the differentiated and undifferentiated

  6. Impact of the arterial input function on microvascularization parameter measurements using dynamic contrast-enhanced ultrasonography

    PubMed Central

    Gauthier, Marianne; Pitre-Champagnat, Stéphanie; Tabarout, Farid; Leguerney, Ingrid; Polrot, Mélanie; Lassau, Nathalie

    2012-01-01

    AIM: To evaluate the sources of variation influencing the microvascularization parameters measured by dynamic contrast-enhanced ultrasonography (DCE-US). METHODS: Firstly, we evaluated, in vitro, the impact of the manual repositioning of the ultrasound probe and the variations in flow rates. Experiments were conducted using a custom-made phantom setup simulating a tumor and its associated arterial input. Secondly, we evaluated, in vivo, the impact of multiple contrast agent injections and of examination day, as well as the influence of the size of region of interest (ROI) associated with the arterial input function (AIF). Experiments were conducted on xenografted B16F10 female nude mice. For all of the experiments, an ultrasound scanner along with a linear transducer was used to perform pulse inversion imaging based on linear raw data throughout the experiments. Semi-quantitative and quantitative analyses were performed using two signal-processing methods. RESULTS: In vitro, no microvascularization parameters, whether semi-quantitative or quantitative, were significantly correlated (P values from 0.059 to 0.860) with the repositioning of the probe. In addition, all semi-quantitative microvascularization parameters were correlated with the flow variation while only one quantitative parameter, the tumor blood flow, exhibited P value lower than 0.05 (P = 0.004). In vivo, multiple contrast agent injections had no significant impact (P values from 0.060 to 0.885) on microvascularization parameters. In addition, it was demonstrated that semi-quantitative microvascularization parameters were correlated with the tumor growth while among the quantitative parameters, only the tissue blood flow exhibited P value lower than 0.05 (P = 0.015). Based on these results, it was demonstrated that the ROI size of the AIF had significant influence on microvascularization parameters: in the context of larger arterial ROI (from 1.17 ± 0.6 mm3 to 3.65 ± 0.3 mm3), tumor blood flow and

  7. Parasite biomass-related inflammation, endothelial activation, microvascular dysfunction and disease severity in vivax malaria.

    PubMed

    Barber, Bridget E; William, Timothy; Grigg, Matthew J; Parameswaran, Uma; Piera, Kim A; Price, Ric N; Yeo, Tsin W; Anstey, Nicholas M

    2015-01-01

    Plasmodium vivax can cause severe malaria, however its pathogenesis is poorly understood. In contrast to P. falciparum, circulating vivax parasitemia is low, with minimal apparent sequestration in endothelium-lined microvasculature, and pathogenesis thought unrelated to parasite biomass. However, the relationships between vivax disease-severity and total parasite biomass, endothelial autocrine activation and microvascular dysfunction are unknown. We measured circulating parasitemia and markers of total parasite biomass (plasma parasite lactate dehydrogenase [pLDH] and PvLDH) in adults with severe (n = 9) and non-severe (n = 53) vivax malaria, and examined relationships with disease-severity, endothelial activation, and microvascular function. Healthy controls and adults with non-severe and severe falciparum malaria were enrolled for comparison. Median peripheral parasitemia, PvLDH and pLDH were 2.4-fold, 3.7-fold and 6.9-fold higher in severe compared to non-severe vivax malaria (p = 0.02, p = 0.02 and p = 0.015, respectively), suggesting that, as in falciparum malaria, peripheral P. vivax parasitemia underestimates total parasite biomass, particularly in severe disease. P. vivax schizonts were under-represented in peripheral blood. Severe vivax malaria was associated with increased angiopoietin-2 and impaired microvascular reactivity. Peripheral vivax parasitemia correlated with endothelial activation (angiopoietin-2, von-Willebrand-Factor [VWF], E-selectin), whereas markers of total vivax biomass correlated only with systemic inflammation (IL-6, IL-10). Activity of the VWF-cleaving-protease, ADAMTS13, was deficient in proportion to endothelial activation, IL-6, thrombocytopenia and vivax disease-severity, and associated with impaired microvascular reactivity in severe disease. Impaired microvascular reactivity correlated with lactate in severe vivax malaria. Findings suggest that tissue accumulation of P. vivax may occur, with the hidden

  8. The development of a dynamic model for microvascular research and practice using human placenta: a preliminary report.

    PubMed

    Waterhouse, N; Moss, A L; Townsend, P L

    1985-07-01

    Human placenta has been investigated in an attempt to develop a non-animal model for microvascular research and practice, with a dynamic artificial circulation. Initial work has been encouraging and further development is in progress.

  9. Descompresión microvascular en neuralgia del trigémino: Reporte de 36 casos y revisión de la literatura

    PubMed Central

    Campero, Alvaro; Ajler, Pablo; Campero, Abraham Agustín

    2014-01-01

    Objetivo: El propósito del presente trabajo es presentar los resultados de 36 pacientes con diagnóstico de neuralgia del trigémino (NT), en los cuales se realizó una descompresión microvascular (DMV). Material y Método: Desde junio de 2005 a mayo de 2012, 36 pacientes con diagnóstico de NT fueron operados por el primer autor (AC), realizando una DMV. Se evaluó: Edad, sexo, tiempo de sintomatología previo a la cirugía, hallazgos intraoperatorios (a través de los videos quirúrgicos), y resultados postoperatorios. Resultados: De los 36 pacientes operados, 25 fueron mujeres y 11 varones. El promedio de edad fue de 48 años. El seguimiento postoperatorio fue en promedio de 38 meses. De los 36 pacientes, 32 (88%) evolucionaron sin dolor hasta la fecha. De los 4 casos con recurrencia de dolor, en dos pacientes se observó como hallazgo intraoperatorio un conflicto venoso. Conclusión: La DMV como tratamiento de la NT es un procedimiento efectivo y seguro. El hallazgo intraoperatorio de una “compresión” venosa podría indicar una evolución postoperatoria desfavorable. PMID:25379343

  10. Multi-physics optimization of three-dimensional microvascular polymeric components

    NASA Astrophysics Data System (ADS)

    Aragón, Alejandro M.; Saksena, Rajat; Kozola, Brian D.; Geubelle, Philippe H.; Christensen, Kenneth T.; White, Scott R.

    2013-01-01

    This work discusses the computational design of microvascular polymeric materials, which aim at mimicking the behavior found in some living organisms that contain a vascular system. The optimization of the topology of the embedded three-dimensional microvascular network is carried out by coupling a multi-objective constrained genetic algorithm with a finite-element based physics solver, the latter validated through experiments. The optimization is carried out on multiple conflicting objective functions, namely the void volume fraction left by the network, the energy required to drive the fluid through the network and the maximum temperature when the material is subjected to thermal loads. The methodology presented in this work results in a viable alternative for the multi-physics optimization of these materials for active-cooling applications.

  11. Platelet lysate gel and endothelial progenitors stimulate microvascular network formation in vitro: tissue engineering implications

    PubMed Central

    Fortunato, Tiago M.; Beltrami, Cristina; Emanueli, Costanza; De Bank, Paul A.; Pula, Giordano

    2016-01-01

    Revascularisation is a key step for tissue regeneration and complete organ engineering. We describe the generation of human platelet lysate gel (hPLG), an extracellular matrix preparation from human platelets able to support the proliferation of endothelial colony forming cells (ECFCs) in 2D cultures and the formation of a complete microvascular network in vitro in 3D cultures. Existing extracellular matrix preparations require addition of high concentrations of recombinant growth factors and allow only limited formation of capillary-like structures. Additional advantages of our approach over existing extracellular matrices are the absence of any animal product in the composition hPLG and the possibility of obtaining hPLG from patients to generate homologous scaffolds for re-implantation. This discovery has the potential to accelerate the development of regenerative medicine applications based on implantation of microvascular networks expanded ex vivo or the generation of fully vascularised organs. PMID:27141997

  12. Capsule independent uptake of the fungal pathogen Cryptococcus neoformans into brain microvascular endothelial cells.

    PubMed

    Sabiiti, Wilber; May, Robin C

    2012-01-01

    Cryptococcosis is a life-threatening fungal disease with a high rate of mortality among HIV/AIDS patients across the world. The ability to penetrate the blood-brain barrier (BBB) is central to the pathogenesis of cryptococcosis, but the way in which this occurs remains unclear. Here we use both mouse and human brain derived endothelial cells (bEnd3 and hCMEC/D3) to accurately quantify fungal uptake and survival within brain endothelial cells. Our data indicate that the adherence and internalisation of cryptococci by brain microvascular endothelial cells is an infrequent event involving small numbers of cryptococcal yeast cells. Interestingly, this process requires neither active signalling from the fungus nor the presence of the fungal capsule. Thus entry into brain microvascular endothelial cells is most likely a passive event that occurs following 'trapping' within capillary beds of the BBB.

  13. Platelet lysate gel and endothelial progenitors stimulate microvascular network formation in vitro: tissue engineering implications.

    PubMed

    Fortunato, Tiago M; Beltrami, Cristina; Emanueli, Costanza; De Bank, Paul A; Pula, Giordano

    2016-01-01

    Revascularisation is a key step for tissue regeneration and complete organ engineering. We describe the generation of human platelet lysate gel (hPLG), an extracellular matrix preparation from human platelets able to support the proliferation of endothelial colony forming cells (ECFCs) in 2D cultures and the formation of a complete microvascular network in vitro in 3D cultures. Existing extracellular matrix preparations require addition of high concentrations of recombinant growth factors and allow only limited formation of capillary-like structures. Additional advantages of our approach over existing extracellular matrices are the absence of any animal product in the composition hPLG and the possibility of obtaining hPLG from patients to generate homologous scaffolds for re-implantation. This discovery has the potential to accelerate the development of regenerative medicine applications based on implantation of microvascular networks expanded ex vivo or the generation of fully vascularised organs. PMID:27141997

  14. Compliance of laser-assisted microvascular anastomosis: a comparative study with manual anastomosis (preliminary results)

    NASA Astrophysics Data System (ADS)

    Demaria, Roland G.; Lhote, Francois-Marie; Dauzat, Michel; Juan, Jean-Marie; Oliva-Lauraire, Marie-Claire; Durrleman, Nicolas; Delacretaz, Guy P.; Albat, Bernard; Frapier, Jean-Marc; Chaptal, Paul-Andre; Godlewski, Guilhem

    1999-01-01

    The compliance of microvascular anastomosis is an important predictive factor for long term patency of graft or vascular reconstruction. This experimental study compare the compliance of manual suture and laser assisted end to end microvascular anastomosis. In nine New-Zealand white rabbits we performed manual end-to-end suture anastomosis on the left femoral artery and laser assisted anastomosis on the right femoral artery, with a diode laser (wavelength 988 nm, power output 500 mW). Compliance was obtained by echotracking (CBI 8000 sonomicrometry system with 20 MHz implantable microprobe from Crystal-Biotech, USA) on the anastomosis site as well as upstream, and downstream from the anastomosis. Vessel compliance was lower on the manual suture side compared to the laser assisted anastomosis side, especially downstream from the anastomosis.

  15. Speckle-correlation monitoring of the internal micro-vascular flow

    NASA Astrophysics Data System (ADS)

    Zimnyakov, D. A.; Khmara, M. B.; Vilensky, M. A.; Kozlov, V. V.; Gorfinkel, I. V.; Zdrajevsky, R. A.

    2009-10-01

    The results of experimental study of possibility to monitor the micro-vascular blood flow in superficial tissues of various organs with the use of endoscope-based full-field speckle correlometer are presented. The blood microcirculation monitoring was carried out in the course of the laparotomy of abdominal cavity of laboratory animals (rats). Transfer of laser light to the area of interest and scattered radiation from the probed zone to the detector (CMOS camera) was carried out via fiber-optic bundles of endoscopic system. Microscopic hemodynamics was analyzed for small intestine, liver, spleen, kidney, and pancreas under different conditions (normal state, provocated peritonitis and ischemia, administration of vasodilative agents such as papaverine, lidocaine). The prospects and problems of internal monitoring of microvascular flow in laboratory and clinical conditions are discussed.

  16. Capsule independent uptake of the fungal pathogen Cryptococcus neoformans into brain microvascular endothelial cells.

    PubMed

    Sabiiti, Wilber; May, Robin C

    2012-01-01

    Cryptococcosis is a life-threatening fungal disease with a high rate of mortality among HIV/AIDS patients across the world. The ability to penetrate the blood-brain barrier (BBB) is central to the pathogenesis of cryptococcosis, but the way in which this occurs remains unclear. Here we use both mouse and human brain derived endothelial cells (bEnd3 and hCMEC/D3) to accurately quantify fungal uptake and survival within brain endothelial cells. Our data indicate that the adherence and internalisation of cryptococci by brain microvascular endothelial cells is an infrequent event involving small numbers of cryptococcal yeast cells. Interestingly, this process requires neither active signalling from the fungus nor the presence of the fungal capsule. Thus entry into brain microvascular endothelial cells is most likely a passive event that occurs following 'trapping' within capillary beds of the BBB. PMID:22530025

  17. Interactions between microvascular and macrovascular disease in diabetes: pathophysiology and therapeutic implications.

    PubMed

    Krentz, Andrew J; Clough, Geraldine; Byrne, Christopher D

    2007-11-01

    Convention partitions the complications of diabetes into two main subtypes. First are the diabetes-specific microvascular complications of retinopathy, nephropathy and neuropathy; second are the atherothrombotic macrovascular complications that account for the majority of premature deaths. Pathological interactions between microvascular and macrovascular complications, for example, nephropathy and macrovascular disease, are common. Similar mechanisms and shared risk factors drive the development and progression of both small and large vessel disease. This concept has therapeutic implications. Mounting evidence points to the need for multifactorial strategies to prevent vascular complications in subjects with diabetes and/or the metabolic syndrome. We advocate a combined therapeutic approach that addresses small and large vessel disease. Preferential use should be made of drug regimens that (i) maximize vascular protection, (ii) reduce the risk of iatrogenic vascular damage and (iii) minimize the increasing problem of polypharmacy. PMID:17924862

  18. Thrombin stimulates albumin transcytosis in lung microvascular endothelial cells via activation of acid sphingomyelinase.

    PubMed

    Kuebler, Wolfgang M; Wittenberg, Claudia; Lee, Warren L; Reppien, Eike; Goldenberg, Neil M; Lindner, Karsten; Gao, Yizhuo; Winoto-Morbach, Supandi; Drab, Marek; Mühlfeld, Christian; Dombrowsky, Heike; Ochs, Matthias; Schütze, Stefan; Uhlig, Stefan

    2016-04-15

    Transcellular albumin transport occurs via caveolae that are abundant in lung microvascular endothelial cells. Stimulation of albumin transcytosis by proinflammatory mediators may contribute to alveolar protein leak in lung injury, yet the regulation of albumin transport and its underlying molecular mechanisms are so far incompletely understood. Here we tested the hypothesis that thrombin may stimulate transcellular albumin transport across lung microvascular endothelial cells in an acid-sphingomyelinase dependent manner. Thrombin increased the transport of fluorescently labeled albumin across confluent human lung microvascular endothelial cell (HMVEC-L) monolayers to an extent that markedly exceeds the rate of passive diffusion. Thrombin activated acid sphingomyelinase (ASM) and increased ceramide production in HMVEC-L, but not in bovine pulmonary artery cells, which showed little albumin transport in response to thrombin. Thrombin increased total caveolin-1 (cav-1) content in both whole cell lysates and lipid rafts from HMVEC-L, and this effect was blocked by inhibition of ASM or de novo protein biosynthesis. Thrombin-induced uptake of albumin into lung microvascular endothelial cells was confirmed in isolated-perfused lungs by real-time fluorescence imaging and electron microscopy of gold-labeled albumin. Inhibition of ASM attenuated thrombin-induced albumin transport both in confluent HMVEC-L and in intact lungs, whereas HMVEC-L treatment with exogenous ASM increased albumin transport and enriched lipid rafts in cav-1. Our findings indicate that thrombin stimulates transcellular albumin transport in an acid sphingomyelinase-dependent manner by inducing de novo synthesis of cav-1 and its recruitment to membrane lipid rafts. PMID:26851257

  19. Metabolic Actions of Angiotensin II and Insulin: A Microvascular Endothelial Balancing Act

    PubMed Central

    Muniyappa, Ranganath; Yavuz, Shazene

    2012-01-01

    Metabolic actions of insulin to promote glucose disposal are augmented by nitric oxide (NO)-dependent increases in microvascular blood flow to skeletal muscle. The balance between NO-dependent vasodilator actions and endothelin-1-dependent vasoconstrictor actions of insulin is regulated by phosphatidylinositol 3-kinase-dependent (PI3K) - and mitogen-activated protein kinase (MAPK)-dependent signaling in vascular endothelium, respectively. Angiotensin II acting on AT2 receptor increases capillary blood flow to increase insulin-mediated glucose disposal. In contrast, AT1 receptor activation leads to reduced NO bioavailability, impaired insulin signaling, vasoconstriction, and insulin resistance. Insulin-resistant states are characterized by dysregulated local renin-angiotensin-aldosterone system (RAAS). Under insulin-resistant conditions, pathway-specific impairment in PI3K-dependent signaling may cause imbalance between production of NO and secretion of endothelin-1, leading to decreased blood flow, which worsens insulin resistance. Similarly, excess AT1 receptor activity in the microvasculature may selectively impair vasodilation while simultaneously potentiating the vasoconstrictor actions of insulin. Therapeutic interventions that target pathway-selective impairment in insulin signaling and the imbalance in AT1 and AT2 receptor signaling in microvascular endothelium may simultaneously ameliorate endothelial dysfunction and insulin resistance. In the present review, we discuss molecular mechanisms in the endothelium underlying microvascular and metabolic actions of insulin and Angiotensin II, the mechanistic basis for microvascular endothelial dysfunction and insulin resistance in RAAS dysregulated clinical states, and the rationale for therapeutic strategies that restore the balance in vasodilator and constrictor actions of insulin and Angiotensin II in the microvasculature. PMID:22684034

  20. [Postoperative monitoring of microvascular flap repair with pulse oximetry--initial experience].

    PubMed

    Strauss, J M; Neukam, F W; Krohn, S; Schmelzeisen, R; Borchard, F

    1994-03-01

    The surgical success of microvascular free flaps or pedicled flaps depends on the function of the nutritive vessels. Complications such as thrombosis or vessel kinking, are dangerous and may result in flap loss. During the last decade, different methods were tested for their capability of monitoring flap perfusion. We report our preliminary experience with the continuous and non-invasive pulse oximetry by using a special reflection sensor positioned on the surface of the flap. PMID:8020852

  1. Withdrawing intra-aortic balloon pump support paradoxically improves microvascular flow

    PubMed Central

    2010-01-01

    Introduction The Intra-Aortic Balloon Pump (IABP) is frequently used to mechanically support the heart. There is evidence that IABP improves microvascular flow during cardiogenic shock but its influence on the human microcirculation in patients deemed ready for discontinuing IABP support has not yet been studied. Therefore we used sidestream dark field imaging (SDF) to test our hypothesis that human microcirculation remains unaltered with or without IABP support in patients clinically ready for discontinuation of mechanical support. Methods We studied 15 ICU patients on IABP therapy. Measurements were performed after the clinical decision was made to remove the balloon catheter. We recorded global hemodynamic parameters and performed venous oximetry during maximal IABP support (1:1) and 10 minutes after temporarily stopping the IABP therapy. At both time points, we also recorded video clips of the sublingual microcirculation. From these we determined indices of microvascular perfusion including perfused vessel density (PVD) and microvascular flow index (MFI). Results Ceasing IABP support lowered mean arterial pressure (74 ± 8 to 71 ± 10 mmHg; P = 0.048) and increased diastolic pressure (43 ± 10 to 53 ± 9 mmHg; P = 0.0002). However, at the level of the microcirculation we found an increase of PVD of small vessels <20 μm (5.47 ± 1.76 to 6.63 ± 1.90; P = 0.0039). PVD for vessels >20 μm and MFI for both small and large vessels were unaltered. During the procedure global oxygenation parameters (ScvO2/SvO2) remained unchanged. Conclusions In patients deemed ready for discontinuing IABP support according to current practice, SDF imaging showed an increase of microcirculatory flow of small vessels after ceasing IABP therapy. This observation may indicate that IABP impairs microvascular perfusion in recovered patients, although this warrants confirmation. PMID:20738876

  2. Effect of decompression-induced bubble formation on highly trained divers microvascular function.

    PubMed

    Lambrechts, Kate; Pontier, Jean-Michel; Mazur, Aleksandra; Buzzacott, Peter; Morin, Jean; Wang, Qiong; Theron, Michael; Guerrero, Francois

    2013-11-01

    We previously showed microvascular alteration of both endothelium-dependent and -independent reactivity after a single SCUBA dive. We aimed to study mechanisms involved in this postdive vascular dysfunction. Ten divers each completed three protocols: (1) a SCUBA dive at 400 kPa for 30 min; (2) a 41-min duration of seawater surface head immersed finning exercise to determine the effect of immersion and moderate physical activity; and (3) a simulated 41-min dive breathing 100% oxygen (hyperbaric oxygen [HBO]) at 170 kPa in order to analyze the effect of diving-induced hyperoxia. Bubble grades were monitored with Doppler. Cutaneous microvascular function was assessed by laser Doppler. Endothelium-dependent (acetylcholine, ACh) and -independent (sodium nitroprusside, SNP) reactivity was tested by iontophoresis. Endothelial cell activation was quantified by plasma Von Willebrand factor and nitric oxide (NO). Inactivation of NO by oxidative stress was assessed by plasma nitrotyrosine. Platelet factor 4 (PF4) was assessed in order to determine platelet aggregation. Blood was also analyzed for measurement of platelet count. Cutaneous vascular conductance (CVC) response to ACh delivery was not significantly decreased by the SCUBA protocol (23 ± 9% before vs. 17 ± 7% after; P = 0.122), whereas CVC response to SNP stimulation decreased significantly (23 ± 6% before vs. 10 ± 1% after; P = 0.039). The HBO and immersion protocols did not affect either endothelial-dependent or -independent function. The immersion protocol induced a significant increase in NO (0.07 ± 0.01 vs. 0.12 ± 0.02 μg/mL; P = 0.035). This study highlighted change in microvascular endothelial-independent but not -dependent function in highly trained divers after a single air dive. The results suggest that the effects of decompression on microvascular function may be modified by diving acclimatization. PMID:24400144

  3. Trigemino-cardiac reflex during microvascular trigeminal decompression in cases of trigeminal neuralgia.

    PubMed

    Schaller, Bernhard

    2005-01-01

    The trigemino-cardiac reflex (TCR) is a well-recognized phenomenon consisting of bradycardia, arterial hypotension, apnea, and gastric hypermotility during ocular surgery or other manipulations in and around the orbit. Thus far, it could bee shown that central stimulation of the trigeminal nerve during transsphenoidal surgery and surgery for tumors in the cerebellopontine angle can lead to TCR. In cases of microvascular trigeminal decompression for trigeminal neuralgia, no data of the possible occurrence of TCR are available. TCR was defined as a drop in mean arterial blood pressure (MABP) and the heart rate (HR) of more than 20% to the baseline values before the stimulus and coinciding with the manipulation of the trigeminal nerve. Electronic anesthetic recorded perioperative HR and MABP values were reviewed retrospectively in 28 patients who received microvascular trigeminal decompression in cases of trigeminal neuralgia and were divided into two subgroups on the basis of occurrence of TCR during surgery. Of the 28 patients, 5 (18%) showed evidence of TCR during manipulation at the trigeminal radix by separation from microvascular structures. Their HR fell 46% and their MABP 57% during operative procedures near the trigeminal nerve as compared with levels immediately before the stimulus. After cessation of manipulation, HR and MABP returned (spontaneously) to levels before the stimulus. Risk factors of TCR were compared with results from the literature. In conclusion, the present results give evidence of TCR during manipulation of the central part of the trigeminal nerve during microvascular trigeminal decompression in cases of trigeminal neuralgia under a standardized anesthetic protocol.

  4. Bone marrow blood vessel ossification and "microvascular dead space" in rat and human long bone.

    PubMed

    Prisby, Rhonda D

    2014-07-01

    Severe calcification of the bone microvascular network was observed in rats, whereby the bone marrow blood vessels appeared ossified. This study sought to characterize the magnitude of ossification in relation to patent blood vessels and adipocyte content in femoral diaphyses. Additionally, this study confirmed the presence of ossified vessels in patients with arteriosclerotic vascular disease and peripheral vascular disease and cellulitis. Young (4-6 month; n=8) and old (22-24 month; n=8) male Fischer-344 rats were perfused with barium sulfate to visualize patent bone marrow blood vessels. Femoral shafts were processed for bone histomorphometry to quantify ossified (Goldner's Trichrome) and calcified (Alizarin Red) vessels. Adipocyte content was also determined. Additional femora (n=5/age group) were scanned via μCT to quantify microvascular ossification. Bone marrow blood vessels from the rats and the human patients were also isolated and examined via microscopy. Ossified vessels (rats and humans) had osteocyte lacunae on the vessel surfaces and "normal" vessels were transitioning into bone. The volume of ossified vessels was 4800% higher (p<0.05) in the old vs. young rats. Calcified and ossified vessel volumes per tissue volume and calcified vessel volume per patent vessel volume were augmented (p<0.05) 262%, 375% and 263%, respectively, in the old vs. young rats. Ossified and patent vessel number was higher (171%) and lower (40%), respectively, in the old vs. young rats. Finally, adipocyte volume per patent vessel volume was higher (86%) with age. This study is the first to report ossification of bone marrow blood vessels in rats and humans. Ossification presumably results in "microvascular dead space" in regard to loss of patency and vasomotor function as opposed to necrosis. Progression of bone microvascular ossification may provide the common link associated with age-related changes in bone and bone marrow. The clinical implications may be evident in the

  5. Myosin light chain kinase-dependent microvascular hyperpermeability in thermal injury.

    PubMed

    Huang, Qiaobing; Xu, Wenjuan; Ustinova, Elena; Wu, Mack; Childs, Ed; Hunter, Felicia; Yuan, Sarah

    2003-10-01

    Although the critical role of systemic inflammatory edema in the development of multiple organ failure in patients with massive burns has been fully recognized, the precise mechanisms responsible for the accumulation of blood fluid and proteins in tissues remote from the burn wound are poorly understood. The aim of this study was to test the hypothesis that circulating factors released during thermal injury cause microvascular leakage by triggering endothelial cell contraction and barrier dysfunction. A third-degree scald burn was induced in rats on the dorsal skin covering 25% total body surface area. The microcirculation and transvascular flux of albumin were observed in the rat mesentery using intravital fluorescence microscopy. The direct effect of circulating factors on microvascular barrier function was assessed by measuring the apparent permeability coefficient of albumin in isolated rat mesenteric venules during perfusion of plasma freshly withdrawn from burned rats. The in vivo study showed that the transvenular flux of albumin was significantly increased over a 6-h period with a maximal response seen at 3 h postburn. Importantly, perfusion of noninjured venules with burn plasma induced a time-dependent increase in albumin permeability. Pharmacological inhibition of protein kinase C, Src tyrosine kinases, or mast cell activation did not significantly affect the hyperpermeability response; however, blockage of myosin light chain phosphorylation with the myosin light chain kinase inhibitor ML-7 greatly attenuated the burn-induced increase in venular permeability in a dose-related pattern. The results support a role for endogenous circulating factors in microvascular leakage during burns. Myosin light chain phosphorylation-dependent endothelial contractile response may serve as an end-point effector leading to microvascular barrier dysfunction. PMID:14501951

  6. Intravenous and Gastric Cerium Dioxide Nanoparticle Exposure Disrupts Microvascular Smooth Muscle Signaling

    PubMed Central

    Minarchick, Valerie C.; Stapleton, Phoebe A.; Fix, Natalie R.; Leonard, Stephen S.; Sabolsky, Edward M.; Nurkiewicz, Timothy R.

    2015-01-01

    Cerium dioxide nanoparticles (CeO2 NP) hold great therapeutic potential, but the in vivo effects of non-pulmonary exposure routes are unclear. The first aim was to determine whether microvascular function is impaired after intravenous and gastric CeO2 NP exposure. The second aim was to investigate the mechanism(s) of action underlying microvascular dysfunction following CeO2 NP exposure. Rats were exposed to CeO2 NP (primary diameter: 4 ± 1 nm, surface area: 81.36 m2/g) by intratracheal instillation, intravenous injection, or gastric gavage. Mesenteric arterioles were harvested 24 h post-exposure and vascular function was assessed using an isolated arteriole preparation. Endothelium-dependent and independent function and vascular smooth muscle (VSM) signaling (soluble guanylyl cyclase [sGC] and cyclic guanosine monophosphate [cGMP]) were assessed. Reactive oxygen species (ROS) generation and nitric oxide (NO) production were analyzed. Compared with controls, endothelium-dependent and independent dilation were impaired following intravenous injection (by 61% and 45%) and gastric gavage (by 63% and 49%). However, intravenous injection resulted in greater microvascular impairment (16% and 35%) compared with gastric gavage at an identical dose (100 µg). Furthermore, sGC activation and cGMP responsiveness were impaired following pulmonary, intravenous, and gastric CeO2 NP treatment. Finally, nanoparticle exposure resulted in route-dependent, increased ROS generation and decreased NO production. These results indicate that CeO2 NP exposure route differentially impairs microvascular function, which may be mechanistically linked to decreased NO production and subsequent VSM signaling. Fully understanding the mechanisms behind CeO2 NP in vivo effects is a critical step in the continued therapeutic development of this nanoparticle. PMID:25481005

  7. Effect of decompression-induced bubble formation on highly trained divers microvascular function.

    PubMed

    Lambrechts, Kate; Pontier, Jean-Michel; Mazur, Aleksandra; Buzzacott, Peter; Morin, Jean; Wang, Qiong; Theron, Michael; Guerrero, Francois

    2013-11-01

    We previously showed microvascular alteration of both endothelium-dependent and -independent reactivity after a single SCUBA dive. We aimed to study mechanisms involved in this postdive vascular dysfunction. Ten divers each completed three protocols: (1) a SCUBA dive at 400 kPa for 30 min; (2) a 41-min duration of seawater surface head immersed finning exercise to determine the effect of immersion and moderate physical activity; and (3) a simulated 41-min dive breathing 100% oxygen (hyperbaric oxygen [HBO]) at 170 kPa in order to analyze the effect of diving-induced hyperoxia. Bubble grades were monitored with Doppler. Cutaneous microvascular function was assessed by laser Doppler. Endothelium-dependent (acetylcholine, ACh) and -independent (sodium nitroprusside, SNP) reactivity was tested by iontophoresis. Endothelial cell activation was quantified by plasma Von Willebrand factor and nitric oxide (NO). Inactivation of NO by oxidative stress was assessed by plasma nitrotyrosine. Platelet factor 4 (PF4) was assessed in order to determine platelet aggregation. Blood was also analyzed for measurement of platelet count. Cutaneous vascular conductance (CVC) response to ACh delivery was not significantly decreased by the SCUBA protocol (23 ± 9% before vs. 17 ± 7% after; P = 0.122), whereas CVC response to SNP stimulation decreased significantly (23 ± 6% before vs. 10 ± 1% after; P = 0.039). The HBO and immersion protocols did not affect either endothelial-dependent or -independent function. The immersion protocol induced a significant increase in NO (0.07 ± 0.01 vs. 0.12 ± 0.02 μg/mL; P = 0.035). This study highlighted change in microvascular endothelial-independent but not -dependent function in highly trained divers after a single air dive. The results suggest that the effects of decompression on microvascular function may be modified by diving acclimatization.

  8. Roles of limbal microvascular net and limbal stroma in regulating maintenance of limbal epithelial stem cells.

    PubMed

    Huang, Minghai; Wang, Bowen; Wan, Pengxia; Liang, Xuanwei; Wang, Xiaoran; Liu, Ying; Zhou, Qiang; Wang, Zhichong

    2015-02-01

    Knowledge of the microenvironment (niche) of stem cells is helpful for stem-cell-based regenerative medicine. In the eye, limbal epithelial stem cells (corneal epithelial stem cells) provide the self-renewal capacity of the corneal epithelium and are essential for maintaining corneal transparency and vision. Limbal epithelial stem cell deficiency results in significant visual deterioration. Successful treatment of this type of blinding disease requires studies of the limbal epithelial stem cells and their microenvironment. We investigate the function of the limbal microvascular net and the limbal stroma in the maintenace of the limbal epithelial stem cell niche in vivo and examine the regulation of limbal epithelial stem cell survival, proliferation and differentiation in vivo. We assess the temporal and spatial changes in the expression patterns of the following markers during a six-month follow-up of various rabbit limbal autograft transplantation models: vascular endothelial cell marker CD31, corneal epithelium differentiation marker K3, limbal epithelial stem-cell-associated markers P63 and ABCG2 and proliferating cell nuclear marker Ki67. Our results suggest that limbal epithelial stem cells cannot maintain their stemness or proliferation without the support of the limbal microvascular net microenvironment. Thus, both the limbal microvascular net and the limbal stroma play important roles as components of the limbal epithelial stem cell niche maintaining limbal epithelial stem cell survival and proliferation and the avoidance of differentiation. The limbal stroma constitutes the structural basis of the limbal epithelial stem cell niche and the limbal microvascular net is a requirement for this niche. These new insights should aid the eventual construction of tissue-engineered cornea for corneal blind patients in the future.

  9. Prevalence of Microvascular Complications in Newly Diagnosed Patients with Type 2 Diabetes

    PubMed Central

    Ali, Alia; Iqbal, Farrukh; Taj, Azeem; Iqbal, Zafar; Amin, Muhammad Joher; Iqbal, Qasim Zafar

    2013-01-01

    Background & Objective: Microvascular complications are the major outcome of type 2 Diabetes Mellitus progression, which reduce the quality of life, incur heavy economic burdens to the health care system and increase diabetic mortality. The aims of this study were to assess the prevalence of microvascular complications among newly diagnosed type 2 diabetic patients and to analyze the association between these complications and poor glycemic control. Methods: This cross sectional hospital based study was carried out in Diabetic Clinic of Shaikh Zayed Postgraduate Medical Institute, Lahore Pakistan. The study was conducted from November 2011 to November 2012 among newly diagnosed type 2 diabetic patients. Relevant information of all patients was recorded with the help of a proforma. They were investigated for retinopathy, nephropathy and neuropathy. Results: We have divided the patients into two groups: Group I with good glycemic control (HbA1c <6.5) and group II with poor glycemic control (HbA1c >6.5). In group II microvascular complications were 89.8%. Neuropathy, nephropathy and retinopathy were present in 68.5%, 56.2% and 31.4% respectively. These similar percentages in Group I were 50%, 0% and 31% respectively and are significantly lower. Conclusion: The study showed that even in newly diagnosed type 2 diabetic patients who had poor glycemic control, frequency of microvascular complications is much higher as compared to those who had average glycemic control. Thus tight glycemic control does count even in newly diagnosed type 2 diabetics to prevent and minimize the occurrence of complications. PMID:24353655

  10. Medición de densidades medias de meteoritos: test del método de inmersión

    NASA Astrophysics Data System (ADS)

    Steren, G.

    Se evaluó una técnica simple para medir las densidades medias de meteoritos, basada en el Método de Arquímedes y que utiliza cuentas de vidrio de 40μ en lugar de un fluído esto presenta la ventaja de no ser intrusivo ni químicamente reactivo (D.Britt and G.Consolmagno, 1996, B.A.A.S.28,1106). El estudio, realizado en junio de este año por participantes de la VI Escuela de Verano del Observatorio del Vaticano, empleó 37 muestras de la colección del Observatorio del Vaticano, de las cuales 26 eran Condritas, 1 Pallasita y 1 Howardita; algunas de ellas ya habian sido estudiadas por otras técnicas aunque también se incluyeron muestras no estudiadas anteriormente.

  11. A Micro-delivery Approach for Studying Microvascular Responses to Localized Oxygen Delivery

    PubMed Central

    Ghonaim, Nour W.; Lau, Leo W. M.; Goldman, Daniel; Ellis, Christopher G.; Yang, Jun

    2011-01-01

    In vivo video microscopy has been used to study blood flow regulation as a function of varying oxygen concentration in microcirculatory networks. However, previous studies have measured the collective response of stimulating large areas of the microvascular network at the tissue surface. Objective We aim to limit the area being stimulated by controlling oxygen availability to highly localized regions of the microvascular bed within intact muscle. Design and Method Gas of varying O2 levels was delivered to specific locations on the surface of the Extensor Digitorum Longus muscle of rat through a set of micro-outlets (100 μm diameter) patterned in ultrathin glass using state-of-the-art microfabrication techniques. O2 levels were oscillated and digitized video sequences were processed for changes in capillary hemodynamics and erythrocyte O2 saturation. Results and Conclusions Oxygen saturations in capillaries positioned directly above the micro-outlets were closely associated with the controlled local O2 oscillations. Radial diffusion from the micro-outlet is limited to ~75 μm from the center as predicted by computational modelling and as measured in vivo. These results delineate a key step in the design of a novel micro-delivery device for controlled oxygen delivery to the microvasculature to understand fundamental mechanisms of microvascular regulation of O2 supply. PMID:21914035

  12. Noninvasive measurement of microvascular leakage in patients with dengue hemorrhagic fever.

    PubMed

    Bethell, D B; Gamble, J; Pham, P L; Nguyen, M D; Tran, T H; Ha, T H; Tran, T N; Dong, T H; Gartside, I B; White, N J; Day, N P

    2001-01-15

    Dengue shock syndrome (DSS) is a potentially lethal complication of dengue virus infection associated with hypotension and leakage of plasma water into the extravascular space. To determine whether the underlying pathophysiology of DSS is distinct from that in milder forms of the disease, we assessed microvascular permeability, by use of strain gauge plethysmography, in Vietnamese children with DSS (n=19), or dengue hemorrhagic fever (DHF) without shock (n=16), and in healthy control children (n=15). At admission and after fluid resuscitation, the mean coefficient of microvascular permeability (K(f)) for the patients with dengue was approximately 50% higher than that for the control patients (P=.02). There was no significant difference in K(f) between the 2 groups of patients with dengue; this suggests the same underlying pathophysiology. We hypothesize that in patients with DSS, the fluctuations in K(f) are larger than those in patients with DHF, which leads to short-lived peaks of markedly increased microvascular permeability and consequent hemodynamic shock.

  13. Comparison of Different Methods for the Calculation of the Microvascular Flow Index

    PubMed Central

    Pozo, Mario O.; Kanoore Edul, Vanina S.; Ince, Can; Dubin, Arnaldo

    2012-01-01

    The microvascular flow index (MFI) is commonly used to semiquantitatively characterize the velocity of microcirculatory perfusion as absent (0), intermittent (1), sluggish (2), or normal (3). There are three approaches to compute MFI: (1) the average of the predominant flow in each of the four quadrants (MFIby quadrants), (2) the direct assessment during the bedside video acquisition (MFIpoint of care), and (3) the mean value of the MFIs determined in each individual vessel (MFIvessel by vessel). We hypothesized that the agreement between the MFIs is poor and that the MFIvessel by vessel better reflects the microvascular perfusion. For this purpose, we analyzed 100 videos from septic patients. In 25 of them, red blood cell (RBC) velocity was also measured. There were wide 95% limits of agreement between MFIby quadrants and MFIpoint of care (1.46), between MFIby quadrants and MFIvessel by vessel (2.85), and between MFIby point of care and MFIvessel by vessel (2.56). The MFIs significantly correlated with the RBC velocity and with the fraction of perfused small vessels, but MFIvessel by vessel showed the best R2. Although the different methods for the calculation of MFI reflect microvascular perfusion, they are not interchangeable and MFIvessel by vessel might be better. PMID:22593824

  14. [Free microvascular transfer of segmental corticocancellous femur for treatment of avascular scaphoid necrosis].

    PubMed

    Bürger, K H; Gaggl, A J; Kukutschki, W; Mueller, E

    2009-02-01

    Successful treatment of scaphoid non-union with avascular necrosis of the proximal poles and humpback deformity with carpal collapse is one of the main problems in reconstructive hand surgery. Vascularised bone transfer is one of the most successful techniques for treating these problems. 15 patients with avascular necrosis and non-union of the scaphoid were treated by a microvascular reanastomosed corticocancellous transplant from the distal medial femur. In all patients the success of the microvascular bone transfer was examined by MRI and conventional radiographs immediately, 6 weeks, 3, 6 and 12 months postoperatively. The transplant vitality, signs of reunion and carpal configuration were registered. Furthermore, the Mayo wrist score was employed for clinical evaluation. All transplants remained vital during the follow-up period of one year. Pseudoarthrosis was treated successfully in every case. In 14 cases there was a significant increase of the Mayo wrist score and in one case there was no difference before and after surgery. The microvascular transfer of corticocancellous femur resulted in a high rate of complete healing of scaphoid pseudoarthrosis and correction of the carpal relation.

  15. Effect of caffeine contained in a cup of coffee on microvascular function in healthy subjects.

    PubMed

    Noguchi, Katsuhiko; Matsuzaki, Toshihiro; Sakanashi, Mayuko; Hamadate, Naobumi; Uchida, Taro; Kina-Tanada, Mika; Kubota, Haruaki; Nakasone, Junko; Sakanashi, Matao; Ueda, Shinichiro; Masuzaki, Hiroaki; Ishiuchi, Shogo; Ohya, Yusuke; Tsutsui, Masato

    2015-02-01

    Recent epidemiological studies have demonstrated that coffee drinking is associated with reduced mortality of cardiovascular disease. However, its precise mechanisms remain to be clarified. In this study, we examined whether single ingestion of caffeine contained in a cup of coffee improves microvascular function in healthy subjects. A double-blind, placebo-controlled, crossover study was performed in 27 healthy volunteers. A cup of either caffeinated or decaffeinated coffee was drunk by the subjects, and reactive hyperemia of finger blood flow was assessed by laser Doppler flowmetry. In an interval of more than 2 days, the same experimental protocol was repeated with another coffee in a crossover manner. Caffeinated coffee intake slightly but significantly elevated blood pressure and decreased finger blood flow as compared with decaffeinated coffee intake. There was no significant difference in heart rate between caffeinated and decaffeinated coffee intake. Importantly, caffeinated coffee intake significantly enhanced post-occlusive reactive hyperemia of finger blood flow, an index of microvascular endothelial function, compared with decaffeinated coffee intake. These results provide the first evidence that caffeine contained in a cup of coffee enhances microvascular function in healthy individuals.

  16. Air Pollution Particulate Matter Collected from an Appalachian Mountaintop Mining Site Induces Microvascular Dysfunction

    PubMed Central

    KNUCKLES, TRAVIS L.; STAPLETON, PHOEBE A.; MINARCHICK, VALERIE C.; ESCH, LAURA; MCCAWLEY, MICHAEL; HENDRYX, MICHAEL; NURKIEWICZ, TIMOTHY R.

    2016-01-01

    Objective Air pollution PM is associated with cardiovascular morbidity and mortality. In Appalachia, PM from mining may represent a health burden to this sensitive population that leads the nation in cardiovascular disease, among others. Cardiovascular consequences following inhalation of PMMTM are unclear, but must be identified to establish causal effects. Methods PM was collected within 1 mile of an active MTM site in southern WV. The PM was extracted and was primarily <10μm in diameter (PM10), consisting largely of sulfur (38%) and silica (24%). Adult male rats were IT with 300 μg PMMTM. Twenty-four hours following exposure, rats were prepared for intravital microscopy, or isolated arteriole experiments. Results PMMTM exposure blunted endothelium-dependent dilation in mesenteric and coronary arterioles by 26%, and 25%, respectively, as well as endothelium-independent dilation. In vivo, PMMTM exposure inhibited endothelium-dependent arteriolar dilation (60% reduction). α-adrenergic receptor blockade inhibited PVNS-induced vasoconstriction in exposed animals compared with sham. Conclusions These data suggest that PMMTM exposure impairs microvascular function in disparate microvascular beds, through alterations in NO-mediated dilation and sympathetic nerve influences. Microvascular dysfunction may contribute to cardiovascular disease in regions with MTM sites. PMID:22963349

  17. Microvascular Reconstruction of Free Jejunal Graft in Larynx-preserving Esophagectomy for Cervical Esophageal Carcinoma

    PubMed Central

    Natori, Yuhei; Komoto, Masakazu; Matsumura, Takashi; Horiguchi, Masatoshi; Yoshizawa, Hidekazu; Iwanuma, Yoshimi; Tsurumaru, Masahioko; Kajiyama, Yoshiaki; Mizuno, Hiroshi

    2016-01-01

    Background: Losing the ability to speak severely affects the quality of life, and patients who have undergone laryngectomy tend to become depressed, which may lead to social withdrawal. Recently, with advancements in chemoradiotherapy and with alternative perspectives on postoperative quality of life, larynx preservation has been pursued; however, the selection of candidates and the optimal reconstructive procedure remain controversial. In this study, we retrospectively reviewed our experience with free jejunal graft for larynx-preserving cervical esophagectomy (LPCE), focusing on microvascular reconstruction. Methods: Seven patients underwent LPCE for cervical esophageal carcinoma, and defects were reconstructed by free jejunal transfer subsequently. We collected preoperative and postoperative data of the patients and assessed the importance of the procedure. Results: We mostly used the transverse cervical artery as the recipient, and a longer operative time was required, particularly for the regrowth cases. The operative field for microvascular anastomosis was more limited and deeper than those in the laryngectomy cases. Two graft necrosis cases were confirmed at postoperative day 9 or 15, and vessels contralateral from the graft were chosen as recipients in both patients. Conclusions: Microvascular reconstruction for free jejunal graft in LPCE differed in several ways from the procedure combined with laryngectomy. Compression from the tracheal cartilage to the pedicle was suspected as the reason of the necrosis clinically and pathologically. Therefore, we should select recipient vessels from the ipsilateral side of the graft, and careful and extended monitoring of the flap should be considered to make this procedure successful. PMID:27257562

  18. Microvascular anastomosis using fibrin glue and venous cuff in rat carotid artery.

    PubMed

    Sacak, Bulent; Tosun, Ugur; Egemen, Onur; Sakiz, Damlanur; Ugurlu, Kemal

    2015-04-01

    Conventional anastomosis with interrupted sutures can be time-consuming, can cause vessel narrowing, and can lead to thrombosis at the site of repair. The amount of suture material inside the lumen can impair the endothelium of the vessel, triggering thrombosis. In microsurgery, fibrin sealants have the potential beneficial effects of reducing anastomosis time and promoting accurate haemostasis at the anastomotic site. However, there has been a general reluctance to use fibrin glue for microvascular anastomoses because the fibrin polymer is highly thrombogenic and may not provide adequate strength. To overcome these problems, a novel technique was defined for microvascular anastomosis with fibrin glue and a venous cuff. Sixty-four rats in two groups are included in the study. In the experimental group (n = 32), end-to-end arterial anastomosis was performed with two stay sutures, fibrin glue, and a venous cuff. In the control group (n = 32), conventional end-to-end arterial anastomosis was performed. Fibrin glue assisted anastomosis with a venous cuff took less time, caused less bleeding at the anastomotic site, and achieved a patency rate comparable to that provided by the conventional technique. Fibrin sealant assisted microvascular anastomosis with venous cuff is a rapid, easy, and reliable technique compared to the end-to-end arterial anastomosis.

  19. Skeletal muscle capillary density and microvascular function are compromised with aging and type 2 diabetes.

    PubMed

    Groen, Bart B L; Hamer, Henrike M; Snijders, Tim; van Kranenburg, Janneau; Frijns, Dionne; Vink, Hans; van Loon, Luc J C

    2014-04-15

    Adequate muscle perfusion is required for the maintenance of skeletal muscle mass. Impairments in microvascular structure and/or function with aging and type 2 diabetes have been associated with the progressive loss of skeletal muscle mass. Our objective was to compare muscle fiber type specific capillary density and endothelial function between healthy young men, healthy older men, and age-matched type 2 diabetes patients. Fifteen healthy young men (24 ± 1 yr), 15 healthy older men (70 ± 2 yr), and 15 age-matched type 2 diabetes patients (70 ± 1 yr) were selected to participate in the present study. Whole body insulin sensitivity, muscle fiber type specific capillary density, sublingual microvascular density, and dimension of the erythrocyte-perfused boundary region were assessed to evaluate the impact of aging and/or type 2 diabetes on microvascular structure and function. Whole body insulin sensitivity was significantly lower at a more advanced age, with lowest values reported in the type 2 diabetic patients. In line, skeletal muscle capillary contacts were much lower in the older and older type 2 diabetic patients when compared with the young. Sidestream darkfield imaging showed a significantly greater thickness of the erythrocyte perfused boundary region in the type 2 diabetic patients compared with the young. Skeletal muscle capillary density is reduced with aging and type 2 diabetes and accompanied by impairments in endothelial glycocalyx function, which is indicative of compromised vascular function. PMID:24577061

  20. Mapping genetic determinants of coronary microvascular remodeling in the spontaneously hypertensive rat.

    PubMed

    Mancini, Massimiliano; Petretto, Enrico; Kleinert, Christina; Scavone, Angela; De, Tisham; Cook, Stuart; Silhavy, Jan; Zidek, Vaclav; Pravenec, Michal; d'Amati, Giulia; Camici, Paolo G

    2013-01-01

    The mechanisms underlying coronary microvascular remodeling and dysfunction, which are critical determinants of abnormal myocardial blood flow regulation in human hypertension, are poorly understood. The spontaneously hypertensive rat (SHR) exhibits many features of human hypertensive cardiomyopathy. We demonstrate that remodeling of intramural coronary arterioles is apparent in the SHR already at 4 weeks of age, i.e. before the onset of systemic hypertension. To uncover possible genetic determinants of coronary microvascular remodeling, we carried out detailed histological and histomorphometric analysis of the heart and coronary vasculature in 30 weeks old SHR, age-matched Brown Norway (BN-Lx) parentals and BXH/HXB recombinant inbred (RI) strains. Using previously mapped expression quantitative trait loci (eQTLs), we carried out a genome-wide association analysis between genetic determinants of cardiac gene expression and histomorphometric traits. This identified 36 robustly mapped eQTLs in the heart which were associated with medial area of intramural coronary arterioles [false discovery rate (FDR) ~5%]. Transcripts, which were both under cis-acting genetic regulation and significantly correlated with medial area (FDR <5%), but not with blood pressure indices, were prioritized and four candidate genes were identified (Rtel1, Pla2g5, Dnaja4 and Rcn2) according to their expression levels and biological functions. Our results demonstrate that genetic factors play a role in the development of coronary microvascular remodeling and suggest blood pressure independent candidate genes for further functional experiments.

  1. Effect of caffeine contained in a cup of coffee on microvascular function in healthy subjects.

    PubMed

    Noguchi, Katsuhiko; Matsuzaki, Toshihiro; Sakanashi, Mayuko; Hamadate, Naobumi; Uchida, Taro; Kina-Tanada, Mika; Kubota, Haruaki; Nakasone, Junko; Sakanashi, Matao; Ueda, Shinichiro; Masuzaki, Hiroaki; Ishiuchi, Shogo; Ohya, Yusuke; Tsutsui, Masato

    2015-02-01

    Recent epidemiological studies have demonstrated that coffee drinking is associated with reduced mortality of cardiovascular disease. However, its precise mechanisms remain to be clarified. In this study, we examined whether single ingestion of caffeine contained in a cup of coffee improves microvascular function in healthy subjects. A double-blind, placebo-controlled, crossover study was performed in 27 healthy volunteers. A cup of either caffeinated or decaffeinated coffee was drunk by the subjects, and reactive hyperemia of finger blood flow was assessed by laser Doppler flowmetry. In an interval of more than 2 days, the same experimental protocol was repeated with another coffee in a crossover manner. Caffeinated coffee intake slightly but significantly elevated blood pressure and decreased finger blood flow as compared with decaffeinated coffee intake. There was no significant difference in heart rate between caffeinated and decaffeinated coffee intake. Importantly, caffeinated coffee intake significantly enhanced post-occlusive reactive hyperemia of finger blood flow, an index of microvascular endothelial function, compared with decaffeinated coffee intake. These results provide the first evidence that caffeine contained in a cup of coffee enhances microvascular function in healthy individuals. PMID:25727960

  2. Inhibition of autophagy ameliorates pulmonary microvascular dilation and PMVECs excessive proliferation in rat experimental hepatopulmonary syndrome

    PubMed Central

    Xu, Duo; Chen, Bing; Gu, Jianteng; Chen, Lin; Belguise, Karine; Wang, Xiaobo; Yi, Bin; Lu, Kaizhi

    2016-01-01

    Hepatopulmonary syndrome (HPS) is a defective liver-induced pulmonary vascular disorder with massive pulmonary microvascular dilation and excessive proliferation of pulmonary microvascular endothelial cells (PMVECs). Growing evidence suggests that autophagy is involved in pulmonary diseases, protectively or detrimentally. Thus, it is interesting and important to explore whether autophagy might be involved in and critical in HPS. In the present study, we report that autophagy was activated in common bile duct ligation (CBDL) rats and cultured pulmonary PMVECs induced by CBDL rat serum, two accepted in vivo and in vitro experimental models of HPS. Furthermore, pharmacological inhibition of autophagy with 3-methyladenine (3-MA) significantly alleviated pathological alterations and typical symptom of HPS in CBDL rats in vivo, and consistently 3-MA significantly attenuated the CBDL rat serum-induced excessive proliferation of PMVECs in vitro. All these changes mediated by 3-MA might explain the observed prominent improvement of pulmonary appearance, edema, microvascular dilatation and arterial oxygenation in vivo. Collectively, these results suggest that autophagy activation may play a critical role in the pathogenesis of HPS, and autophagy inhibition may have a therapeutic potential for this disease. PMID:27480323

  3. Transcranial diffuse optical monitoring of microvascular cerebral hemodynamics after thrombolysis in ischemic stroke

    NASA Astrophysics Data System (ADS)

    Zirak, Peyman; Delgado-Mederos, Raquel; Dinia, Lavinia; Carrera, David; Martí-Fàbregas, Joan; Durduran, Turgut

    2014-01-01

    The ultimate goal of therapeutic strategies for ischemic stroke is to reestablish the blood flow to the ischemic region of the brain. However, currently, the local cerebral hemodynamics (microvascular) is almost entirely inaccessible for stroke clinicians at the patient bed-side, and the recanalization of the major cerebral arteries (macrovascular) is the only available measure to evaluate the therapy, which does not always reflect the local conditions. Here we report the case of an ischemic stroke patient whose microvascular cerebral blood flow and oxygenation were monitored by a compact hybrid diffuse optical monitor during thrombolytic therapy. This monitor combined diffuse correlation spectroscopy and near-infrared spectroscopy. The reperfusion assessed by hybrid diffuse optics temporally correlated with the recanalization of the middle cerebral artery (assessed by transcranial-Doppler) and was in agreement with the patient outcome. This study suggests that upon further investigation, diffuse optics might have a potential for bed-side acute stroke monitoring and therapy guidance by providing hemodynamics information at the microvascular level.

  4. Effects of S-nitrosation on hemoglobin-induced microvascular damage.

    PubMed

    Burke, Tara K; Teng, Xinjun; Patel, Rakesh P; Baldwin, Ann L

    2006-01-01

    Blood substitutes, such as diaspirin cross-linked hemoglobin (Hb), cause microvascular leakiness to macromolecules. Because of the potentially stabilizing effects of nitric acid (NO) on endothelium, experiments were performed to determine whether S-nitrosohemoglobin (SNO-Hb), a potential NO-donor Hb-based blood substitute, would not cause microvascular damage. Release of NO, or its metabolites, from the SNO-Hb was facilitated by addition of glutathione, which aids in the decomposition of S-nitrosothiols. In anesthetized rats, the mesenteric microvasculature was perfused with SNO-Hb with glutathione (six rats), SNO-Hb alone (six rats), or saline (eight rats) for 10 min, followed by fluorescein isothiocyanate (FITC)-albumin for 1 min, and finally fixed for epifluorescence microscopic examination. When comparing the SNO-Hb group with saline, both the numbers and areas of leaks were significantly increased [0.019 +/- 0.003 (SEM) microm vs. 0.0030 +/- 0.0004 and 7.36 +/- 1.50 vs. 0.156 +/- 0.035 (p < 0.005)]. With the addition of glutathione, leakage was still high (0.005 +/- 0.00005 microm and 5.086 +/- 0.064 microm) but decreased compared with SNO-Hb alone (p < 0.005). In conclusion, NO, or a related vasodilator, when released from SNO-Hb, significantly reduces but does not eliminate microvascular damage. Further improvements may result by S-nitrosating a more stable form of modified hemoglobin. PMID:16910757

  5. Atrial natriuretic peptide increases microvascular blood flow and macromolecular escape during renin infusion in the hamster

    SciTech Connect

    Boric, M.P.; Albertini, R. )

    1990-02-01

    The effects of Atrial Natriuretic Peptide (ANP) on microvascular hemodynamics and macromolecular permselectivity were studied in the hamster cheek pouch under resting conditions and during intravenous renin infusion. Fluorescent intravital microscopy was used to observe arteriolar diameters and to detect escape of fluorescent dextran of 150 K-Daltons (FITC-Dx-150). Microvascular plasma flow was estimated by clearance of 51Cr-EDTA and net macromolecular transport by clearance of FITC-Dx-150. At rest, topical ANP (2-250 ng/ml) had no effect on arteriolar diameter, 51Cr-EDTA clearance, relative vascular conductance (RVC) or FITC-Dx-150 clearance. Infusion of renin (10 mU/Kg/Hr, iv) elevated systemic arterial pressure by 30% and reduced cheek pouch RVC by 26%. During renin infusion, topical ANP (50 ng/ml) produced transient arteriolar vasodilation, and increased 51Cr-EDTA clearance (+35%), RVC (+58%) and FITC-Dx-150 clearance (+54%), without affecting systemic pressure. ANP did not induce venular leakage sites under any condition, but changes in FITC-Dx-150 clearance were highly correlated with changes in 51Cr-EDTA clearance, suggesting that the larger macromolecular escape was due to increases in microvascular blood flow and capillary/post-capillary hydrostatic pressure.

  6. Cutaneous microvascular response during local cold exposure - the effect of female sex hormones and cold perception.

    PubMed

    Cankar, Ksenija; Music, Mark; Finderle, Zare

    2016-11-01

    It is generally known that differences exist between males and females with regard to sensitivity to cold. Similar differences even among females in different hormonal balance might influence microvascular response during cold provocation testing. The aim of the present study was to measure sex hormone levels, cold and cold pain perception thresholds and compare them to cutaneous laser-Doppler flux response during local cooling in both the follicular and luteal phases of the menstrual cycle. In the luteal phase a more pronounced decrease in laser-Doppler flux was observed compared to follicular phase during local cooling at 15°C (significant difference by Dunnett's test, p<0.05). In addition, statistically significant correlations between progesterone level and laser-Doppler flux response to local cooling were observed during the follicular (R=-0.552, p=0.0174) and during the luteal phases (R=0.520, p=0.0271). In contrast, the correlation between estradiol level and laser-Doppler flux response was observed only in the follicular phase (R=-0.506, p=0.0324). Our results show that individual sensitivity to cold influences cutaneous microvascular response to local cooling; that microvascular reactivity is more pronounced during the luteal phase of the menstrual cycle; and that reactivity correlates with hormone levels. The effect of specific sex hormone levels is related to the cold-provocation temperature. PMID:27430896

  7. Transmural variation and anisotropy of microvascular flow conductivity in the rat myocardium

    PubMed Central

    Smith, Amy F.; Shipley, Rebecca J.; Lee, Jack; Sands, Gregory B.; LeGrice, Ian J.; Smith, Nicolas P.

    2015-01-01

    Transmural variations in the relationship between structural and fluid transport properties of myocardial capillary networks are determined via continuum modelling approaches using recent three-dimensional (3D) data on the microvascular structure. Specifically, the permeability tensor, which quantifies the inverse of the blood flow resistivity of the capillary network, is computed by volume-averaging flow solutions in synthetic networks with geometrical and topological properties derived from an anatomically-detailed microvascular data set extracted from the rat myocardium. Results show that the permeability is approximately ten times higher in the principal direction of capillary alignment (the ‘longitudinal’ direction) than perpendicular to this direction, reflecting the strong anisotropy of the microvascular network. Additionally, a 30% increase in capillary diameter from subepicardium to subendocardium is shown to translate to a 130% transmural rise in permeability in the longitudinal capillary direction. This result supports the hypothesis that perfusion is preferentially facilitated during diastole in the subendocardial microvasculature to compensate for the severely-reduced systolic perfusion in the subendocardium. PMID:24866569

  8. Determination of Optical and Microvascular Parameters of Port Wine Stains Using Diffuse Reflectance Spectroscopy.

    PubMed

    Qiu, Zhihai; Yao, Guangping; Chen, Defu; Wang, Ying; Gu, Ying; Li, Buhong

    2016-01-01

    Characterizing port wine stains (PWS) with its optical parameters [i.e. absorption coefficient (μ a) and reduced scattering coefficient (μ s')] and microvascular parameters [i.e. blood volume fraction (BVF), mean vessel diameter (MVD), and oxygen saturation (StO2)] is extremely important for elucidating the mechanisms for its light-based treatments, such as pulsed dye laser and photodynamic therapy. In this study, a customized diffuse reflectance spectroscopy (DRS) probe with an appropriate source-detector distance was used to measure the diffuse reflectance spectra of PWS lesions in clinical practice. The results demonstrate that optical parameters of different types of PWS lesions can be accurately extracted by fitting the DRS with diffusion equation. Since the sampling depth of the probe coincides with the depth distribution of abnormal vasculature in PWS, the obtained microvascular parameters of PWS lesions that changed from pink to purple are in agreement with the corresponding physiological conditions. This study suggests that DRS can be utilized to quantitatively determine the optical and microvascular parameters of PWS lesions, which have the potential for planning the protocol and predicting the efficiency for light-based PWS treatments. PMID:27526164

  9. Cerium Dioxide Nanoparticle Exposure Improves Microvascular Dysfunction and Reduces Oxidative Stress in Spontaneously Hypertensive Rats

    PubMed Central

    Minarchick, Valerie C.; Stapleton, Phoebe A.; Sabolsky, Edward M.; Nurkiewicz, Timothy R.

    2015-01-01

    The elevated production of reactive oxygen species (ROS) in the vascular wall is associated with cardiovascular diseases such as hypertension. This increase in oxidative stress contributes to various mechanisms of vascular dysfunction, such as decreased nitric oxide bioavailability. Therefore, anti-oxidants are being researched to decrease the high levels of ROS, which could improve the microvascular dysfunction associated with various cardiovascular diseases. From a therapeutic perspective, cerium dioxide nanoparticles (CeO2 NP) hold great anti-oxidant potential, but their in vivo activity is unclear. Due to this potential anti-oxidant action, we hypothesize that injected CeO2 NP would decrease microvascular dysfunction and oxidative stress associated with hypertension. In order to simulate a therapeutic application, spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats were intravenously injected with either saline or CeO2 NP (100 μg suspended in saline). Twenty-four hours post-exposure mesenteric arteriolar reactivity was assessed via intravital microscopy. Endothelium-dependent and –independent function was assessed via acetylcholine and sodium nitroprusside. Microvascular oxidative stress was analyzed using fluorescent staining in isolated mesenteric arterioles. Finally, systemic inflammation was examined using a multiplex analysis and venular leukocyte flux was counted. Endothelium-dependent dilation was significantly decreased in the SH rats (29.68 ± 3.28%, maximal response) and this microvascular dysfunction was significantly improved following CeO2 NP exposure (43.76 ± 4.33%, maximal response). There was also an increase in oxidative stress in the SH rats, which was abolished following CeO2 NP treatment. These results provided evidence that CeO2 NP act as an anti-oxidant in vivo. There were also changes in the inflammatory profile in the WKY and SH rats. In WKY rats, IL-10 and TNF-α were increased following CeO2 NP treatment. Finally, leukocyte

  10. Glycogen Synthase Kinase-3 Inhibitor Protects Against Microvascular Hyperpermeability Following Hemorrhagic Shock

    PubMed Central

    Sawant, Devendra A.; Tharakan, Binu; Hunter, Felicia A.; Childs, Ed W.

    2015-01-01

    Background Hemorrhagic shock (HS)-induce microvascular hyperpermeability involves disruption of endothelial cell adherens junctions leading to increase in paracellular permeability. β-Catenin, an integral component of the adherens junctional complex and Wnt pathway, and caspase-3 via its apoptotic signaling regulate endothelial cell barrier integrity. We have hypothesized that inhibiting phosphorylation of β-catenin and caspase-3 activity using glycogen synthase kinase-3 (GSK-3) specific inhibitor SB216763, would attenuate microvascular hyperpermeability following HS. Methods In Sprague-Dawley rats, HS was induced by withdrawing blood to reduce mean arterial pressure to 40 mmHg for 60 minutes followed by resuscitation. Rats were given SB216763 (600 μg/kg) intravenously 10 minutes prior to shock. To study microvascular permeability, the rats were injected intravenously with FITC-albumin (50 mg/kg) and its flux across the mesenteric post-capillary venules was determined using intravital microscopy. In cell-culture studies, rat lung microvascular endothelial cell (RLMEC) monolayers grown on Transwell plates were pre-treated with SB216763 (5 μM) followed by BAK (5 μg/mL) and caspase-3 (5 μg/mL) protein transfection. FITC-albumin (5 mg/mL) flux across cell monolayers indicates change in monolayer permeability. Activity of canonical Wnt pathway was determined by luciferase assay. Caspase-3 enzyme activity was assayed fluorometrically. Results The HS group showed significant increase in FITC-albumin extravasation (p<0.05) compared with sham. SB216763 significantly decrease HS-induced FITC-albumin extravasation (p<0.05). Pre-treatment with SB216763, protected against a BAK-induced increase in RLMEC monolayer permeability and caspase-3 activity, but failed to show similar results with a caspase-3-induced increase in monolayer permeability. Wnt3a treatment showed an increase in β-catenin dependent TCF-mediated transcription. Conclusion Inhibiting phosphorylation of

  11. Protein kinase A mediates glucagon-like peptide 1-induced nitric oxide production and muscle microvascular recruitment

    PubMed Central

    Dong, Zhenhua; Chai, Weidong; Wang, Wenhui; Zhao, Lina; Fu, Zhuo; Cao, Wenhong

    2013-01-01

    Glucagon-like peptide-1 (GLP-1) causes vasodilation and increases muscle glucose uptake independent of insulin. Recently, we have shown that GLP-1 recruits muscle microvasculature and increases muscle glucose use via a nitric oxide (NO)-dependent mechanism. Protein kinase A (PKA) is a major signaling intermediate downstream of GLP-1 receptors. To examine whether PKA mediates GLP-1's microvascular action in muscle, GLP-1 was infused to overnight-fasted male rats for 120 min in the presence or absence of H89, a PKA inhibitor. Hindleg muscle microvascular recruitment and glucose use were determined. GLP-1 infusion acutely increased muscle microvascular blood volume within 30 min without altering microvascular blood flow velocity or blood pressure. This effect persisted throughout the 120-min infusion period, leading to a significant increase in muscle microvascular blood flow. These changes were paralleled with an approximately twofold increase in plasma NO levels and hindleg glucose extraction. Systemic infusion of H89 completely blocked GLP-1-mediated muscle microvascular recruitment and increases in NO production and muscle glucose extraction. In cultured endothelial cells, GLP-1 acutely increased PKA activity and stimulated endothelial NO synthase phosphorylation at Ser1177 and NO production. PKA inhibition abolished these effects. In ex vivo studies, perfusion of the distal saphenous artery with GLP-1 induced significant vasorelaxation that was also abolished by pretreatment of the vessels with PKA inhibitor H89. We conclude that GLP-1 recruits muscle microvasculature by expanding microvascular volume and increases glucose extraction in muscle via a PKA/NO-dependent pathway in the vascular endothelium. This may contribute to postprandial glycemic control and complication prevention in diabetes. PMID:23193054

  12. Computer-based analysis of microvascular alterations in a mouse model for Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Heinzer, Stefan; Müller, Ralph; Stampanoni, Marco; Abela, Rafael; Meyer, Eric P.; Ulmann-Schuler, Alexandra; Krucker, Thomas

    2007-03-01

    Vascular factors associated with Alzheimer's disease (AD) have recently gained increased attention. To investigate changes in vascular, particularly microvascular architecture, we developed a hierarchical imaging framework to obtain large-volume, high-resolution 3D images from brains of transgenic mice modeling AD. In this paper, we present imaging and data analysis methods which allow compiling unique characteristics from several hundred gigabytes of image data. Image acquisition is based on desktop micro-computed tomography (µCT) and local synchrotron-radiation µCT (SRµCT) scanning with a nominal voxel size of 16 µm and 1.4 µm, respectively. Two visualization approaches were implemented: stacks of Z-buffer projections for fast data browsing, and progressive-mesh based surface rendering for detailed 3D visualization of the large datasets. In a first step, image data was assessed visually via a Java client connected to a central database. Identified characteristics of interest were subsequently quantified using global morphometry software. To obtain even deeper insight into microvascular alterations, tree analysis software was developed providing local morphometric parameters such as number of vessel segments or vessel tortuosity. In the context of ever increasing image resolution and large datasets, computer-aided analysis has proven both powerful and indispensable. The hierarchical approach maintains the context of local phenomena, while proper visualization and morphometry provide the basis for detailed analysis of the pathology related to structure. Beyond analysis of microvascular changes in AD this framework will have significant impact considering that vascular changes are involved in other neurodegenerative diseases as well as in cancer, cardiovascular disease, asthma, and arthritis.

  13. The study of synchronization of rhythms of microvascular blood flow and oxygen saturation during adaptive changes

    NASA Astrophysics Data System (ADS)

    Dunaev, Andrey V.; Sidorov, Victor V.; Krupatkin, Alexander I.; Rafailov, Ilya E.; Palmer, Scott G.; Sokolovski, Sergei G.; Stewart, Neil A.; Rafailov, Edik U.

    2014-02-01

    Multi-functional laser non-invasive diagnostic systems, such as "LAKK-M", allow the study of a number of microcirculatory parameters, including blood microcirculatory index (Im) (by laser Doppler flowmetry, LDF) and oxygen saturation (StO2) of skin tissue (by tissue reflectance oximetry, TRO). Such systems may provide significant information relevant to physiology and clinical medicine. The aim of this research was to use such a system to study the synchronization of microvascular blood flow and oxygen saturation rhythms under normal and adaptive change conditions. Studies were conducted with 8 healthy volunteers - 3 females and 5 males of 21-49 years. Each volunteer was subjected to basic 3 minute tests. The volunteers were observed for between 1-4 months each, totalling 422 basic tests. Measurements were performed on the palmar surface of the right middle finger and the forearm medial surface. Wavelet analysis was used to study rhythmic oscillations in LDF- and TRO-data. Tissue oxygen consumption (from arterial and venal blood oxygen saturation and nutritive flux volume) was calculated for all volunteers during "adaptive changes" as (617+/-123 AU) and (102+/-38 AU) with and without arteriovenous anastomoses (AVAs) respectively. This demonstrates increased consumption compared to normal (495+/-170 AU) and (69+/-40 AU) with and without AVAs respectively. Data analysis demonstrated the emergence of resonance and synchronization of rhythms of microvascular blood flow and oxygen saturation as an adaptive change in myogenic oscillation (vasomotion) resulting from exercise and potentially from psychoemotional stress. Synchronization of myogenic rhythms during adaptive changes suggest increased oxygen consumption resulting from increased microvascular blood flow velocity.

  14. Effect of medication on microvascular vasodilatation in patients with systemic lupus erythematosus.

    PubMed

    Bengtsson, Christine; Andersson, Sven E; Edvinsson, Lars; Edvinsson, Marie-Louise; Sturfelt, Gunnar; Nived, Ola

    2010-12-01

    The aim of this study was to investigate the microvascular responses in the skin, to local heat, iontophoretically administered acetylcholine and to sodium nitroprusside in relation to cardiovascular damage in patients with systemic lupus erythematosus (SLE) and matched controls. We also wanted to examine if the ongoing medication in SLE patients influenced this vascular response. We investigated 30 women with SLE and compared them with 20 age and sex-matched controls. The cutaneous blood flow response to local heat (+44°C), iontophoretically administered endothelium-dependent (acetylcholine), as well as independent (sodium nitroprusside) vasodilatation, was measured by laser Doppler flowmetry. Clinical data and medication were retrieved from the clinical database and patient records. The cutaneous microvascular reactivity did not differ between SLE patients and a group of matched controls nor did it correlate with cardiovascular damage [assessed by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI)]. However, patients on antimalarial drugs (hydroxychloroquine n = 8 and chloroquine diphosphate n = 3) responded more strongly to sodium nitroprusside (endothelium-independent vasodilatation) compared with those without antimalarial drugs (p < 0.01). The response to acetylcholine was higher among patients on warfarin compared with those without (p < 0.05), whereas glucocorticoid use (≥5 mg daily) was associated with reduced response to acetylcholine (p < 0.05). Smokers in general tended to have a lower response to acetylcholine (p = 0.064). Smoking SLE patients versus non-smoking SLE patients had a significantly lower response to acetylcholine (p = 0.01). Medication with antimalarial drugs-enhanced endothelium-independent vasodilatation, while glucocorticoid use was associated with reduction and warfarin-treatment with enhancement of endothelium-dependent vasodilatation. Therefore, despite there is no

  15. SDF-1/CXCR4 signaling preserves microvascular integrity and renal function in chronic kidney disease.

    PubMed

    Chen, Li-Hao; Advani, Suzanne L; Thai, Kerri; Kabir, M Golam; Sood, Manish M; Gibson, Ian W; Yuen, Darren A; Connelly, Kim A; Marsden, Philip A; Kelly, Darren J; Gilbert, Richard E; Advani, Andrew

    2014-01-01

    The progressive decline of renal function in chronic kidney disease (CKD) is characterized by both disruption of the microvascular architecture and the accumulation of fibrotic matrix. One angiogenic pathway recently identified as playing an essential role in renal vascular development is the stromal cell-derived factor-1α (SDF-1)/CXCR4 pathway. Because similar developmental processes may be recapitulated in the disease setting, we hypothesized that the SDF-1/CXCR4 system would regulate microvascular health in CKD. Expression of CXCR4 was observed to be increased in the kidneys of subtotally nephrectomized (SNx) rats and in biopsies from patients with secondary focal segmental glomerulosclerosis (FSGS), a rodent model and human correlate both characterized by aberration of the renal microvessels. A reno-protective role for local SDF-1/CXCR4 signaling was indicated by i) CXCR4-dependent glomerular eNOS activation following acute SDF-1 administration; and ii) acceleration of renal function decline, capillary loss and fibrosis in SNx rats treated with chronic CXCR4 blockade. In contrast to the upregulation of CXCR4, SDF-1 transcript levels were decreased in SNx rat kidneys as well as in renal fibroblasts exposed to the pro-fibrotic cytokine transforming growth factor β (TGF-β), the latter effect being attenuated by histone deacetylase inhibition. Increased renal SDF-1 expression was, however, observed following the treatment of SNx rats with the ACE inhibitor, perindopril. Collectively, these observations indicate that local SDF-1/CXCR4 signaling functions to preserve microvascular integrity and prevent renal fibrosis. Augmentation of this pathway, either purposefully or serendipitously with either novel or existing therapies, may attenuate renal decline in CKD. PMID:24637920

  16. The relationship between red blood cell deformability metrics and perfusion of an artificial microvascular network

    PubMed Central

    Sosa, Jose M.; Nielsen, Nathan D.; Vignes, Seth M.; Chen, Tanya G.; Shevkoplyas, Sergey S.

    2013-01-01

    The ability of red blood cells (RBC) to undergo a wide range of deformations while traversing the microvasculature is crucial for adequate perfusion. Interpretation of RBC deformability measurements performed in vitro in the context of microvascular perfusion has been notoriously difficult. This study compares the measurements of RBC deformability performed using micropore filtration and ektacytometry with the RBC ability to perfuse an artificial microvascular network (AMVN). Human RBCs were collected from healthy consenting volunteers, leukoreduced, washed and exposed to graded concentrations (0% – 0.08%) of glutaraldehyde (a non-specific protein cross-linker) and diamide (a spectrin-specific protein cross-linker) to impair the deformability of RBCs. Samples comprising cells with two different levels of deformability were created by adding non-deformable RBCs (hardened by exposure to 0.08% glutaraldehyde) to the sample of normal healthy RBCs. Ektacytometry indicated a nearly linear decline in RBC deformability with increasing glutaraldehyde concentration. Micropore filtration showed a significant reduction only for concentrations of glutaraldehyde higher than 0.04%. Neither micropore filtration nor ektacytometry measurements could accurately predict the AMVN perfusion. Treatment with diamide reduced RBC deformability as indicated by ektacytometry, but had no significant effect on either micropore filtration or the AMVN perfusion. Both micropore filtration and ektacytometry showed a linear decline in effective RBC deformability with increasing fraction of non-deformable RBCs in the sample. The corresponding decline in the AMVN perfusion plateaued above 50%, reflecting the innate ability of blood flow in the microvasculature to bypass occluded capillaries. Our results suggest that in vitro measurements of RBC deformability performed using either micropore filtration or ektacytometry may not represent the ability of same RBCs to perfuse microvascular networks

  17. Brain angioarchitecture and intussusceptive microvascular growth in a murine model of Krabbe disease.

    PubMed

    Giacomini, Arianna; Ackermann, Maximilian; Belleri, Mirella; Coltrini, Daniela; Nico, Beatrice; Ribatti, Domenico; Konerding, Moritz A; Presta, Marco; Righi, Marco

    2015-10-01

    Defects of the angiogenic process occur in the brain of twitcher mouse, an authentic model of human Krabbe disease caused by genetic deficiency of lysosomal β-galactosylceramidase (GALC), leading to lethal neurological dysfunctions and accumulation of neurotoxic psychosine in the central nervous system. Here, quantitative computational analysis was used to explore the alterations of brain angioarchitecture in twitcher mice. To this aim, customized ImageJ routines were used to assess calibers, amounts, lengths and spatial dispersion of CD31(+) vessels in 3D volumes from the postnatal frontal cortex of twitcher animals. The results showed a decrease in CD31 immunoreactivity in twitcher brain with a marked reduction in total vessel lengths coupled with increased vessel fragmentation. No significant changes were instead observed for the spatial dispersion of brain vessels throughout volumes or in vascular calibers. Notably, no CD31(+) vessel changes were detected in twitcher kidneys in which psychosine accumulates at very low levels, thus confirming the specificity of the effect. Microvascular corrosion casting followed by scanning electron microscopy morphometry confirmed the presence of significant alterations of the functional angioarchitecture of the brain cortex of twitcher mice with reduction in microvascular density, vascular branch remodeling and intussusceptive angiogenesis. Intussusceptive microvascular growth, confirmed by histological analysis, was paralleled by alterations of the expression of intussusception-related genes in twitcher brain. Our data support the hypothesis that a marked decrease in vascular development concurs to the onset of neuropathological lesions in twitcher brain and suggest that neuroinflammation-driven intussusceptive responses may represent an attempt to compensate impaired sprouting angiogenesis.

  18. AST-120 Improves Microvascular Endothelial Dysfunction in End-Stage Renal Disease Patients Receiving Hemodialysis

    PubMed Central

    Ryu, Jung-Hwa; Yu, Mina; Lee, Sihna; Ryu, Dong-Ryeol; Kim, Seung-Jung; Kang, Duk-Hee

    2016-01-01

    Purpose Endothelial dysfunction (ED) is a pivotal phenomenon in the development of cardiovascular disease (CVD) in patients receiving hemodialysis (HD). Indoxyl sulfate (IS) is a known uremic toxin that induces ED in patients with chronic kidney disease. The aim of this study was to investigate whether AST-120, an absorbent of IS, improves microvascular or macrovascular ED in HD patients. Materials and Methods We conducted a prospective, case-controlled trial. Fourteen patients each were enrolled in respective AST-120 and control groups. The subjects in the AST-120 group were treated with AST-120 (6 g/day) for 6 months. Microvascular function was assessed by laser Doppler flowmetry using iontophoresis of acetylcholine (Ach) and sodium nitroprusside (SNP) at baseline and again at 3 and 6 months. Carotid arterial intima-media thickness (cIMT) and flow-mediated vasodilation were measured at baseline and 6 months. The Wilcoxon rank test was used to compare values before and after AST-120 treatment. Results Ach-induced iontophoresis (endothelium-dependent response) was dramatically ameliorated at 3 months and 6 months in the AST-120 group. SNP-induced response showed delayed improvement only at 6 months in the AST-120 group. The IS level was decreased at 3 months in the AST-120 group, but remained stable thereafter. cIMT was significantly reduced after AST-120 treatment. No significant complications in patients taking AST-120 were reported. Conclusion AST-120 ameliorated microvascular ED and cIMT in HD patients. A randomized study including a larger population will be required to establish a definitive role of AST-120 as a preventive medication for CVD in HD patients. PMID:27189289

  19. A comparison of heparinised saline irrigation solutions in a model of microvascular thrombosis.

    PubMed

    Cox, G W; Runnels, S; Hsu, H S; Das, S K

    1992-07-01

    The use of heparinised irrigation solutions has become common in microvascular surgery, but the concentration of heparin has been determined empirically. A laboratory model of microvascular thrombosis, employing a crush injury, intimal abrasion, and stasis to the rat superficial femoral artery was used to compare heparinised saline irrigation solutions of various concentrations. The solutions included normal saline (Group I, controls) and heparinised normal saline in concentrations of 10 U/ml (Group III), 250 U/ml (Group IV), and 500 U/ml (Group V). Group I animals had a patency rate of 25% at 20 min and 0% at 24 h. Group II showed a patency rate of 75% at 20 min but fell to 37.5% at 24 h. Patency in Group III was 87.5% at 20 min and at 24 h. Group IV had a 100% patency rate at 20 min and at 24 h. Group V animals were 100% patent at 20 min and 87.5% patent at 24 h. The activated partial thromboplastin time was prolonged in animals exposed to 250 U/ml and 500 U/ml of heparinised saline. Patency was significantly improved in animals exposed to 100 U/ml, 250 U/ml and 500 U/ml when compared to the control group (p less than 0.001). These results suggest that topical heparinised saline administration is of benefit in the prevention of microvascular thrombosis. Higher concentrations tested in this study resulted in a significant increase in patency, but also prolonged the activated partial thromboplastin time. 100 U/ml is the ideal concentration of heparinised saline irrigation because it significantly improved patency but did not produce detectable systemic effects in this model.

  20. In vivo microvascular mosaics show air embolism reduction after perfluorocarbon emulsion treatment.

    PubMed

    Torres Filho, Ivo P; Torres, Luciana N; Spiess, Bruce D

    2012-11-01

    Massive arteriolar gas embolism (AGE) has never been evaluated in vivo using intravital microscopy and previous perfluorocarbon (PFC) emulsions were only effective in AGE when administered before AGE. We implemented a new system for quantitative studies of massive AGE using brightfield microscopy and tested a treatment with a third-generation PFC emulsion after massive AGE. We studied bubble dynamics in cremaster muscles from anesthetized rats after AGE was induced by direct air injection into the femoral artery ipsilateral to the studied muscle. Using a motorized microscope stage and a color camera, in vivo microvascular mosaics were produced on-line from over 2000 digital images to evaluate multiple networks in order to investigate the distribution, lodging, breaking, reduction and moving of 105 air bubbles in microvessels. Thirty minutes after PFC treatment, there was a reduction of 80% in bubble volume while untreated and saline-treated rats showed significantly smaller decreases of 33% and 40%, respectively (p<0.05). Air bubbles also dissolved into a larger number of smaller bubbles after PFC treatment. The proposed methodology may prove useful for rapid in vivo data acquisition from large networks. Since large air bubbles broke-up, decreased in length and volume, and moved toward smaller microvessels, the study provides quantitative data to support a mechanism by which PFC may improve tissue blood flow following massive AGE. The findings suggest that this new generation of PFC emulsions administered after severe AGE may reach compromised microvascular networks and provide help to alleviate microvascular obstruction by increasing air bubble reabsorption.

  1. Effect of Irradiation on Microvascular Endothelial Cells of Parotid Glands in the Miniature Pig

    SciTech Connect

    Xu Junji; Yan Xing; Gao Runtao; Mao Lisha; Cotrim, Ana P.; Zheng Changyu; Zhang Chunmei; Baum, Bruce J.; Wang Songlin

    2010-11-01

    Purpose: To evaluate the effect of irradiation on microvascular endothelial cells in miniature pig parotid glands. Methods and Materials: A single 25-Gy dose of irradiation (IR) was delivered to parotid glands of 6 miniature pigs. Three other animals served as non-IR controls. Local blood flow rate in glands was measured pre- and post-IR with an ultrasonic Doppler analyzer. Samples of parotid gland tissue were taken at 4 h, 24 h, 1 week, and 2 weeks after IR for microvascular density (MVD) analysis and sphingomyelinase (SMase) assay. Histopathology and immunohistochemical staining (anti-CD31 and anti-AQP1) were used to assess morphological changes. MVD was determined by calculating the number of CD31- or AQP1-stained cells per field. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay was used to detect apoptotic cells. The activity of acid and neutral Mg{sup 2+}-dependent SMase (ASMase and NSMase, respectively) was also assayed. Results: Local parotid gland blood flow rate decreased rapidly at 4 h post-IR and remained below control levels throughout the 14-day observation period. Parotid MVD also declined from 4 to 24 hours and remained below control levels thereafter. The activity levels of ASMase and NSMase in parotid glands increased rapidly from 4 to 24 h post-IR and then declined gradually. The frequency of detecting apoptotic nuclei in the glands followed similar kinetics. Conclusions: Single-dose IR led to a significant reduction of MVD and local blood flow rate, indicating marked damage to microvascular endothelial cells in miniature pig parotid glands. The significant and rapid increases of ASMase and NSMase activity levels may be important in this IR-induced damage.

  2. Zingiber officinale attenuates retinal microvascular changes in diabetic rats via anti-inflammatory and antiangiogenic mechanisms

    PubMed Central

    Dongare, Shirish; Mathur, Rajani; Saxena, Rohit; Mathur, Sandeep; Agarwal, Renu; Nag, Tapas C.; Srivastava, Sushma; Kumar, Pankaj

    2016-01-01

    Purpose Diabetic retinopathy is a common microvascular complication of long-standing diabetes. Several complex interconnecting biochemical pathways are activated in response to hyperglycemia. These pathways culminate into proinflammatory and angiogenic effects that bring about structural and functional damage to the retinal vasculature. Since Zingiber officinale (ginger) is known for its anti-inflammatory and antiangiogenic properties, we investigated the effects of its extract standardized to 5% 6-gingerol, the major active constituent of ginger, in attenuating retinal microvascular changes in rats with streptozotocin-induced diabetes. Methods Diabetic rats were treated orally with the vehicle or the ginger extract (75 mg/kg/day) over a period of 24 weeks along with regular monitoring of bodyweight and blood glucose and weekly fundus photography. At the end of the 24-week treatment, the retinas were isolated for histopathological examination under a light microscope, transmission electron microscopy, and determination of the retinal tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB), and vascular endothelial growth factor (VEGF) levels. Results Oral administration of the ginger extract resulted in significant reduction of hyperglycemia, the diameter of the retinal vessels, and vascular basement membrane thickness. Improvement in the architecture of the retinal vasculature was associated with significantly reduced expression of NF-κB and reduced activity of TNF-α and VEGF in the retinal tissue in the ginger extract–treated group compared to the vehicle-treated group. Conclusions The current study showed that ginger extract containing 5% of 6-gingerol attenuates the retinal microvascular changes in rats with streptozotocin-induced diabetes through anti-inflammatory and antiangiogenic actions. Although precise molecular targets remain to be determined, 6-gingerol seems to be a potential candidate for further investigation. PMID:27293376

  3. Numerical simulation of red blood cell distributions in three-dimensional microvascular bifurcations.

    PubMed

    Hyakutake, Toru; Nagai, Shinya

    2015-01-01

    We constructed three-dimensional microvascular bifurcation models using a parent vessel of diameter 10μm and investigated the flow behavior of the red blood cells (RBCs) through bifurcations. We considered symmetric and asymmetric model types. Two cases of equal daughter vessel diameter were employed for the asymmetric models, where the first was 10μm, which is the same as the parent vessel and the second was 7.94μm, which satisfies Murray's law. Simulated blood flow was computed using the lattice Boltzmann method in conjunction with the immersed boundary method for incorporating fluid-membrane interactions between the flow field and deformable RBCs. First, we investigated the flow behavior of a single RBC through microvascular bifurcations. In the case of the symmetric bifurcation, the turning point of the fractional plasma flow wherein the RBC flow changed from one daughter vessel to the other was 0.50. This turning point was however different for asymmetric bifurcations. Additionally, we varied the initial offset of RBCs from the centerline of the parent vessel. The simulation results indicated that the RBCs preferentially flow through the branch of a larger flow ratio. Next, we investigated the distribution characteristics of multiple RBCs. Simulations indicated that the results of the symmetric model were similar to those predicted by a previously published empirical model. On the other hand, results of asymmetric models deviated from those of the symmetric and empirical models. These results suggest that the distribution of RBCs varies according to the bifurcation angle and daughter vessel diameter in a microvascular bifurcation of the size considered.

  4. Glaucocalyxin A Ameliorates Myocardial Ischemia-Reperfusion Injury in Mice by Suppression of Microvascular Thrombosis

    PubMed Central

    Liu, Xiaohui; Xu, Dongzhou; Wang, Yuxin; Chen, Ting; Wang, Qi; Zhang, Jian; You, Tao; Zhu, Li

    2016-01-01

    Background The aim of this study was to evaluate the cardio-protective roles of glaucocalyxin A (GLA) in myocardial ischemia-reperfusion injury and to explore the underlying mechanism. Material/Methods Myocardial ischemia-reperfusion in wild-type C57BL/6J mice was induced by transient ligation of the left anterior descending artery. GLA or vehicle (solvent) was administrated intraperitoneally to the mice before reperfusion started. After 24 h of myocardial reperfusion, ischemic size was revealed by Evans blue/TTC staining. Cardiac function was evaluated by echocardiography and microvascular thrombosis was assessed by immunofluorescence staining of affected heart tissue. We also measured the phosphorylation of AKT, ERK, P-GSK-3β, and cleaved caspase 3 in the myocardium. Results Compared to the solvent-treated control group, GLA administration significantly reduced infarct size (GLA 13.85±2.08% vs. Control 18.95±0.97%, p<0.05) and improved left ventricular ejection fraction (LVEF) (GLA 53.13±1.11% vs. Control 49.99±1.25%, p<0.05) and left ventricular fractional shortening (LVFS) (28.34±0.71% vs. Control 25.11±0.74%, p<0.05) in mice subjected to myocardial ischemia-reperfusion. GLA also attenuated microvascular thrombosis (P<0.05) and increased the phosphorylation of pro-survival kinase AKT (P<0.05) and GSK-3β (P<0.05) in the myocardium upon reperfusion injury. Conclusions Administration of GLA before reperfusion ameliorates myocardial ischemia-reperfusion injury in mice. The cardio-protective roles of GLA may be mediated through the attenuation of microvascular thrombosis. PMID:27716735

  5. Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction

    PubMed Central

    Scioli, Maria Giovanna; Lo Giudice, Pietro; Bielli, Alessandra; Tarallo, Valeria; De Rosa, Alfonso; De Falco, Sandro; Orlandi, Augusto

    2015-01-01

    Background Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO) production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC) is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery. Methods and Results We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS) reduction, inducible nitric oxide synthase (iNOS) and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and reduction of NADPH-oxidase 4 (Nox4) expression. In serum-deprived human dermal microvascular endothelial cell cultures, PLC ameliorated endothelial dysfunction by increasing iNOS, PlGF, VEGF receptors 1 and 2 expression and NO level. In addition, PLC counteracted serum deprivation-induced impairment of mitochondrial β-oxidation, Nox4 and cellular adhesion molecule (CAM) expression, ROS generation and leukocyte adhesion. Moreover, dermal microvascular endothelial cell dysfunction was prevented by Nox4 inhibition. Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction. Conclusion PLC treatment improved rat skin flap viability, accelerated wound healing and dermal angiogenesis. The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction

  6. Cathepsin S Cleavage of Protease-Activated Receptor-2 on Endothelial Cells Promotes Microvascular Diabetes Complications.

    PubMed

    Kumar Vr, Santhosh; Darisipudi, Murthy N; Steiger, Stefanie; Devarapu, Satish Kumar; Tato, Maia; Kukarni, Onkar P; Mulay, Shrikant R; Thomasova, Dana; Popper, Bastian; Demleitner, Jana; Zuchtriegel, Gabriele; Reichel, Christoph; Cohen, Clemens D; Lindenmeyer, Maja T; Liapis, Helen; Moll, Solange; Reid, Emma; Stitt, Alan W; Schott, Brigitte; Gruner, Sabine; Haap, Wolfgang; Ebeling, Martin; Hartmann, Guido; Anders, Hans-Joachim

    2016-06-01

    Endothelial dysfunction is a central pathomechanism in diabetes-associated complications. We hypothesized a pathogenic role in this dysfunction of cathepsin S (Cat-S), a cysteine protease that degrades elastic fibers and activates the protease-activated receptor-2 (PAR2) on endothelial cells. We found that injection of mice with recombinant Cat-S induced albuminuria and glomerular endothelial cell injury in a PAR2-dependent manner. In vivo microscopy confirmed a role for intrinsic Cat-S/PAR2 in ischemia-induced microvascular permeability. In vitro transcriptome analysis and experiments using siRNA or specific Cat-S and PAR2 antagonists revealed that Cat-S specifically impaired the integrity and barrier function of glomerular endothelial cells selectively through PAR2. In human and mouse type 2 diabetic nephropathy, only CD68(+) intrarenal monocytes expressed Cat-S mRNA, whereas Cat-S protein was present along endothelial cells and inside proximal tubular epithelial cells also. In contrast, the cysteine protease inhibitor cystatin C was expressed only in tubules. Delayed treatment of type 2 diabetic db/db mice with Cat-S or PAR2 inhibitors attenuated albuminuria and glomerulosclerosis (indicators of diabetic nephropathy) and attenuated albumin leakage into the retina and other structural markers of diabetic retinopathy. These data identify Cat-S as a monocyte/macrophage-derived circulating PAR2 agonist and mediator of endothelial dysfunction-related microvascular diabetes complications. Thus, Cat-S or PAR2 inhibition might be a novel strategy to prevent microvascular disease in diabetes and other diseases.

  7. Printing Cancer Cells into Intact Microvascular Networks: A Model for Investigating Cancer Cell Dynamics during Angiogenesis

    PubMed Central

    Phamduy, Theresa B.; Sweat, Richard S.; Azimi, Mohammad S.; Burow, Matthew E.; Murfee, Walter L.; Chrisey, Douglas B.

    2016-01-01

    While cancer cell invasion and metastasis is dependent on cancer cell-stroma, cancer cell-blood vessel, and cancer cell-lymphatic vessel interactions, our understanding of these interactions remain largely unknown. A need exists for physiologically-relevant models that more closely mimic the complexity of cancer cell dynamics in a real tissue environment. The objective of this study was to combine laser-based cell printing and tissue culture methods to create a novel ex vivo model in which cancer cell dynamics can be tracked during angiogenesis in an intact microvascular network. Laser direct-write (LDW) was utilized to reproducibly deposit breast cancer cells (MDA-MB-231 and MCF-7) and fibroblasts into spatially-defined patterns on cultured rat mesenteric tissues. In addition, heterogeneous patterns containing co-printed MDA-MB-231/fibroblasts or MDA-MB-231/MCF-7 cells were generated for fibroblast-directed and collective cell invasion models. Printed cells remained viable and the cells retained the ability to proliferate in serum-rich media conditions. Over a culture period of five days, time-lapse imaging confirmed fibroblast and MDA-MB-231 cell migration within the microvascular networks. Confocal microscopy indicated that printed MDA-MB-231 cells infiltrated the tissue thickness and were capable of interacting with endothelial cells. Angiogenic network growth in tissue areas containing printed cancer cells was characterized by significantly increased capillary sprouting compared to control tissue areas containing no printed cells. Our results establish an innovative ex vivo experimental platform that enables time-lapse evaluation of cancer cell dynamics during angiogenesis within a real microvascular network scenario. PMID:26190039

  8. Neuropathological analysis of lacunes and microvascular lesions in late-onset depression

    PubMed Central

    Santos, Micaela; Gold, Gabriel; Kövari, Enikö; Herrmann, François R.; Hof, Patrick R.; Bouras, Constantin; Giannakopoulos, Panteleimon

    2010-01-01

    Aims Previous neuropathological studies documented that small vascular and microvascular pathology is associated with cognitive decline. More recently, we showed that thalamic and basal ganglia lacunes are associated with post-stroke depression and may affect emotional regulation. The present study examines whether this is also the case for late-onset depression. Methods We performed a detailed analysis of small macrovascular and microvascular pathology in the postmortem brains of 38 patients with late-onset major depression (LOD) and 29 healthy elderly controls. A clinical diagnosis of LOD was established while the subjects were alive using the DSM-IV criteria. Additionally, we retrospectively reviewed all charts for the presence of clinical criteria of vascular depression. Neuropathological evaluation included bilateral semiquantitative assessment of lacunes, deep white matter and periventricular demyelination, cortical microinfarcts and both focal and diffuse gliosis. The association between vascular burden and LOD was investigated using Fisher’s exact test and univariate and multivariate logistic regression models. Results Neither the existence of lacunes nor the presence of microvascular ischaemic lesions was related to occurrence of LOD. Similarly, there was no relationship between vascular lesion scores and LOD. This was also the case within the subgroup of LOD patients fulfilling the clinical criteria for vascular depression. Conclusions Our results challenge the vascular depression hypothesis by showing that neither deep white matter nor periventricular demyelination is associated with LOD. In conjunction with our previous observations in stroke patients, they also imply that the impact of lacunes on mood may be significant solely in the presence of acute brain compromise. PMID:20609111

  9. Diet Induced Obesity in Sprague Dawley Rats Causes Microvascular and Neural Dysfunction

    PubMed Central

    Davidson, Eric P.; Coppey, Lawrence J.; Calcutt, Nigel A.; Oltman, Christine L.; Yorek, Mark A.

    2010-01-01

    Background The objective was to determine the effect of diet induced obesity (DIO) on microvascular and neural function. Methods Rats were fed a standard or high fat diet for up to 32 weeks. Measurements were performed of vasodilation in epineurial arterioles by videomicroscopy, endoneurial blood flow by hydrogen clearance, nerve conduction velocity by electrical stimulation, size-frequency distribution of myelinated fibers of the sciatic nerve, intraepidermal nerve fiber density using confocal microscopy and thermal nociception using the Hargreaves method. Results Rats fed a high fat diet for 32 weeks developed sensory neuropathy as indicated by slowing of sensory nerve conduction velocity and thermal hypoalgesia. Motor nerve conduction velocity and endoneurial blood flow were not impaired. Mean axonal diameter of myelinated fibers of the sciatic nerve was unchanged in high fat fed rats compared to control. Intraepidermal nerve fiber density was significantly reduced in high fat fed rats. Vascular relaxation to acetylcholine and calcitonin gene-related peptide was decreased and expression of neutral endopeptidase (NEP) increased in epineurial arterioles of rats fed a high fat diet. In contrast, insulin-mediated vascular relaxation was increased in epineurial arterioles. NEP activity was significantly increased in the skin of the hindpaw. Markers of oxidative stress were increased in the aorta and serum of high fat fed rats but not in epineurial arterioles. Conclusion Chronic obesity causes microvascular and neural dysfunction. This is associated with increased expression of NEP but not oxidative stress in epineurial arterioles. NEP degrades vasoactive peptides which may explain the decrease in microvascular function. PMID:20503263

  10. Retinal Microvascular Abnormalities and Risk of Renal Failure in Asian Populations

    PubMed Central

    Yip, WanFen; Sabanayagam, Charumathi; Teo, Boon Wee; Tay, Wan Ting; Ikram, M. Kamran; Tai, E. Shyong; Chow, Khuan Yew; Wong, Tien Y.; Cheung, Carol Y.

    2015-01-01

    Background Retinal microvascular signs may provide insights into the structure and function of small vessels that are associated with renal disease. We examined the relationship of retinal microvascular signs with both prevalent and incident end-stage renal disease (ESRD) in a multi-ethnic Asian population. Methods A total of 5763 subjects (aged ≥40 years) from two prospective population-based studies (the Singapore Malay Eye Study and the Singapore Prospective Study) were included for the current analysis. Retinopathy was graded using the modified Airlie House classification system. Retinal vascular parameters were measured using computer-assisted programs to quantify the retinal vessel widths (arteriolar and venular caliber) and retinal vascular network (fractal dimension). Data on ESRD was obtained by record linkage with the ESRD cases registered by National Registry of Diseases Office, Singapore. Multi-variable adjusted regression analyses were performed to assess the associations of baseline retinal vascular parameters and prevalent and incident ESRD. Results At baseline, 21(0.36%) persons had prevalent ESRD. During a median follow-up of 4.3 years, 33 (0.57%) subjects developed ESRD. In our analyses, retinopathy was associated with prevalent ESRD (multi-variable adjusted odds ratio [OR], 3.21, 95% confidence interval [CI]: 1.28–8.05) and incident ESRD (multi-variable adjusted hazard ratio [HR], 2.51, 95%CI: 1.14–5.54). This association was largely seen in person with diabetes (HR, 2.60, 95%CI: 1.01–6.66) and not present in persons without diabetes (HR, 1.65, 95%CI: 0.14–18.98). Retinal arteriolar caliber, retinal venular caliber and retinal vascular fractal dimension were not associated with ESRD. Conclusion Retinopathy signs in persons with diabetes are related to an increased risk of ESRD; however, other microvascular changes in the retina are not associated with ESRD. PMID:25658337

  11. Optical measurements of microvascular circulatory function in the foot for detection of peripheral neuropathy

    NASA Astrophysics Data System (ADS)

    Zamora, G.; Chekh, V.; Burge, M.; Barriga, E. S.; Luan, S.; Heintz, P.; Edwards, A.; McGrew, E.; Soliz, P.

    2012-03-01

    The purpose of this research is to quantify functional signals in the microvascular circulation of the plantar. Our device is based on thermal and spectral technologies that can be easily adopted in clinical and tele-screening settings. Eightytwo thousand amputations are performed annually on diabetics in the US. The cost of foot disorder diagnosis and management are estimated at $10.9 billion dollars annually. Our experiments on normal controls and diabetics assess the temperature recovery time characteristics due to cold provocation to the bottom of the foot (plantar). A difference in the nature of the recovery time between normal controls and diabetics was observed.

  12. Association of low educational status with microvascular complications in type 2 diabetes: Jaipur diabetes registry-1

    PubMed Central

    Sharma, Niharikaa; Sharma, Surendra Kumar; Maheshwari, Vitthal D.; Sharma, Krishna Kumar; Gupta, Rajeev

    2015-01-01

    Objective: To determine the association of educational status (ES), as a marker of socioeconomic status, with the prevalence of microvascular complications in diabetes. Methods: Successive patients (n = 1214) presenting to our centre were evaluated for sociodemographic, anthropometric, clinical, and therapeutic variables. Subjects were classified according to ES into Group 1 (illiterate, 216); Group 2 (microvascular disease (peripheral, ocular or renal) in 20.7%. Microvascular disease was significantly greater in illiterate (25.9%) and low (23.6%) compared to middle (15.0%) and high (14.7%) ES groups (P < 0.05). Age- and sex-adjusted logistic regression analysis revealed that in illiterate and low ES groups respectively, prevalence of smoking/tobacco use (odds ratio 3.84, confidence intervals 2.09–7.05 and 2.15, 1.36–3.41); low fruit/vegetable (2.51, 1.53–4.14 and 1.99, 1.30–3.04) and low fibre intake (4.02, 2.50–6.45 and 1.78, 1.23–2.59) was greater compared to high ES. Poor diabetes control (HbA1c >8.0%) was significantly greater in illiterate (38.0%), low (46.0%) and middle (41.0%) compared to high (31.5%) ES subjects (P < 0.05). Conclusions: There is a greater prevalence of the microvascular disease in illiterate and low ES diabetes patients in India. This is associated with the higher prevalence of smoking/tobacco use, poor quality diet and sub-optimal diabetes control. PMID:26425480

  13. Association of low educational status with microvascular complications in type 2 diabetes: Jaipur diabetes registry

    PubMed Central

    Sharma, Niharikaa; Sharma, Surendra Kumar; Maheshwari, Vitthal D.; Sharma, Krishna Kumar; Gupta, Rajeev

    2015-01-01

    Objective: To determine the association of educational status (ES), as marker of socioeconomic status, with the prevalence of microvascular complications in diabetes. Methods: Successive patients (n = 1214) presenting to our center were evaluated for sociodemographic, anthropometric, clinical, and therapeutic variables. Subjects were classified according to ES into Group 1 (illiterate, 216); Group 2 (≤ primary, 537), Group 3 (≤ higher secondary, 312), and Group 4 (any college, 149). Descriptive statistics is reported. Results: Mean age of patients was 52 ± 10 years, duration of diabetes 7 ± 7 years and 55% were men. Prevalence of various risk factors was smoking/tobacco 25.5%, obesity body mass index ≥25 kg/m2 64.0%, abdominal obesity 63.4%, hypertension 67.5%, high fat diet 14.5%, low fruits/vegetables 31.8%, low fiber intake 60.0%, high salt diet 16.9%, physical inactivity 27.5%, coronary or cerebrovascular disease 3.0%, and microvascular disease (peripheral, ocular or renal) in 20.7%. Microvascular disease was significantly greater in illiterate (25.9%) and low (23.6%) compared to middle (15.0%) and high (14.7%) ES groups (P < 0.05). Age- and sex-adjusted logistic regression analysis revealed that in illiterate and low ES groups respectively, prevalence of smoking/tobacco use (odds ratio 3.84, confidence interval: 09–7.05 and 2.15, 1.36–3.41); low fruit/vegetable (2.51, 1.53–4.14 and 1.99, 1.30–3.04) and low fiber intake (4.02, 2.50–6.45 and 1.78, 1.23–2.59) was greater compared to high ES. Poor diabetes control (HbA1c >.0%) was significantly greater in illiterate (38.0%), low (46.0%), and middle (41.0%) compared to high (31.5%) ES subjects (P < 0.05). Conclusions: There is a greater prevalence of the microvascular disease in illiterate and low ES diabetes patients in India. This is associated with the higher prevalence of smoking/tobacco use, poor quality diet, and sub-optimal diabetes control. PMID:26693427

  14. [Reconstruction of oral mucosa with a micro-vascularized fascia-cutaneous flap from the forearm].

    PubMed

    Burgueño García, Miguel; Cebrián Carretero, José Luis; Muñoz Caro, Jesús Manuel; Arias Gallo, Javier

    2002-01-01

    Epidermoid carcinoma of jugal mucosa is an aggressive tumor. Its treatment is based on broad excision and reconstruction in order to avoid fibrosis and restriction of mouth opening. Neck dissection and radiotherapy are indicated in selected cases. We display our experience with microvascularized flaps with the aim of preventing the flaws. We reconsider 8 patients (representing 10 flaps) handle in our Department. Besides we discuss other therapeutic alternatives after the growth's removal. The conclusion reached is that the mucovascularized forearm flaps give a great quantity of thin tissue and therefore so results to be the best option for the reconstruction of the jugal mucosa.

  15. Early Activation of Primary Brain Microvascular Endothelial Cells by Nipah Virus Glycoprotein-Containing Particles.

    PubMed

    Freitag, Tanja C; Maisner, Andrea

    2016-03-01

    Nipah virus (NiV) is a highly pathogenic paramyxovirus that causes pronounced infection of brain endothelia and central nervous system (CNS) inflammation. Using primary porcine brain microvascular endothelial cells, we showed that upregulation of E-selectin precedes cytokine induction and is induced not only by infectious NiV but also by NiV-glycoprotein-containing virus-like particles. This demonstrates that very early events in NiV brain endothelial infection do not depend on NiV replication but can be triggered by the NiV glycoproteins alone. PMID:26676791

  16. Non-Invasive Measurement of Skin Microvascular Response during Pharmacological and Physiological Provocations

    PubMed Central

    Iredahl, Fredrik; Löfberg, Andreas; Sjöberg, Folke; Farnebo, Simon; Tesselaar, Erik

    2015-01-01

    Introduction Microvascular changes in the skin due to pharmacological and physiological provocations can be used as a marker for vascular function. While laser Doppler flowmetry (LDF) has been used extensively for measurement of skin microvascular responses, Laser Speckle Contrast Imaging (LSCI) and Tissue Viability Imaging (TiVi) are novel imaging techniques. TiVi measures red blood cell concentration, while LDF and LSCI measure perfusion. Therefore, the aim of this study was to compare responses to provocations in the skin using these different techniques. Method Changes in skin microcirculation were measured in healthy subjects during (1) iontophoresis of sodium nitroprusside (SNP) and noradrenaline (NA), (2) local heating and (3) post-occlusive reactive hyperemia (PORH) using LDF, LSCI and TiVi. Results Iontophoresis of SNP increased perfusion (LSCI: baseline 40.9±6.2 PU; 10-min 100±25 PU; p<0.001) and RBC concentration (TiVi: baseline 119±18; 10-min 150±41 AU; p = 0.011). No change in perfusion (LSCI) was observed after iontophoresis of NA (baseline 38.0±4.4 PU; 10-min 38.9±5.0 PU; p = 0.64), while RBC concentration decreased (TiVi: baseline 59.6±11.8 AU; 10-min 54.4±13.3 AU; p = 0.021). Local heating increased perfusion (LDF: baseline 8.8±3.6 PU; max 112±55 PU; p<0.001, LSCI: baseline 50.8±8.0 PU; max 151±22 PU; p<0.001) and RBC concentration (TiVi: baseline 49.2±32.9 AU; max 99.3±28.3 AU; p<0.001). After 5 minutes of forearm occlusion with prior exsanguination, a decrease was seen in perfusion (LDF: p = 0.027; LSCI: p<0.001) and in RBC concentration (p = 0.045). Only LSCI showed a significant decrease in perfusion after 5 minutes of occlusion without prior exsanguination (p<0.001). Coefficients of variation were lower for LSCI and TiVi compared to LDF for most responses. Conclusion LSCI is more sensitive than TiVi for measuring microvascular changes during SNP-induced vasodilatation and forearm occlusion. TiVi is more sensitive to noradrenaline

  17. Influence of non-Newtonian viscosity of blood on microvascular impairment.

    PubMed

    Moh, Jeong-Hah; Cho, Young I; Cho, Daniel J; Kim, Doosang; Banerjee, Rupak K

    2014-01-01

    The present research investigated the role of blood viscosity on flow within a microvascular network to identify the conditions of blood flow stagnation. When the yield stress of blood was less than 0.005 Pa, there were no stagnant regions in the microvasculature. However, when the yield stress increased to 0.05 Pa, stagnant or reduced flow areas began to appear, which grew and expanded rapidly with further increase in the yield stress. Thus, the yield stress determined from blood viscosity profile of a patient can be utilized to evaluate the risk of circulatory impairment. PMID:24584322

  18. Influence of non-Newtonian viscosity of blood on microvascular impairment.

    PubMed

    Moh, Jeong-Hah; Cho, Young I; Cho, Daniel J; Kim, Doosang; Banerjee, Rupak K

    2014-01-01

    The present research investigated the role of blood viscosity on flow within a microvascular network to identify the conditions of blood flow stagnation. When the yield stress of blood was less than 0.005 Pa, there were no stagnant regions in the microvasculature. However, when the yield stress increased to 0.05 Pa, stagnant or reduced flow areas began to appear, which grew and expanded rapidly with further increase in the yield stress. Thus, the yield stress determined from blood viscosity profile of a patient can be utilized to evaluate the risk of circulatory impairment.

  19. Multiple microvascular and astroglial 5-hydroxytryptamine receptor subtypes in human brain: molecular and pharmacologic characterization.

    PubMed

    Cohen, Z; Bouchelet, I; Olivier, A; Villemure, J G; Ball, R; Stanimirovic, D B; Hamel, E

    1999-08-01

    Physiologic and anatomic evidence suggest that 5-hydroxytryptamine (5-HT) neurons regulate local cerebral blood flow and blood-brain barrier permeability. To evaluate the possibility that some of these effects occur directly on the blood vessels, molecular and/or pharmacologic approaches were used to assess the presence of 5-HT receptors in human brain microvascular fractions, endothelial and smooth muscle cell cultures, as well as in astroglial cells which intimately associate with intraparenchymal blood vessels. Isolated microvessels and capillaries consistently expressed messages for the h5-HT1B, h5-HT1D, 5-HT1F, 5-HT2A but not 5-HT7 receptors. When their distribution within the vessel wall was studied in more detail, it was found that capillary endothelial cells exhibited mRNA for the h5-HT1D and for the 5-HT7 receptors whereas microvascular smooth muscle cells, in addition to h5-HT1D and 5-HT7, also showed polymerase chain reaction products for h5-HT1B receptors. Expression of 5-HT1F and 5-HT2A receptor mRNAs was never detected in any of the microvascular cell cultures. In contrast, messages for all 5-HT receptors tested were detected in human brain astrocytes with a predominance of the 5-HT2A and 5-HT7 subtypes. In all cultures, sumatriptan inhibited (35-58%, P < .05) the forskolin-stimulated production of cyclic AMP, an effect blocked by the 5-HT1B/1D receptor antagonists GR127935 and GR55562. In contrast, 5-carboxamidotryptamine induced strong increases (> or = 400%, P < .005) in basal cyclic AMP levels that were abolished by mesulergine, a nonselective 5-HT7 receptor antagonist. Only astroglial cells showed a ketanserin-sensitive increase (177%, P < .05) in IP3 formation when exposed to 5-HT. These results show that specific populations of functional 5-HT receptors are differentially distributed within the various cellular compartments of the human cortical microvascular bed, and that human brain astroglial cells are endowed with multiple 5-HT receptors

  20. In vivo microvascular network imaging of the human retina combined with an automatic three-dimensional segmentation method

    PubMed Central

    Huang, Shenghai; Piao, Zhonglie; Zhu, Jiang; Lu, Fan; Chen, Zhongping

    2015-01-01

    Abstract. Microvascular network of the retina plays an important role in diagnosis and monitoring of various retinal diseases. We propose a three-dimensional (3-D) segmentation method with intensity-based Doppler variance (IBDV) based on swept-source optical coherence tomography. The automatic 3-D segmentation method is used to obtain seven surfaces of intraretinal layers. The microvascular network of the retina, which is acquired by the IBDV method, can be divided into six layers. The microvascular network of the six individual layers is visualized, and the morphology and contrast images can be improved by using the segmentation method. This method has potential for earlier diagnosis and precise monitoring in retinal vascular diseases. PMID:26169790

  1. Soluble CD40L in children and adolescents with type 1 diabetes: relation to microvascular complications and glycemic control.

    PubMed

    El-Asrar, Mohamed A; Adly, Amira Am; Ismail, Eman A

    2012-12-01

    CD40-soluble CD40 ligand (sCD40L) interactions might constitute an important mediator for vascular inflammation that initiates diabetic microangiopathy. Little is known about the relation between sCD40L and glycemic control. Therefore, this study aimed to evaluate sCD40L levels in patients with type 1 diabetes and its relation to microvascular complications and metabolic control. Sixty patients with type 1 diabetes were compared with 30 healthy control subjects. Detailed medical history, thorough clinical examination, and laboratory assessment of high-sensitivity C-reactive protein, glycemic control, and the presence of microvascular complications were performed. Measurement of serum sCD40L levels was done using enzyme-linked immunosorbent assay. Patients were divided into two groups according to the presence of microvascular complications. Serum sCD40L levels were significantly elevated in patients with type 1 diabetes in both groups compared with healthy controls (p < 0.001). Patients with microvascular complications had higher serum sCD40L concentrations than non-complicated cases (median, 13 000 vs. 450 pg/mL; p < 0.001). Serum sCD40L cutoff value of 530 pg/mL was able to differentiate complicated from non-complicated cases (p < 0.001). Patients with microalbuminuria or peripheral neuropathy showed higher levels of sCD40L when compared with patients without these complications (p < 0.05). Serum sCD40L levels were positively correlated with hemoglobin A1c and urinary albumin excretion (p < 0.001). We suggest that serum sCD40L levels are elevated in type 1 diabetes, particularly in patients with microvascular complications and a significant correlation with glycemic control exists. Therefore, measurement of serum sCD40L levels in poorly controlled patients would help to identify those at high risk of developing microvascular complications.

  2. Case Series of Pulmonary Tumor Embolism and Intravascular Lymphoma: Evaluation of the Usefulness of Pulmonary Microvascular Cytology.

    PubMed

    Ishiguro, Takashi; Takayanagi, Noboru; Baba, Yuri; Kagiyama, Naho; Miyamoto, Takashi; Mutoh, Makoto; Shimizu, Yoshihiko; Sugita, Yutaka

    2016-01-01

    Pulmonary tumor embolism (PTE) and intravascular lymphoma cause rapidly progressive deterioration and an antemortem diagnosis is difficult. The usefulness of pulmonary microvascular cytology (PMC) in the diagnosis of these disorders has been reported in sporadic case reports. We retrospectively evaluated the records of 7 patients with tumor cells in the pulmonary microvasculature (4 with PTE and 3 with malignant lymphoma) who underwent pulmonary microvascular cytology. Two of the 4 patients with PTE and 2 of the 3 patients with malignant lymphoma (all 3 had intravascular metastasis) had positive PMC results. These findings suggested that PMC may be useful in the diagnosis of these disorders. PMID:27629967

  3. The vascular pattern and viability of microvascularized rib grafts based on periosteal circulation--an experimental study

    SciTech Connect

    Papanastasiou, V.W.; Lalonde, D.H.; Williams, H.B.

    1984-11-01

    Previous reports have stressed the importance of the nutrient blood supply in rib grafts transferred by microvascular anastomoses. In the present experimental study, we have demonstrated that a rib graft transferred by microvascular anastomoses based on periosteal vessels can survive; vascular clearing studies demonstrated that the vascularity of these grafts extends not only into the cortex but the medulla as well. The relative facility of harvesting these grafts (compared with those based on nutrient vessels) should make them the favored choice. Technetium bone scintigraphy proved accurate in the assessment of both vascular pattern and microanastomotic patency. Tetracycline labeling did not correlate well with the patency of a rib graft's pedicle blood supply.

  4. Descompresión microvascular en espasmo hemifacial: Reporte de 13 casos y revisión de la literatura

    PubMed Central

    Campero, Alvaro; Herreros, Isabel Cuervo-Arango; Barrenechea, Ignacio; Andjel, Germán; Ajler, Pablo; Rhoton, Albert

    2016-01-01

    Objetivo: El propósito del presente trabajo es presentar los resultados de 13 pacientes con diagnóstico de espasmo hemifacial (EHF), en los cuales se realizó una descompresión microvascular (DMV). Material y Método: Desde Junio de 2005 a Mayo de 2014, 13 pacientes con diagnóstico de EHF fueron intervenidos quirúrgicamente, realizando una DMV. Se evaluó: edad, sexo, tiempo de evolución de la sintomatología, hallazgos intraoperatorios y resultados postoperatorios. Resultados: De los 13 pacientes intervenidos, 7 fueron mujeres y 6 varones. La media de edad fue de 53 años. El tiempo medio entre el inicio de la sintomatología y la intervención quirúrgica osciló entre 3 y 9 años. En todos los casos el EHF era típico, uno de ellos con neuralgia trigeminal concomitante, observándose en todos compresión neurovascular intraoperatoria. Por orden decreciente de frecuencia la causa de la compresión fue arteria cerebelosa anteroinferior, arteria cerebelosa posteroinferior, arteria dolicomega basilar y arteria dolicomega vertebral. El seguimiento postoperatorio fue en promedio de 24 meses. El 62% presentó desaparición postquirúrgica inmediata de la sintomatología preoperatoria, el 30% desaparición tras un período de 3 semanas a 2 meses (8% con mejoría parcial), y en el 8% no hubo mejoría. En cuanto a las complicaciones postoperatorias: 3 pacientes presentaron paresia facial II-III en la escala de House-Brackman (se recuperaron en un período de 6 meses), y 1 paciente presentó fístula de líquido cefalorraquídeo. Ninguno de los pacientes de la serie presentaron hipoacusia transitorio o permanente. Conclusión: La DMV como tratamiento del EHF es un procedimiento efectivo y seguro, que permite la resolución completa de la patología en la mayoría de los casos. PMID:27127708

  5. Microvascular destruction identifies murine allografts that cannot be rescued from airway fibrosis

    PubMed Central

    Babu, Ashok N.; Murakawa, Tomohiro; Thurman, Joshua M.; Miller, Edmund J.; Henson, Peter M.; Zamora, Martin R.; Voelkel, Norbert F.; Nicolls, Mark R.

    2007-01-01

    Small airway fibrosis (bronchiolitis obliterans syndrome) is the primary obstacle to long-term survival following lung transplantation. Here, we show the importance of functional microvasculature in the prevention of epithelial loss and fibrosis due to rejection and for the first time, relate allograft microvascular injury and loss of tissue perfusion to immunotherapy-resistant rejection. To explore the role of alloimmune rejection and airway ischemia in the development of fibroproliferation, we used a murine orthotopic tracheal transplant model. We determined that transplants were reperfused by connection of recipient vessels to donor vessels at the surgical anastomosis site. Microcirculation through the newly formed vascular anastomoses appeared partially dependent on VEGFR2 and CXCR2 pathways. In the absence of immunosuppression, the microvasculature in rejecting allografts exhibited vascular complement deposition, diminished endothelial CD31 expression, and absent perfusion prior to the onset of fibroproliferation. Rejecting grafts with extensive endothelial cell injury were refractory to immunotherapy. After early microvascular loss, neovascularization was eventually observed in the membranous trachea, indicating a reestablishment of graft perfusion in established fibrosis. One implication of this study is that bronchial artery revascularization at the time of lung transplantation may decrease the risk of subsequent airway fibrosis. PMID:18060031

  6. Mechanisms underlying the cerebral microvascular responses to angiotensin II-induced hypertension.

    PubMed

    Vital, Shantel A; Terao, Satoshi; Nagai, Mutsumi; Granger, D Neil

    2010-11-01

    Angiotensin II (AngII) and AngII type-1 receptors (AT1r) have been implicated in the pathogenesis of hypertension and ischemic stroke. The objectives of this study was to determine if/how chronic AngII administration affects blood-brain barrier (BBB) function and blood cell adhesion in the cerebral microvasculature. AngII-loaded osmotic pumps were implanted in wild type (WT) and mutant mice. Leukocyte and platelet adhesion were monitored in cerebral venules by intravital microscopy and BBB permeability detected by Evans blue leakage. AngII (two week) infusion increased blood pressure in WT mice. This was accompanied by an increased BBB permeability and a high density of adherent leukocytes and platelets. AT1r (on the vessel wall, but not on blood cells) was largely responsible for the microvascular responses to AngII. Immunodeficient (Rag-1(-/-) ) mice exhibited blunted blood cell recruitment responses without a change in BBB permeability. A similar protection pattern was noted in RANTES(-/-) and P-selectin(-/-) mice, with bone marrow chimeras (blood cell deficiency only) yielding responses comparable to the respective knockouts. These findings implicate AT1r in the microvascular dysfunction associated with AngII-induced hypertension and suggest that immune cells and blood cell-associated RANTES and P-selectin contribute to the blood cell recruitment, but not the BBB failure, elicited by AngII. PMID:21044218

  7. Epidermal devices for noninvasive, precise, and continuous mapping of macrovascular and microvascular blood flow.

    PubMed

    Webb, R Chad; Ma, Yinji; Krishnan, Siddharth; Li, Yuhang; Yoon, Stephen; Guo, Xiaogang; Feng, Xue; Shi, Yan; Seidel, Miles; Cho, Nam Heon; Kurniawan, Jonas; Ahad, James; Sheth, Niral; Kim, Joseph; Taylor, James G; Darlington, Tom; Chang, Ken; Huang, Weizhong; Ayers, Joshua; Gruebele, Alexander; Pielak, Rafal M; Slepian, Marvin J; Huang, Yonggang; Gorbach, Alexander M; Rogers, John A

    2015-10-01

    Continuous monitoring of variations in blood flow is vital in assessing the status of microvascular and macrovascular beds for a wide range of clinical and research scenarios. Although a variety of techniques exist, most require complete immobilization of the subject, thereby limiting their utility to hospital or clinical settings. Those that can be rendered in wearable formats suffer from limited accuracy, motion artifacts, and other shortcomings that follow from an inability to achieve intimate, noninvasive mechanical linkage of sensors with the surface of the skin. We introduce an ultrathin, soft, skin-conforming sensor technology that offers advanced capabilities in continuous and precise blood flow mapping. Systematic work establishes a set of experimental procedures and theoretical models for quantitative measurements and guidelines in design and operation. Experimental studies on human subjects, including validation with measurements performed using state-of-the-art clinical techniques, demonstrate sensitive and accurate assessment of both macrovascular and microvascular flow under a range of physiological conditions. Refined operational modes eliminate long-term drifts and reduce power consumption, thereby providing steps toward the use of this technology for continuous monitoring during daily activities. PMID:26601309

  8. Gestational Diabetes Reduces Adenosine Transport in Human Placental Microvascular Endothelium, an Effect Reversed by Insulin

    PubMed Central

    Salomón, Carlos; Westermeier, Francisco; Puebla, Carlos; Arroyo, Pablo; Guzmán-Gutiérrez, Enrique; Pardo, Fabián; Leiva, Andrea; Casanello, Paola; Sobrevia, Luis

    2012-01-01

    Gestational diabetes mellitus (GDM) courses with increased fetal plasma adenosine concentration and reduced adenosine transport in placental macrovascular endothelium. Since insulin modulates human equilibrative nucleoside transporters (hENTs) expression/activity, we hypothesize that GDM will alter hENT2-mediated transport in human placental microvascular endothelium (hPMEC), and that insulin will restore GDM to a normal phenotype involving insulin receptors A (IR-A) and B (IR-B). GDM effect on hENTs expression and transport activity, and IR-A/IR-B expression and associated cell signalling cascades (p42/44 mitogen-activated protein kinases (p42/44mapk) and Akt) role in hPMEC primary cultures was assayed. GDM associates with elevated umbilical whole and vein, but not arteries blood adenosine, and reduced hENTs adenosine transport and expression. IR-A/IR-B mRNA expression and p42/44mapk/Akt ratios (‘metabolic phenotype’) were lower in GDM. Insulin reversed GDM-reduced hENT2 expression/activity, IR-A/IR-B mRNA expression and p42/44mapk/Akt ratios to normal pregnancies (‘mitogenic phenotype’). It is suggested that insulin effects required IR-A and IR-B expression leading to differential modulation of signalling pathways restoring GDM-metabolic to a normal-mitogenic like phenotype. Insulin could be acting as protecting factor for placental microvascular endothelial dysfunction in GDM. PMID:22808198

  9. Lipopolysaccharide Induces Human Pulmonary Micro-Vascular Endothelial Apoptosis via the YAP Signaling Pathway

    PubMed Central

    Yi, Lei; Huang, Xiaoqin; Guo, Feng; Zhou, Zengding; Chang, Mengling; Tang, Jiajun; Huan, Jingning

    2016-01-01

    Gram-negative bacterial lipopolysaccharide (LPS) induces a pathologic increase in lung vascular leakage under septic conditions. LPS-induced human pulmonary micro-vascular endothelial cell (HPMEC) apoptosis launches and aggravates micro-vascular hyper-permeability and acute lung injury (ALI). Previous studies show that the activation of intrinsic apoptotic pathway is vital for LPS-induced EC apoptosis. Yes-associated protein (YAP) has been reported to positively regulate intrinsic apoptotic pathway in tumor cells apoptosis. However, the potential role of YAP protein in LPS-induced HPMEC apoptosis has not been determined. In this study, we found that LPS-induced activation and nuclear accumulation of YAP accelerated HPMECs apoptosis. LPS-induced YAP translocation from cytoplasm to nucleus by the increased phosphorylation on Y357 resulted in the interaction between YAP and transcription factor P73. Furthermore, inhibition of YAP by small interfering RNA (siRNA) not only suppressed the LPS-induced HPMEC apoptosis but also regulated P73-mediated up-regulation of BAX and down-regulation of BCL-2. Taken together, our results demonstrated that activation of the YAP/P73/(BAX and BCL-2)/caspase-3 signaling pathway played a critical role in LPS-induced HPMEC apoptosis. Inhibition of the YAP might be a potential therapeutic strategy for lung injury under sepsis. PMID:27807512

  10. Hearing outcomes after loss of brainstem auditory evoked potentials during microvascular decompression.

    PubMed

    Thirumala, Parthasarathy D; Krishnaiah, Balaji; Habeych, Miguel E; Balzer, Jeffrey R; Crammond, Donald J

    2015-04-01

    The primary aim of this paper is to study the pre-operative characteristics, intra-operative changes and post-operative hearing outcomes in patients after complete loss of wave V of the brainstem auditory evoked potential. We retrospectively analyzed the brainstem auditory evoked potential data of 94 patients who underwent microvascular decompression for hemifacial spasm at our institute. Patients were divided into two groups - those with and those without loss of wave V. The differences between the two groups and outcomes were assessed using t-test and chi-squared tests. In our study 23 (24%) patients out of 94 had a complete loss of wave V, with 11 (48%) patients experiencing transient loss and 12 (52%) patients experiencing permanent loss. The incidence of hearing loss in patients with no loss of wave V was 5.7% and 26% in patients who did experience wave V loss. The incidence of hearing change in patients with no loss of wave V was 12.6% and 30.43% in patients who did experience wave V loss. Loss of wave V during the procedure or at the end of procedure significantly increases the odds of hearing loss. Hearing change is a significant under-reported clinical condition after microvascular decompression in patients who have loss of wave V.

  11. Quality improvement of microsurgery through telecommunication--the postoperative care after microvascular transfer of intestine.

    PubMed

    Chen, Hung-Chi; Kuo, Hsin-Chih; Chung, Kuo-Piao; Chen, Shih-Heng; Tang, Yueh-Bih; Su, Syi

    2012-02-01

    The purpose of this report is to describe the use of telecommunication to improve the quality of postoperative care following microsurgery, especially following microvascular transfer of intestinal transfer for which shortening of ischemia time is of utmost importance to achieve high success rate. From 2003 to 2009 microvascular transfer of intestinal flaps had been performed in 112 patients. After surgery the patients were put in intensive care unit and the flaps were checked every 1 hour. The image for circulatory status of the flaps was sent directly to the attending surgeon for judgment. The information was sent through intranet and the surgeon can get access to the intranet through internet if necessary. Among the 112 cases, there were 9 cases of reexploration. The average duration between the time of problem detection and the time of starting reexploration was 54 min in 7 cases, and other 2 cases were delayed to enter the operating room which had been occupied by other cases of major trauma. Only two flaps were lost completely, two patients developed narrowing at the junction of cervical esophagus and thoracic esophagus. The rate of salvage for intestinal flap is apparently higher than those reported in the literature. In the postoperative management of microsurgery in ICU, telecommunication can help to reduce the ischemia time after vascular compromise in the transfer of free intestinal flap. Telecommunication is really an easy and effective tool in improving the outcome of reconstructive surgery.

  12. Association of Microvascular Function and Endothelial Biomarkers With Clinical Outcome in Dengue: An Observational Study

    PubMed Central

    Yacoub, Sophie; Lam, Phung Khanh; Vu, Le Hoang Mai; Le, Thi Lien; Ha, Ngo Thanh; Toan, Tran Thi; Van, Nguyen Thu; Quyen, Nguyen Than Ha; Le Duyen, Huynh Thi; Van Kinh, Nguyen; Fox, Annette; Mongkolspaya, Juthathip; Wolbers, Marcel; Simmons, Cameron Paul; Screaton, Gavin Robert; Wertheim, Heiman; Wills, Bridget

    2016-01-01

    Background. The hallmark of severe dengue is increased microvascular permeability, but alterations in the microcirculation and their evolution over the course of dengue are unknown. Methods. We conducted a prospective observational study to evaluate the sublingual microcirculation using side-stream dark-field imaging in patients presenting early (<72 hours after fever onset) and patients hospitalized with warning signs or severe dengue in Vietnam. Clinical findings, microvascular function, global hemodynamics assessed with echocardiography, and serological markers of endothelial activation were determined at 4 time points. Results. A total of 165 patients were enrolled. No difference was found between the microcirculatory parameters comparing dengue with other febrile illnesses. The proportion of perfused vessels (PPV) and the mean flow index (MFI) were lower in patients with dengue with plasma than those without leakage (PPV, 88.1% vs 90.6% [P = .01]; MFI, 2.1 vs 2.4 [P = .007]), most markedly during the critical phase. PPV and MFI were correlated with the endothelial activation markers vascular cell adhesion molecule 1 (P < .001 for both) and angiopoietin 2 (P < .001 for both), negatively correlated. Conclusions. Modest microcirculatory alterations occur in dengue, are associated with plasma leakage, and are correlate with molecules of endothelial activation, angiopoietin 2 and vascular cell adhesion molecule 1. PMID:27230099

  13. Microvascular function in younger adults with obesity and metabolic syndrome: role of oxidative stress

    PubMed Central

    Limberg, Jacqueline K.; Harrell, John W.; Johansson, Rebecca E.; Eldridge, Marlowe W.; Proctor, Lester T.; Sebranek, Joshua J.

    2013-01-01

    Older adults with cardiovascular disease exhibit microvascular dysfunction and increased levels of reactive oxygen species (ROS). We hypothesized that microvascular impairments begin early in the disease process and can be improved by scavenging ROS. Forearm blood flow (Doppler ultrasound) was measured in 45 young (32 ± 2 yr old) adults (n = 15/group) classified as lean, obese, and metabolic syndrome (MetSyn). Vasodilation in response to endothelial (ACh) and vascular smooth muscle [nitroprusside (NTP) and epoprostenol (Epo)] agonists was tested before and after intra-arterial infusion of ascorbic acid to scavenge ROS. Vasodilation was assessed as a rise in relative vascular conductance (ml·min−1·dl−1·100 mmHg−1). ACh and NTP responses were preserved (P = 0.825 and P = 0.924, respectively), whereas Epo responses were lower in obese and MetSyn adults (P < 0.05) than in lean controls. Scavenging of ROS via infusion of ascorbic acid resulted in an increase in ACh-mediated (P < 0.001) and NTP-mediated (P < 0.001) relative vascular conductance across all groups, suggesting that oxidative stress influences vascular responsiveness in adults with and without overt cardiovascular disease risk. Ascorbic acid had no effect on Epo-mediated vasodilation (P = 0.267). These results suggest that obese and MetSyn adults exhibit preserved endothelium-dependent vasodilation with reduced dependence on prostacyclin and are consistent with an upregulation of compensatory vascular control mechanisms. PMID:23934859

  14. Dammarenediol-II Prevents VEGF-Mediated Microvascular Permeability in Diabetic Mice.

    PubMed

    Kim, Su-Hyeon; Jung, Se-Hui; Lee, Yeon-Ju; Han, Jung Yeon; Choi, Yong-Eui; Hong, Hae-Deun; Jeon, Hye-Yoon; Hwang, JongYun; Na, SungHun; Kim, Young-Myeong; Ha, Kwon-Soo

    2015-12-01

    Diabetic retinopathy is a major diabetic complication predominantly caused by vascular endothelial growth factor (VEGF)-induced vascular permeability in the retina; however, treatments targeting glycemic control have not been successful. Here, we investigated the protective effect of dammarenediol-II, a precursor of triterpenoid saponin biosynthesis, on VEGF-induced vascular leakage using human umbilical vein endothelial cells (HUVECs) and diabetic mice. We overproduced the compound in transgenic tobacco expressing Panax ginseng dammarenediol-II synthase gene and purified using column chromatography. Analysis of the purified compound using a gas chromatography-mass spectrometry system revealed identical retention time and fragmentation pattern to those of authentic standard dammarenediol-II. Dammarenediol-II inhibited VEGF-induced intracellular reactive oxygen species generation, but it had no effect on the levels of intracellular Ca(2+) in HUVECs. We also found that dammarenediol-II inhibited VEGF-induced stress fiber formation and vascular endothelial-cadherin disruption, both of which play critical roles in modulating endothelial permeability. Notably, microvascular leakage in the retina of diabetic mice was successfully inhibited by intravitreal dammarenediol-II injection. Our results suggest that the natural drug dammarenediol-II may have the ability to prevent diabetic microvascular complications, including diabetic retinopathy. PMID:26400610

  15. 3D functional and perfusable microvascular networks for organotypic microfluidic models.

    PubMed

    Bersini, Simone; Moretti, Matteo

    2015-05-01

    The metastatic dissemination of cancer cells from primary tumors to secondary loci is a complex and multistep process including local invasion, intravasation, survival in the blood stream and extravasation towards the metastatic site. It is well known cancer metastases follow organ-specific pathways with selected primary tumors mainly metastasizing towards a specific panel of secondary organs (Steven Paget's theory 1889). However, circulatory patterns and microarchitecture of capillary networks play a key role in the metastatic spread as well (James Ewing's theory 1929). Taking into account both these factors would be critical to develop more complex and physiologically relevant in vitro cancer models. This review presents recent advances in the generation of microvascularized systems through microfluidic approaches and discusses promising results achieved by organ-on-a-chip platforms mimicking the pathophysiology of the functional units of specific organs. The combination of physiologically-like microvascular networks and organotypic microenvironments would foster a new generation of in vitro cancer models to more effectively screen new therapeutics, design personalized medicine treatments and investigate molecular pathways involved in cancer metastases. PMID:25893395

  16. Microvascular anastomosis in rodent model evaluated by Fourier domain Doppler optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Huang, Yong; Tong, Dedi; Zhu, Shan; Wu, Lehao; Ibrahim, Zuhaib; Lee, WP Andrew; Brandacher, Gerald; Kang, Jin U.

    2014-03-01

    Vascular and microvascular anastomosis are critical components of reconstructive microsurgery, vascular surgery and transplant surgery. Imaging modality that provides immediate, real-time in-depth view and 3D structure and flow information of the surgical site can be a great valuable tool for the surgeon to evaluate surgical outcome following both conventional and innovative anastomosis techniques, thus potentially increase the surgical success rate. Microvascular anastomosis for vessels with outer diameter smaller than 1.0 mm is extremely challenging and effective evaluation of the outcome is very difficult if not impossible using computed tomography (CT) angiograms, magnetic resonance (MR) angiograms and ultrasound Doppler. Optical coherence tomography (OCT) is a non-invasive high-resolution (micron level), high-speed, 3D imaging modality that has been adopted widely in biomedical and clinical applications. Phaseresolved Doppler OCT that explores the phase information of OCT signals has been shown to be capable of characterizing dynamic blood flow clinically. In this work, we explore the capability of Fourier domain Doppler OCT as an evaluation tool to detect commonly encountered post-operative complications that will cause surgical failure and to confirm positive result with surgeon's observation. Both suture and cuff based techniques were evaluated on the femoral artery and vein in the rodent model.

  17. Joint Effect of Early Microvascular Damage in the Eye & Kidney on Risk of Cardiovascular Events

    PubMed Central

    Yip, Wanfen; Sabanayagam, Charumathi; Ong, Peng Guan; Patel, Uptal D; Chow, Khuan Yew; Tai, E Shyong; Ling, Lieng H; Wong, Tien Yin; Cheung, Carol Yim-lui

    2016-01-01

    Microalbuminuria is associated with an increased risk of cardiovascular disease (CVD), but not all individuals require treatment. Retinal microvascular abnormalities and microalbuminuria reflect early systemic microvascular changes. We examined the joint effect of retinal abnormalities and microalbuminuria on CVD risk in an Asian cohort. We conducted a prospective, population-based study. Retinal abnormalities were defined as presence of retinopathy and/or retinal venular widening. Microalbuminuria was defined as urinary albumin: creatinine ratio between 30–300 mg/g. Incident CVD was defined as newly diagnosed clinical stroke, acute myocardial infarction or CVD death. Cox regression models were performed to determine the associations between retinal abnormalities and microalbuminuria with risk of CVD, while controlling for established risk factors. 3,496 participants (aged ≥ 40) were free of prevalent CVD. During the follow-up (5.8 years), 126 (3.60%) participants developed CVD. Persons presenting with both retinal abnormalities and microalbuminuria were 6.71 times (95% CI, 2.68, 16.79) as likely to have incident CVD compared with those without either abnormalities. There was a significant interaction effect between retinal abnormalities and microalbuminuria on incident CVD. Assessment of retinal abnormalities in patients with microalbuminuria may provide additional value in identifying persons at risk of developing CVD. PMID:27273133

  18. Quantitative Contrast-Enhanced Ultrasonic Imaging Reflects Microvascularization in Hepatocellular Carcinoma and Prognosis after Resection.

    PubMed

    Zou, Ru-Hai; Lin, Qing-Guang; Huang, Wei; Li, Xiao-Ling; Cao, Yun; Zhang, Jing; Zhou, Jian-Hua; Li, An-Hua; Beretta, Laura; Qian, Chao-Nan

    2015-10-01

    Our aim was to evaluate the correlation between tumor vasculature detected by pre-surgical contrast-enhanced ultrasonography and the post-surgical prognosis of patients with hepatocellular carcinoma. One hundred ninety-five patients with hepatocellular carcinoma who had undergone curative resection and pre-operative contrast-enhanced ultrasonography were enrolled. Intra-tumoral microvessels were evaluated by immunohistochemical staining for anti-CD31 and anti-CD34. On the basis of the immunohistochemical staining and morphology patterns, tumors were divided into capillary-like and sinusoid-like microvessel subtypes. The rise time of tumors was shorter in the capillary-like microvessel subtype than in the sinusoid-like microvasculature subtype (p = 0.026). Intra-tumor microvascular density (p < 0.001, hazard ratio = 0.137) and rise time (p = 0.006, hazard ratio = 2.475) were independent factors corresponding to different microvasculature types. Microvascular density, vascular invasion and wash-in perfusion index were determined to be independent factors in recurrence-free survival and overall survival. In conclusion, contrast-enhanced ultrasonography may serve as a means of non-invasive assessment of tumor angiogenesis and may be associated with the survival of patients with hepatocellular carcinoma after resection. PMID:26210785

  19. Human growth hormone stimulates proliferation of human retinal microvascular endothelial cells in vitro

    SciTech Connect

    Rymaszewski, Z.; Cohen, R.M.; Chomczynski, P. )

    1991-01-15

    Growth hormone (GH) has been implicated in the pathogenesis of proliferative diabetic retinopathy. The authors sought to determine whether this could be mediated by an effect of GH on proliferation of endothelial cells, and, for this purpose, established long-term cultures of human retinal microvascular endothelial cells (hREC) from normal postmortem human eyes. High-purity hREC preparations were selected for experiments, based on immunogluorescence with acetylated low density lipoprotein (LDL) and anti-factor VIII-related antigen. Growth requirements for these cells were complex, including serum for maintenance at slow growth rates and additional mitogens for more rapid proliferation. Exposure of hREC to physiologic doses of human GH (hGH) resulted in 100% greater cell number vs. control but could be elicited only in the presence of serum. When differing serum conditions were compared, hGH stimulated ({sup 3}H)thymidine incorporation up to 1.6- to 2.2-fold under each condition and increased DNA content significantly in the presence of human, horse, and fetal calf serum. In summary, hREC respond to physiologic concentrations of hGH in vitro with enhanced proliferation. This specific effect of GH on retinal microvascular endothelial cells supports the hypothesis of role for GH in endothelial cell biology.

  20. Joint Effect of Early Microvascular Damage in the Eye &Kidney on Risk of Cardiovascular Events.

    PubMed

    Yip, Wanfen; Sabanayagam, Charumathi; Ong, Peng Guan; Patel, Uptal D; Chow, Khuan Yew; Tai, E Shyong; Ling, Lieng H; Wong, Tien Yin; Cheung, Carol Yim-Lui

    2016-01-01

    Microalbuminuria is associated with an increased risk of cardiovascular disease (CVD), but not all individuals require treatment. Retinal microvascular abnormalities and microalbuminuria reflect early systemic microvascular changes. We examined the joint effect of retinal abnormalities and microalbuminuria on CVD risk in an Asian cohort. We conducted a prospective, population-based study. Retinal abnormalities were defined as presence of retinopathy and/or retinal venular widening. Microalbuminuria was defined as urinary albumin: creatinine ratio between 30-300 mg/g. Incident CVD was defined as newly diagnosed clinical stroke, acute myocardial infarction or CVD death. Cox regression models were performed to determine the associations between retinal abnormalities and microalbuminuria with risk of CVD, while controlling for established risk factors. 3,496 participants (aged ≥ 40) were free of prevalent CVD. During the follow-up (5.8 years), 126 (3.60%) participants developed CVD. Persons presenting with both retinal abnormalities and microalbuminuria were 6.71 times (95% CI, 2.68, 16.79) as likely to have incident CVD compared with those without either abnormalities. There was a significant interaction effect between retinal abnormalities and microalbuminuria on incident CVD. Assessment of retinal abnormalities in patients with microalbuminuria may provide additional value in identifying persons at risk of developing CVD. PMID:27273133

  1. Overweight status is associated with extensive signs of microvascular dysfunction and cardiovascular risk

    PubMed Central

    Patel, Sunni R.; Bellary, Srikanth; Karimzad, Said; Gherghel, Doina

    2016-01-01

    The aim of this present study was to investigate if overweight individuals exhibit signs of vascular dysfunction associated with a high risk for cardiovascular disease (CVD). One hundred lean and 100 overweight participants were recruited for the present study. Retinal microvascular function was assessed using the Dynamic Retinal Vessel Analyser (DVA), and systemic macrovascular function by means of flow-mediated dilation (FMD). Investigations also included body composition, carotid intimal-media thickness (c-IMT), ambulatory blood pressure monitoring (BP), fasting plasma glucose, triglycerides (TG), cholesterol levels (HDL-C and LDL-C), and plasma von Willebrand factor (vWF). Overweight individuals presented with higher right and left c-IMT (p = 0.005 and p = 0.002, respectively), average 24-h BP values (all p < 0.001), plasma glucose (p = 0.008), TG (p = 0.003), TG: HDL-C ratio (p = 0.010), and vWF levels (p = 0.004). Moreover, overweight individuals showed lower retinal arterial microvascular dilation (p = 0.039) and baseline-corrected flicker (bFR) responses (p = 0.022), as well as, prolonged dilation reaction time (RT, p = 0.047). These observations emphasise the importance of vascular screening and consideration of preventive interventions to decrease vascular risk in all individuals with adiposity above normal range. PMID:27578554

  2. Ghrelin stimulates angiogenesis in human microvascular endothelial cells: Implications beyond GH release

    SciTech Connect

    Li Aihua; Cheng Guangli; Zhu Genghui; Tarnawski, Andrzej S. . E-mail: atarnawski@yahoo.com

    2007-02-09

    Ghrelin, a peptide hormone isolated from the stomach, releases growth hormone and stimulates appetite. Ghrelin is also expressed in pancreas, kidneys, cardiovascular system and in endothelial cells. The precise role of ghrelin in endothelial cell functions remains unknown. We examined the expression of ghrelin and its receptor (GHSR1) mRNAs and proteins in human microvascular endothelial cells (HMVEC) and determined whether ghrelin affects in these cells proliferation, migration and in vitro angiogenesis; and whether MAPK/ERK2 signaling is important for the latter action. We found that ghrelin and GHSR1 are constitutively expressed in HMVEC. Treatment of HMVEC with exogenous ghrelin significantly increased in these cells proliferation, migration, in vitro angiogenesis and ERK2 phosphorylation. MEK/ERK2 inhibitor, PD 98059 abolished ghrelin-induced in vitro angiogenesis. This is First demonstration that ghrelin and its receptor are expressed in human microvascular endothelial cells and that ghrelin stimulates HMVEC proliferation, migration, and angiogenesis through activation of ERK2 signaling.

  3. [Microvascular and macrovascular complications in children and adolescents with type 1 diabetes mellitus].

    PubMed

    Fröhlich-Reiterer, Elke E; Borkenstein, Martin H

    2010-08-01

    Diabetes-related microvascular and macrovascular complications, as retinopathy, nephropathy and neuropathy are life-threatening complications in children and adolescents with type 1 diabetes mellitus (T1DM). Risk factors for the development of complications are longer duration of diabetes, older age and puberty. Further risk factors include smoking, hypertension, higher body mass index and dyslipoproteinaemia. Therefore prevention and screening for complications is an important part in the care of children and adolescents with T1DM. Target levels to reduce the risk of microvascular and macrovascular complications in children and adolescents with T1DM are the following: HbA1c<7.5%, lipids in normal range, blood pressure<90th percentile by age, sex and height, BMI<95th percentile, no smoking and physical activity. Screening for retinopathy and microalbuminuria should start from 11 years with two years diabetes duration and from 9 years with 5 years duration and after 2 years diabetes duration in an adolescent. Thereafter screening should be performed annually. Blood pressure should be measured at least annually. Screening for fasting blood lipids should be performed soon after diagnosis in all children with T1DM aged over 12 years. If normal results are obtained, this should be repeated every 5 years.

  4. Epidermal devices for noninvasive, precise, and continuous mapping of macrovascular and microvascular blood flow

    PubMed Central

    Webb, R. Chad; Ma, Yinji; Krishnan, Siddharth; Li, Yuhang; Yoon, Stephen; Guo, Xiaogang; Feng, Xue; Shi, Yan; Seidel, Miles; Cho, Nam Heon; Kurniawan, Jonas; Ahad, James; Sheth, Niral; Kim, Joseph; Taylor VI, James G.; Darlington, Tom; Chang, Ken; Huang, Weizhong; Ayers, Joshua; Gruebele, Alexander; Pielak, Rafal M.; Slepian, Marvin J.; Huang, Yonggang; Gorbach, Alexander M.; Rogers, John A.

    2015-01-01

    Continuous monitoring of variations in blood flow is vital in assessing the status of microvascular and macrovascular beds for a wide range of clinical and research scenarios. Although a variety of techniques exist, most require complete immobilization of the subject, thereby limiting their utility to hospital or clinical settings. Those that can be rendered in wearable formats suffer from limited accuracy, motion artifacts, and other shortcomings that follow from an inability to achieve intimate, noninvasive mechanical linkage of sensors with the surface of the skin. We introduce an ultrathin, soft, skin-conforming sensor technology that offers advanced capabilities in continuous and precise blood flow mapping. Systematic work establishes a set of experimental procedures and theoretical models for quantitative measurements and guidelines in design and operation. Experimental studies on human subjects, including validation with measurements performed using state-of-the-art clinical techniques, demonstrate sensitive and accurate assessment of both macrovascular and microvascular flow under a range of physiological conditions. Refined operational modes eliminate long-term drifts and reduce power consumption, thereby providing steps toward the use of this technology for continuous monitoring during daily activities. PMID:26601309

  5. Early postoperative bone scintigraphy in the evaluation of microvascular bone grafts in head and neck reconstruction

    PubMed Central

    Schuepbach, Jonas; Dassonville, Olivier; Poissonnet, Gilles; Demard, Francois

    2007-01-01

    Background Bone scintigraphy was performed to monitor anastomotic patency and bone viability. Methods In this retrospective study, bone scans were carried out during the first three postoperative days in a series of 60 patients who underwent microvascular bone grafting for reconstruction of the mandible or maxilla. Results In our series, early bone scans detected a compromised vascular supply to the bone with high accuracy (p < 10-6) and a sensitivity that was superior to the sensitivity of clinical monitoring (92% and 75% respectively). Conclusion When performing bone scintigraphy during the first three postoperative days, it not only helps to detect complications with high accuracy, as described in earlier studies, but it is also an additional reliable monitoring tool to decide whether or not microvascular revision surgery should be performed. Bone scans were especially useful in buried free flaps where early postoperative monitoring depended exclusively on scans. According to our experience, we recommend bone scans as soon as possible after surgery and immediately in cases suspicious of vascularized bone graft failure. PMID:17448223

  6. [Application of intraoperative microvascular dopplerography in surgical treatment of arterial aneurysm of the brain].

    PubMed

    Hloba, M V; Lytvak, S O

    2013-10-01

    The possibilities and results of the intraoperative microvascular dopplerography application in microsurgical exclusion of the brain arterial aneurysm (BAA) were estimated. The investigation was conducted during operative intervention in 30 patients, suffering hemorrhagic type of the brain acute blood flow disorder as a consequence of the BAA rupture. In an acute period (the first-14th day) 23 patients were operated, in the early restoration period (after 30th day)--7. Intraoperative express estimation of the blood flow have permitted to diagnose and to correct timely some typical technical complications, in particular, noncomplete BAA exclusion from the blood flow, the arterial lumen, containing the clipped aneurysm, stenosing; to reveal the arterial segments vasospasm objectively in the patients, operated on in an acute period of hemorrhage, and to diagnose a reactive spasm during manipulations on the arteries. All the patients, operated on in the early restoration period and 82.6% of patients, operated on in an acute period of subarachnoidal hemorrhage, have had reconvalesced. Application of the microvascular dopplerography secures objectivization, simplifies intraoperative estimation of the BAA radicality and the according arterial segments passability in the operative intervention zone, what promotes reduction of the ischemic complications rate and positively impacts the results of treatment.

  7. Endotoxin, interleukin-1, and tumor necrosis factor cause neutrophil-dependent microvascular leakage in postcapillary venules.

    PubMed Central

    Yi, E. S.; Ulich, T. R.

    1992-01-01

    Acute inflammation is characterized mainly by the egress of neutrophils from postcapillary venules and by increased vascular permeability leading to the formation of edema. The microvascular site of increased vascular permeability in local acute inflammatory lesions was investigated after the injection of endotoxin (LPS), interleukin-1 (IL-1), and tumor necrosis factor (TNF) into the dermis overlying the cremasteric and rectus abdominis muscles of rats. LPS caused leakage of colloidal carbon peaking at 3 to 4 hours at the level of the postcapillary venules and capillary leak was variably observed at later time points. IL-1 and TNF also caused postcapillary venular leakage. IL-1 was as potent as LPS and more so than TNF. The microvascular leak caused by LPS, IL-1, and TNF was accompanied by the tissue accumulation of neutrophils, and was neutrophil-dependent because LPS, IL-1, and TNF did not cause vascular labelling in neutropenic rats. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:1546745

  8. Overweight status is associated with extensive signs of microvascular dysfunction and cardiovascular risk.

    PubMed

    Patel, Sunni R; Bellary, Srikanth; Karimzad, Said; Gherghel, Doina

    2016-01-01

    The aim of this present study was to investigate if overweight individuals exhibit signs of vascular dysfunction associated with a high risk for cardiovascular disease (CVD). One hundred lean and 100 overweight participants were recruited for the present study. Retinal microvascular function was assessed using the Dynamic Retinal Vessel Analyser (DVA), and systemic macrovascular function by means of flow-mediated dilation (FMD). Investigations also included body composition, carotid intimal-media thickness (c-IMT), ambulatory blood pressure monitoring (BP), fasting plasma glucose, triglycerides (TG), cholesterol levels (HDL-C and LDL-C), and plasma von Willebrand factor (vWF). Overweight individuals presented with higher right and left c-IMT (p = 0.005 and p = 0.002, respectively), average 24-h BP values (all p < 0.001), plasma glucose (p = 0.008), TG (p = 0.003), TG: HDL-C ratio (p = 0.010), and vWF levels (p = 0.004). Moreover, overweight individuals showed lower retinal arterial microvascular dilation (p = 0.039) and baseline-corrected flicker (bFR) responses (p = 0.022), as well as, prolonged dilation reaction time (RT, p = 0.047). These observations emphasise the importance of vascular screening and consideration of preventive interventions to decrease vascular risk in all individuals with adiposity above normal range. PMID:27578554

  9. Vascular endothelial growth factor (VEGF) expression and microvascular density in salivary gland tumours.

    PubMed

    Faur, Alexandra Corina; Lazar, Elena; Cornianu, Marioara

    2014-05-01

    This study investigates whether salivary tumours with different morphology and evolution also differ in terms of neovascularization and VEGF expression and the prognostic value of the results. Surgical specimens from 45 patients - 8 pleomorphic adenomas (PA), 7 Warthin tumours (WT), 5 basal cell adenomas (BA), 6 carcinomas ex-pleomorphic adenoma (CEPA), 6 mucoepidermoid carcinomas (MEC), 5 acinic cell carcinomas (AC), 4 adenoid cystic carcinomas (ACC) and 4 adenocarcinomas not otherwise specified (ADK NOS) - were immunostained. In malignant salivary tumours, the following mean microvascular density (MVD) values were recorded (± SD = Standard Deviation): 27.61 (SD ± 2.27) in cases with CEPA, 27.08 (DS ± 7.81) in AC and 32.93 (SD ± 7.76) in ADK NOS, with lower values for MEC 24.31(SD ± 2.88) and for ACC 22.13 (SD ± 5.44). For benign tumours, an MVD of 35.71 (SD ± 2.09) was recorded in WT and lower average values in PA (MVD = 14.84; SD ± 4.86) and in BA (MVD = 23.96; SD ± 9.13). MVD did not correlate with the investigated clinicopathological parameters. The VEGF expression is significantly more important (p = 0.001) in malignant salivary tumours as compared with benign ones. The VEGF expression and the microvascularization in salivary gland tumours are important elements to be considered when formulating a diagnosis and assessing case evolutions in patients with such tumours.

  10. Microvascular responses to body tilt in cutaneous maximus muscle of conscious rats

    NASA Technical Reports Server (NTRS)

    Puri, Rohit K.; Segal, Steven S.

    1994-01-01

    We investigated microvascular responses to head-up tilt (HUT) and head-down tilt (HDT) in striated muscle of conscious male rats. To observe the microcirculation in the cutaneous maximus muscle, a transparent polycarbonate chamber was implanted aseptically into a skin fold created between the shoulders. Rats were trained to sit quietly during HUT and HDT while positioned on a horizontal microscope that rotated in the sagittal plane. At 4-5 days after surgery, arteriole and venule diameters were recorded using videomicroscopy while the rat experienced 10 min each (in random order) of HUT or HDT at 20 deg or 40 deg separated by 2-h rest periods. HUT had no affect on microvessel diameter; 20 deg HDT had little affect. In response to 40 deg HDT, 'large' arterioles constricted by 18 +/- 2% and 'small' arterioles dilated by 21 +/- 3%; this difference suggested variation in mechanisms controlling arteriolar responses. Venules exhibited a larger fluctuation in diameter during 40 deg HDT compared with other body positions, suggesting that venomotor activity may be induced with sufficient fluid shift or change in central venous pressure. These observations illustrate a viable model for studying microvascular responses to gravitational stress in conscious rats.

  11. Evaluation of microvascular structure in humans: a 'state-of-the-art' document of the Working Group on Macrovascular and Microvascular Alterations of the Italian Society of Arterial Hypertension.

    PubMed

    Virdis, Agostino; Savoia, Carmine; Grassi, Guido; Lembo, Giuseppe; Vecchione, Carmine; Seravalle, Gino; Taddei, Stefano; Volpe, Massimo; Rosei, Enrico Agabiti; Rizzoni, Damiano

    2014-11-01

    The evaluation of microvascular structure is, in general, not an easy task. Among the methods that may be applied to humans, plethysmographic evaluation of small arteries and wire or pressure micromyography were extensively used in the last decades. The media-to-lumen ratio of small arteries evaluated by micromyography was demonstrated to possess a strong prognostic significance; however, its extensive evaluation is limited by the local invasiveness of the assessment. Noninvasive approaches were then proposed, including capillaroscopy, which provides information about microvascular rarefaction. Recently, the interest of investigators was focused on the retinal microvascular bed. In particular, a noninvasive measurement of the wall-to-lumen ratio of retinal arterioles using scanning laser Doppler flowmetry has been introduced.Recent data suggest a rather good agreement between this approach and micromyographic measurements, generally considered the gold standard approach. Therefore, the evaluation of microvascular structure is progressively moving from bench to bedside, and it could represent, in the immediate future, an evaluation to be performed in all hypertensive patients, in order to obtain a better stratification of cardiovascular risk.

  12. Modeling of Cerebral Oxygen Transport Based on In vivo Microscopic Imaging of Microvascular Network Structure, Blood Flow, and Oxygenation

    PubMed Central

    Gagnon, Louis; Smith, Amy F.; Boas, David A.; Devor, Anna; Secomb, Timothy W.; Sakadžić, Sava

    2016-01-01

    Oxygen is delivered to brain tissue by a dense network of microvessels, which actively control cerebral blood flow (CBF) through vasodilation and contraction in response to changing levels of neural activity. Understanding these network-level processes is immediately relevant for (1) interpretation of functional Magnetic Resonance Imaging (fMRI) signals, and (2) investigation of neurological diseases in which a deterioration of neurovascular and neuro-metabolic physiology contributes to motor and cognitive decline. Experimental data on the structure, flow and oxygen levels of microvascular networks are needed, together with theoretical methods to integrate this information and predict physiologically relevant properties that are not directly measurable. Recent progress in optical imaging technologies for high-resolution in vivo measurement of the cerebral microvascular architecture, blood flow, and oxygenation enables construction of detailed computational models of cerebral hemodynamics and oxygen transport based on realistic three-dimensional microvascular networks. In this article, we review state-of-the-art optical microscopy technologies for quantitative in vivo imaging of cerebral microvascular structure, blood flow and oxygenation, and theoretical methods that utilize such data to generate spatially resolved models for blood flow and oxygen transport. These “bottom-up” models are essential for the understanding of the processes governing brain oxygenation in normal and disease states and for eventual translation of the lessons learned from animal studies to humans.

  13. Pulmonary tumor thrombotic microangiopathy associated with urothelial carcinoma of the urinary bladder: antemortem diagnosis by pulmonary microvascular cytology.

    PubMed

    Yamakawa, Hideaki; Yoshida, Masahiro; Yamada, Masami; Ishikawa, Takeo; Takagi, Masamichi; Katagi, Hiroaki; Yoshida, Jun; Kosuga, Tsuneharu; Kuwano, Kazuyoshi

    2015-09-01

    PTTM (Pulmonary tumor thrombotic microangiopathy) is very difficult to diagnose before death. We report a case of urothelial carcinoma of the urinary bladder associated with PTTM in which an antemortem diagnosis by PMC (pulmonary microvascular cytology). PMC may represent the only chance for diagnosis and achievement of remission in PTTM. PMID:26401277

  14. Modeling of Cerebral Oxygen Transport Based on In vivo Microscopic Imaging of Microvascular Network Structure, Blood Flow, and Oxygenation

    PubMed Central

    Gagnon, Louis; Smith, Amy F.; Boas, David A.; Devor, Anna; Secomb, Timothy W.; Sakadžić, Sava

    2016-01-01

    Oxygen is delivered to brain tissue by a dense network of microvessels, which actively control cerebral blood flow (CBF) through vasodilation and contraction in response to changing levels of neural activity. Understanding these network-level processes is immediately relevant for (1) interpretation of functional Magnetic Resonance Imaging (fMRI) signals, and (2) investigation of neurological diseases in which a deterioration of neurovascular and neuro-metabolic physiology contributes to motor and cognitive decline. Experimental data on the structure, flow and oxygen levels of microvascular networks are needed, together with theoretical methods to integrate this information and predict physiologically relevant properties that are not directly measurable. Recent progress in optical imaging technologies for high-resolution in vivo measurement of the cerebral microvascular architecture, blood flow, and oxygenation enables construction of detailed computational models of cerebral hemodynamics and oxygen transport based on realistic three-dimensional microvascular networks. In this article, we review state-of-the-art optical microscopy technologies for quantitative in vivo imaging of cerebral microvascular structure, blood flow and oxygenation, and theoretical methods that utilize such data to generate spatially resolved models for blood flow and oxygen transport. These “bottom-up” models are essential for the understanding of the processes governing brain oxygenation in normal and disease states and for eventual translation of the lessons learned from animal studies to humans. PMID:27630556

  15. Modeling of Cerebral Oxygen Transport Based on In vivo Microscopic Imaging of Microvascular Network Structure, Blood Flow, and Oxygenation.

    PubMed

    Gagnon, Louis; Smith, Amy F; Boas, David A; Devor, Anna; Secomb, Timothy W; Sakadžić, Sava

    2016-01-01

    Oxygen is delivered to brain tissue by a dense network of microvessels, which actively control cerebral blood flow (CBF) through vasodilation and contraction in response to changing levels of neural activity. Understanding these network-level processes is immediately relevant for (1) interpretation of functional Magnetic Resonance Imaging (fMRI) signals, and (2) investigation of neurological diseases in which a deterioration of neurovascular and neuro-metabolic physiology contributes to motor and cognitive decline. Experimental data on the structure, flow and oxygen levels of microvascular networks are needed, together with theoretical methods to integrate this information and predict physiologically relevant properties that are not directly measurable. Recent progress in optical imaging technologies for high-resolution in vivo measurement of the cerebral microvascular architecture, blood flow, and oxygenation enables construction of detailed computational models of cerebral hemodynamics and oxygen transport based on realistic three-dimensional microvascular networks. In this article, we review state-of-the-art optical microscopy technologies for quantitative in vivo imaging of cerebral microvascular structure, blood flow and oxygenation, and theoretical methods that utilize such data to generate spatially resolved models for blood flow and oxygen transport. These "bottom-up" models are essential for the understanding of the processes governing brain oxygenation in normal and disease states and for eventual translation of the lessons learned from animal studies to humans. PMID:27630556

  16. Como Lo Hago Yo: Myelomeningocele

    PubMed Central

    Lazareff, Jorge

    2014-01-01

    Fortificación con ádico fólico es efectiva, pero aún falta conciencia en los jóvenes. La legalidad del aborto aumenta la importancia de la consulta prenatal. Realizo la cirugía bajo microcoscopio por razones didácticas. Irrigación continua para reducir la temperatura del tejido. Trato a la plaqueta como tejido viable. No suturo la plaqueta. No cierro músculo. ATB por una semana después de cirugía. Hidrocefalia: Válvula en todos los casos de ventriculomegalia. Médula anclada: Desanclar una sola vez. Chiari II: Revisar la válvula. Incluir en el seguimiento rendimiento escolar, puede indicar obstrucción de la válvula o médula anclada. PMID:24791217

  17. Microvascular perfusion during focal vasogenic brain edema: a scanning laser fluorescence microscopy study.

    PubMed

    Lindsberg, P J; Sirén, A L; Hallenbeck, J M

    1997-01-01

    Controversy exists about the effect of tissue edema on cerebral microcirculation. High spatial resolution is required for observation of extravasation and microcirculation during focal vasogenic edema formation. To study the relationship between tissue edema and perfusion, we developed a technique for simultaneous visualization of extravasation and microvessel perfusion in rats. Focal intracortical microvascular injury was generated with a 1-sec Nd-YAG laser pulse. Evans blue albumin (EBA) was infused 30 min before decapitation to study extravasation and FITC-dextran was injected 30 sec prior to decapitation to examine microvessel perfusion. Computerized scanning laser-excited fluorescence microscopy followed by high resolution image analysis permitted quantitative assessment of both parameters on single fresh-frozen brain sections. Studied at 30 min (3.66 +/- 0.15 mm), 2 hr (4.14 +/- 0.08 mm, P < .05), and 8 hr (4.69 +/- 0.18 mm, P < .01) after injury, the diameter of the circular, sharply demarcated zone of EBA-extravasation increased progressively. At 30 min, microvessels at a zone surrounding the area of EBA-extravasation contained 69 +/- 14% (P < .05) more fluorescent FITC-filling than in the control hemisphere, but the density of perfused microvessels was unchanged. At 2 hr, secondary tissue changes had already occurred in a zone surrounding the initial laser lesion. While severe reduction in the density (-76 +/- 13%, P < .05) of perfused microvessels was observed within 400 to 240 microm inside the border of EBA extravasation, perfusion indexes were normal despite the presence of extravasated plasma constituents within 0-80 microm from the border. In a narrow zone (80 microm) outside the border of extravasation, individual microvessels contained 34 +/- 9% (P < .01) less FITC-fluorescence than those in a homologous area of the uninjured contralateral hemisphere. This report demonstrates the feasibility of simultaneous measurement and high-resolution mapping

  18. Skeletal muscle microvascular oxygenation dynamics in heart failure: exercise training and nitric oxide-mediated function.

    PubMed

    Hirai, Daniel M; Copp, Steven W; Holdsworth, Clark T; Ferguson, Scott K; McCullough, Danielle J; Behnke, Bradley J; Musch, Timothy I; Poole, David C

    2014-03-01

    Chronic heart failure (CHF) impairs nitric oxide (NO)-mediated regulation of skeletal muscle O2 delivery-utilization matching such that microvascular oxygenation falls faster (i.e., speeds PO2mv kinetics) during increases in metabolic demand. Conversely, exercise training improves (slows) muscle PO2mv kinetics following contractions onset in healthy young individuals via NO-dependent mechanisms. We tested the hypothesis that exercise training would improve contracting muscle microvascular oxygenation in CHF rats partly via improved NO-mediated function. CHF rats (left ventricular end-diastolic pressure = 17 ± 2 mmHg) were assigned to sedentary (n = 11) or progressive treadmill exercise training (n = 11; 5 days/wk, 6-8 wk, final workload of 60 min/day at 35 m/min; -14% grade downhill running) groups. PO2mv was measured via phosphorescence quenching in the spinotrapezius muscle at rest and during 1-Hz twitch contractions under control (Krebs-Henseleit solution), sodium nitroprusside (SNP; NO donor; 300 μM), and N(G)-nitro-l-arginine methyl ester (L-NAME, nonspecific NO synthase blockade; 1.5 mM) superfusion conditions. Exercise-trained CHF rats had greater peak oxygen uptake and spinotrapezius muscle citrate synthase activity than their sedentary counterparts (p < 0.05 for both). The overall speed of the PO2mv fall during contractions (mean response time; MRT) was slowed markedly in trained compared with sedentary CHF rats (sedentary: 20.8 ± 1.4, trained: 32.3 ± 3.0 s; p < 0.05), and the effect was not abolished by L-NAME (sedentary: 16.8 ± 1.5, trained: 31.0 ± 3.4 s; p > 0.05). Relative to control, SNP increased MRT in both groups such that trained CHF rats had slower kinetics (sedentary: 43.0 ± 6.8, trained: 55.5 ± 7.8 s; p < 0.05). Improved NO-mediated function is not obligatory for training-induced improvements in skeletal muscle microvascular oxygenation (slowed PO2mv kinetics) following contractions onset in rats with CHF.

  19. (-)-Epicatechin administration and exercising skeletal muscle vascular control and microvascular oxygenation in healthy rats.

    PubMed

    Copp, Steven W; Inagaki, Tadakatsu; White, Michael J; Hirai, Daniel M; Ferguson, Scott K; Holdsworth, Clark T; Sims, Gabrielle E; Poole, David C; Musch, Timothy I

    2013-01-15

    Consumption of the dietary flavanol (-)-epicatechin (EPI) is associated with enhanced endothelial function and augmented skeletal muscle capillarity and mitochondrial volume density. The potential for EPI to improve peripheral vascular function and muscle oxygenation during exercise is unknown. We tested the hypothesis that EPI administration in healthy rats would improve treadmill exercise performance secondary to elevated skeletal muscle blood flow and vascular conductance [VC, blood flow/mean arterial pressure (MAP)] and improved skeletal muscle microvascular oxygenation. Rats received water (control, n = 12) or 4 mg/kg EPI (n = 12) via oral gavage daily for 24 days. Exercise endurance capacity and peak O(2) uptake (Vo(2) peak) were measured via treadmill runs to exhaustion. MAP (arterial catheter) and blood flow (radiolabeled microspheres) were measured and VC was calculated during submaximal treadmill exercise (25 m/min, 5% grade). Spinotrapezius muscle microvascular O(2) pressure (Po(2mv)) was measured (phosphorescence quenching) during electrically induced twitch (1 Hz) contractions. In conscious rats, EPI administration resulted in lower (↓~5%) resting (P = 0.03) and exercising (P = 0.04) MAP. There were no differences in exercise endurance capacity, Vo(2) peak, total exercising hindlimb blood flow (control, 154 ± 13; and EPI, 159 ± 8 ml·min(-1)·100 g(-1), P = 0.68), or VC (control, 1.13 ± 0.10; and EPI, 1.24 ± 0.08 ml·min(-1)·100 g(-1)·mmHg(-1), P = 0.21) between groups. Following anesthesia, EPI resulted in lower MAP (↓~16%) but did not impact resting Po(2mv) or any kinetics parameters (P > 0.05 for all) during muscle contractions compared with control. EPI administration (4 mg·kg(-1)·day(-1)) improved modestly cardiovascular function (i.e., ↓MAP) with no impact on exercise performance, total exercising skeletal muscle blood flow and VC, or contracting muscle microvascular oxygenation in healthy rats.

  20. Androgens influence microvascular dilation in PCOS through ET-A and ET-B receptors.

    PubMed

    Wenner, Megan M; Taylor, Hugh S; Stachenfeld, Nina S

    2013-10-01

    Hyperandrogenism and vascular dysfunction often coexist in women with polycystic ovary syndrome (PCOS). We hypothesized that testosterone compromises cutaneous microvascular dilation in women with PCOS via the endothelin-1 ET-B subtype receptor. To control and isolate testosterone's effects on microvascular dilation, we administered a gonadotropin-releasing hormone antagonist (GnRHant) for 11 days in obese, otherwise healthy women [controls, 22.0 (4) yr, 36.0 (3.2) kg/m(2)] or women with PCOS [23 (4) yr, 35.4 (1.3) kg/m(2)], adding testosterone (T; 2.5 mg/day) on days 8-11. Using laser Doppler flowmetry and cutaneous microdialysis, we measured changes in skin microcirculatory responsiveness (ΔCVC) to local heating while perfusing ET-A (BQ-123) and ET-B (BQ-788) receptor antagonists under three experimental conditions: baseline (BL; prehormone intervention), GnRHant (day 4 of administration), and T administration. At BL, ET-A receptor inhibition enhanced heat-induced vasodilation in both groups [ΔCVC control 2.03 (0.65), PCOS 2.10 (0.25), AU/mmHg, P < 0.05]; ET-B receptor inhibition reduced vasodilation in controls only [ΔCVC 0.98 (0.39), 1.41 (0.45) AU/mmHg for controls, PCOS] compared with saline [ΔCVC controls 1.27 (0.48), PCOS 1.31 (0.13) AU/mmHg]. GnRHant enhanced vasodilation in PCOS [saline ΔCVC 1.69 (0.23) AU/mmHg vs. BL, P < 0.05] and abolished the ET-A effect in both groups, a response reasserted with T in controls. ET-B receptor inhibition reduced heat-induced vasodilation in both groups during GnRHant and T [ΔCVC, controls: 0.95 (0.21) vs. 0.51 (13); PCOS: 1.27 (0.23) vs. 0.84 (0.27); for GnRHant vs. T, P < 0.05]. These data demonstrate that androgen suppression improves microvascular dilation in PCOS via ET-A and ET-B receptors.

  1. Role of genetic polymorphisms of ion channels in the pathophysiology of coronary microvascular dysfunction and ischemic heart disease.

    PubMed

    Fedele, Francesco; Mancone, Massimo; Chilian, William M; Severino, Paolo; Canali, Emanuele; Logan, Suzanna; De Marchis, Maria Laura; Volterrani, Maurizio; Palmirotta, Raffaele; Guadagni, Fiorella

    2013-11-01

    Conventionally, ischemic heart disease (IHD) is equated with large vessel coronary disease. However, recent evidence has suggested a role of compromised microvascular regulation in the etiology of IHD. Because regulation of coronary blood flow likely involves activity of specific ion channels, and key factors involved in endothelium-dependent dilation, we proposed that genetic anomalies of ion channels or specific endothelial regulators may underlie coronary microvascular disease. We aimed to evaluate the clinical impact of single-nucleotide polymorphisms in genes encoding for ion channels expressed in the coronary vasculature and the possible correlation with IHD resulting from microvascular dysfunction. 242 consecutive patients who were candidates for coronary angiography were enrolled. A prospective, observational, single-center study was conducted, analyzing genetic polymorphisms relative to (1) NOS3 encoding for endothelial nitric oxide synthase (eNOS); (2) ATP2A2 encoding for the Ca²⁺/H⁺-ATPase pump (SERCA); (3) SCN5A encoding for the voltage-dependent Na⁺ channel (Nav1.5); (4) KCNJ8 and KCNJ11 encoding for the Kir6.1 and Kir6.2 subunits of K-ATP channels, respectively; and (5) KCN5A encoding for the voltage-gated K⁺ channel (Kv1.5). No significant associations between clinical IHD manifestations and polymorphisms for SERCA, Kir6.1, and Kv1.5 were observed (p > 0.05), whereas specific polymorphisms detected in eNOS, as well as in Kir6.2 and Nav1.5 were found to be correlated with IHD and microvascular dysfunction. Interestingly, genetic polymorphisms for ion channels seem to have an important clinical impact influencing the susceptibility for microvascular dysfunction and IHD, independent of the presence of classic cardiovascular risk factors.

  2. Diagnostic Ultrasound Induced Inertial Cavitation to Non-Invasively Restore Coronary and Microvascular Flow in Acute Myocardial Infarction

    PubMed Central

    Xie, Feng; Gao, Shunji; Wu, Juefei; Lof, John; Radio, Stanley; Vignon, Francois; Shi, William; Powers, Jeffry; Unger, Evan; Everbach, E. Carr; Liu, Jinjin; Porter, Thomas R.

    2013-01-01

    Ultrasound induced cavitation has been explored as a method of dissolving intravascular and microvascular thrombi in acute myocardial infarction. The purpose of this study was to determine the type of cavitation required for success, and whether longer pulse duration therapeutic impulses (sustaining the duration of cavitation) could restore both microvascular and epicardial flow with this technique. Accordingly, in 36 hyperlipidemic atherosclerotic pigs, thrombotic occlusions were induced in the mid-left anterior descending artery. Pigs were then randomized to either a) ½ dose tissue plasminogen activator (0.5 mg/kg) alone; or same dose plasminogen activator and an intravenous microbubble infusion with either b) guided high mechanical index short pulse (2.0 MI; 5 usec) therapeutic ultrasound impulses; or c) guided 1.0 mechanical index long pulse (20 usec) impulses. Passive cavitation detectors indicated the high mechanical index impulses (both long and short pulse duration) induced inertial cavitation within the microvasculature. Epicardial recanalization rates following randomized treatments were highest in pigs treated with the long pulse duration therapeutic impulses (83% versus 59% for short pulse, and 49% for tissue plasminogen activator alone; p<0.05). Even without epicardial recanalization, however, early microvascular recovery occurred with both short and long pulse therapeutic impulses (p<0.005 compared to tissue plasminogen activator alone), and wall thickening improved within the risk area only in pigs treated with ultrasound and microbubbles. We conclude that although short pulse duration guided therapeutic impulses from a diagnostic transducer transiently improve microvascular flow, long pulse duration therapeutic impulses produce sustained epicardial and microvascular re-flow in acute myocardial infarction. PMID:23922797

  3. The association between microvascular and macrovascular endothelial function in patients with rheumatoid arthritis: a cross-sectional study

    PubMed Central

    2011-01-01

    Introduction Patients with rheumatoid arthritis (RA) are at an increased risk for cardiovascular disease (CVD). One of the earliest manifestations of CVD is endothelial dysfunction (ED). ED can occur in both the microcirculation and the macrocirculation, and these manifestations might be relatively independent of each other. Little is known about the association between endothelial function in the microcirculation and the macrocirculation in RA. The objectives of the present study were to examine the relationship between microvascular and macrovascular endothelial function in patients with RA. Methods Ninety-nine RA patients (72 females, mean age (± SD) 56 ± 12 years), underwent assessments of endothelial-dependent (acetylcholine) and endothelial-independent (sodium nitroprusside) microvascular vasodilatory function (laser Doppler imaging with iontophoresis), as well as endothelial-dependent (flow-mediated dilation) and endothelial-independent (glyceryl trinitrate-mediated dilation) macrovascular vasodilatory function. Vasodilatory function was calculated as the percentage increase after each stimulus was applied relative to baseline values. Results Pearson correlations showed that microvascular endothelial-dependent function was not associated with macrovascular endothelial-dependent function (r (90 patients) = 0.10, P = 0.34). Similarly, microvascular endothelial-independent function was not related to macrovascular endothelial-independent function (r (89 patients) = 0.00, P = 0.99). Conclusions Microvascular and macrovascular endothelial function were independent of each other in patients with RA, suggesting differential regulation of endothelial function in these two vascular beds. Assessments of both vascular beds may provide more meaningful clinical information on vascular risk in RA, but this hypothesis needs to be confirmed in long-term prospective studies. PMID:21693023

  4. An observational cohort study of the kynurenine to tryptophan ratio in sepsis: association with impaired immune and microvascular function.

    PubMed

    Darcy, Christabelle J; Davis, Joshua S; Woodberry, Tonia; McNeil, Yvette R; Stephens, Dianne P; Yeo, Tsin W; Anstey, Nicholas M

    2011-01-01

    Both endothelial and immune dysfunction contribute to the high mortality rate in human sepsis, but the underlying mechanisms are unclear. In response to infection, interferon-γ activates indoleamine 2,3-dioxygenase (IDO) which metabolizes the essential amino acid tryptophan to the toxic metabolite kynurenine. IDO can be expressed in endothelial cells, hepatocytes and mononuclear leukocytes, all of which contribute to sepsis pathophysiology. Increased IDO activity (measured by the kynurenine to tryptophan [KT] ratio in plasma) causes T-cell apoptosis, vasodilation and nitric oxide synthase inhibition. We hypothesized that IDO activity in sepsis would be related to plasma interferon-γ, interleukin-10, T cell lymphopenia and impairment of microvascular reactivity, a measure of endothelial nitric oxide bioavailability. In an observational cohort study of 80 sepsis patients (50 severe and 30 non-severe) and 40 hospital controls, we determined the relationship between IDO activity (plasma KT ratio) and selected plasma cytokines, sepsis severity, nitric oxide-dependent microvascular reactivity and lymphocyte subsets in sepsis. Plasma amino acids were measured by high performance liquid chromatography and microvascular reactivity by peripheral arterial tonometry. The plasma KT ratio was increased in sepsis (median 141 [IQR 64-235]) compared to controls (36 [28-52]); p<0.0001), and correlated with plasma interferon-γ and interleukin-10, and inversely with total lymphocyte count, CD8+ and CD4+ T-lymphocytes, systolic blood pressure and microvascular reactivity. In response to treatment of severe sepsis, the median KT ratio decreased from 162 [IQR 100-286] on day 0 to 89 [65-139] by day 7; p = 0.0006) and this decrease in KT ratio correlated with a decrease in the Sequential Organ Failure Assessment score (p<0.0001). IDO-mediated tryptophan catabolism is associated with dysregulated immune responses and impaired microvascular reactivity in sepsis and may link these two

  5. Microvascular dysfunction and efficacy of PDE5 inhibitors in BPH-LUTS.

    PubMed

    Cellek, Selim; Cameron, Norman E; Cotter, Mary A; Fry, Christopher H; Ilo, Dapo

    2014-04-01

    Benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS) and erectile dysfunction commonly coexist, and both respond to phosphodiesterase (PDE) 5 inhibitors, suggesting a shared pathophysiological mechanism. We propose that both BPH-LUTS and erectile dysfunction are caused by microvascular dysfunction within the pelvic organs, and we present an overview of preclinical and clinical studies supporting the hypothesis that, within both the penis and the lower urinary tract, a combination of endothelial and neural dysfunction leads to a vicious cycle of hypoxia, vasoconstriction, altered smooth muscle contractility, and degeneration of autonomic neurons and ganglia. This hypothesis explains much of the preclinical and clinical research relating to these two conditions, and provides a rationale for further investigation into the effects of PDE5 inhibitors on the pathophysiology and symptoms of BPH-LUTS.

  6. [Effective Microvascular Decompression of the Trigeminal Nerve in a Patient with SUNCT].

    PubMed

    Kikui, Shoji; Miyahara, Jun-Ichi; Sugiyama, Hanako; Kashiwaya, Yoshihiro; Takeshima, Takao

    2016-08-01

    A 43-year-old man presented with severe, saw-tooth pattern pain around the right eye that started with conjunctival injection, lacrimation and nasal discharge, lasting for about 1 hour, 4 months after the initial onset of lancinating pain in the same area. The patient was diagnosed with SUNCT (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) according to the International Classification of Headache Disorders 3rd edition (beta version). The symptoms improved in 2 months but recurred 6 months later. He developed a toxic eruption after receiving a variety of antiepileptic agents including lamotrigine, which suggested refractory SUNCT. Head magnetic resonance imaging (MRI) showed neurovascular compression (NVC) involving the right trigeminal nerve. Microvascular decompression (MVD) was performed, and the pain was relieved postoperatively. MVD should be considered when treating refractory SUNCT because NVC may be involved in some cases. (Received February 29, 2016; Accepted April 4, 2016; Published August 1, 2016). PMID:27503824

  7. Quantitative changes in mast cells and microvascular pattern associated with dietary gastric ulceration in rats.

    PubMed

    Jayaraj, A P; Tovey, F I; Riley, P A; Clark, C G

    1985-01-01

    The regional distribution of mast cells and the microvascular pattern in the stomach of Wistar rats fed on an ulcerogenic diet were compared with those of control animals. Mounts of the distended stomach were made and stained for blood vessels and mast cells in the subserosal layer. Measurements made under dark ground illumination in 12 operationally defined regions of the serosa demonstrated that the stomach wall in the region around the oesophagus is more richly vascularised and possesses a greater number of mast cells (60 cells per mm2) than other regions. Changes in the mast cells and microvasculature were observed in rats fed an ulcerogenic diet, notably in the zone around the oesophagus, where more than 30% mast cells were degranulated and the mean vascular diameter increased by 26%. The severity of the vascular changes correlated with the location of the ulcers of which 50% were in the zone surrounding the oesophagus.

  8. Microvascular decompression of trigeminal nerve root for treatment of a patient with hemimasticatory spasm.

    PubMed

    Dou, Ning-Ning; Zhong, Jun; Zhou, Qiu-Meng; Zhu, Jin; Wang, Yong-Nan; Li, Shi-Ting

    2014-05-01

    Hemimasticatory spasm is a rare disease; with little knowledge of the pathogenesis, it has still been intractable today. We presented a 56-year-old woman with involuntary painful spasm in her left masseter muscle for 11 years. The patient was successfully treated with microvascular decompression surgery. An offending superior cerebellar artery was found to contact with the motor branch of the trigeminal nerve root, which was then removed away and pieces of soft wadding were interposed between the nerve and the vessel to assure the separation. Postoperatively, the symptom totally disappeared and no recurrence was observed during the 7 months' follow-up. The treatment as well as the pathogenesis of the disease was reviewed, and we put forward a new hypothesis.

  9. Magnetic particle spectroscopy allows precise quantification of nanoparticles after passage through human brain microvascular endothelial cells

    NASA Astrophysics Data System (ADS)

    Gräfe, C.; Slabu, I.; Wiekhorst, F.; Bergemann, C.; von Eggeling, F.; Hochhaus, A.; Trahms, L.; Clement, J. H.

    2016-06-01

    Crossing the blood-brain barrier is an urgent requirement for the treatment of brain disorders. Superparamagnetic iron oxide nanoparticles (SPIONs) are a promising tool as carriers for therapeutics because of their physical properties, biocompatibility, and their biodegradability. In order to investigate the interaction of nanoparticles with endothelial cell layers in detail, in vitro systems are of great importance. Human brain microvascular endothelial cells are a well-suited blood-brain barrier model. Apart from generating optimal conditions for the barrier-forming cell units, the accurate detection and quantification of SPIONs is a major challenge. For that purpose we use magnetic particle spectroscopy to sensitively and directly quantify the SPION-specific iron content. We could show that SPION concentration depends on incubation time, nanoparticle concentration and location. This model system allows for further investigations on particle uptake and transport at cellular barriers with regard to parameters including particles’ shape, material, size, and coating.

  10. The Brain Microvascular Endothelium Supports T Cell Proliferation and Has Potential for Alloantigen Presentation

    PubMed Central

    Wheway, Julie; Obeid, Stephanie; Couraud, Pierre-Olivier; Combes, Valery; Grau, Georges E. R.

    2013-01-01

    Endothelial cells (EC) form the inner lining of blood vessels and are positioned between circulating lymphocytes and tissues. Hypotheses have formed that EC may act as antigen presenting cells based on the intimate interactions with T cells, which are seen in diseases like multiple sclerosis, cerebral malaria (CM) and viral neuropathologies. Here, we investigated how human brain microvascular EC (HBEC) interact with and support the proliferation of T cells. We found HBEC to express MHC II, CD40 and ICOSL, key molecules for antigen presentation and co-stimulation and to take up fluorescently labeled antigens via macropinocytosis. In co-cultures, we showed that HBEC support and promote the proliferation of CD4+ and CD8+ T cells, which both are key in CM pathogenesis, particularly following T cell receptor activation and co-stimulation. Our findings provide novel evidence that HBEC can trigger T cell activation, thereby providing a novel mechanism for neuroimmunological complications of infectious diseases. PMID:23320074

  11. Micro-vascular shape-memory polymer actuators with complex geometries obtained by laser stereolithography

    NASA Astrophysics Data System (ADS)

    Díaz Lantada, Andrés; de Blas Romero, Adrián; Chacón Tanarro, Enrique

    2016-06-01

    In our work we present the complete development process of geometrically complex micro-vascular shape-memory polymer actuators. The complex geometries and three-dimensional networks are designed by means of computer aided design resources. Manufacture is accomplished, in a single step, by means of laser stereolithography, directly from the computer-aided design files with the three dimensional geometries of the different actuators under development. To our knowledge, laser stereolithography is applied here for the first time to the development of shape memory polymer devices with complex geometries and inner micro-vasculatures for their activation using a thermal fluid. Final testing of the developed actuators helps to validate the approach and to put forward some present challenges.

  12. Magnetic particle spectroscopy allows precise quantification of nanoparticles after passage through human brain microvascular endothelial cells

    NASA Astrophysics Data System (ADS)

    Gräfe, C.; Slabu, I.; Wiekhorst, F.; Bergemann, C.; von Eggeling, F.; Hochhaus, A.; Trahms, L.; Clement, J. H.

    2016-06-01

    Crossing the blood–brain barrier is an urgent requirement for the treatment of brain disorders. Superparamagnetic iron oxide nanoparticles (SPIONs) are a promising tool as carriers for therapeutics because of their physical properties, biocompatibility, and their biodegradability. In order to investigate the interaction of nanoparticles with endothelial cell layers in detail, in vitro systems are of great importance. Human brain microvascular endothelial cells are a well-suited blood–brain barrier model. Apart from generating optimal conditions for the barrier-forming cell units, the accurate detection and quantification of SPIONs is a major challenge. For that purpose we use magnetic particle spectroscopy to sensitively and directly quantify the SPION-specific iron content. We could show that SPION concentration depends on incubation time, nanoparticle concentration and location. This model system allows for further investigations on particle uptake and transport at cellular barriers with regard to parameters including particles’ shape, material, size, and coating.

  13. ROLE OF ATP IN REGULATING RENAL MICROVASCULAR FUNCTION AND IN HYPERTENSION

    PubMed Central

    Guan, Zhengrong; Inscho, Edward W.

    2011-01-01

    Adenosine triphosphate (ATP) is an essential energy substrate for cellular metabolism but it can also influence many biological processes when released into the extracellular milieu. Research has established that extracellular ATP acts as an autocrine/paracrine factor that regulates many physiological functions. Alternatively, excessive extracellular ATP levels contribute to pathophysiological processes such as inflammation, cell proliferation and apoptosis, and atherosclerosis. Renal P2 receptors are widely distributed throughout glomeruli, vasculature and tubular segments, and participate in controlling renal vascular resistance, mediating renal autoregulation, and regulating tubular transport function. This review will focus on the role of ATP-P2 receptor signaling in regulating renal microvascular function and autoregulation, recent advances on the role of ATP-P2 signaling in hypertension-associated renal vascular injury, and emerging new directions. PMID:21768526

  14. Class IIA ring avulsion injuries: an absolute indication for microvascular repair.

    PubMed

    Nissenbaum, M

    1984-11-01

    The class II ring avulsion category, includes those patients in whom only digital arteries are damaged but all other structures are intact and functional (here labeled class IIA). Current literature suggests this is a rare lesion. Seven patients with this specific injury in whom the affected digits were nonviable are reported. Four of the seven were misdiagnosed on initial emergency room evaluation. Two did not seek additional medical attention and the condition progressed to necrosis and amputation. The other two, who sought additional treatment because of progressive ischemia, and three additional patients who were correctly diagnosed on initial examination underwent simple digital arterial repair. All digits operated on survived and demonstrated near normal function. Since failure to operate results in digital loss, this is an absolute indication for microvascular repair.

  15. Microvascular permeability changes might explain cardiac tamponade after alcohol septal ablation for hypertrophic cardiomyopathy.

    PubMed

    Hsu, Jen-Te; Hsiao, Ju-Feng; Chang, Jung-Jung; Chung, Chang-Min; Chang, Shih-Tai; Pan, Kuo-Li

    2014-04-01

    Various sequelae of alcohol septal ablation for hypertrophic obstructive cardiomyopathy have been reported. Of note, some cases of cardiac tamponade after alcohol septal ablation cannot be well explained. We describe the case of a 78-year-old woman with hypertrophic obstructive cardiomyopathy in whom cardiac tamponade developed one hour after alcohol septal ablation, probably unrelated to mechanical trauma. At that time, we noted a substantial difference in the red blood cell-to-white blood cell ratio between the pericardial effusion (1,957.4) and the peripheral blood (728.3). In addition to presenting the patient's case, we speculate that a possible mechanism for acute tamponade--alcohol-induced changes in microvascular permeability--is a reasonable explanation for cases of alcohol septal ablation that are complicated by otherwise-unexplainable massive pericardial effusions. PMID:24808788

  16. Coronary Microvascular Function and Beyond: The Crosstalk between Hormones, Cytokines, and Neurotransmitters

    PubMed Central

    Dal Lin, Carlo; Tona, Francesco

    2015-01-01

    Beyond its hemodynamic function, the heart also acts as a neuroendocrine and immunoregulatory organ. A dynamic communication between the heart and other organs takes place constantly to maintain cardiovascular homeostasis. The current understanding highlights the importance of the endocrine, immune, and nervous factors to fine-tune the crosstalk of the cardiovascular system with the entire body. Once disrupted, this complex interorgan communication may promote the onset and the progression of cardiovascular diseases. Thus, expanding our knowledge on how these factors influence the cardiovascular system can lead to novel therapeutic strategies to improve patient care. In the present paper, we review novel concepts on the role of endocrine, immune, and nervous factors in the modulation of microvascular coronary function. PMID:26124827

  17. Microvascular Staged Phalloplasty Preserving Original Glans in a Severe Hypospadias: A Case Report

    PubMed Central

    Cavadas, Pedro C.; Rubi, Carlos G.

    2015-01-01

    Summary: Penile reconstruction is usually performed in patients with gender dysphoria; with penile loss because of trauma, infection, and tumors; and with congenital deformities like severe hypospadias, in which standard techniques do not achieve a good result. Hypospadias are one of the most common inherent genital anomalies in boys. Many surgical procedures have been published for total phallic reconstruction aiming at a functionally and aesthetically pleasing. We present a case of reconstruction of the penis in a severe hypospadias in a 40-year-old man by transferring the original glans to the forearm flap and a stiffening procedure with an osteocutaneous fibular flap 3 months after first surgery. Three months postoperatively, the final result was an acceptable sexual intercourse, normal voiding, and quite normal appearance. Microvascular staged phalloplasty preserving original glans in a severe hypospadia could be considered a surgical option for micropenis. Technical difficulties and microsurgical advanced skills are the main drawback of this approach. PMID:26894013

  18. Coronary Microvascular Function and Beyond: The Crosstalk between Hormones, Cytokines, and Neurotransmitters.

    PubMed

    Dal Lin, Carlo; Tona, Francesco; Osto, Elena

    2015-01-01

    Beyond its hemodynamic function, the heart also acts as a neuroendocrine and immunoregulatory organ. A dynamic communication between the heart and other organs takes place constantly to maintain cardiovascular homeostasis. The current understanding highlights the importance of the endocrine, immune, and nervous factors to fine-tune the crosstalk of the cardiovascular system with the entire body. Once disrupted, this complex interorgan communication may promote the onset and the progression of cardiovascular diseases. Thus, expanding our knowledge on how these factors influence the cardiovascular system can lead to novel therapeutic strategies to improve patient care. In the present paper, we review novel concepts on the role of endocrine, immune, and nervous factors in the modulation of microvascular coronary function.

  19. Microvascular dysfunction and efficacy of PDE5 inhibitors in BPH-LUTS.

    PubMed

    Cellek, Selim; Cameron, Norman E; Cotter, Mary A; Fry, Christopher H; Ilo, Dapo

    2014-04-01

    Benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS) and erectile dysfunction commonly coexist, and both respond to phosphodiesterase (PDE) 5 inhibitors, suggesting a shared pathophysiological mechanism. We propose that both BPH-LUTS and erectile dysfunction are caused by microvascular dysfunction within the pelvic organs, and we present an overview of preclinical and clinical studies supporting the hypothesis that, within both the penis and the lower urinary tract, a combination of endothelial and neural dysfunction leads to a vicious cycle of hypoxia, vasoconstriction, altered smooth muscle contractility, and degeneration of autonomic neurons and ganglia. This hypothesis explains much of the preclinical and clinical research relating to these two conditions, and provides a rationale for further investigation into the effects of PDE5 inhibitors on the pathophysiology and symptoms of BPH-LUTS. PMID:24619381

  20. Magnetic particle spectroscopy allows precise quantification of nanoparticles after passage through human brain microvascular endothelial cells.

    PubMed

    Gräfe, C; Slabu, I; Wiekhorst, F; Bergemann, C; von Eggeling, F; Hochhaus, A; Trahms, L; Clement, J H

    2016-06-01

    Crossing the blood-brain barrier is an urgent requirement for the treatment of brain disorders. Superparamagnetic iron oxide nanoparticles (SPIONs) are a promising tool as carriers for therapeutics because of their physical properties, biocompatibility, and their biodegradability. In order to investigate the interaction of nanoparticles with endothelial cell layers in detail, in vitro systems are of great importance. Human brain microvascular endothelial cells are a well-suited blood-brain barrier model. Apart from generating optimal conditions for the barrier-forming cell units, the accurate detection and quantification of SPIONs is a major challenge. For that purpose we use magnetic particle spectroscopy to sensitively and directly quantify the SPION-specific iron content. We could show that SPION concentration depends on incubation time, nanoparticle concentration and location. This model system allows for further investigations on particle uptake and transport at cellular barriers with regard to parameters including particles' shape, material, size, and coating. PMID:27163489

  1. Repeated self-healing of microvascular carbon fibre reinforced polymer composites

    NASA Astrophysics Data System (ADS)

    Coope, T. S.; Wass, D. F.; Trask, R. S.; Bond, I. P.

    2014-11-01

    A self-healing, high performance, carbon fibre reinforced polymer (CFRP) composite is demonstrated by embedding a Lewis-acid catalytic curing agent within a laminate, manufactured using out of autoclave (OOA) composite manufacturing methods. Two configurations of healing agent delivery, pre-mixed and autonomous mixing, are investigated via injection of a healing agent through bio-inspired microvascular channels exposed on Mode I fractured crack planes. Healing is effected when an epoxy resin-solvent healing agent mixture reaches the boundary of embedded solid-state scandium(III) triflate (Sc(OTf)3) catalyst, located on the crack plane, to initiate the ring-opening polymerisation (ROP) of epoxides. Tailored self-healing agents confer high healing efficiency values after multiple healing cycles (69-108%) to successfully mitigate against crack propagation within the composite microstructure.

  2. Microvascular Permeability Changes Might Explain Cardiac Tamponade after Alcohol Septal Ablation for Hypertrophic Cardiomyopathy

    PubMed Central

    Hsu, Jen-Te; Hsiao, Ju-Feng; Chang, Jung-Jung; Chung, Chang-Min; Chang, Shih-Tai; Pan, Kuo-Li

    2014-01-01

    Various sequelae of alcohol septal ablation for hypertrophic obstructive cardiomyopathy have been reported. Of note, some cases of cardiac tamponade after alcohol septal ablation cannot be well explained. We describe the case of a 78-year-old woman with hypertrophic obstructive cardiomyopathy in whom cardiac tamponade developed one hour after alcohol septal ablation, probably unrelated to mechanical trauma. At that time, we noted a substantial difference in the red blood cell-to-white blood cell ratio between the pericardial effusion (1,957.4) and the peripheral blood (728.3). In addition to presenting the patient's case, we speculate that a possible mechanism for acute tamponade—alcohol-induced changes in microvascular permeability—is a reasonable explanation for cases of alcohol septal ablation that are complicated by otherwise-unexplainable massive pericardial effusions. PMID:24808788

  3. Ranolazine: Drug overview and possible role in primary microvascular angina management.

    PubMed

    Cattaneo, Mattia; Porretta, Alessandra Pia; Gallino, Augusto

    2015-02-15

    Ranolazine is a novel well-tolerated anti-ischemic drug, which selectively inhibits late sodium current and exerts metabolic properties without any hemodynamic effect. Ranolazine has been approved as a second-line medical treatment for symptomatic stable coronary artery disease. Primary microvascular angina (MVA) is suspected when angina symptoms occur in patients with demonstrated myocardial ischemia, absence of myocardial disease and normal coronary artery angiography. Recent clinical data suggest that MVA represents a complex entity, which has been increasingly recognized as a significant cause of morbidity. High variability and low response to traditional anti-anginal treatment characterize primary MVA. Despite the fact that clinical and preclinical evidence provides information regarding ranolazine usefulness in primary MVA management, only three recent small randomized trials have investigated this issue. By selecting peer-reviewed literature in Pubmed and Cochrane Library, this review provides an overview on ranolazine pharmacology and efficacy, focusing on recent evidence suggesting its usefulness in management of primary MVA.

  4. Impact of long-term exposure to cigarette smoking on skin microvascular function.

    PubMed

    Rossi, M; Pistelli, F; Pesce, M; Aquilini, F; Franzoni, F; Santoro, G; Carrozzi, L

    2014-05-01

    In order to evaluate the impact of cigarettes smoking and smokers' clinical characteristics on skin microvascular function, we measured the skin forearm blood flux, basally and during post-occlusive reactive hyperaemia, in 100 current smokers (mean age 51±11 years; range: 18 to 86 years) and in 66 healthy never-smokers matched for age and sex, by using laser Doppler fluximetry (LDF). Basal and post-ischemic LDF tracings were analyzed in the frequency domain within 0.009-0.02 Hz, 0.021-0.06 Hz and 0.061-0.2 Hz ranges, related to endothelial-dependent, sympathetic-dependent and myogenic-dependent vasomotion, respectively, using an adapted version of the Fourier analysis. The post-ischemic percentage change from baseline of the area under the LDF curve (AUC%) was significantly lower in smokers than in never-smokers [162.5% (139.3-183.0) vs 190.1% (156.3-216.8); p=0.00016]. Compared to controls, smokers also showed a reduced basal power spectral density (PSD) in the myogenic-dependent vasomotion (p=0.0034) and a reduced post-ischemic percentage increase in PSD of the endothelial-dependent vasomotion (p=0.0010) and sympathetic-dependent vasomotion (p=0.0016). An inverse relationship was observed in smokers between AUC% and smoking exposure duration (r=0.23, p=0.018), pack-years (r=0.33, p=0.0007), age (r=0.26, p=0.008) and body mass index (r=0.21, p=0.037). In the multiple linear regression model, pack-years was the only variable independently associated with AUC% (r=0.21, p=0.03). This study confirms that smoking is associated with cutaneous microvascular dysfunction and shows that the severity of this impairment is independently related to the duration and intensity of the exposure to smoking.

  5. GLP-1 increases microvascular recruitment but not glucose uptake in human and rat skeletal muscle

    PubMed Central

    Sjøberg, Kim A.; Holst, Jens J.; Rattigan, Stephen; Richter, Erik A.

    2013-01-01

    The insulinotropic gut hormone glucagon-like peptide-1 (GLP-1) has been proposed to have effects on vascular function and glucose disposal. However, whether GLP-1 is able to increase microvascular recruitment (MVR) in humans has not been investigated. GLP-1 was infused in the femoral artery in overnight-fasted, healthy young men. Microvascular recruitment was measured with real-time contrast-enhanced ultrasound and leg glucose uptake by the leg balance technique with and without inhibition of the insulinotropic response of GLP-1 by coinfusion of octreotide. As a positive control, MVR and leg glucose uptake were measured during a hyperinsulinemic-euglycemic clamp. Infusion of GLP-1 caused a rapid increase (P < 0.05) of 20 ± 12% (mean ± SE) in MVR in the vastus lateralis muscle of the infused leg after 5 min, and MVR further increased to 60 ± 8% above preinfusion levels by 60 min infusion. The effect was slightly slower but similar in magnitude in the noninfused contralateral leg, in which GLP-1 concentration was within the physiological range. Octreotide infusion did not prevent the GLP-1-induced increase in MVR. GLP-1 infusion did not increase leg glucose uptake with or without octreotide coinfusion. GLP-1 infusion in rats increased MVR by 28% (P < 0.05) but did not increase muscle glucose uptake. During the hyperinsulinemic clamp, MVR increased ∼40%, and leg glucose uptake increased 35-fold. It is concluded that GLP-1 in physiological concentrations causes a rapid insulin-independent increase in muscle MVR but does not affect muscle glucose uptake. PMID:24302010

  6. Preparation of a designed poly(trimethylene carbonate) microvascular network by stereolithography.

    PubMed

    Schüller-Ravoo, Sigrid; Zant, Erwin; Feijen, Jan; Grijpma, Dirk W

    2014-12-01

    Designed flexible and elastic network structures are prepared by stereolithography using a photo-crosslinkable resin based on a poly(trimethylene carbonate) (PTMC) macromer with a molecular weight of 3150 g/mol. Physical properties and the compatibility with human umbilical vein endothelial cells (HUVECs) are evaluated. The hydrophobic networks are found to be flexible and elastic, with an E modulus of 7.9 ± 0.1 MPa, a tensile strength of 3.5 ± 0.1 MPa and an elongation at break of 76.7 ± 0.7%. HUVECs attach and proliferate well on the surfaces of the built structures. A three-dimensional microvascular network is designed to serve as a perfusable scaffold for tissue engineering. In the design, 5 generations of open channels each branch into 4 smaller channels yielding a microvascular region with a high density of capillaries. The overall cross-sectional area through which medium or blood can be perfused remains constant. These structures would ensure efficient nourishment of cells in a large volume of tissue. Built by stereolithography using the PTMC resin, the smallest channels of these structures have square cross-sectional areas, with inner widths of approximately 224 μm and wall thicknesses of approximately 152 μm. The channels are open, allowing water to perfuse the scaffold at 0.279 ± 0.006 mL/s at 80 mmHg and 0.335 ± 0.009 mL/s at 120 mmHg.

  7. Diminished Alveolar Microvascular Reserves in Type 2 Diabetes Reflect Systemic Microangiopathy

    PubMed Central

    Chance, William W.; Rhee, Chanhaeng; Yilmaz, Cuneyt; Dane, D. Merrill; Pruneda, M. Lourdes; Raskin, Philip; Hsia, Connie C.W.

    2008-01-01

    OBJECTIVE—Alveolar microvascular function is moderately impaired in type 1 diabetes, as manifested by restriction of lung volume and diffusing capacity (DLCO). We examined whether similar impairment develops in type 2 diabetes and defined the physiologic sources of impairment as well as the relationships to glycemia and systemic microangiopathy. RESEARCH DESIGN AND METHODS—A cross-sectional study was conducted at a university-affiliated diabetes treatment center and outpatient diabetes clinic, involving 69 nonsmoking type 2 diabetic patients without overt cardiopulmonary disease. Lung volume, pulmonary blood flow (Q̇), DLCO, membrane diffusing capacity (measured from nitric oxide uptake [DLNO]), and pulmonary capillary blood volume (VC) were determined at rest and exercise for comparison with those in 45 healthy nonsmokers as well as with normal reference values. RESULTS—In type 2 diabetic patients, peak levels of oxygen uptake, Q̇ and DLCO, DLNO, and VC at exercise were 10–25% lower compared with those in control subjects. In nonobese patients (BMI <30 kg/m2), reductions in DLCO, DLNO, and VC were fully explained by the lower lung volume and peak Q̇, but these factors did not fully explain the impairment in obese patients (BMI >30 kg/m2). The slope of the increase in VC with respect to Q̇ was reduced ∼20% in patients regardless of BMI, consistent with impaired alveolar-capillary recruitment. Functional impairment was directly related to A1C level, retinopathy, neuropathy, and microalbuminuria in a sex-specific manner. CONCLUSIONS—Alveolar microvascular reserves are reduced in type 2 diabetes, reflecting restriction of lung volume, alveolar perfusion, and capillary recruitment. This reduction correlates with glycemic control and extrapulmonary microangiopathy and is aggravated by obesity. PMID:18492945

  8. Microvascular pathology and morphometrics of sporadic and hereditary small vessel diseases of the brain.

    PubMed

    Craggs, Lucinda J L; Yamamoto, Yumi; Deramecourt, Vincent; Kalaria, Raj N

    2014-09-01

    Small vessel diseases (SVDs) of the brain are likely to become increasingly common in tandem with the rise in the aging population. In recent years, neuroimaging and pathological studies have informed on the pathogenesis of sporadic SVD and several single gene (monogenic) disorders predisposing to subcortical strokes and diffuse white matter disease. However, one of the limitations toward studying SVD lies in the lack of consistent assessment criteria and lesion burden for both clinical and pathological measures. Arteriolosclerosis and diffuse white matter changes are the hallmark features of both sporadic and hereditary SVDs. The pathogenesis of the arteriopathy is the key to understanding the differential progression of disease in various SVDs. Remarkably, quantification of microvascular abnormalities in sporadic and hereditary SVDs has shown that qualitatively the processes involved in arteriolar degeneration are largely similar in sporadic SVD compared with hereditary disorders such as cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Important significant regional differences in lesion location within the brain may enable one to distinguish SVDs, where frontal lobe involvement appears consistently with almost every SVD, but others bear specific pathologies in other lobes, such as the temporal pole in CADASIL and the pons in pontine autosomal dominant microangiopathy and leukoencephalopathy or PADMAL. Additionally, degenerative changes in the vascular smooth muscle cells, the cerebral endothelium and the basal lamina are often rapid and more aggressive in genetic disorders. Further quantification of other microvascular elements and even neuronal cells is needed to fully characterize SVD pathogenesis and to differentiate the usefulness of vascular interventions and treatments on the resulting pathology.

  9. Pericyte abundance affects sucrose permeability in cultures of rat brain microvascular endothelial cells.

    PubMed

    Parkinson, Fiona E; Hacking, Cindy

    2005-07-01

    The blood-brain barrier is a physical and metabolic barrier that restricts diffusion of blood-borne substances into brain. In vitro models of the blood-brain barrier are used to characterize this structure, examine mechanisms of damage and repair and measure permeability of test substances. The core component of in vitro models of the blood-brain barrier is brain microvascular endothelial cells. We cultured rat brain microvascular endothelial cells (RBMEC) from isolated rat cortex microvessels. After 2-14 days in vitro (DIV), immunohistochemistry of these cells showed strong labeling for zona occludens 1 (ZO-1), a tight junction protein expressed in endothelial cells. Pericytes were also present in these cultures, as determined by expression of alpha-actin. The present study was performed to test different cell isolation methods and to compare the resulting cell cultures for abundance of pericytes and for blood-brain barrier function, as assessed by 14C-sucrose flux. Two purification strategies were used. First, microvessels were preabsorbed onto uncoated plastic for 4 h, then unattached microvessels were transferred to coated culture ware. Second, microvessels were incubated with an antibody to platelet-endothelial cell adhesion molecule 1 (PECAM-1; CD31) precoupled to magnetic beads, and a magnetic separation procedure was performed. Our results indicate that immunopurification, but not preadsorption, was an effective method to purify microvessels and reduce pericyte abundance in the resulting cultures. This purification significantly reduced 14C-sucrose fluxes across cell monolayers. These data indicate that pericytes can interfere with the development of blood-brain barrier properties in in vitro models that utilize primary cultures of RBMECs.

  10. Microvascular reactivity in normotensive subjects with a familial predisposition to hypertension.

    PubMed

    Maver, J; Strucl, M

    2000-11-01

    Using the laser-Doppler method we measured blood flow on the nailfold skin to compare the reactivity of cutaneous microcirculation in three groups of normotensive subjects: 11 subjects with a familial predisposition to hypertension without a previous record of high blood pressure, 6 predisposed subjects with a previous record of high blood pressure, and 13 subjects with no predisposition to hypertension. The flow was measured after direct and indirect skin cooling and heating and during postocclusive reactive hyperemia (PRH) after a 10-min occlusion of digital arteries. The frequency of flow oscillations in the second part of the PRH was established. Heart rate spectral analysis was performed based on the monitoring of the peripheral pulse frequency by means of the finapres device. In comparison to the other two groups of subjects, the group with a predisposition and a previous record of high blood pressure displayed a larger surface area in the low frequency band (0.05 to 0.15 Hz) of the heart rate variability power spectrum (the Bonferroni test, P < 0.05). As compared to subjects without predisposition, both groups of predisposed subjects exhibited higher frequency of flow oscillations in the second part of the PRH (the Bonferroni test, P < 0.05). Our results indicate that there could be a change in cutaneous microvascular reactivity of local (most probably myogenic) origin even in normotensive subjects with a predisposition to hypertension, whereas in normotensives with a predisposition and a previous record of high blood pressure there could be also a different cutaneous microvascular reactivity of central (nonvascular) origin. PMID:11078640

  11. Phthalimide neovascular factor 1 (PNF1) modulates MT1-MMP activity in human microvascular endothelial cells.

    PubMed

    Wieghaus, Kristen A; Gianchandani, Erwin P; Neal, Rebekah A; Paige, Mikell A; Brown, Milton L; Papin, Jason A; Botchwey, Edward A

    2009-07-01

    We are creating synthetic pharmaceuticals with angiogenic activity and potential to promote vascular invasion. We previously demonstrated that one of these molecules, phthalimide neovascular factor 1 (PNF1), significantly expands microvascular networks in vivo following sustained release from poly(lactic-co-glycolic acid) (PLAGA) films. In addition, to probe PNF1 mode of action, we recently applied a novel pathway-based compendium analysis to a multi-timepoint, controlled microarray data set of PNF1-treated (vs. control) human microvascular endothelial cells (HMVECs), and we identified induction of tumor necrosis factor-alpha (TNF-alpha) and, subsequently, transforming growth factor-beta (TGF-beta) signaling networks by PNF1. Here we validate this microarray data set with quantitative real-time polymerase chain reaction (RT-PCR) analysis. Subsequently, we probe this data set and identify three specific TGF-beta-induced genes with regulation by PNF1 conserved over multiple timepoints-amyloid beta (A4) precursor protein (APP), early growth response 1 (EGR-1), and matrix metalloproteinase 14 (MMP14 or MT1-MMP)-that are also implicated in angiogenesis. We further focus on MMP14 given its unique role in angiogenesis, and we validate MT1-MMP modulation by PNF1 with an in vitro fluorescence assay that demonstrates the direct effects that PNF1 exerts on functional metalloproteinase activity. We also utilize endothelial cord formation in collagen gels to show that PNF1-induced stimulation of endothelial cord network formation in vitro is in some way MT1-MMP-dependent. Ultimately, this new network analysis of our transcriptional footprint characterizing PNF1 activity 1-48 h post-supplementation in HMVECs coupled with corresponding validating experiments suggests a key set of a few specific targets that are involved in PNF1 mode of action and important for successful promotion of the neovascularization that we have observed by the drug in vivo. PMID:19326468

  12. Platelets, acting in part via P-selectin, mediate cytomegalovirus-induced microvascular dysfunction.

    PubMed

    Khoretonenko, Mikhail V; Brunson, Jerry L; Senchenkov, Evgeny; Leskov, Igor L; Marks, Christian R; Stokes, Karen Y

    2014-12-15

    Cytomegalovirus (CMV) infects a majority of the population worldwide. It has been implicated in cardiovascular disease, induces microvascular dysfunction, and synergizes with hypercholesterolemia to promote leukocyte and platelet recruitment in venules. Although platelets and platelet-associated P-selectin contribute to cardiovascular disease inflammation, their role in CMV-induced vascular responses is unknown. We assessed the role of platelets in CMV-induced microvascular dysfunction by depleting platelets and developing bone marrow chimeric mice deficient in platelet P-selectin. Wild-type and chimeric mice received mock or murine (m)CMV intraperitoneally. Five weeks later, some mice were switched to a high-cholesterol diet (HC) to investigate the synergism between mCMV and HC. Arteriolar vasodilation and recruitment of leukocytes and donor platelets in venules were measured at 11wk. mCMV with or without HC caused significant endothelial dysfunction in arterioles. Platelet depletion restored normal vasodilation in mCMV-HC but not mCMV-ND mice, whereas protection was seen in both groups for platelet P-selectin chimeras. Only mCMV + HC elevated leukocyte and platelet recruitment in venules. Leukocyte adhesion was reduced to mock levels by acute platelet depletion but was only partially decreased in platelet P-selectin chimeras. Platelets from mCMV-HC mice and, to a lesser extent, mCMV-ND but not mock-HC mice showed significant adhesion in mCMV-HC recipients. Our findings implicate a role for platelets, acting through P-selectin, in CMV-induced arteriolar dysfunction and suggest that the addition of HC leads to a platelet-dependent, inflammatory infiltrate that is only partly platelet P-selectin dependent. CMV appeared to have a stronger activating influence than HC on platelets and may represent an additional therapeutic target in vulnerable patients.

  13. Deep-brain stimulation associates with improved microvascular integrity in the subthalamic nucleus in Parkinson's disease.

    PubMed

    Pienaar, Ilse S; Lee, Cecilia Heyne; Elson, Joanna L; McGuinness, Louisa; Gentleman, Stephen M; Kalaria, Raj N; Dexter, David T

    2015-02-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an accepted treatment for motor symptoms in a subset of Parkinson's disease (PD) patients. The mechanisms why DBS is effective are incompletely understood, but previous studies show that DBS targeted in brain structures other than the STN may modify the microvasculature. However, this has not been studied in PD subjects who have received STN-DBS. Here we investigated the extent and nature of microvascular changes in post-mortem STN samples from STN-DBS PD patients, compared to aged controls and PD patients who had not been treated with STN-DBS. We used immunohistochemical and immunofluorescent methods to assess serial STN-containing brain sections from PD and STN-DBS PD cases, compared to similar age controls using specific antibodies to detect capillaries, an adherens junction and tight junction-associated proteins as well as activated microglia. Cellular features in stained sections were quantified by confocal fluorescence microscopy and stereological methods in conjunction with in vitro imaging tools. We found significant upregulation of microvessel endothelial cell thickness, length and density but lowered activated microglia density and striking upregulation of all analysed adherens junction and tight junction-associated proteins in STN-DBS PD patients compared to non-DBS PD patients and controls. Moreover, in STN-DBS PD samples, expression of an angiogenic factor, vascular endothelial growth factor (VEGF), was significantly upregulated compared to the other groups. Our findings suggest that overexpressed VEGF and downregulation of inflammatory processes may be critical mechanisms underlying the DBS-induced microvascular changes. PMID:25533682

  14. Intermedin/adrenomedullin-2 is a hypoxia-induced endothelial peptide that stabilizes pulmonary microvascular permeability

    PubMed Central

    Aslam, Muhammad; Paddenberg, Renate; Quanz, Karin; Chang, Chia L.; Park, Jae-Il; Gries, Barbara; Rafiq, Amir; Faulhammer, Petra; Goldenberg, Anna; Papadakis, Tamara; Noll, Thomas; Hsu, Sheau Y. T.; Weissmann, Norbert; Kummer, Wolfgang

    2009-01-01

    Accumulating evidence suggests a pivotal role of the calcitonin receptor-like receptor (CRLR) signaling pathway in preventing damage of the lung by stabilizing pulmonary barrier function. Intermedin (IMD), also termed adrenomedullin-2, is the most recently identified peptide targeting this receptor. Here we investigated the effect of hypoxia on the expression of IMD in the murine lung and cultured murine pulmonary microvascular endothelial cells (PMEC) as well as the role of IMD in regulating vascular permeability. Monoclonal IMD antibodies were generated, and transcript levels were assayed by quantitative RT-PCR. The promoter region of IMD gene was analyzed, and the effect of hypoxia-inducible factor (HIF)-1α on IMD expression was investigated in HEK293T cells. Isolated murine lungs and a human lung microvascular endothelial cell monolayer model were used to study the effect of IMD on vascular permeability. IMD was identified as a pulmonary endothelial peptide by immunohistochemistry and RT-PCR. Hypoxia caused an upregulation of IMD mRNA in the murine lung and PMEC. As shown by these results, HIF-1α enhances IMD promoter activity. Our functional studies showed that IMD abolished the increase in pressure-induced endothelial permeability. Moreover, IMD decreased basal and thrombin-induced hyperpermeability of an endothelial cell monolayer in a receptor-dependent manner and activated PKA in these cells. In conclusion, IMD is a novel hypoxia-induced gene and a potential interventional agent for the improvement of endothelial barrier function in systemic inflammatory responses and hypoxia-induced vascular leakage. PMID:19684198

  15. Induced hypothermia during resuscitation from hemorrhagic shock attenuates microvascular inflammation in the rat mesenteric microcirculation.

    PubMed

    Coyan, Garrett N; Moncure, Michael; Thomas, James H; Wood, John G

    2014-12-01

    Microvascular inflammation occurs during resuscitation following hemorrhagic shock, causing multiple organ dysfunction and mortality. Preclinical evidence suggests that hypothermia may have some benefit in selected patients by decreasing this inflammation, but this effect has not been extensively studied. Intravital microscopy was used to visualize mesenteric venules of anesthetized rats in real time to evaluate leukocyte adherence and mast cell degranulation. Animals were randomly allocated to normotensive or hypotensive groups and further subdivided into hypothermic and normothermic resuscitation (n = 6 per group). Animals in the shock groups underwent mean arterial blood pressure reduction to 40 to 45 mmHg for 1 h via blood withdrawal. During the first 2 h following resuscitation by infusion of shed blood plus double that volume of normal saline, rectal temperature of the hypothermic groups was maintained at 32°C to 34°C, whereas the normothermic groups were maintained between 36°C to 38°C. The hypothermic group was then rewarmed for the final 2 h of resuscitation. Leukocyte adherence was significantly lower after 2 h of hypothermic resuscitation compared with normothermic resuscitation: (2.8 ± 0.8 vs. 8.3 ± 1.3 adherent leukocytes, P = 0.004). Following rewarming, leukocyte adherence remained significantly different between hypothermic and normothermic shock groups: (4.7 ± 1.2 vs. 9.5 ± 1.6 adherent leukocytes, P = 0.038). Mast cell degranulation index (MDI) was significantly decreased in the hypothermic (1.02 ± 0.04 MDI) versus normothermic (1.22 ± 0.07 MDI) shock groups (P = 0.038) after the experiment. Induced hypothermia during resuscitation following hemorrhagic shock attenuates microvascular inflammation in rat mesentery. Furthermore, this decrease in inflammation is carried over after rewarming takes place.

  16. High Intracranial Pressure Effects on Cerebral Cortical Microvascular Flow in Rats

    PubMed Central

    Bush, Rachel C.; Müller, Wolfgang S.; Nemoto, Edwin M.

    2011-01-01

    Abstract To manage patients with high intracranial pressure (ICP), clinicians need to know the critical cerebral perfusion pressure (CPP) required to maintain cerebral blood flow (CBF). Historically, the critical CPP obtained by decreasing mean arterial pressure (MAP) to lower CPP was 60 mm Hg, which fell to 30 mm Hg when CPP was reduced by increasing ICP. We examined whether this decrease in critical CPP was due to a pathological shift from capillary (CAP) to high-velocity microvessel flow or thoroughfare channel (TFC) shunt flow. Cortical microvessel red blood cell velocity and NADH fluorescence were measured by in vivo two-photon laser scanning microscopy in rats at CPP of 70, 50, and 30 mm Hg by increasing ICP or decreasing MAP. Water content was measured by wet/dry weight, and cortical perfusion by laser Doppler flux. Reduction of CPP by raising ICP increased TFC shunt flow from 30.4±2.3% to 51.2±5.2% (mean±SEM, p<0.001), NADH increased by 20.3±6.8% and 58.1±8.2% (p<0.01), and brain water content from 72.9±0.47% to 77.8±2.42% (p<0.01). Decreasing CPP by MAP decreased TFC shunt flow with a smaller rise in NADH and no edema. Doppler flux decreased less with increasing ICP than decreasing MAP. The decrease seen in the critical CPP with increased ICP is likely due to a redistribution of microvascular flow from capillary to microvascular shunt flow or TFC shunt flow, resulting in a pathologically elevated CBF associated with tissue hypoxia and brain edema, characteristic of non-nutritive shunt flow. PMID:21395499

  17. A dynamic opto-physiological model to effectively interpret retinal microvascular circulation

    NASA Astrophysics Data System (ADS)

    Hassan, Harnani; Hu, Sijung; Dwyer, Vincent M.

    2015-03-01

    The demand of non-invasive ocular screening is rapidly growing due to an increase of age related eye diseases worldwide. An indeed in-depth understanding of optical properties is required to elucidate nature of retinal tissue. The research aims to investigate an effective biomedical engineering approach to allow process region of interests (ROIs) in eyes to reveal physiological status. A dynamic opto-physiological model (DOPM) representing retinal microvascular circulation underlying a diffusion approximation to solve radiative transport theorem (RTT) has being developed to interpret patho-physiological phenomena. DOPM is being applied in imaging photoplethysmography (iPPG) to extract PPG signals from a series of 2D matrix images to access blood perfusion and oxygen saturation distributions. A variation of microvascular circulation could be mapped for an effectively diagnostic screening. The work presents mathematical modelling based ten layers of ocular tissue tested with four set of controlled parameters demontrated detection ratio between normal tissue damage or abnormal tissue and significant change of AC signal amplitude in these tissues. The result shows signicant change of AC signal amplitude in abnormal tissue. The preliminary results show extractable PPG signals from eye fundus video; experimented at five ROIs: whole fundus, optical disk, main vein vessel, lesion area and affected area. The outcome shows optical disk region gave a better performance compared to whole fundus region and main vein vessel. The robustness, miniaturization and artefact reduction capability of DOPM to discriminate oxygenation levels in retina could offer a new insight to access retinal patho-physiological status.

  18. Acute Cutaneous Microvascular Flow Responses to Whole-Body Tilting in Humans

    NASA Technical Reports Server (NTRS)

    Breit, Gregory A.; Watenpaugh, Donald E.; Ballard, Richard E.; Hargens, Alan R.

    1993-01-01

    The transition from upright to head-down tilt (HDT) posture in humans increases blood pressure superior to the heart and decreases pressure inferior to the heart. Consequently, above heart level, myogenic arteriolar tone probably increases with HDT, in opposition to the withdrawal of baroreceptor-mediated sympathetic tone. We hypothesized that due to antagonism between central and local controls, the response of the facial cutaneous micro- circulation to acute postural change will be weaker than that in the leg, where these two mechanisms reinforce each other. Cutaneous microvascular flow was measured by laser Doppler flowmetry simultaneously at the shin and the neck of 7 male and 3 female subjects. Subjects underwent a stepwise tilt protocol from standing control to 54 deg head-up tilt (HUT), 30 deg, 12 deg, 0 deg, -6 deg (HDT), -12 deg, -6 deg, 0 deg, 12 deg, 30 deg, 54 deg, and standing, for 30-sec periods with 10-sec transitions between postures. Flows at the shin and the neck increased significantly (P < 0.05) from standing baseline to 12 deg HUT (252 +/- 55 and 126 +/- 9% (bar-X +/- SE) of baseline, respectively). From 12 deg to -12 deg tilt, flows continued to increase at the shin (509 +/- 71% of baseline) but decreased at the neck to baseline levels (100 +/- 15% of baseline). Cutaneous microvascular flow recovered at both sites during the return to standing posture with significant hysteresis. Flow increases from standing to near-supine posture are attributed at both sites to baroreceptor-mediated vasodilation. The great dissimilarity in flow response magnitudes at the two measurement sites may be indicative of central/local regulatory antagonism above heart level and reinforcement below heart level.

  19. Acute Cutaneous Microvascular Flow Responses to Whole-Body Tilting in Humans

    NASA Technical Reports Server (NTRS)

    Breit, Gregory A.; Watenpaugh, Donald E.; Ballard, Richard E.; Hargens, Alan R.

    1993-01-01

    The transition from upright to head-down tilt (HDT) posture in humans increases blood pressure superior to the heart and decreases pressure inferior to the heart. Consequently, above heart level, myogenic arteriolar tone probably increases with HDT, in opposition to the withdrawal of baroreceptor-mediated sympathetic tone. We hypothesized that due to antagonism between central and local controls, the response of the facial cutaneous microcirculation to acute postural change will be weaker than that in the leg, where these two mechanisms reinforce each other. Cutaneous microvascular flow was measured by laser Doppler flowmetry simultaneously at the shin and the neck of 7 male and 3 female subjects. Subjects underwent a stepwise tilt protocol from standing control to 54 deg head-up tilt (HUT), 30 deg, 12 deg, O deg, -6 deg (HDT), -12 deg, -6 deg, O deg, 12 deg, 30 deg, 54 deg, and standing, for 30-sec periods with 10-sec transitions between postures. Flows at the shin and the neck increased significantly (P less than 0.05) from standing baseline to 12 deg HUT (252 +/- 55 and 126 +/- 9% (bar X +/- SE) of baseline, respectively). From 12 deg to -12 deg tilt, flows continued to increase at the shin (509 +/- 71% of baseline) but decreased at the neck to baseline levels (100 +/- 15% of baseline). Cutaneous microvascular flow recovered at both sites during the return to standing posture with significant hysteresis. Flow increases from standing to near-supine posture are attributed at both sites to baroreceptor-mediated vasodilation. The great dissimilarity in flow response magnitudes at the two measurement sites may be indicative of central/local regulatory antagonism above heart level and reinforcement below heart level.

  20. Aging alters reactivity of microvascular resistance networks in mouse gluteus maximus muscle

    PubMed Central

    Sinkler, Shenghua Y.

    2014-01-01

    Aging occurs with enhanced sympathetic nerve activity and endothelial dysfunction; however, little is known of how successive branches of microvascular resistance networks are affected in vivo. We questioned whether vascular reactivity is altered differentially along resistance networks with advanced age. The left gluteus maximus muscle of anesthetized 4-mo-old and 24-mo-old male C57BL/6 mice (Young and Old, respectively) was exposed for intravital microscopy and superfused with physiological salt solution (3 ml/min; pH 7.4, 34°C). Spontaneous vasomotor tone increased progressively from proximal feed arteries (FA) and first-order (1A) arterioles through distal second-order (2A) and third-order (3A) arterioles and was ∼15% greater in 2A and 3A of Old versus Young. Vasoconstriction during elevated superfusion Po2 increased with branch order and to a greater extent in Young. Peak constrictions to phenylephrine [α1 adrenoreceptor (α1AR) agonist] were similar for FA and 1A of both ages and ∼20% greater for 2A and 3A of Young. Across arterioles (but not FA), constrictions to UK 14304 (α2AR agonist) were depressed ∼30% in Old versus Young. Thus advanced age attenuated vasoconstriction to O2 throughout networks while blunting vasoconstriction to α1AR and α2AR activation in arterioles. With ACh, endothelium-dependent dilation (EDD) was ∼20% greater in FA of Young yet was approximately twofold greater for 2A and 3A of Old. Sodium nitroprusside evoked maximal dilations similar to ACh. Thus, with advanced age, EDD was attenuated in FA while robust in distal arterioles having enhanced vasomotor tone. We conclude that advanced age differentially alters reactivity among branches of microvascular resistance networks. PMID:25015968

  1. Reduced toxicity polyester resins and microvascular pre-preg tapes for advanced composites manufacturing

    NASA Astrophysics Data System (ADS)

    Poillucci, Richard

    Advanced composites manufacturing broadly encapsulates topics ranging from matrix chemistries to automated machines that lay-up fiber-reinforced materials. Environmental regulations are stimulating research to reduce matrix resin formulation toxicity. At present, composites fabricated with polyester resins expose workers to the risk of contact with and inhalation of styrene monomer, which is a potential carcinogen, neurotoxin, and respiratory irritant. The first primary goal of this thesis is to reduce the toxicity associated with polyester resins by: (1) identification of potential monomers to replace styrene, (2) determination of monomer solubility within the polyester, and (3) investigation of approaches to rapidly screen a large resin composition parameter space. Monomers are identified based on their ability to react with polyester and their toxicity as determined by the Globally Harmonized System (GHS) and a green screen method. Solubilities were determined by the Hoftyzer -- Van Krevelen method, Hansen solubility parameter database, and experimental mixing of monomers. A combinatorial microfluidic mixing device is designed and tested to obtain distinct resin compositions from two input chemistries. The push for safer materials is complemented by a thrust for multifunctional composites. The second primary goal of this thesis is to design and implement the manufacture of sacrificial fiber materials suitable for use in automated fiber placement of microvascaular multifunctional composites. Two key advancements are required to achieve this goal: (1) development of a roll-to-roll method to place sacrificial fibers onto carbon fiber pre-preg tape; and (2) demonstration of feasible manufacture of microvascular carbon fiber plates with automated fiber placement. An automated method for placing sacrificial fibers onto carbon fiber tapes is designed and a prototype implemented. Carbon fiber tows with manual placement of sacrificial fibers is implemented within an

  2. Real-time 3D Fourier-domain optical coherence tomography guided microvascular anastomosis

    NASA Astrophysics Data System (ADS)

    Huang, Yong; Ibrahim, Zuhaib; Lee, W. P. A.; Brandacher, Gerald; Kang, Jin U.

    2013-03-01

    Vascular and microvascular anastomosis is considered to be the foundation of plastic and reconstructive surgery, hand surgery, transplant surgery, vascular surgery and cardiac surgery. In the last two decades innovative techniques, such as vascular coupling devices, thermo-reversible poloxamers and suture-less cuff have been introduced. Intra-operative surgical guidance using a surgical imaging modality that provides in-depth view and 3D imaging can improve outcome following both conventional and innovative anastomosis techniques. Optical coherence tomography (OCT) is a noninvasive high-resolution (micron level), high-speed, 3D imaging modality that has been adopted widely in biomedical and clinical applications. In this work we performed a proof-of-concept evaluation study of OCT as an assisted intraoperative and post-operative imaging modality for microvascular anastomosis of rodent femoral vessels. The OCT imaging modality provided lateral resolution of 12 μm and 3.0 μm axial resolution in air and 0.27 volume/s imaging speed, which could provide the surgeon with clearly visualized vessel lumen wall and suture needle position relative to the vessel during intraoperative imaging. Graphics processing unit (GPU) accelerated phase-resolved Doppler OCT (PRDOCT) imaging of the surgical site was performed as a post-operative evaluation of the anastomosed vessels and to visualize the blood flow and thrombus formation. This information could help surgeons improve surgical precision in this highly challenging anastomosis of rodent vessels with diameter less than 0.5 mm. Our imaging modality could not only detect accidental suture through the back wall of lumen but also promptly diagnose and predict thrombosis immediately after reperfusion. Hence, real-time OCT can assist in decision-making process intra-operatively and avoid post-operative complications.

  3. Malvidin’s Effects on Rat Pial Microvascular Permeability Changes Due to Hypoperfusion and Reperfusion Injury

    PubMed Central

    Lapi, Dominga; Chiurazzi, Martina; Di Maro, Martina; Mastantuono, Teresa; Battiloro, Laura; Sabatino, Lina; Ricci, Serena; Di Carlo, Angelina; Starita, Noemy; Guida, Bruna; Santillo, Mariarosaria; Colantuoni, Antonio

    2016-01-01

    The present study was aimed to evaluate the malvidin’s protective effects on damage induced by 30 min bilateral common carotid artery occlusion (BCCAO) and 60 min reperfusion (RE) in rat pial microcirculation. Rat pial microcirculation was observed using fluorescence microscopy through a closed cranial window. Western blotting analysis was performed to investigate the endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) and matrix metalloproteinase 9 (MMP-9) expression. Moreover, MMP-9 activity was evaluated by zymography. Finally, neuronal damage and radical oxygen species (ROS) formation were assessed. In all animals, pial arterioles were classified in five orders of branching according to Strahler’s method. In hypoperfused rats, 30 min BCCAO and 60 min RE caused a decrease in arteriolar diameter, an increase in microvascular leakage and leukocyte adhesion, accompanied by decreased capillary perfusion and red blood cell velocity (VRBC). Moreover, marked neuronal damage and evident ROS generation were detected. Conversely, malvidin administration induced arteriolar dilation in dose-related manner, reducing microvascular leakage as well as leukocyte adhesion. Capillary perfusion and VRBC were protected. Nitric oxide (NO) synthase inhibition significantly attenuated malvidin’s effects on arteriolar diameter. Western blotting analysis revealed an increase in eNOS and p-eNOS expression, while zymography indicated a decrease in MMP-9 activity after malvidin’s administration. Furthermore, malvidin was able to prevent neuronal damage and to decrease ROS generation. In conclusion, malvidin protects rat pial microcirculation against BCCAO/RE injury, preventing blood-brain impairment and neuronal loss. Malvidin’s effects appear to be mediated by eNOS activation and scavenger activity. PMID:27445688

  4. Microvascular Pathology and Morphometrics of Sporadic and Hereditary Small Vessel Diseases of the Brain

    PubMed Central

    Craggs, Lucinda JL; Yamamoto, Yumi; Deramecourt, Vincent; Kalaria, Raj N

    2014-01-01

    Small vessel diseases (SVDs) of the brain are likely to become increasingly common in tandem with the rise in the aging population. In recent years, neuroimaging and pathological studies have informed on the pathogenesis of sporadic SVD and several single gene (monogenic) disorders predisposing to subcortical strokes and diffuse white matter disease. However, one of the limitations toward studying SVD lies in the lack of consistent assessment criteria and lesion burden for both clinical and pathological measures. Arteriolosclerosis and diffuse white matter changes are the hallmark features of both sporadic and hereditary SVDs. The pathogenesis of the arteriopathy is the key to understanding the differential progression of disease in various SVDs. Remarkably, quantification of microvascular abnormalities in sporadic and hereditary SVDs has shown that qualitatively the processes involved in arteriolar degeneration are largely similar in sporadic SVD compared with hereditary disorders such as cerebral autosomal arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Important significant regional differences in lesion location within the brain may enable one to distinguish SVDs, where frontal lobe involvement appears consistently with almost every SVD, but others bear specific pathologies in other lobes, such as the temporal pole in CADASIL and the pons in pontine autosomal dominant microangiopathy and leukoencephalopathy or PADMAL. Additionally, degenerative changes in the vascular smooth muscle cells, the cerebral endothelium and the basal lamina are often rapid and more aggressive in genetic disorders. Further quantification of other microvascular elements and even neuronal cells is needed to fully characterize SVD pathogenesis and to differentiate the usefulness of vascular interventions and treatments on the resulting pathology. PMID:25323665

  5. Microvascular inflammation and acute tubular necrosis are major histologic features of hantavirus nephropathy.

    PubMed

    Gnemmi, Viviane; Verine, Jérôme; Vrigneaud, Laurence; Glowacki, François; Ratsimbazafy, Anderson; Copin, Marie-Christine; Dewilde, Anny; Buob, David

    2015-06-01

    Hantavirus nephropathy (HVN) is an uncommon etiology of acute renal failure due to hantavirus infection. Pathological features suggestive of HVN historically reported are medullary interstitial hemorrhages in a background of acute interstitial nephritis (AIN). However, interstitial hemorrhages may be lacking because of medullary sampling error. This emphasizes that other pathological criteria may be of interest. We performed a retrospective clinicopathological study of 17 serologically proven HVN cases with renal biopsy from 2 nephrology centers in northern France. Histologic analysis was completed by immunohistochemistry with anti-CD3, anti-CD68, and anti-CD34 antibodies. Three control groups were not related to hantavirus infection: acute tubular necrosis (ATN) of ischemic or toxic etiology and AIN were used for comparison. Renal biopsy analysis showed that almost all HVN cases with medullary sampling (9/10) displayed interstitial hemorrhages, whereas focal hemorrhages were detected in 2 of the 7 "cortex-only" specimens. ATN was common, as it was present in 15 (88.2%) of 17 HVN cases. By contrast, interstitial inflammation was scarce with no inflammation or only slight inflammation, representing 15 (88.2%) of 17 cases. Moreover, HVN showed inflammation of renal microvessels with cortical peritubular capillaritis and medullary vasa recta inflammation; peritubular capillaritis was significantly higher in HVN after comparison with ischemic and toxic ATN controls (P = .0001 and P = .003, respectively), but not with AIN controls. Immunohistochemical studies highlighted the involvement of T cells and macrophages in renal microvascular inflammation related to HVN. Our study showed that microvascular inflammation, especially cortical peritubular capillaritis, and ATN are important histologic features of HVN. PMID:25791582

  6. Pulmonary Microvascular Blood Flow in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The MESA COPD Study

    PubMed Central

    Hueper, Katja; Vogel-Claussen, Jens; Parikh, Megha A.; Austin, John H. M.; Bluemke, David A.; Carr, James; Choi, Jiwoong; Goldstein, Thomas A.; Gomes, Antoinette S.; Hoffman, Eric A.; Kawut, Steven M.; Lima, Joao; Michos, Erin D.; Post, Wendy S.; Po, Ming Jack; Prince, Martin R.; Liu, Kiang; Rabinowitz, Dan; Skrok, Jan; Smith, Ben M.; Watson, Karol; Yin, Youbing; Zambeli-Ljepovic, Alan M.

    2015-01-01

    Rationale: Smoking-related microvascular loss causes end-organ damage in the kidneys, heart, and brain. Basic research suggests a similar process in the lungs, but no large studies have assessed pulmonary microvascular blood flow (PMBF) in early chronic lung disease. Objectives: To investigate whether PMBF is reduced in mild as well as more severe chronic obstructive pulmonary disease (COPD) and emphysema. Methods: PMBF was measured using gadolinium-enhanced magnetic resonance imaging (MRI) among smokers with COPD and control subjects age 50 to 79 years without clinical cardiovascular disease. COPD severity was defined by standard criteria. Emphysema on computed tomography (CT) was defined by the percentage of lung regions below −950 Hounsfield units (−950 HU) and by radiologists using a standard protocol. We adjusted for potential confounders, including smoking, oxygenation, and left ventricular cardiac output. Measurements and Main Results: Among 144 participants, PMBF was reduced by 30% in mild COPD, by 29% in moderate COPD, and by 52% in severe COPD (all P < 0.01 vs. control subjects). PMBF was reduced with greater percentage emphysema−950HU and radiologist-defined emphysema, particularly panlobular and centrilobular emphysema (all P ≤ 0.01). Registration of MRI and CT images revealed that PMBF was reduced in mild COPD in both nonemphysematous and emphysematous lung regions. Associations for PMBF were independent of measures of small airways disease on CT and gas trapping largely because emphysema and small airways disease occurred in different smokers. Conclusions: PMBF was reduced in mild COPD, including in regions of lung without frank emphysema, and may represent a distinct pathological process from small airways disease. PMBF may provide an imaging biomarker for therapeutic strategies targeting the pulmonary microvasculature. PMID:26067761

  7. A prospective case-control study to investigate retinal microvascular changes in acute dengue infection.

    PubMed

    Tan, Petrina; Lye, David C; Yeo, Tun Kuan; Cheung, Carol Y; Thein, Tun-Linn; Wong, Joshua G; Agrawal, Rupesh; Li, Ling-Jun; Wong, Tien-Yin; Gan, Victor C; Leo, Yee-Sin; Teoh, Stephen C

    2015-01-01

    Dengue infection can affect the microcirculation by direct viral infection or activation of inflammation. We aimed to determine whether measured retinal vascular parameters were associated with acute dengue infection. Patients with acute dengue were recruited from Communicable Diseases Center, Singapore and age-gender-ethnicity matched healthy controls were selected from a population-based study. Retinal photographs were taken on recruitment and convalescence. A spectrum of quantitative retinal microvascular parameters (retinal vascular caliber, fractal dimension, tortuosity and branching angle) was measured using a semi-automated computer-based program. (Singapore I Vessel Assessment, version 3.0). We included 62 dengue patients and 127 controls. Dengue cases were more likely to have wider retinal arteriolar and venular calibers (158.3 μm vs 144.3 μm, p < 0.001; 227.7 μm vs 212.8 μm, p < 0.001; respectively), higher arteriolar and venular fractal dimensions (1.271 vs 1.249, p = 0.002; 1.268 vs. 1.230, p < 0.001, respectively), higher arteriolar and venular tortuosity (0.730 vs 0.546 [x10(4)], p < 0.001; 0.849 vs 0.658 [x10(4)], p < 0.001; respectively), compared to controls. Resolution of acute dengue coincided with decrease in retinal vascular calibers and venular fractal dimension. Dengue patients have altered microvascular network in the retina; these changes may reflect pathophysiological processes in the immune system.

  8. Regulation of the microvascular circulation in the leg muscles, pancreas and small intestine in rats.

    PubMed

    Maeda, Hisashi; Kurose, Tomoyuki; Kawamata, Seiichi

    2015-01-01

    To study the microvascular circulation, we examined the proportion of open and functioning capillaries in the leg muscles, pancreas and small intestine of anesthetized rats. Fluorescein isothiocyanate (FITC)-labeled Lycopersicon esculentum lectin was injected into the heart and allowed to circulate for 3 min to label open and functioning capillaries. Specimens were removed, frozen, sectioned and double-immunostained. Using one section, open and functioning capillaries were detected by immunostaining for this lectin bound to endothelial cells, while all capillaries were visualized by immunostaining for platelet endothelial cell adhesion molecule-1 (PECAM-1 or CD31). These capillaries were semi-automatically detected and counted by fluorescence microscopy. The percentages of open and functioning capillaries were as follows: the soleus muscle, 93.0 ± 5.5%; superficial zone of the gastrocnemius muscle, 90.8 ± 6.2%; deep zone of the gastrocnemius muscle, 95.6 ± 4.0%; the plantaris muscle, 94.1 ± 2.7%; the pancreas, 86.3 ± 11.7%; and the small intestine, 91.1 ± 4.9% (n = 8, each). There was no significant difference among these data by the Kruskal-Wallis test. This study clearly demonstrated that the proportions of open and functioning capillaries are high and similar among the leg muscles, pancreas and small intestine in spite of their structural and functional differences. This finding agrees with previous studies and supports the notion that the microvascular circulation is mainly controlled by changing of the blood flow in each capillary rather than changing the proportion of open and functioning capillaries. PMID:26140259

  9. Coronary Microvascular Disease in Chronic Chagas Cardiomyopathy Including an Overview on History, Pathology, and Other Proposed Pathogenic Mechanisms

    PubMed Central

    Rossi, Marcos A.; Tanowitz, Herbert B.; Malvestio, Lygia M.; Celes, Mara R.; Campos, Erica C.; Blefari, Valdecir; Prado, Cibele M.

    2010-01-01

    This review focuses on the short and bewildered history of Brazilian scientist Carlos Chagas's discovery and subsequent developments, the anatomopathological features of chronic Chagas cardiomyopathy (CCC), an overview on the controversies surrounding theories concerning its pathogenesis, and studies that support the microvascular hypothesis to further explain the pathological features and clinical course of CCC. It is our belief that knowledge of this particular and remarkable cardiomyopathy will shed light not only on the microvascular involvement of its pathogenesis, but also on the pathogenetic processes of other cardiomyopathies, which will hopefully provide a better understanding of the various changes that may lead to an end-stage heart disease with similar features. This review is written to celebrate the 100th anniversary of the discovery of Chagas disease. PMID:20824217

  10. An Innovative Ultrasound Technique for Evaluation of Tumor Vascularity in Breast Cancers: Superb Micro-Vascular Imaging

    PubMed Central

    Park, Ah Young; Cha, Sang Hoon; Yeom, Suk Keu; Lee, Seung Wha; Chung, Hwan Hoon

    2016-01-01

    Tumor vascularity is an important indicator for differential diagnosis, tumor growth, and prognosis. Superb micro-vascular imaging (SMI) is an innovative ultrasound technique for vascular examination that uses a multidimensional filter to eliminate clutter and preserve extremely low-velocity flows. Theoretically, SMI could depict more vessels and more detailed vascular morphology, due to the increased sensitivity of slow blood flow. Here, we report the early experience of using SMI in 21 breast cancer patients. We evaluated tumor vascular features in breast cancer and compared SMI and conventional color or power Doppler imaging. SMI was superior to color or power Doppler imaging in detecting tumor vessels, the details of vessel morphology, and both peripheral and central vascular distribution. In conclusion, SMI is a promising ultrasound technique for evaluating microvascular information of breast cancers. PMID:27382399

  11. Multimodal reconstruction of microvascular-flow distributions using combined two-photon microscopy and Doppler optical coherence tomography

    PubMed Central

    Gagnon, Louis; Sakadžić, Sava; Lesage, Fréderic; Mandeville, Emiri T.; Fang, Qianqian; Yaseen, Mohammad A.; Boas, David A.

    2015-01-01

    Abstract. Computing microvascular cerebral blood flow (μCBF) in real cortical angiograms is challenging. Here, we investigated whether the use of Doppler optical coherence tomography (DOCT) flow measurements in individual vessel segments can help in reconstructing μCBF across the entire vasculature of a truncated cortical angiogram. A μCBF computational framework integrating DOCT measurements is presented. Simulations performed on a synthetic angiogram showed that the addition of DOCT measurements, especially close to large inflowing or outflowing vessels, reduces the impact of pressure boundary conditions and estimated vessel resistances resulting in a more accurate reconstruction of μCBF. Our technique was then applied to reconstruct microvascular flow distributions in the mouse cortex down to 660  μm by combining two-photon laser scanning microscopy angiography with DOCT. PMID:26157987

  12. Multimodal reconstruction of microvascular-flow distributions using combined two-photon microscopy and Doppler optical coherence tomography.

    PubMed

    Gagnon, Louis; Sakadžić, Sava; Lesage, Fréderic; Mandeville, Emiri T; Fang, Qianqian; Yaseen, Mohammad A; Boas, David A

    2015-01-01

    Computing microvascular cerebral blood flow ([Formula: see text]) in real cortical angiograms is challenging. Here, we investigated whether the use of Doppler optical coherence tomography (DOCT) flow measurements in individual vessel segments can help in reconstructing [Formula: see text] across the entire vasculature of a truncated cortical angiogram. A [Formula: see text] computational framework integrating DOCT measurements is presented. Simulations performed on a synthetic angiogram showed that the addition of DOCT measurements, especially close to large inflowing or outflowing vessels, reduces the impact of pressure boundary conditions and estimated vessel resistances resulting in a more accurate reconstruction of [Formula: see text]. Our technique was then applied to reconstruct microvascular flow distributions in the mouse cortex down to [Formula: see text] by combining two-photon laser scanning microscopy angiography with DOCT.

  13. Citrulline does not enhance blood flow, microvascular circulation, or myofibrillar protein synthesis in elderly men at rest or following exercise.

    PubMed

    Churchward-Venne, Tyler A; Cotie, Lisa M; MacDonald, Maureen J; Mitchell, Cameron J; Prior, Todd; Baker, Steven K; Phillips, Stuart M

    2014-07-01

    Aging is associated with anabolic resistance, a reduced sensitivity of myofibrillar protein synthesis (MPS) to postprandial hyperaminoacidemia, particularly with low protein doses. Impairments in postprandial skeletal muscle blood flow and/or microvascular perfusion with hyperaminoacidemia and hyperinsulinemia may contribute to anabolic resistance. We examined whether providing citrulline, a precursor for arginine and nitric oxide synthesis, would increase arterial blood flow, skeletal muscle microvascular perfusion, MPS, and signaling through mTORC1. Twenty-one elderly males (65-80 yr) completed acute unilateral resistance exercise prior to being assigned to ingest a high dose (45 g) of whey protein (WHEY) or a low dose (15 g) of whey protein with 10 g of citrulline (WHEY + CIT) or with 10 g of nonessential amino acids (WHEY + NEAA). A primed, continuous infusion of L-[ring-(13)C6] phenylalanine with serial muscle biopsies was used to measure MPS and protein phosphorylation, whereas ultrasound was used to measure microvascular circulation under basal and postprandial conditions in both a rested (FED) and exercised (EX-FED) leg. Argininemia was greater in WHEY + CIT vs. WHEY and WHEY + NEAA from 30 to 300 min postexercise (P < 0.001), but there were no treatment differences in blood flow or microvascular perfusion (all P > 0.05). Phosphorylation of p70S6K-Thr(389) was greater in WHEY vs. WHEY + NEAA (P = 0.02). Postprandial MPS was greater in WHEY vs. WHEY + CIT and WHEY + NEAA under both FED (WHEY: ~128%; WHEY + CIT: ~56%; WHEY + NEAA: ~38%) and EX-FED (WHEY: ~251%; WHEY + CIT: ~124%; WHEY + NEAA: ~108%) conditions (P = 0.003). Citrulline coingestion with a low quantity of protein was ineffective in augmenting the anabolic properties of protein compared with nonessential amino acids.

  14. Peripheral Microvascular Responses to Whole-Body Tilting, G(z) Centrifugation, and Lower Body Negative Pressure Stresses in Humans

    NASA Technical Reports Server (NTRS)

    Breit, G. A.; Watenpaugh, D. E.; Buckley, T. M.; Ballard, R. E.; Murthy, G.; Hargens, A. R.

    1994-01-01

    The response of the cutaneous microcirculation to orthostatic stress varies along the length of the body due to the interaction of central controls with regional responses to local blood pressure. We hypothesize that artificial orthostatic stresses such as Gz centrifugation and LBNP differ from whole-body tilting in terms of the distribution of microvascular blood flow. Cutaneous microvascular flows were measured by laser Doppler flowmetry at the neck, thigh, and leg of 15 normal subjects. Volunteers underwent stepwise head-up tilt (HUT) and short- and long-arm centrifugation protocols from supine control (0 Gz) to 0.2, 0.4, 0.6, 0.8, 1.0, 0.8, 0.6, 0.4, 0.2, and 0 Gz at the feet, for 30-s periods with 10-s transitions between levels. The same subjects underwent a corresponding supine LBNP protocol, up to 100 mmHg (in 20 mmHg increments) and back to zero pressure, which produced transmural pressure across blood vessels in the foot approximately equal to the HUT protocol. In general, application of all orthostatic stresses produced significant flow reductions in the lower body (p less than 0.05) and inconsistent changes in the neck. At low levels of each stress (0.4 Gz, 40 mmHg), LBNP generated the greatest relative reduction in flow in the lower body (-66.9+/-5.7%, thigh; -60.6 +/-5.7%, leg, mean +/- SE). HUT caused a less severe flow reduction than LBNP at the thigh and leg (-39.9 +/- 8.1% and -55.9+/-4.8%), while the effects induced by both forms of centrifugation were the least profound. Higher levels of each stress generally resulted in similar responses. These responses exhibit a consistent relationship to hypothesized changes in local microvascular transmural pressure, suggesting that myogenic and veno-arteriolar reflexes play a significant role in determining microvascular perfusion during orthostatic stress.

  15. Acute cocoa flavanol supplementation improves muscle macro- and microvascular but not anabolic responses to amino acids in older men.

    PubMed

    Phillips, Bethan E; Atherton, Philip J; Varadhan, Krishna; Limb, Marie C; Williams, John P; Smith, Kenneth

    2016-05-01

    The anabolic effects of nutrition on skeletal muscle may depend on adequate skeletal muscle perfusion, which is impaired in older people. Cocoa flavanols have been shown to improve flow-mediated dilation, an established measure of endothelial function. However, their effect on muscle microvascular blood flow is currently unknown. Therefore, the objective of this study was to explore links between the consumption of cocoa flavanols, muscle microvascular blood flow, and muscle protein synthesis (MPS) in response to nutrition in older men. To achieve this objective, leg blood flow (LBF), muscle microvascular blood volume (MBV), and MPS were measured under postabsorptive and postprandial (intravenous Glamin (Fresenius Kabi, Germany), dextrose to sustain glucose ∼7.5 mmol·L(-1)) conditions in 20 older men. Ten of these men were studied with no cocoa flavanol intervention and a further 10 were studied with the addition of 350 mg of cocoa flavanols at the same time that nutrition began. Leg (femoral artery) blood flow was measured by Doppler ultrasound, muscle MBV by contrast-enhanced ultrasound using Definity (Lantheus Medical Imaging, Mass., USA) perflutren contrast agent and MPS using [1, 2-(13)C2]leucine tracer techniques. Our results show that although older individuals do not show an increase in LBF or MBV in response to feeding, these absent responses are apparent when cocoa flavanols are given acutely with nutrition. However, this restoration in vascular responsiveness is not associated with improved MPS responses to nutrition. We conclude that acute cocoa flavanol supplementation improves muscle macro- and microvascular responses to nutrition, independently of modifying muscle protein anabolism.

  16. Acute cocoa flavanol supplementation improves muscle macro- and microvascular but not anabolic responses to amino acids in older men.

    PubMed

    Phillips, Bethan E; Atherton, Philip J; Varadhan, Krishna; Limb, Marie C; Williams, John P; Smith, Kenneth

    2016-05-01

    The anabolic effects of nutrition on skeletal muscle may depend on adequate skeletal muscle perfusion, which is impaired in older people. Cocoa flavanols have been shown to improve flow-mediated dilation, an established measure of endothelial function. However, their effect on muscle microvascular blood flow is currently unknown. Therefore, the objective of this study was to explore links between the consumption of cocoa flavanols, muscle microvascular blood flow, and muscle protein synthesis (MPS) in response to nutrition in older men. To achieve this objective, leg blood flow (LBF), muscle microvascular blood volume (MBV), and MPS were measured under postabsorptive and postprandial (intravenous Glamin (Fresenius Kabi, Germany), dextrose to sustain glucose ∼7.5 mmol·L(-1)) conditions in 20 older men. Ten of these men were studied with no cocoa flavanol intervention and a further 10 were studied with the addition of 350 mg of cocoa flavanols at the same time that nutrition began. Leg (femoral artery) blood flow was measured by Doppler ultrasound, muscle MBV by contrast-enhanced ultrasound using Definity (Lantheus Medical Imaging, Mass., USA) perflutren contrast agent and MPS using [1, 2-(13)C2]leucine tracer techniques. Our results show that although older individuals do not show an increase in LBF or MBV in response to feeding, these absent responses are apparent when cocoa flavanols are given acutely with nutrition. However, this restoration in vascular responsiveness is not associated with improved MPS responses to nutrition. We conclude that acute cocoa flavanol supplementation improves muscle macro- and microvascular responses to nutrition, independently of modifying muscle protein anabolism. PMID:27120341

  17. A scanning electron microscopic study of microvascular anastomoses on irradiated vessels: short-term effect of irradiation

    SciTech Connect

    De Wilde, R.; Boeckx, W.; Van Der Schueren, E.; Guelinckx, P.; Gruwez, J.

    1983-01-01

    Experiments were carried out to determine the effect of previous irradiation on microvascular arterial anastomoses. The study focused on regeneration of endothelial cells and thrombus formation. Careful examination with scanning electron microscopy (SEM) showed a difference between irradiated animals and a control group. In the irradiated group one can notice a decreased regeneration, a greater amount of fibrin and platelets, and a higher incidence of microthrombi.

  18. Retinal Microvascular Responses to Short-Term Changes in Particulate Air Pollution in Healthy Adults

    PubMed Central

    Louwies, Tijs; Kicinski, Michal; De Boever, Patrick; Nawrot, Tim S.

    2013-01-01

    Background: Microcirculation plays an important role in the physiology of cardiovascular health. Air pollution is an independent risk factor for the development and progression of cardiovascular diseases, but the number of studies on the relation between air pollution and the microcirculation is limited. Objectives: We examined the relationship between short-term changes in air pollution and microvascular changes. Methods: We measured retinal microvasculature using fundus image analysis in a panel of 84 healthy adults (52% female), 22–63 years of age, during January–May 2012. Blood vessels were measured as central retinal arteriolar/venular equivalent (CRAE/CRVE), with a median of 2 measurements (range, 1–3). We used monitoring data on particulate air pollution (PM10) and black carbon (BC). Mixed-effect models were used to estimate associations between CRAE/CRVE and exposure to PM10 and BC using various exposure windows. Results: CRAE and CRVE were associated with PM10 and BC concentrations, averaged over the 24 hr before the retinal examinations. Each 10-µg/m3 increase in PM10 was associated with a 0.93-µm decrease (95% CI: –1.42, –0.45; p = 0.0003) in CRAE and a 0.86-µm decrease (95% CI: –1.42, –0.30; p = 0.004) in CRVE after adjusting for individual characteristics and time varying conditions such as ambient temperature. Each 1-µg/m3 increase in BC was associated with a 1.84-µm decrease (95% CI: –3.18, –0.51; p < 0.001) in CRAE. Conclusions: Our findings suggest that the retinal microvasculature responds to short-term changes in air pollution levels. These results support a mechanistic pathway through which air pollution can act as a trigger of cardiovascular events at least in part through effects on the microvasculature. Citation: Louwies T, Int Panis L, Kicinski M, De Boever P, Nawrot TS. 2013. Retinal microvascular responses to short-term changes in particulate air pollution in healthy adults. Environ Health Perspect 121:1011–1016;

  19. Cardiac Microvascular Barrier Function Mediates the Protection of Tongxinluo against Myocardial Ischemia/Reperfusion Injury

    PubMed Central

    Qi, Kang; Li, Lujin; Li, Xiangdong; Zhao, Jinglin; Wang, Yang; You, Shijie; Hu, Fenghuan; Zhang, Haitao; Cheng, Yutong; Kang, Sheng; Cui, Hehe; Duan, Lian; Jin, Chen; Zheng, Qingshan; Yang, Yuejin

    2015-01-01

    Objective Tongxinluo (TXL) has been shown to decrease myocardial necrosis after ischemia/reperfusion (I/R) by simulating ischemia preconditioning (IPC). However, the core mechanism of TXL remains unclear. This study was designed to investigate the key targets of TXL against I/R injury (IRI) among the cardiac structure-function network. Materials and Methods To evaluate the severity of lethal IRI, a mathematical model was established according to the relationship between myocardial no-reflow size and necrosis size. A total of 168 mini-swine were employed in myocardial I/R experiment. IRI severity among different interventions was compared and IPC and CCB groups were identified as the mildest and severest groups, respectively. Principal component analysis was applied to further determine 9 key targets of IPC in cardioprotection. Then, the key targets of TXL in cardioprotection were confirmed. Results Necrosis size and no-reflow size fit well with the Sigmoid Emax model. Necrosis reduction space (NRS) positively correlates with I/R injury severity and necrosis size (R2=0.92, R2=0.57, P<0.01, respectively). Functional and structural indices correlate positively with NRS (R2=0.64, R2=0.62, P<0.01, respectively). TXL recovers SUR2, iNOS activity, eNOS activity, VE-cadherin, β-catenin, γ-catenin and P-selectin with a trend toward the sham group. Moreover, TXL increases PKA activity and eNOS expression with a trend away from the sham group. Among the above nine indices, eNOS activity, eNOS, VE-cadherin, β-catenin and γ-catenin expression were significantly up-regulated by TXL compared with IPC (P>0.05) or CCB (P<0.05) and these five microvascular barrier-related indices may be the key targets of TXL in minimizing IRI. Conclusions Our study underlines the lethal IRI as one of the causes of myocardial necrosis. Pretreatment with TXL ameliorates myocardial IRI through promoting cardiac microvascular endothelial barrier function by simulating IPC. PMID:25781461

  20. Hyperglycemia and Diabetes Downregulate the Functional Expression of TRPV4 Channels in Retinal Microvascular Endothelium.

    PubMed

    Monaghan, Kevin; McNaughten, Jennifer; McGahon, Mary K; Kelly, Catriona; Kyle, Daniel; Yong, Phaik Har; McGeown, J Graham; Curtis, Tim M

    2015-01-01

    Retinal endothelial cell dysfunction is believed to play a key role in the etiology and pathogenesis of diabetic retinopathy. Numerous studies have shown that TRPV4 channels are critically involved in maintaining normal endothelial cell function. In the current paper, we demonstrate that TRPV4 is functionally expressed in the endothelium of the retinal microcirculation and that both channel expression and activity is downregulated by hyperglycaemia. Quantitative PCR and immunostaining demonstrated molecular expression of TRPV4 in cultured bovine retinal microvascular endothelial cells (RMECs). Functional TRPV4 activity was assessed in cultured RMECs from endothelial Ca2+-responses recorded using fura-2 microfluorimetry and electrophysiological recordings of membrane currents. The TRPV4 agonist 4α-phorbol 12,13-didecanoate (4-αPDD) increased [Ca2+]i in RMECs and this response was largely abolished using siRNA targeted against TRPV4. These Ca2+-signals were completely inhibited by removal of extracellular Ca2+, confirming their dependence on influx of extracellular Ca2+. The 4-αPDD Ca2+-response recorded in the presence of cyclopiazonic acid (CPA), which depletes the intracellular stores preventing any signal amplification through store release, was used as a measure of Ca2+-influx across the cell membrane. This response was blocked by HC067047, a TRPV4 antagonist. Under voltage clamp conditions, the TRPV4 agonist GSK1016790A stimulated a membrane current, which was again inhibited by HC067047. Following incubation with 25 mM D-glucose TRPV4 expression was reduced in comparison with RMECs cultured under control conditions, as were 4αPDD-induced Ca2+-responses in the presence of CPA and ion currents evoked by GSK1016790A. Molecular expression of TRPV4 in the retinal vascular endothelium of 3 months' streptozotocin-induced diabetic rats was also reduced in comparison with that in age-matched controls. We conclude that hyperglycaemia and diabetes reduce the

  1. Human dermal microvascular endothelial cells in vitro: effect of cyclic AMP on cellular morphology and proliferation rate.

    PubMed

    Davison, P M; Karasek, M A

    1981-02-01

    Macrovascular endothelial cells isolated from the human umbilical vein and microvessel endothelium from the newborn foreskin dermis differ in their requirements for optimal growth in vitro. In the presence of 5 X 10(-4) M dibutyryl cyclic AMP (Bt2cAMP), human dermal microvessel endothelial cell proliferation rate increased to give a cell number of 203% of controls values by day 10 in culture. The cells retained their characteristic endothelial cell morphology, reached confluence, and could be serially passaged. Cells grown in the absence of Bt2cAMP did not proliferate readily and grew in a disorganized pattern. The effect of Bt2cAMP on microvascular endothelial cell proliferation rate and morphology could be duplicated by cholera toxin (CT) used together with isobutyl methylxanthine (IMX). These agents were found to elevate intracellular levels of cyclic AMP in microvascular endothelium over 40-fold. Human umbilical vein cells in culture failed to respond to either Bt2cAMP or CT together with IMX. The growth-promoting effect of dibutyryl cyclic AMP (Bt2cAMP) on human foreskin dermal microvascular endothelium in vitro is in marked contrast to the lack of response of human umbilical vein cells. These results provide further evidence of differences in the mechanisms that regulate macro and microvessel endothelial cell proliferation in vitro.

  2. In vivo microstructural and microvascular imaging of the human corneo-scleral limbus using optical coherence tomography

    PubMed Central

    Li, Peng; An, Lin; Reif, Roberto; Shen, Tueng T.; Johnstone, Murray; Wang, Ruikang K

    2011-01-01

    The corneo-scleral limbus contains several biological components, which are important constituents for understanding, diagnosing and managing several ocular pathologies, such as glaucoma and corneal abnormalities. An anterior segment optical coherence tomography (AS-OCT) system integrated with optical microangiography (OMAG) is used in this study to non-invasively visualize the three-dimensional microstructural and microvascular properties of the limbal region. Advantages include first the ability to correct optical distortion of microstructural images enabling quantification of relationships in the anterior chamber angle. Second, microvascular images enable the visualization of the microcirculation in the limbal area without the use of exogenous contrast agents. Third, by combining the microstructural and microvascular information, the aqueous outflow pathway can be identified. The proposed AS-OCT can serve as a useful tool for ophthalmological research to determine normal and pathologic changes in the outflow system. As a clinical tool it has the potential to detect early aqueous outflow system abnormalities that lead to the pressure elevation in glaucoma. Recent surgical innovations and their implementations also rely on an assessment of outflow system structure and function, which can be revealed by AS-OCT. PMID:22076271

  3. CEREBRAL CORTICAL MICROVASCULAR RAREFACTION IN METABOLIC SYNDROME IS DEPENDENT ON INSULIN RESISTANCE AND LOSS OF NITRIC OXIDE BIOAVAILABILITY

    PubMed Central

    Chantler, Paul D.; Shrader, Carl D.; Tabone, Lawrence E.; d’Audiffret, Alexandre C.; Huseynova, Khumara; Brooks, Steven D.; Branyan, Kayla W.; Grogg, Kristin A.; Frisbee, Jefferson C.

    2015-01-01

    Objective Chronic presentation of the metabolic syndrome (MS) is associated with an increased likelihood for stroke and poor stroke outcomes following occlusive cerebrovascular events. However, the physiological mechanisms contributing to compromised outcomes remain unclear, and the degree of cerebral cortical microvascular density (MVD) may represent a central determinant of stroke outcomes. Methods This study used the obese Zucker rat (OZR) model of MS and clinically-relevant, chronic interventions to determine the impact on cerebral cortical microvascular rarefaction via immunohistochemistry with a parallel determination of cerebrovascular function to identify putative mechanistic contributors. Results OZR exhibited a progressive rarefaction (to ~80% control MVD) of the cortical microvascular networks vs. lean Zucker rats. Chronic treatment with anti-hypertensive agents (captopril/hydralazine) had limited effectiveness in blunting rarefaction, although treatments improving glycemic control (metformin/rosiglitazone) were superior, maintaining ~94% control MVD. Chronic treatment with the antioxidant TEMPOL severely blunted rarefaction in OZR, although this ameliorative effect was prevented by concurrent NOS inhibition. Conclusions Further analyses revealed that the maintenance of glycemic control and vascular nitric oxide bioavailability were stronger predictors of cerebral cortical MVD in OZR than was prevention of hypertension, and this may have implications for chronic treatment of CVD risk under stroke-prone conditions. PMID:26014499

  4. Effect of microvascular distribution and its density on interstitial fluid pressure in solid tumors: A computational model.

    PubMed

    Mohammadi, M; Chen, P

    2015-09-01

    Solid tumors with different microvascular densities (MVD) have been shown to have different outcomes in clinical studies. Other studies have demonstrated the significant correlation between high MVD, elevated interstitial fluid pressure (IFP) and metastasis in cancers. Elevated IFP in solid tumors prevents drug macromolecules reaching most cancerous cells. To overcome this barrier, antiangiogenesis drugs can reduce MVD within the tumor and lower IFP. A quantitative approach is essential to compute how much reduction in MVD is required for a specific tumor to reach a desired amount of IFP for drug delivery purposes. Here we provide a computational framework to investigate how IFP is affected by the tumor size, the MVD, and location of vessels within the tumor. A general physiologically relevant tumor type with a heterogenous vascular structure surrounded by normal tissue is utilized. Then the continuity equation, Darcy's law, and Starling's equation are applied in the continuum mechanics model, which can calculate IFP for different cases of solid tumors. High MVD causes IFP elevation in solid tumors, and IFP distribution correlates with microvascular distribution within tumor tissue. However, for tumors with constant MVD but different microvascular structures, the average values of IFP were found to be the same. Moreover, for a constant MVD and vascular distribution, an increase in tumor size leads to increased IFP.

  5. Microvascular anastomosis guidance and evaluation using real-time three-dimensional Fourier-domain Doppler optical coherence tomography

    PubMed Central

    Ibrahim, Zuhaib; Tong, Dedi; Zhu, Shan; Mao, Qi; Pang, John; Andrew Lee, Wei Ping; Brandacher, Gerald; Kang, Jin U.

    2013-01-01

    Abstract. Vascular and microvascular anastomoses are critical components of reconstructive microsurgery, vascular surgery, and transplant surgery. Intraoperative surgical guidance using a surgical imaging modality that provides an in-depth view and three-dimensional (3-D) imaging can potentially improve outcome following both conventional and innovative anastomosis techniques. Objective postoperative imaging of the anastomosed vessel can potentially improve the salvage rate when combined with other clinical assessment tools, such as capillary refill, temperature, blanching, and skin turgor. Compared to other contemporary postoperative monitoring modalities—computed tomography angiograms, magnetic resonance (MR) angiograms, and ultrasound Doppler—optical coherence tomography (OCT) is a noninvasive high-resolution (micron-level), high-speed, 3-D imaging modality that has been adopted widely in biomedical and clinical applications. For the first time, to the best of our knowledge, the feasibility of real-time 3-D phase-resolved Doppler OCT (PRDOCT) as an assisted intra- and postoperative imaging modality for microvascular anastomosis of rodent femoral vessels is demonstrated, which will provide new insights and a potential breakthrough to microvascular and supermicrovascular surgery. PMID:23856833

  6. Pathophysiological roles of microvascular alterations in pulmonary inflammatory diseases: possible implications of tumor necrosis factor-alpha and CXC chemokines

    PubMed Central

    Orihara, Kanami; Matsuda, Akio

    2008-01-01

    Chronic obstructive pulmonary disease (COPD) and bronchial asthma are common respiratory diseases that are caused by chronic inflammation of the airways. Although these diseases are mediated by substantially distinct immunological reactions, especially in mild cases, they both show increased numbers of neutrophils, increased production of tumor necrosis factor-alpha (TNF-α) and poor responses to corticosteroids, particularly in patients with severe diseases. These immunological alterations may contribute strongly to airway structural changes, commonly referred to as airway remodeling. Microvascular alterations, a component of airway remodeling and caused by chronic inflammation, are observed and appear to be clinically involved in both diseases. It has been well established that vascular endothelial growth factor (VEGF) plays important roles in the airway microvascular alterations in mild and moderate cases of both diseases, but any role that VEGF might play in severe cases of these diseases remains unclear. Here, we review recent research findings, including our own data, and discuss the possibility that TNF-α and its associated CXC chemokines play roles in microvascular alterations that are even more crucial than those of VEGF in patients with severe COPD or asthma. PMID:19281078

  7. Skin microvascular flow during hypobaric exposure with and without a mechanical counter-pressure space suit glove

    NASA Technical Reports Server (NTRS)

    Tanaka, Kunihiko; Waldie, James; Steinbach, Gregory C.; Webb, Paul; Tourbier, Dietmar; Knudsen, Jeffrey; Jarvis, Christine W.; Hargens, Alan R.

    2002-01-01

    INTRODUCTION: Current space suits are rigid, gas-pressurized shells that protect astronauts from the vacuum of space. A tight elastic garment or mechanical-counter-pressure (MCP) suit generates pressure by compression and may have several advantages over current space suit technology. In this study, we investigated local microcirculatory effects produced with and without a prototype MCP glove. METHODS: The right hand of eight normal volunteers was studied at normal ambient pressure and during exposure to -50, -100 and -150 mm Hg with and without the MCP glove. Measurements included the pressure against the hand, skin microvascular flow, temperature on the dorsum of the hand, and middle finger girth. RESULTS: Without the glove, skin microvascular flow and finger girth significantly increased with negative pressure, and the skin temperature decreased compared with the control condition. The MCP glove generated approximately 200 mm Hg at the skin surface; all measured values remained at control levels during exposure to negative pressure. DISCUSSION: Without the glove, skin microvascular flow and finger girth increased with negative pressure, probably due to a blood shift toward the hand. The elastic compression of the material of the MCP glove generated pressure on the hand similar to that in current gas-pressurized space suit gloves. The MCP glove prevented the apparent blood shift and thus maintained baseline values of the measured variables despite exposure of the hand to negative pressure.

  8. Identification of serologic biomarkers for predicting microvascular invasion in hepatocellular carcinoma

    PubMed Central

    Jin, Yun; Zhou, Jia-Le; Geng, Yan-Hua; Jin, Xing; Zhang, Xiao-Xiao; Yang, Jun-Jie; Qian, Cheng-Ming; Zhou, Dong-Er; Liu, Da-Ren; Peng, Shu-You; Luo, Yan; Zheng, Lei; Li, Jiang-Tao

    2016-01-01

    Microvascular invasion (MVI) of hepatocellular carcinoma (HCC) is a major risk factor for early recurrence and poor survival after curative surgical therapies. However, MVI can only be diagnosed by pathological examination following resection. The aim of this study is to identify serologic biomarkers for predicting MVI preoperatively to help facilitate treatment decisions. We used the sero-proteomic approach to identify antigens that induce corresponding antibody responses either specifically in the serum from MVI (+) patients or from MVI (−) patients. Six antigens were subsequently identified as HSP 70, HSP 90, alpha-enolase (Eno-1), Annexin A2, glutathione synthetase and beta-actin by mass spectrometry. The antibodies titers in sera corresponding to four of these six antigens were measured by ELISA and compared between 35 MVI (+) patients and 26 MVI (−) patients. The titers of anti-HSP 70 antibodies were significantly higher in MVI (−) patients than those in MVI (+) patients; and the titers of anti-Eno-1 antibodies were significantly lower in MVI (−) patients than those in MVI (+) patients. The results were subjected to multivariate analysis together with other clinicopathologic factors, suggesting that antibodies against HSP 70 and Eno-1 in sera are potential biomarkers for predicting MVI in HCC prior to surgical resection. These biomarkers should be further investigated as potential therapeutic targets. PMID:26918350

  9. Microvascular pressure measurement reveals a coronary vascular waterfall in arterioles larger than 110 microm.

    PubMed

    Versluis, J P; Heslinga, J W; Sipkema, P; Westerhof, N

    2001-11-01

    Pressure-flow relationships at the entrance of the coronary circulation in the diastolic myocardium exhibit a zero-flow pressure intercept (P(int)). We tested whether this intercept is the same throughout the vascular bed. Microvascular pressure-flow relationships were therefore measured in vessels of various sizes of the maximally dilated vasculature of perfused unstimulated papillary muscle using the servo-null technique. From these relationships, P(int) were calculated with nonlinear regression. The P(int) at the level of the septal artery (diameter, 150-250 microm) was 23.2 +/- 4.4 cmH2O (n = 12). In arterioles with a diameter range between 24 and 110 microm, P(int) was 1.7 +/- 0.5 cmH2O (n = 6, P < 0.01), significantly lower than in the septal artery but significantly higher than zero, and not dependent on vessel size. In venules with the same diameters, P(int) was 1.1 +/- 1.1 cmH2O (n = 4), which was not different from zero. We conclude that, in the dilated vascular bed of the papillary muscle, two vascular waterfalls are found. The first waterfall is located in arterioles between 150 and 110 microm. The second waterfall is probably located in the small postcapillary venules. PMID:11668051

  10. Microvascular decompression for trigeminal neuralgia with special reference to delayed recurrence.

    PubMed

    Goya, T; Wakisaka, S; Kinoshita, K

    1990-07-01

    Thirty-five patients with trigeminal neuralgia underwent microvascular decompression. Complete remission was obtained in 33 patients, while one was fair and another unchanged postoperatively. The clinical and operative findings were reviewed, analyzing the direction of vascular compression of the trigeminal nerve and the distribution of pain in the peripheral regions. There were some weak correlations between the direction of vascular compression and the distribution of pain. Neuralgia in the region of second branch of the trigeminal nerve (V2) or in the regions of V2 and third branch of the nerve (V3) was caused by compression from the ventral or ventro-rostral direction, in the region of first branch of the nerve from the ventro-caudal direction, and in the V3 region from the ventral, rostral, and dorsal directions of the nerve in general. In two patients who had had complete remission after first operation, trigeminal neuralgia recurred. They had typical intermittent painful attacks with a background of continuous dull pain or painful dysesthesia caused by Ivalon sponges inserted between the nerve and the offending vessel. Complete remission was again obtained after removal of these sponge pieces. We would like to stress continuous dull pain or painful dysesthesia in cases of delayed recurrence as indicators for re-exploration. PMID:1701856

  11. Obesity and coronary microvascular disease - implications for adipose tissue-mediated remote inflammatory response.

    PubMed

    Bagi, Zsolt; Broskova, Zuzana; Feher, Attila

    2014-05-01

    It is believed that obesity has detrimental effects on the coronary circulation. These include immediate changes in coronary arterial vasomotor responsiveness and the development of occlusive large coronary artery disease. Despite its critical role in regulating myocardial perfusion, the altered behavior of coronary resistance arteries, which gives rise to coronary microvascular disease (CMD) is poorly understood in obesity. A chronic, low-grade vascular inflammation has been long considered as one of the main underlying pathology behind CMD. The expanded adipose tissue and the infiltrating macrophages are the major sources of pro-inflammatory mediators that have been implicated in causing inadequate myocardial perfusion and, in a long term, development of heart failure in obese patients. Much less is known the mechanisms regulating the release of these cytokines into the circulation that enable them to exert their remote effects in the coronary microcirculation. This mini review aims to examine recent studies describing alterations in the vasomotor function of coronary resistance arteries and the role of adipose tissue-derived pro-inflammatory cytokines and adipokines in contributing to CMD in obesity. We provide examples of regulatory mechanisms by which adipokines are released from adipose tissue to exert their remote inflammatory effects on coronary microvessels. We identify some of the important challenges and opportunities going forward.

  12. Value of MR histogram analyses for prediction of microvascular invasion of hepatocellular carcinoma

    PubMed Central

    Huang, Ya-Qin; Liang, He-Yue; Yang, Zhao-Xia; Ding, Ying; Zeng, Meng-Su; Rao, Sheng-Xiang

    2016-01-01

    Abstract The objective is to explore the value of preoperative magnetic resonance (MR) histogram analyses in predicting microvascular invasion (MVI) of hepatocellular carcinoma (HCC). Fifty-one patients with histologically confirmed HCC who underwent diffusion-weighted and contrast-enhanced MR imaging were included. Histogram analyses were performed and mean, variance, skewness, kurtosis, 1th, 10th, 50th, 90th, and 99th percentiles were derived. Quantitative histogram parameters were compared between HCCs with and without MVI. Receiver operating characteristics (ROC) analyses were generated to compare the diagnostic performance of tumor size, histogram analyses of apparent diffusion coefficient (ADC) maps, and MR enhancement. The mean, 1th, 10th, and 50th percentiles of ADC maps, and the mean, variance. 1th, 10th, 50th, 90th, and 99th percentiles of the portal venous phase (PVP) images were significantly different between the groups with and without MVI (P <0.05), with area under the ROC curves (AUCs) of 0.66 to 0.74 for ADC and 0.76 to 0.88 for PVP. The largest AUC of PVP (1th percentile) showed significantly higher accuracy compared with that of arterial phase (AP) or tumor size (P <0.001). MR histogram analyses—in particular for 1th percentile for PVP images—held promise for prediction of MVI of HCC. PMID:27368028

  13. Slit2-Robo4 receptor responses inhibit ANDV directed permeability of human lung microvascular endothelial cells.

    PubMed

    Gorbunova, Elena E; Gavrilovskaya, Irina N; Mackow, Erich R

    2013-08-01

    Hantaviruses nonlytically infect human endothelial cells (ECs) and cause edematous and hemorrhagic diseases. Andes virus (ANDV) causes hantavirus pulmonary syndrome (HPS), and Hantaan virus (HTNV) causes hemorrhagic fever with renal syndrome (HFRS). Hantaviruses enhance vascular endothelial growth factor directed EC permeability resulting in the disassembly of inter-endothelial cell adherens junctions (AJs). Recent studies demonstrate that Slit2 binding to Robo1/Robo4 receptors on ECs has opposing effects on AJ disassembly and vascular fluid barrier functions. Here we demonstrate that Slit2 inhibits ANDV and HTNV induced permeability and AJ disassembly of pulmonary microvascular ECs (PMECs) by interactions with Robo4. In contrast, Slit2 had no effect on the permeability of ANDV infected human umbilical vein ECs (HUVECs). Analysis of Robo1/Robo4 expression determined that PMECs express Robo4, but not Robo1, while HUVECs expressed both Robo4 and Robo1 receptors. SiRNA knockdown of Robo4 in PMECs prevented Slit2 inhibition of ANDV induced permeability demonstrating that Robo4 receptors determine PMEC responsiveness to Slit2. Collectively, this data demonstrates a selective role for Slit2/Robo4 responses within PMECs that inhibits ANDV induced permeability and AJ disassembly. These findings suggest Slit2s utility as a potential HPS therapeutic that stabilizes the pulmonary endothelium and antagonizes ANDV induced pulmonary edema.

  14. Paracrine crosstalk between human hair follicle dermal papilla cells and microvascular endothelial cells.

    PubMed

    Bassino, Eleonora; Gasparri, Franco; Giannini, Valentina; Munaron, Luca

    2015-05-01

    Human follicle dermal papilla cells (FDPC) are a specialized population of mesenchymal cells located in the skin. They regulate hair follicle (HF) development and growth, and represent a reservoir of multipotent stem cells. Growing evidence supports the hypothesis that HF cycling is associated with vascular remodeling. Follicular keratinocytes release vascular endothelial growth factor (VEGF) that sustains perifollicular angiogenesis leading to an increase of follicle and hair size. Furthermore, several human diseases characterized by hair loss, including Androgenetic Alopecia, exhibit alterations of skin vasculature. However, the molecular mechanisms underlying HF vascularization remain largely unknown. In vitro coculture approaches can be successfully employed to greatly improve our knowledge and shed more light on this issue. Here we used Transwell-based co-cultures to show that FDPC promote survival, proliferation and tubulogenesis of human microvascular endothelial cells (HMVEC) more efficiently than fibroblasts. Accordingly, FDPC enhance the endothelial release of VEGF and IGF-1, two well-known proangiogenic growth factors. Collectively, our data suggest a key role of papilla cells in vascular remodeling of the hair follicle.

  15. Microvascular hemodynamics in experimental arthritis: disparity between the distribution of microspheres and plasma flow in bone.

    PubMed

    Hansen, E S; Søballe, K; Kjølseth, D; Henriksen, T B; He, S Z

    1990-09-01

    The microcirculation in normal and arthritic juxtaarticular bone was studied in 16 young dogs with carragheenan-induced arthritis of one knee. The regional blood flow was determined by the tissue uptake of intracardially injected 15-microns 141Ce-labeled microspheres, and the microvascular plasma volume was determined by the distribution space of circulating 125I-fibrinogen. Disparities between the distribution of plasma flow and microspheres, introduced by plasma skimming or nonentrapment of spheres in the intraosseous circulation, were estimated by 59Fe-transferrin, a third intravascular tracer, injected as a bolus intracardially and trapped peripherally after 15 sec by prompt circulatory arrest. The tissue uptake of the plasma flow tracer was compared to that of microspheres by the ratio between observed and expected activity of 59Fe-transferrin, the expected activity being calculated from the microsphere distribution. The transferrin and microsphere uptake agreed well in patella, marginal epiphyseal bone, and cortical bone, whereas observed activity of transferrin was twice the expected in central epiphyseal bone, three times higher in marrow, and up to eightfold higher in metaphyses adjacent to growth plates. This discrepancy was significantly greater in arthritic bone when the metaphyses were examined in toto. The microsphere method thus appears to underestimate blood flow to cancellous bone and marrow due to uneven distribution of plasma and formed elements from profound plasma skimming and perhaps also by AV shunting. PMID:2250600

  16. Small Spacecraft Active Thermal Control: Micro-Vascular Composites Enable Small Satellite Cooling

    NASA Technical Reports Server (NTRS)

    Ghosh, Alexander

    2016-01-01

    The Small Spacecraft Integrated Power System with Active Thermal Control project endeavors to achieve active thermal control for small spacecraft in a practical and lightweight structure by circulating a coolant through embedded micro-vascular channels in deployable composite panels. Typically, small spacecraft rely on small body mounted passive radiators to discard heat. This limits cooling capacity and leads to the necessity to design for limited mission operations. These restrictions severely limit the ability of the system to dissipate large amounts of heat from radios, propulsion systems, etc. An actively pumped cooling system combined with a large deployable radiator brings two key advantages over the state of the art for small spacecraft: capacity and flexibility. The use of a large deployable radiator increases the surface area of the spacecraft and allows the radiation surface to be pointed in a direction allowing the most cooling, drastically increasing cooling capacity. With active coolant circulation, throttling of the coolant flow can enable high heat transfer rates during periods of increased heat load, or isolate the radiator during periods of low heat dissipation.

  17. Transplanted microvascular endothelial cells promote oligodendrocyte precursor cell survival in ischemic demyelinating lesions.

    PubMed

    Iijima, Keiya; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Puentes, Sandra; Imai, Hideaki; Yoshimoto, Yuhei; Mikuni, Masahiko; Ishizaki, Yasuki

    2015-11-01

    We previously showed that transplantation of brain microvascular endothelial cells (MVECs) greatly stimulated remyelination in the white matter infarct of the internal capsule (IC) induced by endothelin-1 injection and improved the behavioral outcome. In the present study, we examined the effect of MVEC transplantation on the infarct volume using intermittent magnetic resonance image and on the behavior of oligodendrocyte lineage cells histochemically. Our results in vivo show that MVEC transplantation reduced the infarct volume in IC and apoptotic death of oligodendrocyte precursor cells (OPCs). These results indicate that MVECs have a survival effect on OPCs, and this effect might contribute to the recovery of the white matter infarct. The conditioned-medium from cultured MVECs reduced apoptosis of cultured OPCs, while the conditioned medium from cultured fibroblasts did not show such effect. These results suggest a possibility that transplanted MVECs increased the number of OPCs through the release of humoral factors that prevent their apoptotic death. Identification of such humoral factors may lead to the new therapeutic strategy against ischemic demyelinating diseases.

  18. Citrobacter freundii invades and replicates in human brain microvascular endothelial cells.

    PubMed

    Badger, J L; Stins, M F; Kim, K S

    1999-08-01

    Neonatal bacterial meningitis remains a disease with unacceptable rates of morbidity and mortality despite the availability of effective antimicrobial therapy. Citrobacter spp. cause neonatal meningitis but are unique in their frequent association with brain abscess formation. The pathogenesis of Citrobacter spp. causing meningitis and brain abscess is not well characterized; however, as with other meningitis-causing bacteria (e.g., Escherichia coli K1 and group B streptococci), penetration of the blood-brain barrier must occur. In an effort to understand the pathogenesis of Citrobacter spp. causing meningitis, we have used the in vitro blood-brain barrier model of human brain microvascular endothelial cells (HBMEC) to study the interaction between C. freundii and HBMEC. In this study, we show that C. freundii is capable of invading and trancytosing HBMEC in vitro. Invasion of HBMEC by C. freundii was determined to be dependent on microfilaments, microtubules, endosome acidification, and de novo protein synthesis. Immunofluorescence microscopy studies revealed that microtubules aggregated after HBMEC came in contact with C. freundii; furthermore, the microtubule aggregation was time dependent and seen with C. freundii but not with noninvasive E. coli HB101 and meningitic E. coli K1. Also in contrast to other meningitis-causing bacteria, C. freundii is able to replicate within HBMEC. This is the first demonstration of a meningitis-causing bacterium capable of intracellular replication within BMEC. The important determinants of the pathogenesis of C. freundii causing meningitis and brain abscess may relate to invasion of and intracellular replication in HBMEC.

  19. Evidence of endoplasmic reticulum-related Ca sup 2+ ATPase in human microvascular endothelial cells

    SciTech Connect

    Bikfalvi, A.; Enouf, J.; Bredoux, R.; Dupuy, E.; Bourdeau, N.; Levy-Toledano, S.; Tobelem, G. ); Lompre, A. )

    1989-09-01

    The authors demonstrated by immunological and molecular methods the presence of a reticulum endoplasmic-related Ca{sup 2+}-ATPase in human omental microvascular endothelial cells (HOME cells). HOME cells reacted positively with a previously characterized sarcoplasmic reticulum Ca{sup 2+}-ATPase antibody as demonstrated by indirect immunofluorescence. Western blotting revealed that the antibody recognized a 95-100 kDa protein. {sup 35}S-Metabolic labeling led to the detection of a similar protein with which the purified sarcoplasmic reticulum Ca{sup 2+}-ATPase compete. Dot-blotting experiments indicated that a substantial amount of Ca{sup 2+}-ATPase was present in HOME cell membranes. In addition, Northern blot analysis using a cDNA probe from cardiac sarcoplasmic reticulum showed the presence of mRNA species of 4 kb. As these experiments were conducted in comparison with cell types with well-defined Ca{sup 2+}-ATPases, the results suggest the presence of a endoplasmic reticulum-related Ca{sup 2+}-ATPase in HOME cells.

  20. Binding, internalization, and degradation of basic fibroblast growth factor in human microvascular endothelial cells

    SciTech Connect

    Bikfalvi, A.; Dupuy, E.; Inyang, A.L.; Tobelem, G. ); Fayein, N.; Courtois, Y. ); Leseche, G. )

    1989-03-01

    The binding, internalization, and degradation of basic fibroblast growth factor (bFGF) in human omental microvascular endothelial cells (HOME cells) were investigated. Binding studies of bFGF in human endothelial cells have not yet been reported. Basic FGF bound to HOME cells. The number of low-affinity binding sites was found to be variable. Washing the cells with 2 M phosphate-buffered saline removed completely {sup 125}I-bFGF bound to low-affinity binding sites but decreased also the high-affinity binding. The majority of the surface-bound {sup 125}I-bFGF was removed by washing the cells with acetic acid buffer at pH 3. At this temperature, degradation of the internalized ligand was followed after 1 hour by the appearance of three major bands of 15,000 10,000, and 8,000 Da and was inhibited by chloroquine. These results demonstrated two classes of binding sites for bFGF in HOME cells; the number of high-affinity binding sites being larger than the number reported for bovine capillary endothelial cells. The intracellular processing of bFGF in HOME cells seems to be different from that of heparin binding growth factor-1 in murine lung capillary endothelial cells and of eye-derived growth factor-1 in Chinese hamster fibroblasts.

  1. Acute Thermotherapy Prevents Impairments in Cutaneous Microvascular Function Induced by a High Fat Meal

    PubMed Central

    Harvey, Jennifer C.; Roseguini, Bruno T.; Goerger, Benjamin M.; Fallon, Elizabeth A.

    2016-01-01

    We tested the hypothesis that a high fat meal (HFM) would impair cutaneous vasodilation, while thermotherapy (TT) would reverse the detrimental effects. Eight participants were instrumented with skin heaters and laser-Doppler (LD) probes and tested in three trials: control, HFM, and HFM + TT. Participants wore a water-perfused suit perfused with 33°C (control and HFM) or 50°C (HFM + TT) water. Participants consumed 1 g fat/kg body weight. Blood samples were taken at baseline and two hours post-HFM. Blood pressure was measured every 5–10 minutes. Microvascular function was assessed via skin local heating from 33°C to 39°C two hours after HFM. Cutaneous vascular conductance (CVC) was calculated and normalized to maximal vasodilation (%CVCmax). HFM had no effect on initial peak (48 ± 4 %CVCmax) compared to control (49 ± 4 %CVCmax) but attenuated the plateau (51 ± 4 %CVCmax) compared to control (63 ± 4 %CVCmax, P < 0.001). Initial peak was augmented in HFM + TT (66 ± 4 %CVCmax) compared to control and HFM (P < 0.05), while plateau (73 ± 3 % CVCmax) was augmented only compared to the HFM trial (P < 0.001). These data suggest that HFM negatively affects cutaneous vasodilation but can be minimized by TT. PMID:27595112

  2. Myocardial steatosis as a possible mechanistic link between diastolic dysfunction and coronary microvascular dysfunction in women.

    PubMed

    Wei, Janet; Nelson, Michael D; Szczepaniak, Edward W; Smith, Laura; Mehta, Puja K; Thomson, Louise E J; Berman, Daniel S; Li, Debiao; Bairey Merz, C Noel; Szczepaniak, Lidia S

    2016-01-01

    Women with coronary microvascular dysfunction (CMD) and no obstructive coronary artery disease (CAD) have increased rates of heart failure with preserved ejection fraction (HFpEF). The mechanisms of HFpEF are not well understood. Ectopic fat deposition in the myocardium, termed myocardial steatosis, is frequently associated with diastolic dysfunction in other metabolic diseases. We investigated the prevalence of myocardial steatosis and diastolic dysfunction in women with CMD and subclinical HFpEF. In 13 women, including eight reference controls and five women with CMD and evidence of subclinical HFpEF (left ventricular end-diastolic pressure >12 mmHg), we measured myocardial triglyceride content (TG) and diastolic function, by proton magnetic resonance spectroscopy and magnetic resonance tissue tagging, respectively. When compared with reference controls, women with CMD had higher myocardial TG content (0.83 ± 0.12% vs. 0.43 ± 0.06%; P = 0.025) and lower diastolic circumferential strain rate (168 ± 12 vs. 217 ± 15%/s; P = 0.012), with myocardial TG content correlating inversely with diastolic circumferential strain rate (r = -0.779; P = 0.002). This study provides proof-of-concept that myocardial steatosis may play an important mechanistic role in the development of diastolic dysfunction in women with CMD and no obstructive CAD. Detailed longitudinal studies are warranted to explore specific treatment strategies targeting myocardial steatosis and its effect on diastolic function.

  3. Hyperbaric oxygen induces a cytoprotective and angiogenic response in human microvascular endothelial cells.

    PubMed

    Godman, Cassandra A; Chheda, Kousanee P; Hightower, Lawrence E; Perdrizet, George; Shin, Dong-Guk; Giardina, Charles

    2010-07-01

    A genome-wide microarray analysis of gene expression was carried out on human microvascular endothelial cells (HMEC-1) exposed to hyperbaric oxygen treatment (HBOT) under conditions that approximated clinical settings. Highly up-regulated genes included immediate early transcription factors (FOS, FOSB, and JUNB) and metallothioneins. Six molecular chaperones were also up-regulated immediately following HBOT, and all of these have been implicated in protein damage control. Pathway analysis programs identified the Nrf-2-mediated oxidative stress response as one of the primary responders to HBOT. Several of the microarray changes in the Nrf2 pathway and a molecular chaperone were validated using quantitative PCR. For all of the genes tested (Nrf2, HMOX1, HSPA1A, M1A, ACTC1, and FOS), HBOT elicited large responses, whereas changes were minimal following treatment with 100% O(2) in the absence of elevated pressure. The increased expression of immediate early and cytoprotective genes corresponded with an HBOT-induced increase in cell proliferation and oxidative stress resistance. In addition, HBOT treatment enhanced endothelial tube formation on Matrigel plates, with particularly dramatic effects observed following two daily HBO treatments. Understanding how HBOT influences gene expression changes in endothelial cells may be beneficial for improving current HBOT-based wound-healing protocols. These data also point to other potential HBOT applications where stimulating protection and repair of the endothelium would be beneficial, such as patient preconditioning prior to major surgery.

  4. A new microvascular model for noninvasive nuclear magnetic resonance spectroscopy of the transplanted kidney.

    PubMed

    Haug, C E; Shapiro, J I; Chan, L; Weil, R

    1988-03-01

    The cellular biology of graft rejection is not well understood. Phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy is a new noninvasive technique for the measurement of intracellular pH and relative amounts of phosphorus-containing compounds, such as adenosine triphosphate (ATP), inorganic phosphate, phosphocreatine, and sugar phosphates, in any tissue from which a clear signal can be obtained. Biochemical analysis of such precision, without the need for tissue destruction, represents an unusual opportunity for analysis of in vivo cellular metabolism under varying conditions, including graft rejection. 31P NMR study of intra-abdominal viscera has not been feasible in most laboratories without laparotomy because of signal interference from abdominal wall muscle. In this study, to eliminate this interference, a rat kidney was transplanted to the groin, where it could be serially studied without overlying skeletal muscle. This new vascular technique was successful in 11 of 11 attempts and maintained normal serum creatinines in 10 chronic survivors after removal of both native kidneys. The 31P NMR spectroscopic signal from the groin kidney is clear and highly reproducible. This new microvascular model will make it possible to carry out noninvasive long-term spectroscopic studies that could potentially identify a reliable marker for allograft rejection. PMID:3278404

  5. Acute Thermotherapy Prevents Impairments in Cutaneous Microvascular Function Induced by a High Fat Meal.

    PubMed

    Harvey, Jennifer C; Roseguini, Bruno T; Goerger, Benjamin M; Fallon, Elizabeth A; Wong, Brett J

    2016-01-01

    We tested the hypothesis that a high fat meal (HFM) would impair cutaneous vasodilation, while thermotherapy (TT) would reverse the detrimental effects. Eight participants were instrumented with skin heaters and laser-Doppler (LD) probes and tested in three trials: control, HFM, and HFM + TT. Participants wore a water-perfused suit perfused with 33°C (control and HFM) or 50°C (HFM + TT) water. Participants consumed 1 g fat/kg body weight. Blood samples were taken at baseline and two hours post-HFM. Blood pressure was measured every 5-10 minutes. Microvascular function was assessed via skin local heating from 33°C to 39°C two hours after HFM. Cutaneous vascular conductance (CVC) was calculated and normalized to maximal vasodilation (%CVCmax). HFM had no effect on initial peak (48 ± 4 %CVCmax) compared to control (49 ± 4 %CVCmax) but attenuated the plateau (51 ± 4 %CVCmax) compared to control (63 ± 4 %CVCmax, P < 0.001). Initial peak was augmented in HFM + TT (66 ± 4 %CVCmax) compared to control and HFM (P < 0.05), while plateau (73 ± 3 % CVCmax) was augmented only compared to the HFM trial (P < 0.001). These data suggest that HFM negatively affects cutaneous vasodilation but can be minimized by TT. PMID:27595112

  6. Inhibition and regression of tumors in hamster DMBA model following laser microvascular targeting

    NASA Astrophysics Data System (ADS)

    McMillan, Kathleen; Wang, Zhi; Shapshay, Stanley M.

    1998-07-01

    Vascular targeting is a recent approach to cancer therapy that aims at damaging tumor vasculature to induce tumor cell hypoxia and subsequent cell death. Squamous cell cancer arises in the superficial mucosal and cutaneous epithelial layers, and tumor microvasculature therefore may be particularly well suited for targeting by selective photothermolysis. An initial evaluation of the effect of selective eradication of microvasculature on tumor development was undertaken here using the chemically-induced hamster cheek pouch model and a 585 nm pulsed dye laser. In a first group of 6 hamsters, progression of premalignant mucosal lesions was compared between control and laser treatment groups, and laser-induced regression of established tumors was evaluated. In a second group of 12 hamsters, the number of laser treatments required to produce complete regression of tumors of the buccal mucosa was determined. The effect of the laser on tumors appearing on the skin in these animals was also investigated. These experiments showed that laser treatment inhibited tumor development and caused complete regression of established tumors 10 mm3 or smaller. Photothermal microvascular targeting may be useful in treating dyplasia and early tumors of the upper aerodigestive tract and skin, with fewer adverse sequelae than existing modalities.

  7. Acute Thermotherapy Prevents Impairments in Cutaneous Microvascular Function Induced by a High Fat Meal

    PubMed Central

    Harvey, Jennifer C.; Roseguini, Bruno T.; Goerger, Benjamin M.; Fallon, Elizabeth A.

    2016-01-01

    We tested the hypothesis that a high fat meal (HFM) would impair cutaneous vasodilation, while thermotherapy (TT) would reverse the detrimental effects. Eight participants were instrumented with skin heaters and laser-Doppler (LD) probes and tested in three trials: control, HFM, and HFM + TT. Participants wore a water-perfused suit perfused with 33°C (control and HFM) or 50°C (HFM + TT) water. Participants consumed 1 g fat/kg body weight. Blood samples were taken at baseline and two hours post-HFM. Blood pressure was measured every 5–10 minutes. Microvascular function was assessed via skin local heating from 33°C to 39°C two hours after HFM. Cutaneous vascular conductance (CVC) was calculated and normalized to maximal vasodilation (%CVCmax). HFM had no effect on initial peak (48 ± 4 %CVCmax) compared to control (49 ± 4 %CVCmax) but attenuated the plateau (51 ± 4 %CVCmax) compared to control (63 ± 4 %CVCmax, P < 0.001). Initial peak was augmented in HFM + TT (66 ± 4 %CVCmax) compared to control and HFM (P < 0.05), while plateau (73 ± 3 % CVCmax) was augmented only compared to the HFM trial (P < 0.001). These data suggest that HFM negatively affects cutaneous vasodilation but can be minimized by TT.

  8. Microvascular pressure measurement reveals a coronary vascular waterfall in arterioles larger than 110 microm.

    PubMed

    Versluis, J P; Heslinga, J W; Sipkema, P; Westerhof, N

    2001-11-01

    Pressure-flow relationships at the entrance of the coronary circulation in the diastolic myocardium exhibit a zero-flow pressure intercept (P(int)). We tested whether this intercept is the same throughout the vascular bed. Microvascular pressure-flow relationships were therefore measured in vessels of various sizes of the maximally dilated vasculature of perfused unstimulated papillary muscle using the servo-null technique. From these relationships, P(int) were calculated with nonlinear regression. The P(int) at the level of the septal artery (diameter, 150-250 microm) was 23.2 +/- 4.4 cmH2O (n = 12). In arterioles with a diameter range between 24 and 110 microm, P(int) was 1.7 +/- 0.5 cmH2O (n = 6, P < 0.01), significantly lower than in the septal artery but significantly higher than zero, and not dependent on vessel size. In venules with the same diameters, P(int) was 1.1 +/- 1.1 cmH2O (n = 4), which was not different from zero. We conclude that, in the dilated vascular bed of the papillary muscle, two vascular waterfalls are found. The first waterfall is located in arterioles between 150 and 110 microm. The second waterfall is probably located in the small postcapillary venules.

  9. Long-Term Follow-Up of Microvascular Decompression for Trigeminal Neuralgia

    PubMed Central

    Oesman, Chenur; Mooij, Jan Jakob A.

    2011-01-01

    We conducted a study to evaluate the follow-up characteristics of patients with trigeminal neuralgia (TN) and to evaluate the factors affecting long-term outcome of microvascular decompression (MVD) in TN. Between 1983 and 2003, 156 patients with TN treated with MVD by 4 neurosurgeons at University Medical Centre Groningen/the Netherlands were evaluated. Baseline data from operative outcome were evaluated using univariate and multivariate analysis. The group consisted of 156 patients with TN: 90 females and 66 males with a median follow-up period of 9.7 years. The average age of initial symptoms was 51 years. The average duration of symptoms was 58 months. Postoperative 22 patients had a facial hyperpathia or hyperesthesia. Postoperatively, 137 patients had immediate relief. Postoperatively 1 year, 140 patients still had a good outcome of the operation. Twenty-seven patients with good immediate postoperative results had recurrent pain. From the group of patients with typical TN, 82% had good long-term results after operation. Patients with typical TN and immediate postoperative remission, in univariate analysis, had significantly more often an excellent/good postoperative outcome. Immediate postoperative remission is an independent predictive factor for a good long-term outcome. The long-term results of MVD in majority of patients were good with no mortalities and no major morbidities. Patients with typical TN had better long-term outcomes and less recurrence. PMID:22451832

  10. Generation of Shear Adhesion Map Using SynVivo Synthetic Microvascular Networks

    PubMed Central

    Smith, Ashley M.; Prabhakarpandian, Balabhaskar; Pant, Kapil

    2014-01-01

    Cell/particle adhesion assays are critical to understanding the biochemical interactions involved in disease pathophysiology and have important applications in the quest for the development of novel therapeutics. Assays using static conditions fail to capture the dependence of adhesion on shear, limiting their correlation with in vivo environment. Parallel plate flow chambers that quantify adhesion under physiological fluid flow need multiple experiments for the generation of a shear adhesion map. In addition, they do not represent the in vivo scale and morphology and require large volumes (~ml) of reagents for experiments. In this study, we demonstrate the generation of shear adhesion map from a single experiment using a microvascular network based microfluidic device, SynVivo-SMN. This device recreates the complex in vivo vasculature including geometric scale, morphological elements, flow features and cellular interactions in an in vitro format, thereby providing a biologically realistic environment for basic and applied research in cellular behavior, drug delivery, and drug discovery. The assay was demonstrated by studying the interaction of the 2 µm biotin-coated particles with avidin-coated surfaces of the microchip. The entire range of shear observed in the microvasculature is obtained in a single assay enabling adhesion vs. shear map for the particles under physiological conditions. PMID:24893648

  11. The Effect of Microvascular Decompression for Hemifacial Spasm Caused by Vertebrobasilar Dolichoectasia

    PubMed Central

    Kang, Jeong-Han; Kang, Dong-Wan; Chung, Sang Sup

    2012-01-01

    Objective Hemifacial spasm (HFS) caused by vertebrobasilar dolichoectasia (VBD) is very rare, and in theses cases, it is difficult to decompress the nerve from its vascular compression. The objective of this study was to investigate the outcome of microvascular decompression (MVD) for HFS caused by VBD. Methods There were 10 patients of HFS caused by VBD at our hospital between September 1978 and September 2008. We evaluated magnetic resonance angiography (MRA) and time of flight magnetic resonance imaginge (TOF MRI) findings using the criteria for VBD. We compared the clinical outcomes of MVD for the 10 patients with VBD with the overall outcomes of the total 2058 MVDs performed for HFS. Results The results of MVD for HFS caused by VBD were successful in 90.9% of cases. The postoperative complication rate in VBD was 45.5%. Offending vessels in patients with VBD were identified visually during surgery. Adverse effects after MVD were found in 4 patients. We found that the diameter of VBD was significantly greater in patients with complications than in those with no complications (p=0.028). Conclusion Our data shows that MVD may be a good treatment modality for HFS caused by VBD but care must be taken to avoid adverse effects from the procedure. It is important to detach the dolichoectatic artery from its surrounding structures sufficiently to allow it to be easily movable. In addition, attempts should be made to lessen the retraction of the cerebellum during release of the dolichoectatic artery. PMID:23091664

  12. Application of a Novel Microvascular Imaging Technique in Breast Lesion Evaluation.

    PubMed

    Yongfeng, Zhao; Ping, Zhou; Wengang, Liu; Yang, Shao; Shuangming, Tian

    2016-09-01

    Conventional power Doppler imaging (PDI) and the novel Superb Microvascular Imaging (SMI) technique were applied to observe the distribution of microvessels in 135 breast lesions, using semi-quantitative grading, penetrating vessel evaluation and flow distribution pattern to evaluate diagnostic efficacy. Compared with PDI, SMI detected more flow signals and details of microvessels. Further, when a centrally distributed branching or diffusing mode was used as a criterion for diagnosing malignancy, SMI improved diagnosis of breast masses. Sensitivity, specificity, positive predictive value and negative predictive value of SMI-assessed flow distribution were 85.4%, 92.6%, 83.3% and 93.5%, respectively, compared with 70.7%, 92.6%, 80.5% and 87.9% for PDI. We also found that flow distribution pattern analysis is superior to semi-quantitative grading and the penetrating vessel method in differentiating malignant breast lesions. Our work here further supports SMI as a novel and promising technique in visualizing microvasculature in breast lesions that may be of paramount use in initial diagnosis as well as follow-up assessment in various treatment regimes.

  13. Signal Intensity of Superb Microvascular Imaging Correlates with the Severity of Acute Cholecystitis

    PubMed Central

    Tomizawa, Minoru; Shinozaki, Fuminobu; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Ishige, Naoki

    2016-01-01

    Evaluation of the severity of acute cholecystitis is critical for the management of this condition. Superb microvascular imaging (SMI) enables the assessment of slow blood flow of small vessels without any contrast medium. An 84-year-old man visited our hospital with right upper abdominal pain. Computed tomography and abdominal ultrasonography showed a slight thickening of the gallbladder. White blood cell count and C-reactive protein levels were elevated. He was diagnosed with acute cholecystitis and treated conservatively with antibiotics. Two days later, his condition worsened and percutaneous transhepatic gallbladder drainage (PTGBD) was performed. The patient recovered and was discharged, and his drainage was withdrawn 7 days later. On admission, color-coded SMI (cSMI) showed pulsatory signals on the slightly thickened gallbladder wall. On the day of PTGBD, the intensity of the signal on cSMI had increased. Once the patient was cured, no further signal was observed on the gallbladder wall with either cSMI or mSMI. In conclusion, the strong pulsatory signal correlated with the severity of acute cholecystitis observed with cSMI and mSMI. Illustrating the signal intensity is useful for the evaluation of the severity of acute cholecystitis. PMID:27721732

  14. The Diagnostic Value of Superb Microvascular Imaging (SMI) in Detecting Blood Flow Signals of Breast Lesions

    PubMed Central

    Ma, Yan; Li, Gang; Li, Jing; Ren, Wei-dong

    2015-01-01

    Abstract The correlation between color Doppler flow imaging (CDFI) and Superb Microvascular Imaging (SMI) for detecting blood flow in breast lesions was investigated, as was the diagnostic value of SMI in differentiating benign from malignant breast lesions. These lesions were evaluated using both CDFI and SMI according to Adler's method. Pathologic examination showed 57 malignant lesions and 66 benign lesions. The number of blood vessels in a single mass was detected by 2 techniques (SMI and CDFI), and the difference between the 2 values (SMI-CDFI) was calculated. The optimal threshold for the diagnosis of malignant neoplasms and the diagnostic performances of SMI, CDFI, and SMI-CDFI were calculated. For the total lesions and malignant lesions alone, the difference between SMI and CDFI for detecting blood flow was significant (P < 0.01), but the difference was not significant for benign lesions (P = 0.15). The area under the receiver operating characteristic curve was 0.73 (95% confidence interval [CI]: 0.64–0.82) for CDFI; 0.81 (95% CI: 0.74–0.89) for SMI; and 0.89 (95% CI: 0.82–0.95) for SMI-CDFI. Furthermore, the modality of “SMI-CDFI” showed the best diagnostic performance. SMI provides further microvessel information in breast lesions. The diagnostic modality of “SMI-CDFI” can improve the diagnostic performance of ultrasound in the differentiation between benign and malignant masses. PMID:26356718

  15. Dysfunctional resident lung mesenchymal stem cells contribute to pulmonary microvascular remodeling.

    PubMed

    Chow, Kelsey; Fessel, Joshua P; Kaoriihida-Stansbury; Schmidt, Eric P; Gaskill, Christa; Alvarez, Diego; Graham, Brian; Harrison, David G; Wagner, David H; Nozik-Grayck, Eva; West, James D; Klemm, Dwight J; Majka, Susan M

    2013-01-01

    Pulmonary vascular remodeling and oxidative stress are common to many adult lung diseases. However, little is known about the relevance of lung mesenchymal stem cells (MSCs) in these processes. We tested the hypothesis that dysfunctional lung MSCs directly participate in remodeling of the microcirculation. We employed a genetic model to deplete extracellular superoxide dismutase (EC-SOD) in lung MSCs coupled with lineage tracing analysis. We crossed (floxp)sod3 and mT/mG reporter mice to a strain expressing Cre recombinase under the control of the ABCG2 promoter. We demonstrated In vivo that depletion of EC-SOD in lung MSCs resulted in their contribution to microvascular remodeling in the smooth muscle actin positive layer. We further characterized lung MSCs to be multipotent vascular precursors, capable of myofibroblast, endothelial and pericyte differentiation in vitro. EC-SOD deficiency in cultured lung MSCs accelerated proliferation and apoptosis, restricted colony-forming ability, multilineage differentiation potential and promoted the transition to a contractile phenotype. Further studies correlated cell dysfunction to alterations in canonical Wnt/β-catenin signaling, which were more evident under conditions of oxidative stress. Our data establish that lung MSCs are a multipotent vascular precursor population, a population which has the capacity to participate in vascular remodeling and their function is likely regulated in part by the Wnt/β-catenin signaling pathway. These studies highlight an important role for microenviromental regulation of multipotent MSC function as well as their potential to contribute to tissue remodeling.

  16. Bioglue-Coated Teflon Sling Technique in Microvascular Decompression for Hemifacial Spasm Involving the Vertebral Artery

    PubMed Central

    Lee, Seong Ho; Park, Jae Sung

    2016-01-01

    Objective Microvascular decompression (MVD) for hemifacial spasm (HFS) involving the vertebral artery (VA) can be technically challenging. We investigated the therapeutic effects of a bioglue-coated Teflon sling technique on the VA during MVD in 42 cases. Methods A bioglue-coated Teflon sling was crafted by the surgeon and applied to patients in whom neurovascular compression was caused by the VA. The radiologic data, intra-operative findings with detailed introduction of the procedure, and the clinical outcomes of each patient were reviewed and analyzed. Results The 42 patients included in the analysis consisted of 22 females and 20 males, with an average follow-up duration of 76 months (range 24–132 months). Intraoperative investigation revealed that an artery other than the VA was responsible for the neurovascular compression in all cases : posterior inferior cerebellar artery (PICA) in 23 patients (54.7%) and anterior inferior cerebellar artery (AICA) in 11 patients (26.2%). All patients became symptom-free after MVD. Neither recurrence nor postoperative neurological deficit was noted during the 2-year follow-up, except in one patient who developed permanent deafness. Cerebrospinal fluid (CSF) leak occurred in three patients, and one required dural repair. Conclusion Transposition of the VA using a bioglue-coated Teflon sling is a safe and effective surgical technique for HFS involving the VA. A future prospective study to compare clinical outcomes between groups with and without use of this novel technique is required. PMID:27651870

  17. Human brain microvascular endothelial cells resist elongation due to shear stress.

    PubMed

    Reinitz, Adam; DeStefano, Jackson; Ye, Mao; Wong, Andrew D; Searson, Peter C

    2015-05-01

    Endothelial cells in straight sections of vessels are known to elongate and align in the direction of flow. This phenotype has been replicated in confluent monolayers of bovine aortic endothelial cells and human umbilical vein endothelial cells (HUVECs) in cell culture under physiological shear stress. Here we report on the morphological response of human brain microvascular endothelial cells (HBMECs) in confluent monolayers in response to shear stress. Using a microfluidic platform we image confluent monolayers of HBMECs and HUVECs under shear stresses up to 16 dyne cm(-2). From live-cell imaging we quantitatively analyze the cell morphology and cell speed as a function of time. We show that HBMECs do not undergo a classical transition from cobblestone to spindle-like morphology in response to shear stress. We further show that under shear stress, actin fibers are randomly oriented in the cells indicating that there is no cytoskeletal remodeling. These results suggest that HBMECs are programmed to resist elongation and alignment under shear stress, a phenotype that may be associated with the unique properties of the blood-brain barrier.

  18. LPS-induced microvascular leukocytosis can be assessed by blue-field entoptic phenomenon.

    PubMed

    Kolodjaschna, Julia; Berisha, Fatmire; Lung, Solveig; Schaller, Georg; Polska, Elzbieta; Jilma, Bernd; Wolzt, Michael; Schmetterer, Leopold

    2004-08-01

    Administration of low doses of Escherichia coli endotoxin [a lipopolysaccharide (LPS)] to humans enables the study of inflammatory mechanisms. The purpose of the present study was to investigate whether the blue-field entoptic technique may be used to quantify the increase in circulating leukocytes in the ocular microvasculature after LPS infusion. In addition, combined laser Doppler velocimetry and retinal vessel size measurement were used to study red blood cell movement. Twelve healthy male volunteers received 20 IU/kg iv LPS as a bolus infusion. Outcome parameters were measured at baseline and 4 h after LPS administration. In the first protocol (n = 6 subjects), ocular hemodynamic effects were assessed with the blue-field entoptic technique, the retinal vessel analyzer, and laser Doppler velocimetry. In the second protocol (n = 6 subjects), white blood cell (WBC) counts from peripheral blood samples and blue-field entoptic technique measurements were performed. LPS caused peripheral blood leukocytosis and increased WBC density in ocular microvessels (by 49%; P = 0.036) but did not change WBC velocity. In addition, retinal venous diameter was increased (by 9%; P = 0.008), but red blood cell velocity remained unchanged. The LPS-induced changes in retinal WBC density and leukocyte counts were significantly correlated (r = 0.87). The present study indicates that the blue-field entoptic technique can be used to assess microvascular leukocyte recruitment in vivo. In addition, our data indicate retinal venous dilation in response to endotoxin.

  19. Noninvasive Measurement of Microvascular and Interstitial Oxygen Profiles in a Human Tumor in SCID Mice

    NASA Astrophysics Data System (ADS)

    Torres Filho, Ivo P.; Leunig, Michael; Yuan, Fan; Intaglietta, Marcos; Jain, Rakesh K.

    1994-03-01

    Simultaneous measurements of intravascular and interstitial oxygen partial pressure (Po_2) in any tissue have not previously been reported, despite the importance of oxygen in health and in disease. This is due to the limitations of current techniques, both invasive and noninvasive. We have optically measured microscopic profiles of Po_2 with high spatial resolution in subcutaneous tissue and transplanted tumors in mice by combining an oxygen-dependent phosphorescence quenching method and a transparent tissue preparation. The strengths of our approach include the ability to follow Po_2 in the same location for several weeks and to relate these measurements to local blood flow and vascular architecture. Our results show that (i) Po_2 values in blood vessels in well-vascularized regions of a human colon adenocarcinoma xenograft are comparable to those in surrounding arterioles and venules, (ii) carbogen (95% O_2/5% CO_2) breathing increases microvascular Po_2 in tumors, and (iii) in unanesthetized and anesthetized mice Po_2 drops to hypoxic values at <200 μm from isolated vessels but drops by <5 mmHg (1 mmHg = 133 Pa) in highly vascularized tumor regions. Our method should permit noninvasive evaluations of oxygen-modifying agents and offer further mechanistic information about tumor pathophysiology in tissue preparations where the surface of the tissue can be observed.

  20. Glutathione in Cerebral Microvascular Endothelial Biology and Pathobiology: Implications for Brain Homeostasis

    PubMed Central

    Li, Wei; Busu, Carmina; Circu, Magdalena L.; Aw, Tak Yee

    2012-01-01

    The integrity of the vascular endothelium of the blood-brain barrier (BBB) is central to cerebrovascular homeostasis. Given the function of the BBB as a physical and metabolic barrier that buffers the systemic environment, oxidative damage to the endothelial monolayer will have significant deleterious impact on the metabolic, immunological, and neurological functions of the brain. Glutathione (GSH) is a ubiquitous major thiol within mammalian cells that plays important roles in antioxidant defense, oxidation-reduction reactions in metabolic pathways, and redox signaling. The existence of distinct GSH pools within the subcellular organelles supports an elegant mode for independent redox regulation of metabolic processes, including those that control cell fate. GSH-dependent homeostatic control of neurovascular function is relatively unexplored. Significantly, GSH regulation of two aspects of endothelial function is paramount to barrier preservation, namely, GSH protection against oxidative endothelial cell injury and GSH control of postdamage cell proliferation in endothelial repair and/or wound healing. This paper highlights our current insights and hypotheses into the role of GSH in cerebral microvascular biology and pathobiology with special focus on endothelial GSH and vascular integrity, oxidative disruption of endothelial barrier function, GSH regulation of endothelial cell proliferation, and the pathological implications of GSH disruption in oxidative stress-associated neurovascular disorders, such as diabetes and stroke. PMID:22745639

  1. Force control of endothelium permeability in mechanically stressed pulmonary micro-vascular endothelial cells.

    PubMed

    Wang, Bin; Caluch, Adam; Fodil, Redouane; Féréol, Sophie; Zadigue, Patricia; Pelle, Gabriel; Louis, Bruno; Isabey, Daniel

    2012-01-01

    Mechanical factors play a key role in the pathogenesis of Acute Respiratory Distress Syndrome (ARDS) and Ventilator-Induced Lung Injury (VILI) as contributing to alveolo-capillary barrier dysfunction. This study aims at elucidating the role of the cytoskeleton (CSK) and cell-matrix adhesion system in the stressed endothelium and more precisely in the loss of integrity of the endothelial barrier. We purposely develop a cellular model made of a monolayer of confluent Human Pulmonary Microvascular Endothelial Cells (HPMVECs) whose cytoskeleton (CSK) is directly exposed to sustained cyclic mechanical stress for 1 and 2 h. We used RGD-coated ferromagnetic beads and measured permeability before and after stress application. We find that endothelial permeability increases in the stressed endothelium, hence reflecting a loss of integrity. Structural and mechanical results suggest that this endothelial barrier alteration would be due to physically-founded discrepancies in latero-basal reinforcement of adhesion sites in response to the global increase in CSK stiffness or centripetal intracellular forces. Basal reinforcement of adhesion is presently evidenced by the marked redistribution of αvβ3 integrin with cluster formation in the stressed endothelium. PMID:22766716

  2. Characterization of tumor microvascular structure and permeability: comparison between magnetic resonance imaging and intravital confocal imaging

    PubMed Central

    Reitan, Nina Kristine; Thuen, Marte; Goa, Pål Erik; de Lange Davies, Catharina

    2010-01-01

    Solid tumors are characterized by abnormal blood vessel organization, structure, and function. These abnormalities give rise to enhanced vascular permeability and may predict therapeutic responses. The permeability and architecture of the microvasculature in human osteosarcoma tumors growing in dorsal window chambers in athymic mice were measured by confocal laser scanning microscopy (CLSM) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Dextran (40 kDa) and Gadomer were used as molecular tracers for CLSM and DCE-MRI, respectively. A significant correlation was found between permeability indicators. The extravasation rate Ki as measured by CLSM correlated positively with DCE-MRI parameters, such as the volume transfer constant Ktrans and the initial slope of the contrast agent concentration-time curve. This demonstrates that these two techniques give complementary information. Extravasation was further related to microvascular structure and was found to correlate with the fractal dimension and vascular density. The structural parameter values that were obtained from CLSM images were higher for abnormal tumor vasculature than for normal vessels. PMID:20615006

  3. Role of arterioles in management of microvascular decompression in patients with hemifacial spasm.

    PubMed

    Zhu, Jin; Li, Shi-Ting; Zhong, Jun; Guan, Hong-Xin; Ying, Ting-Ting; Yang, Min; Yang, Xiaosheng; Zhou, Qiumeng; Jiao, Wei

    2012-03-01

    Although microvascular decompression (MVD) is accepted as an effective therapy for hemifacial spasm (HFS), some operations fail. While performing MVD, many surgeons focus on the large arteries but ignore the arterioles. Failure to identify involved arterioles may account for unsuccessful MVD. We aimed to refine the MVD surgery and improve post-operative outcomes by proper management of involved arterioles. Clinical data were collected from 69 consecutive patients who underwent MVD. Intraoperative electromyography (EMG) was employed for each MVD. Each operation was reviewed with a focus on the involved arterioles. All patients were followed up for between nine and 12 months. An abnormal muscle response (AMR) wave was identified by EMG in all patients before decompression, but vanished in most patients as soon as the involved arteries were removed from the cranial nerve (CN). However, in nine of 69 patients, the AMR did not immediately disappear. Further dissection and exploration of the entire CN VII identified an arteriole in contact with, or in some patients embedded in, the nerve. Once the arteriole was isolated from the CN, the AMR disappeared. After surgery, spasms ceased in all patients and no recurrence was found up to the one-year follow-up. To achieve a positive post-operative outcome, exploration of the entire CN VII is necessary, with a focus on the small arterioles. AMR can be a good adjuvant to identify the involved arterioles.

  4. Ionizing radiation induces immediate protein acetylation changes in human cardiac microvascular endothelial cells

    PubMed Central

    Barjaktarovic, Zarko; Kempf, Stefan J.; Sriharshan, Arundhathi; Merl-Pham, Juliane; Atkinson, Michael J.; Tapio, Soile

    2015-01-01

    Reversible lysine acetylation is a highly regulated post-translational protein modification that is known to regulate several signaling pathways. However, little is known about the radiation-induced changes in the acetylome. In this study, we analyzed the acute post-translational acetylation changes in primary human cardiac microvascular endothelial cells 4 h after a gamma radiation dose of 2 Gy. The acetylated peptides were enriched using anti-acetyl conjugated agarose beads. A total of 54 proteins were found to be altered in their acetylation status, 23 of which were deacetylated and 31 acetylated. Pathway analyses showed three protein categories particularly affected by radiation-induced changes in the acetylation status: the proteins involved in the translation process, the proteins of stress response, and mitochondrial proteins. The activation of the canonical and non-canonical Wnt signaling pathways affecting actin cytoskeleton signaling and cell cycle progression was predicted. The protein expression levels of two nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, sirtuin 1 and sirtuin 3, were significantly but transiently upregulated 4 but not 24 h after irradiation. The status of the p53 protein, a target of sirtuin 1, was found to be rapidly stabilized by acetylation after radiation exposure. These findings indicate that post-translational modification of proteins by acetylation and deacetylation is essentially affecting the radiation response of the endothelium. PMID:25840449

  5. Transplanted microvascular endothelial cells promote oligodendrocyte precursor cell survival in ischemic demyelinating lesions.

    PubMed

    Iijima, Keiya; Kurachi, Masashi; Shibasaki, Koji; Naruse, Masae; Puentes, Sandra; Imai, Hideaki; Yoshimoto, Yuhei; Mikuni, Masahiko; Ishizaki, Yasuki

    2015-11-01

    We previously showed that transplantation of brain microvascular endothelial cells (MVECs) greatly stimulated remyelination in the white matter infarct of the internal capsule (IC) induced by endothelin-1 injection and improved the behavioral outcome. In the present study, we examined the effect of MVEC transplantation on the infarct volume using intermittent magnetic resonance image and on the behavior of oligodendrocyte lineage cells histochemically. Our results in vivo show that MVEC transplantation reduced the infarct volume in IC and apoptotic death of oligodendrocyte precursor cells (OPCs). These results indicate that MVECs have a survival effect on OPCs, and this effect might contribute to the recovery of the white matter infarct. The conditioned-medium from cultured MVECs reduced apoptosis of cultured OPCs, while the conditioned medium from cultured fibroblasts did not show such effect. These results suggest a possibility that transplanted MVECs increased the number of OPCs through the release of humoral factors that prevent their apoptotic death. Identification of such humoral factors may lead to the new therapeutic strategy against ischemic demyelinating diseases. PMID:26212499

  6. Inhibition of dipeptidyl peptidase 4 regulates microvascular endothelial growth induced by inflammatory cytokines

    SciTech Connect

    Takasawa, Wataru; Ohnuma, Kei; Hatano, Ryo; Endo, Yuko; Dang, Nam H.

    2010-10-08

    Research highlights: {yields} TNF-{alpha} or IL-1{beta} induces EC proliferation with reduction of CD26 expression. {yields} CD26 siRNA or DPP-4 inhibition enhances TNF-{alpha} or IL-1{beta}-induced EC proliferation. {yields} Loss of CD26/DPP-4 enhances aortic sprouting induced by TNF-{alpha} or IL-1{beta}. {yields} Capillary formation induced by TNF-{alpha} or IL-1{beta} is enahced in the CD26{sup -/-} mice. -- Abstract: CD26/DPP-4 is abundantly expressed on capillary of inflamed lesion as well as effector T cells. Recently, CD26/dipeptidyl peptidase 4 (DPP-4) inhibition has been used as a novel oral therapeutic approach for patients with type 2 diabetes. While accumulating data indicate that vascular inflammation is a key feature of both micro- and macro-vascular complications in diabetes, the direct role of CD26/DPP-4 in endothelial biology is to be elucidated. We herein showed that proinflammatory cytokines such as tumor necrosis factor or interleukin-1 reduce expression of CD26 on microvascular endothelial cells, and that genetical or pharmacological inhibition of CD26/DPP-4 enhances endothelial growth both in vitro and in vivo. With DPP-4 inhibitors being used widely in the treatment of type 2 diabetes, our data strongly suggest that DPP-4 inhibition plays a pivotal role in endothelial growth and may have a potential role in the recovery of local circulation following diabetic vascular complications.

  7. Microvascular decompression for glossopharyngeal neuralgia using intraoperative neurophysiological monitoring: Technical case report

    PubMed Central

    Motoyama, Yasushi; Nakagawa, Ichiro; Takatani, Tsunenori; Park, Hun-Soo; Kotani, Yukiko; Tanaka, Yoshitaka; Gurung, Pritam; Park, Young-Soo; Nakase, Hiroyuki

    2016-01-01

    Background: Glossopharyngeal neuralgia (GN) is a rare functional disorder representing around 1% of cases of trigeminal neuralgia. Lancinating throat and ear pain while swallowing are the typical manifestations, and are initially treated using anticonvulsants such as carbamazepine. Medically refractory GN is treated surgically. Microvascular decompression (MVD) is reportedly effective against GN, superseding rhizotomy and tractotomy. Methods: We encountered three patients with medically refractory GN who underwent MVD using intraoperative neurophysiological monitoring (IONM). The offending vessels were the posterior inferior cerebellar arteries, which were confirmed intraoperatively via a transcondylar fossa approach to be affecting the root exit zones of the glossopharyngeal and vagus nerves. As IONM, facial motor-evoked potentials (MEPs) and brainstem auditory-evoked potentials were monitored during microsurgery in all three patients. Pharyngeal and vagal MEPs were added for two patients to avoid postoperative dysphagia. Results: GN disappeared immediately after surgery with complete preservation of hearing acuity and facial nerve function. Transient mild swallowing disturbance was observed in 1 patient without pharyngeal or vagal MEPs, whereas the remaining two patients with pharyngeal and vagal MEPs demonstrated no postoperative dysphagia. Conclusion: Although control of severe pain is expected in surgical intervention for GN, lower cranial nerves are easily damaged because of their fragility, even in MVD. IONM including pharyngeal and vagal MEPs appears very useful for avoiding postoperative sequelae during MVD for GN. PMID:26862458

  8. Microvascular Obstruction Evaluation Using Cardiovascular Magnetic Resonance (CMR) in ST-Elevated Myocardial Infarction (STEMI) Patients

    PubMed Central

    Piotrowska-Kownacka, Dorota; Kownacki, Łukasz; Kochman, Janusz; Kołodzińska, Agnieszka; Kobylecka, Małgorzata; Królicki, Leszek

    2015-01-01

    Summary Backround Restoration of blood flow in epicardial coronary artery in patients with acute myocardial infarction can, but does not have to restore efficient blood flow in coronary circulation. The aim of the study was a direct comparison of microvascular obstruction (MVO) detected by rest and stress perfusion imaging and gadolinium enhancement obtained 2 min. (early MVO) and 15 min. (delayed MVO) post contrast. Material/Methods 106 patients with first anterior myocardial infarction were studied. Cardiovascular magnetic resonance (CMR) was performed 5±2 days after primary percutaneous coronary intervention (pPCI). Stress and rest perfusion imaging was performed as well as early and delayed gadolinium enhancement and systolic function assessment. Scoring of segmental function, perfusion defect, MVO and scar transmurality was performed in 16 segment left ventricular model. Results The prevalence of MVO varies significantly between imaging techniques ranging from 48.8% for delayed MVO to 94% with stress perfusion. Median sum of scores was significantly different for each technique: stress perfusion 13 (7; 18), rest perfusion 3 (0.5; 6), early MVO 3 (0; 8), delayed MVO 0 (0; 4); p<0.05. Infarct size, stress and rest perfusion defects were independent predictors of LV EF at discharge from hospital. Conclusions Imaging protocol has a significant impact on MVO results. The study is the first to describe a stress-induced MVO in STEMI patients. Further research is needed to evaluate its impact on a long term prognosis. PMID:26740825

  9. Sacrificial component fabrication for optimised production of micro-vascular polymer composite

    NASA Astrophysics Data System (ADS)

    Dalton, B.; Dixon, D.; McIlhagger, A.; Archer, E.

    2015-02-01

    Smart functional materials are a viable future goal for advanced applications in aerospace, space and medical applications. In this work micro-vascular polymer composite systems have been developed using sacrificial fibres produced from catalyst loaded Poly(lactic acid). The sacrificial fibres have been produced via a published technique which treated PLA in a solvent catalyst mixture of 60% Trifluoroethanol, 40% H2O dispersed with 10 wt% tin (II) oxalate catalyst. A second process of polymer extrusion of PLA using graded fill contents of tin (II) oxalate has also been developed for the up scaled production of fibres as an alternative to solution treatment. Thermal analysis (TGA) was used to compare sacrificial fibre specimens. PLA fibres produced via the polymer extrusion method outperformed solution treated fibres displaying a lower degradation onset temperature (average 25°C lower), higher degradation rates (observed through a derivative curve comparison) and lower residual catalyst content (0.67% solvent treated fibre against 0.16% extruded fibre). The continuous extrusion process is solvent free and is suitable for high volume production. This work has been carried out to fully understand the fabrication issues with sacrificial components.

  10. Estrogen promotes microvascular pathology in female stroke-prone spontaneously hypertensive rats.

    PubMed

    Stier, Charles T; Chander, Praveen N; Rosenfeld, Louis; Powers, C Andrew

    2003-07-01

    Estrogen produces both beneficial and adverse effects on cardiovascular health via mechanisms that remain unclear. Stroke-prone spontaneously hypertensive rats (SHRSP) maintained on Stroke-Prone Rodent Diet and 1% NaCl drinking water (starting at 8 wk of age) rapidly develop stroke and malignant nephrosclerosis that can be prevented, despite continued hypertension, by drugs targeting angiotensin II and aldosterone actions. This study evaluated estrogen's effects in the SHRSP model. Female SHRSP that were sham operated (SHAM), ovariectomized (OVX) at 4 wk of age, or OVX and treated with estradiol benzoate (E2,30 microg x kg-1 x wk-1) were studied. In a survival protocol, OVX rats lived significantly longer (15.1 +/- 0.3 wk) compared with SHAM (13.6 +/- 0.2 wk) or OVX+E2 rats (12.4 +/- 0.2 wk). In a protocol in which animals were matched for age, at 11.5 wk, terminal systolic blood pressure and urine protein excretion were elevated in SHAM and OVX+E2 rats compared with OVX rats; blood urea nitrogen, renal microvascular and glomerular lesions, and plasma renin concentration were elevated in OVX+E2 relative to SHAM or OVX rats. In a survival protocol using intact female SHRSP, treatment with an antiestrogen (tamoxifen, 7 mg.kg-1.wk-1) prolonged survival by >2 wk compared with controls (P < 0.01). The data indicate that estrogen promotes microangiopathy in the kidney and stroke in saline-drinking SHRSP.

  11. Concise Review: Tissue-Specific Microvascular Endothelial Cells Derived from Human Pluripotent Stem Cells

    PubMed Central

    Wilson, Hannah K.; Canfield, Scott G.; Shusta, Eric V.; Palecek, Sean P.

    2014-01-01

    Accumulating evidence suggests that endothelial cells (ECs) display significant heterogeneity across tissue types, playing an important role in tissue regeneration and homeostasis. Recent work demonstrating the derivation of tissue-specific microvascular endothelial cells (TS-MVECs) from human pluripotent stem cells (hPSCs) has ignited the potential to generate tissue-specific models which may be applied to regenerative medicine and in vitro modeling applications. Here we review techniques by which hPSC-derived TS-MVECs have been made to date and discuss how current hPSC-EC differentiation protocols may be directed towards tissue-specific fates. We begin by discussing the nature of EC tissue specificity in vivo and review general hPSC-EC differentiation protocols generated over the last decade. Finally, we describe how specificity can be integrated into hPSC-EC protocols to generate hPSC-derived TS-MVECs in vitro, including EC and parenchymal cell co-culture, directed differentiation, and direct reprogramming strategies. PMID:25070152

  12. TIMP-1 inhibits microvascular endothelial cell migration by MMP-dependent and MMP-independent mechanisms.

    PubMed

    Akahane, Takemi; Akahane, Manabu; Shah, Amy; Connor, Christine M; Thorgeirsson, Unnur P

    2004-12-10

    It was reported over a decade ago that tissue inhibitor of metalloproteinases-1 (TIMP-1) suppresses angiogenesis in experimental models but the mechanism is still incompletely understood. This in vitro study focused on the molecular basis of TIMP-1-mediated inhibition of endothelial cell (EC) migration, a key step in the angiogenic process. Both recombinant human TIMP-1 and the synthetic MMP inhibitors, GM6001 and MMP-2-MMP-9 Inhibitor III, suppressed migration of human dermal microvascular endothelial cells (HDMVEC) in a dose-dependent fashion. The MMP-dependent inhibition of migration was associated with increased expression of the junctional adhesion proteins, VE-cadherin and PECAM-1, and VE-cadherin accumulation at cell-cell junctions. TIMP-1 also caused MMP-independent dephosphorylation of focal adhesion kinase (FAK) (pY397) and paxillin, which was associated with reduced number of F-actin stress fibers and focal adhesions. Moreover, TIMP-1 stimulated expression of PTEN that has been shown to reduce phosphorylation of FAK and inhibit cell migration. Our data suggest that TIMP-1 inhibits HDMVEC migration through MMP-dependent stimulation of VE-cadherin and MMP-independent stimulation of PTEN with subsequent dephosphorylation of FAK and cytoskeletal remodeling. PMID:15530852

  13. Effective plasmid DNA and small interfering RNA delivery to diseased human brain microvascular endothelial cells.

    PubMed

    Slanina, H; Schmutzler, M; Christodoulides, M; Kim, K S; Schubert-Unkmeir, A

    2012-01-01

    Expression of exogenous DNA or small interfering RNA (siRNA) in vitro is significantly affected by the particular delivery system utilized. In this study, we evaluated the transfection efficiency of plasmid DNA and siRNA into human brain microvascular endothelial cells (HBMEC) and meningioma cells, which constitute the blood-cerebrospinal fluid barrier, a target of meningitis-causing pathogens. Chemical transfection methods and various lipofection reagents including Lipofectamin™, FuGene™, or jetPRIME®, as well as physical transfection methods and electroporation techniques were applied. To monitor the transfection efficiencies, HBMEC and meningioma cells were transfected with the reporter plasmid pTagGFP2-actin vector, and efficiency of transfection was estimated by fluorescence microscopy and flow cytometry. We established protocols based on electroporation using Cell Line Nucleofector® Kit V with the Amaxa® Nucleofector® II system from Lonza and the Neon® Transfection system from Invitrogen resulting in up to 41 and 82% green fluorescent protein-positive HBMEC, respectively. Optimal transfection solutions, pulse programs and length were evaluated. We furthermore demonstrated that lipofection is an efficient method to transfect meningioma cells with a transfection efficiency of about 81%. Finally, we applied the successful electroporation protocols to deliver synthetic siRNA to HBMEC and analyzed the role of the actin-binding protein cortactin in Neisseria meningitidis pathogenesis. PMID:23036990

  14. Hepatocyte growth factor enhances the barrier function in primary cultures of rat brain microvascular endothelial cells.

    PubMed

    Yamada, Narumi; Nakagawa, Shinsuke; Horai, Shoji; Tanaka, Kunihiko; Deli, Maria A; Yatsuhashi, Hiroshi; Niwa, Masami

    2014-03-01

    The effects of hepatocyte growth factor (HGF) on barrier functions were investigated by a blood-brain barrier (BBB) in vitro model comprising a primary culture of rat brain capillary endothelial cells (RBEC). In order to examine the response of the peripheral endothelial cells to HGF, human umbilical vascular endothelial cells (HUVEC) and human dermal microvascular endothelial cells (HMVEC) were also treated with HGF. HGF decreased the permeability of RBEC to sodium fluorescein and Evans blue albumin, and dose-dependently increased transendothelial electrical resistance (TEER) in RBEC. HGF altered the immunochemical staining pattern of F-actin bands and made ZO-1 staining more distinct on the linear cell borders in RBEC. In contrast, HGF increased sodium fluorescein and Evans blue albumin permeability in HMVEC and HUVEC, and decreased TEER in HMVEC. In HMVEC, HGF reduced cortical actin bands and increased stress fiber density, and increased the zipper-like appearance of ZO-1 staining. Western blot analysis showed that HGF significantly increased the amount of ZO-1 and VE-cadherin. HGF seems to act on the BBB to strengthen BBB integrity. These findings indicated that cytoskeletal rearrangement and cell-cell adhesion, such as through VE-cadherin and ZO-1, are candidate mechanisms for the influence of HGF on the BBB. The possibility that HGF has therapeutic significance in protecting the BBB from damage needs to be considered. PMID:24370951

  15. Application of microvascular free osteocutaneous flaps in the management of post-radiation recurrent oral cancer

    SciTech Connect

    Rosen, I.B.; Manktelow, R.T.; Zuker, R.M.; Boyd, B.

    1985-10-01

    Fifty-nine patients underwent free flap osteocutaneous reconstruction that consisted of flaps of the dorsum of the foot in 26 patients and iliac crest flaps in 33 with a success rate of 92 percent and a mortality rate of 1.6 percent. These flaps, which require the expertise of microvascular surgeons, are time-consuming and complicate operating room and time management, but they represent a remarkable advance in reconstruction that can facilitate cosmetic and functional recovery of the patient. In particular, they promote healing in radiation-recurrent oral cancer and represent a definitive form of management for established radionecrosis of the mandible. The large volume of tissue available with iliac crest osteocutaneous grafts permits the management of patients with extensive cancer involving the skin, mucosa, and bone, but cancer control may still be disappointing and there is a need for improved adjuvant chemotherapy protocols. This technique appears to be a dependable, repeatable, and significant advance in management of the patient with head and neck cancer.

  16. Hepatitis C virus infection induces elevation of CXCL10 in human brain microvascular endothelial cells.

    PubMed

    Liu, Yuan; Chen, Li; Zou, Ziying; Zhu, Bing; Hu, Zonghai; Zeng, Ping; Wu, Lijuan; Xiong, Jie

    2016-09-01

    Hepatitis C virus (HCV) primarily infects liver tissues, while pathogenesis of extrahepatic tissues has been reported. About 50% of patients with HCV infection suffer from neurological disease. The underlying molecular mechanisms remain unclear. In the present study, we aimed to investigate the induction of CXC chemokine ligand 10 (CXCL10) in human brain microvascular endothelial cells (HBMECs) by HCV infection. CXCL10 and its receptor CXCR3 were constitutively expressed in HBMECs. HCV infection induced CXCL10 elevation in HBMECs. The elevation of CXCL10 in HBMECs was eliminated when HCV infection was blocked by neutralizing antibodies. NF-κB is a positive regulator for CXCL10 transcription. HCV infection led to an increased phosphorylation of NF-κB (ser536) in HBMECs, and CXCL10 induced by HCV was slightly decreased when an inhibitor of NF-κB was added. IL1 beta and IFN gama were also upregulated in HCV infected HBMECs, and could be depressed by inhibitor of NF-κB. Thus, HCV infection leads to upregulated expression of CXCL10 in HBMECs, which is probably via the phosphorylation of NF-κB. The findings of this study provide potential mechanisms and novel targets for HCV induced neuroinflammation. J. Med. Virol. 88:1596-1603, 2016. © 2016 Wiley Periodicals, Inc.

  17. Speech aerodynamics and nasalance in oral cancer patients treated with microvascular transfers.

    PubMed

    Markkanen-Leppänen, Mari; Isotalo, Elina; Mäkitie, Antti A; Suominen, Erkki; Asko-Seljavaara, Sirpa; Haapanen, Marja-Leena

    2005-11-01

    The purpose of the current study was to assess speech aerodynamics and nasal acoustic energy during a follow-up period of 12 months in patients having undergone microvascular free flap reconstruction after tumor ablation from the oral cavity or oropharynx, usually followed by radiotherapy. Velopharyngeal function was assessed in terms of velopharyngeal orifice size by a pressure-flow measurement technique as well as by determining the instrumental correlate of perceived nasality (i.e., nasalance) during speech production. Velopharyngeal closure and nasalance were estimated to be adequate before operation both in oral cavity and oropharyngeal cancer patients. After the operation, at the group level, the oral cavity patients showed adequate velopharyngeal closure and nasalance. In contrast, the postoperative velopharynx orifice size was significantly bigger in the oropharyngeal cancer patients as compared with the oral cavity patients 6 months after operation. However, based on average aerodynamic as well as the nasalance data, the impairment of velopharyngeal function was not regarded clinically significant at the group level in either group of patients. The present treatment protocol served to maintain the prerequisites for normal or close to normal speech physiology.

  18. Continuous Dynamic Registration of Microvascularization of Liver Tumors with Contrast-Enhanced Ultrasound

    PubMed Central

    Wiesinger, Isabel; Stroszczynski, Christian; Wiggermann, Philipp; Jung, Ernst-Michael

    2014-01-01

    Aim. To evaluate the diagnostic value of quantification of liver tumor microvascularization using contrast-enhanced ultrasound (CEUS) measured continuously from the arterial phase to the late phase (3 minutes). Material and Methods. We present a retrospective analysis of 20 patients with malignant (n = 13) or benign (n = 7) liver tumors. The tumors had histopathologically been proven or clearly identified using contrast-enhanced reference imaging with either 1.5 T MRI (liver specific contrast medium) or triphase CT and follow-up. CEUS was performed using a multifrequency transducer (1–5 MHz) and a bolus injection of 2.4 mL sulphur hexafluoride microbubbles. A retrospective perfusion analysis was performed to determine TTP (time-to-peak), RBV (regional blood volume), RBF (regional blood flow), and Peak. Results. Statistics revealed a significant difference (P < 0.05) between benign and malignant tumors in the RBV, RBF, and Peak but not in TTP (P = 0.07). Receiver operating curves (ROC) were generated for RBV, RBF, Peak, and TTP with estimated ROC areas of 0.97, 0.96, 0.98, and 0.76, respectively. Conclusion. RBV, RBF, and Peak continuously measured over a determined time period of 3 minutes could be of valuable support in differentiating malignant from benign liver tumors. PMID:24991432

  19. The preparation and use of fluorescent-protein conjugates for microvascular research.

    PubMed

    McDonagh, P F; Williams, S K

    1984-01-01

    A procedure is described for making large quantities (100 ml) of fluorochrome-labeled albumin. Chromatographic techniques are described for the purification of commercial albumin (BSA) and the purification of albumin from serum. We report experimentally determined optimal conditions for the covalent attachment of fluorescent dyes (rhodamine isothiocyanate (RITC) and fluorescein isothiocyanate (FITC] to albumin. Subsequent removal of all unreacted fluorescent material (UFM) was achieved using charcoal adsorption. We observed no loss of protein following charcoal treatment. The final protein conjugate was analyzed by polyacrylamide gel electrophoresis, gel chromatography, and isoelectric focusing. The conjugates were determined to be free of UFM and homogeneous with respect to molecular weight. However, FITC conjugation lowered the average isoelectric point of albumin by 0.1 to 0.3 pH units. Illustrations of combining fluorescence microscopy with FITC-BSA and RITC-BSA to view microvascular phenomena in skeletal muscle and the heart are given. Knowledge of the biochemical characteristics of the fluorochrome employed is important for proper interpretation of experimental results using this technique.

  20. Microvascular architecture of the near-term uterine caruncles in water buffaloes (Bubalus bubalis).

    PubMed

    Abd-Elnaeim, M M M; Miglino, M A; Leiser, R

    2007-06-01

    The present investigation was carried out on five near-term pregnant water buffaloes for studying the microvascular architecture of the uterine caruncles. The vascular casts were obtained by injection of 4:1 mixture of mercox and methylmethacrylate through the branches of the uterine arteries. After complete polymerization of the plastic, corrosion was conducted in 20% potassium hydroxide, then the vessel casts were immersed in distilled water, cut into small pieces, sputter coated with gold, and examined by using a scanning electron microscope. The buffalo uterine caruncle is highly vascularized through two slightly convoluted arteries and a single less tortuous vein. The arteries branch into several stem arteries at the base of the uterine caruncle, which follow nearly straight course in the primary septa towards the fetal side. During the courses of these stem arteries arterioles of variable diameters arise. The arterioles run in the secondary and tertiary septae and at this location arterioles and venules are connected through a voluminous capillary complex. The latter consists of capillaries of greatly variable diameters with vigorous coiling and sinusoidally dilated zones. From the capillary complexes the blood is driven through postcapillary venules back to the tertiary, secondary and primary septa, respectively, and then converge into stem veins which leave the caruncles through the branches of the uterine vein.

  1. Bioglue-Coated Teflon Sling Technique in Microvascular Decompression for Hemifacial Spasm Involving the Vertebral Artery

    PubMed Central

    Lee, Seong Ho; Park, Jae Sung

    2016-01-01

    Objective Microvascular decompression (MVD) for hemifacial spasm (HFS) involving the vertebral artery (VA) can be technically challenging. We investigated the therapeutic effects of a bioglue-coated Teflon sling technique on the VA during MVD in 42 cases. Methods A bioglue-coated Teflon sling was crafted by the surgeon and applied to patients in whom neurovascular compression was caused by the VA. The radiologic data, intra-operative findings with detailed introduction of the procedure, and the clinical outcomes of each patient were reviewed and analyzed. Results The 42 patients included in the analysis consisted of 22 females and 20 males, with an average follow-up duration of 76 months (range 24–132 months). Intraoperative investigation revealed that an artery other than the VA was responsible for the neurovascular compression in all cases : posterior inferior cerebellar artery (PICA) in 23 patients (54.7%) and anterior inferior cerebellar artery (AICA) in 11 patients (26.2%). All patients became symptom-free after MVD. Neither recurrence nor postoperative neurological deficit was noted during the 2-year follow-up, except in one patient who developed permanent deafness. Cerebrospinal fluid (CSF) leak occurred in three patients, and one required dural repair. Conclusion Transposition of the VA using a bioglue-coated Teflon sling is a safe and effective surgical technique for HFS involving the VA. A future prospective study to compare clinical outcomes between groups with and without use of this novel technique is required.

  2. The Development and Future of Reconstructive and Microvascular Surgery of the Hand

    PubMed Central

    Malahias, Marco; Jordan, Daniel J; Hindocha, Sandip; Khan, Wasim; Juma, Ali

    2014-01-01

    The hand is often thought of as a key discriminator in what makes humans human. The hand is both intricate and fascinating in its design and function, allowing humans to interact with their surroundings, and each other. Due to its use in manipulation of the person’s environment, injury to the hand is common. Devastating hand injuries have a profound, physical, psychological, financial and socially crippling effect on patients. Advances in operative techniques and improvements in microscopes and instruments allowed Malt &McKhann to perform the first successful arm replantation in 1962 [1]. This was followed by a myriad of autologous free flaps of varying composition, that were discovered after the mapping of the cutaneous blood circulation by Taylor and Palmer [2] and Mathes & Nahai’s classification of muscle flaps [3] providing us with countless options to harvest and transfer healthy, well vascularised tissues into areas of injury. Since the late sixties, with the emerging subspecialty of microvascular reconstruction, surgeons have had the technical ability to salvage many amputated parts, even entire limbs. The measure of functional outcomemust incorporate the evaluation and severity ofthe initial injury and the subsequent reconstructive surgeries [4]. PMID:25408783

  3. RNA-seq analysis of transcriptomes in thrombin-treated and control human pulmonary microvascular endothelial cells.

    PubMed

    Cheranova, Dilyara; Gibson, Margaret; Chaudhary, Suman; Zhang, Li Qin; Heruth, Daniel P; Grigoryev, Dmitry N; Ye, Shui Qing

    2013-01-01

    The characterization of gene expression in cells via measurement of mRNA levels is a useful tool in determining how the transcriptional machinery of the cell is affected by external signals (e.g. drug treatment), or how cells differ between a healthy state and a diseased state. With the advent and continuous refinement of next-generation DNA sequencing technology, RNA-sequencing (RNA-seq) has become an increasingly popular method of transcriptome analysis to catalog all species of transcripts, to determine the transcriptional structure of all expressed genes and to quantify the changing expression levels of the total set of transcripts in a given cell, tissue or organism. RNA-seq is gradually replacing DNA microarrays as a preferred method for transcriptome analysis because it has the advantages of profiling a complete transcriptome, providing a digital type datum (copy number of any transcript) and not relying on any known genomic sequence. Here, we present a complete and detailed protocol to apply RNA-seq to profile transcriptomes in human pulmonary microvascular endothelial cells with or without thrombin treatment. This protocol is based on our recent published study entitled "RNA-seq Reveals Novel Transcriptome of Genes and Their Isoforms in Human Pulmonary Microvascular Endothelial Cells Treated with Thrombin," in which we successfully performed the first complete transcriptome analysis of human pulmonary microvascular endothelial cells treated with thrombin using RNA-seq. It yielded unprecedented resources for further experimentation to gain insights into molecular mechanisms underlying thrombin-mediated endothelial dysfunction in the pathogenesis of inflammatory conditions, cancer, diabetes, and coronary heart disease, and provides potential new leads for therapeutic targets to those diseases. The descriptive text of this protocol is divided into four parts. The first part describes the treatment of human pulmonary microvascular endothelial cells with

  4. RNA-seq analysis of transcriptomes in thrombin-treated and control human pulmonary microvascular endothelial cells.

    PubMed

    Cheranova, Dilyara; Gibson, Margaret; Chaudhary, Suman; Zhang, Li Qin; Heruth, Daniel P; Grigoryev, Dmitry N; Ye, Shui Qing

    2013-02-13

    The characterization of gene expression in cells via measurement of mRNA levels is a useful tool in determining how the transcriptional machinery of the cell is affected by external signals (e.g. drug treatment), or how cells differ between a healthy state and a diseased state. With the advent and continuous refinement of next-generation DNA sequencing technology, RNA-sequencing (RNA-seq) has become an increasingly popular method of transcriptome analysis to catalog all species of transcripts, to determine the transcriptional structure of all expressed genes and to quantify the changing expression levels of the total set of transcripts in a given cell, tissue or organism. RNA-seq is gradually replacing DNA microarrays as a preferred method for transcriptome analysis because it has the advantages of profiling a complete transcriptome, providing a digital type datum (copy number of any transcript) and not relying on any known genomic sequence. Here, we present a complete and detailed protocol to apply RNA-seq to profile transcriptomes in human pulmonary microvascular endothelial cells with or without thrombin treatment. This protocol is based on our recent published study entitled "RNA-seq Reveals Novel Transcriptome of Genes and Their Isoforms in Human Pulmonary Microvascular Endothelial Cells Treated with Thrombin," in which we successfully performed the first complete transcriptome analysis of human pulmonary microvascular endothelial cells treated with thrombin using RNA-seq. It yielded unprecedented resources for further experimentation to gain insights into molecular mechanisms underlying thrombin-mediated endothelial dysfunction in the pathogenesis of inflammatory conditions, cancer, diabetes, and coronary heart disease, and provides potential new leads for therapeutic targets to those diseases. The descriptive text of this protocol is divided into four parts. The first part describes the treatment of human pulmonary microvascular endothelial cells with

  5. Studies of pathological dynamics after microvascular injury using nonlinear optical methods

    NASA Astrophysics Data System (ADS)

    Rosidi, Nathanael L.

    Microvascular lesions are a common feature in the aging brain and clinical evidence has correlated microvascular pathology with the development of neurodegenerative diseases such as Alzheimer's disease and dementia. Traditional animal models that replicate hemorrhagic and ischemic lesions in the brain typically affect large regions in the cortex and do not reproduce the small-scale lesions linked to neurodegeneration that likely stem from injuries to single microvessels. Due in part to this lack of small-scale injury animal models, there remains an incomplete understanding of the cellular and pathophysiological dynamics following small-scale vascular lesions, making progress on therapeutic strategies difficult. We used tightly focused femtosecond laser pulses to injure single penetrating arterioles (PA) (i.e., arterioles that plunge into the brain) in the cortex of live anesthetized rodents and used two-photon excited fluorescence (2PEF) imaging to quantify blood flow changes and to determine the time course of pathological consequences in the brain after injury. We find that after ischemic occlusion of a PA, nearby pial and penetrating arterioles do not actively compensate for the reduction of blood flow observed near the occluded blood vessel. We find that capillaries connected downstream to the clotted vessel dilate but other capillaries in the vicinity do not, suggesting that any compensatory signal that results in a physiological response travels vascularly. We ruptured individual PAs to induce microhemorrhages that resulted in extravasation of blood into the parenchyma. We find that tissue compression due to the hematoma does not collapse capillaries and cause acute ischemia. 2PEF imaging of mice expressing yellow fluorescent protein (YFP) in a subset of cortical neurons revealed no dendrite degeneration out to seven days after microhemorrhage. However, we did observe an inflammatory response by microglia/macrophages as quickly as 1.5-hrs after

  6. A novel effective method for the assessment of microvascular function in male patients with coronary artery disease: a pilot study using laser speckle contrast imaging.

    PubMed

    Borges, J P; Lopes, G O; Verri, V; Coelho, M P; Nascimento, P M C; Kopiler, D A; Tibirica, E

    2016-01-01

    Evaluation of microvascular endothelial function is essential for investigating the pathophysiology and treatment of cardiovascular and metabolic diseases. Although laser speckle contrast imaging technology is well accepted as a noninvasive methodology for assessing microvascular endothelial function, it has never been used to compare male patients with coronary artery disease with male age-matched healthy controls. Thus, the aim of this study was to determine whether laser speckle contrast imaging could be used to detect differences in the systemic microvascular functions of patients with established cardiovascular disease (n=61) and healthy age-matched subjects (n=24). Cutaneous blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with the transdermal iontophoretic delivery of acetylcholine and post-occlusive reactive hyperemia. The maximum increase in skin blood flow induced by acetylcholine was significantly reduced in the cardiovascular disease patients compared with the control subjects (74 vs 116%; P<0.01). With regard to post-occlusive reactive hyperemia-induced vasodilation, the patients also presented reduced responses compared to the controls (0.42±0.15 vs 0.50±0.13 APU/mmHg; P=0.04). In conclusion, laser speckle contrast imaging can identify endothelial and microvascular dysfunctions in male individuals with cardiovascular disease. Thus, this technology appears to be an efficient non-invasive technique for evaluating systemic microvascular and endothelial functions, which could be valuable as a peripheral marker of atherothrombotic diseases in men. PMID:27599202

  7. A novel effective method for the assessment of microvascular function in male patients with coronary artery disease: a pilot study using laser speckle contrast imaging

    PubMed Central

    Borges, J.P.; Lopes, G.O.; Verri, V.; Coelho, M.P.; Nascimento, P.M.C.; Kopiler, D.A.; Tibirica, E.

    2016-01-01

    Evaluation of microvascular endothelial function is essential for investigating the pathophysiology and treatment of cardiovascular and metabolic diseases. Although laser speckle contrast imaging technology is well accepted as a noninvasive methodology for assessing microvascular endothelial function, it has never been used to compare male patients with coronary artery disease with male age-matched healthy controls. Thus, the aim of this study was to determine whether laser speckle contrast imaging could be used to detect differences in the systemic microvascular functions of patients with established cardiovascular disease (n=61) and healthy age-matched subjects (n=24). Cutaneous blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with the transdermal iontophoretic delivery of acetylcholine and post-occlusive reactive hyperemia. The maximum increase in skin blood flow induced by acetylcholine was significantly reduced in the cardiovascular disease patients compared with the control subjects (74 vs 116%; P<0.01). With regard to post-occlusive reactive hyperemia-induced vasodilation, the patients also presented reduced responses compared to the controls (0.42±0.15 vs 0.50±0.13 APU/mmHg; P=0.04). In conclusion, laser speckle contrast imaging can identify endothelial and microvascular dysfunctions in male individuals with cardiovascular disease. Thus, this technology appears to be an efficient non-invasive technique for evaluating systemic microvascular and endothelial functions, which could be valuable as a peripheral marker of atherothrombotic diseases in men. PMID:27599202

  8. A novel effective method for the assessment of microvascular function in male patients with coronary artery disease: a pilot study using laser speckle contrast imaging.

    PubMed

    Borges, J P; Lopes, G O; Verri, V; Coelho, M P; Nascimento, P M C; Kopiler, D A; Tibirica, E

    2016-09-01

    Evaluation of microvascular endothelial function is essential for investigating the pathophysiology and treatment of cardiovascular and metabolic diseases. Although laser speckle contrast imaging technology is well accepted as a noninvasive methodology for assessing microvascular endothelial function, it has never been used to compare male patients with coronary artery disease with male age-matched healthy controls. Thus, the aim of this study was to determine whether laser speckle contrast imaging could be used to detect differences in the systemic microvascular functions of patients with established cardiovascular disease (n=61) and healthy age-matched subjects (n=24). Cutaneous blood flow was assessed in the skin of the forearm using laser speckle contrast imaging coupled with the transdermal iontophoretic delivery of acetylcholine and post-occlusive reactive hyperemia. The maximum increase in skin blood flow induced by acetylcholine was significantly reduced in the cardiovascular disease patients compared with the control subjects (74 vs 116%; P<0.01). With regard to post-occlusive reactive hyperemia-induced vasodilation, the patients also presented reduced responses compared to the controls (0.42±0.15 vs 0.50±0.13 APU/mmHg; P=0.04). In conclusion, laser speckle contrast imaging can identify endothelial and microvascular dysfunctions in male individuals with cardiovascular disease. Thus, this technology appears to be an efficient non-invasive technique for evaluating systemic microvascular and endothelial functions, which could be valuable as a peripheral marker of atherothrombotic diseases in men.

  9. Pharmacological versus microvascular decompression approaches for the treatment of trigeminal neuralgia: clinical outcomes and direct costs

    PubMed Central

    Lemos, Laurinda; Alegria, Carlos; Oliveira, Joana; Machado, Ana; Oliveira, Pedro; Almeida, Armando

    2011-01-01

    In idiopathic trigeminal neuralgia (TN) the neuroimaging evaluation is usually normal, but in some cases a vascular compression of trigeminal nerve root is present. Although the latter condition may be referred to surgery, drug therapy is usually the first approach to control pain. This study compared the clinical outcome and direct costs of (1) a traditional treatment (carbamazepine [CBZ] in monotherapy [CBZ protocol]), (2) the association of gabapentin (GBP) and analgesic block of trigger-points with ropivacaine (ROP) (GBP+ROP protocol), and (3) a common TN surgery, microvascular decompression of the trigeminal nerve (MVD protocol). Sixty-two TN patients were randomly treated during 4 weeks (CBZ [n = 23] and GBP+ROP [n = 17] protocols) from cases of idiopathic TN, or selected for MVD surgery (n = 22) due to intractable pain. Direct medical cost estimates were determined by the price of drugs in 2008 and the hospital costs. Pain was evaluated using the Numerical Rating Scale (NRS) and number of pain crises; the Hospital Anxiety and Depression Scale, Sickness Impact Profile, and satisfaction with treatment and hospital team were evaluated. Assessments were performed at day 0 and 6 months after the beginning of treatment. All protocols showed a clinical improvement of pain control at month 6. The GBP+ROP protocol was the least expensive treatment, whereas surgery was the most expensive. With time, however, GBP+ROP tended to be the most and MVD the least expensive. No sequelae resulted in any patient after drug therapies, while after MDV surgery several patients showed important side effects. Data reinforce that, (1) TN patients should be carefully evaluated before choosing therapy for pain control, (2) different pharmacological approaches are available to initiate pain control at low costs, and (3) criteria for surgical interventions should be clearly defined due to important side effects, with the initial higher costs being strongly reduced with time. PMID:21941455

  10. Effects of cold on microvascular fluid movement in the cat limb.

    PubMed

    Zhang, J X; Wolf, M B

    1991-08-01

    We investigated the effects of low temperatures down to approximately 5 degrees C on postcapillary resistance (Rv) and isogravimetric capillary pressure (Pci) in the isolated constant-flow-perfused cat hindlimb to see if a low-temperature-induced increase in Rv and decrease in Pci could lead to an increase in filtration pressure and edema formation. A low-viscosity perfusate (20% cat plasma, 80% albumin-electrolyte solution; viscosity approximately 1 cP) was used. Isoproterenol (10(-7) M) was added to vasodilate the limb and achieve normal microvascular permeability. Rv and Pci were estimated from the slope and zero-flow intercept, respectively, of the straight-line fit to the isogravimetric venous pressure vs. flow data. Rv and Pci were determined in each experiment at an initial 37 degrees C control, at a lowered temperature (30, 23, 15, or 5-10 degrees C), and then at 37 degrees C again. The ratio of Rv at the low temperatures relative to the initial 37 degrees C control increased almost linearly as temperature was reduced. The increase was 3.4 times control at the lowest temperature. Pci decreased significantly from control only in the lowest temperature group where the change was -5.4 mmHg. Analysis of our data with the low-viscosity perfusate shows that the limb can become edematous if temperature is lowered to approximately 5 degrees C unless venous pressure (Pv) is lowered to venous collapse and flow reduced to less than approximately 20 ml.min-1.100g-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1938745

  11. Secretory phospholipase A2 inhibitor PX-18 preserves microvascular reactivity after cerebral ischemia in piglets.

    PubMed

    Domoki, Ferenc; Zimmermann, Alíz; Lenti, Laura; Tóth-Szuki, Valéria; Pardeike, Jana; Müller, Rainer H; Bari, Ferenc

    2009-09-01

    Cerebral ischemia/reperfusion (I/R) results in cellular energy failure and dysfunction of the neurovascular unit that contribute to subsequent neuronal cell death in the neonate. PX-18 is a putative neuroprotective inhibitor of secretory phospholipase A(2) (sPLA(2)) but its in vivo testing has been limited by its poor solubility. Our purpose was to assess whether PX-18 preserved neuronal-vascular reactivity to I/R-sensitive endothelium-dependent (hypercapnia, bradykinin) and/or neuron-dependent (N-methyl-D-aspartate; NMDA) stimuli. To make the drug available for in vivo studies, PX-18 was formulated as a 3% nanosuspension applying high pressure homogenization. Newborn piglets (1-day old, n=40) were anesthetized and ventilated, and cerebrovascular reactivity to the above stimuli was determined by measuring changes in pial arteriolar diameters using the closed cranial window/intravital videomicroscopy technique. Intravenous infusion of PX-18 nanosuspension (6 mg/kg, 20 min) did not affect baseline arteriolar diameters, or hypercapnia-, bradykinin-, or NMDA-induced pial arteriolar vasodilation under normoxic conditions. Global cerebral ischemia (10 min) followed by 1 h of reperfusion significantly attenuated hypercapnia-, bradykinin-, and NMDA-induced vasodilation in untreated or vehicle-treated controls. However, PX-18 resulted in nearly full preservation of cerebrovascular reactivity to all these stimuli. In conclusion, inhibition of sPLA(2) by PX-18 improves neurovascular function both at the neuronal and the microvascular level following I/R. This effect of PX-18 likely contributes to its neuroprotective effect. PMID:19555699

  12. Transient increase in interleukin-8 and pulmonary microvascular permeability following aortic surgery.

    PubMed

    Raijmakers, P G; Groeneveld, A B; Rauwerda, J A; Schneider, A J; Teule, G J; Hack, C E; Thijs, L G

    1995-03-01

    Aortic surgery results in ischemia/reperfusion of the lower body. This may liberate inflammatory mediators that activate neutrophils, and may result in lung microvascular changes with increased permeability and respiratory failure. We studied circulating inflammatory mediators and the pulmonary leak index (PLI) of 67Ga, a measure of transvascular transferrin transport and permeability, in patients scheduled for elective aortic and peripheral vascular surgery, before and after surgery. Aortic surgery patients in Groups 1 (n = 10) and 2 (n = 7) were studied before and at a median of 2.5 and 21.0 h after surgery, respectively. A control Group 3 (n = 6) was studied before and at a median of 2.9 h after peripheral vascular surgery. The PLI (median) increased from a median of 9.1 (range, 6.6 to 14.7) before to a median of 23.4 (range, 18.7 to 86.4) x 10(-3)/min after surgery in Group 1 but not in the other groups (p < 0.001). The postoperative increase in circulating neutrophils and elastase-alpha 1-antitrypsin, a marker of neutrophil activation, was similar among the groups. Plasma levels of activated complement 3a and tumor necrosis factor (TNF-alpha) did not change in any of the groups. In contrast, plasma levels of interleukin-8 (IL-8) increased in Group 1 from < 3 (range, < 3 to 37) before to 324 (range, 36 to 868) pg/ml after surgery, but did not change in the other groups (p < 0.005). The decrease in plasma levels of angiotensin converting enzyme (ACE) was greater in Group 1 than in the other groups (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Differential regulation of TRPV1 channels by H2O2: implications for diabetic microvascular dysfunction.

    PubMed

    DelloStritto, Daniel J; Connell, Patrick J; Dick, Gregory M; Fancher, Ibra S; Klarich, Brittany; Fahmy, Joseph N; Kang, Patrick T; Chen, Yeong-Renn; Damron, Derek S; Thodeti, Charles K; Bratz, Ian N

    2016-03-01

    We demonstrated previously that TRPV1-dependent coupling of coronary blood flow (CBF) to metabolism is disrupted in diabetes. A critical amount of H2O2 contributes to CBF regulation; however, excessive H2O2 impairs responses. We sought to determine the extent to which differential regulation of TRPV1 by H2O2 modulates CBF and vascular reactivity in diabetes. We used contrast echocardiography to study TRPV1 knockout (V1KO), db/db diabetic, and wild type C57BKS/J (WT) mice. H2O2 dose-dependently increased CBF in WT mice, a response blocked by the TRPV1 antagonist SB366791. H2O2-induced vasodilation was significantly inhibited in db/db and V1KO mice. H2O2 caused robust SB366791-sensitive dilation in WT coronary microvessels; however, this response was attenuated in vessels from db/db and V1KO mice, suggesting H2O2-induced vasodilation occurs, in part, via TRPV1. Acute H2O2 exposure potentiated capsaicin-induced CBF responses and capsaicin-mediated vasodilation in WT mice, whereas prolonged luminal H2O2 exposure blunted capsaicin-induced vasodilation. Electrophysiology studies re-confirms acute H2O2 exposure activated TRPV1 in HEK293A and bovine aortic endothelial cells while establishing that H2O2 potentiate capsaicin-activated TRPV1 currents, whereas prolonged H2O2 exposure attenuated TRPV1 currents. Verification of H2O2-mediated activation of intrinsic TRPV1 specific currents were found in isolated mouse coronary endothelial cells from WT mice and decreased in endothelial cells from V1KO mice. These data suggest prolonged H2O2 exposure impairs TRPV1-dependent coronary vascular signaling. This may contribute to microvascular dysfunction and tissue perfusion deficits characteristic of diabetes.

  14. Management of patients with type 2 diabetes before and after bariatric surgery: evolution and microvascular complications.

    PubMed

    Chuah, L L; le Roux, Carel W

    2013-03-01

    Bariatric surgery is increasingly seen as a treatment option for patient with type 2 diabetes (T2DM) and severe complex obesity (SCO). There is however no consensus on how to manage this cohort preoperatively and postoperatively. Patients with T2DM having cardiac surgery benefit from glycaemic optimisation prior to surgery. National Health Service Diabetes in the United Kingdom recommends that glucose is optimised prior to all elective surgery. However, bariatric surgery such as gastric bypass (RYGB) is distinct from general surgery. Glycaemic control improves immediately after RYGB and thus all T2DM patients need a review of their glucose lowering medications postoperatively. Preoperatively most bariatric centres use a low calorie diet (LCD) which improved glycaemic control and may predisposed patients using insulin or sulphonylureas to risks of hypoglycaemia. There are no protocols and consensus among bariatric centres on how best to manage patients with T2DM preoperatively and postoperatively. Moreover patients with difficult to control T2DM are at risk of microvascular complications of diabetes. So far, there is little evidence on the impact of bariatric surgery on diabetes nephropathy, retinopathy and neuropathy. In conclusion, bariatric surgery improves glycaemic control; however, there are limited studies, and no guidelines on how to manage patients with T2DM pre and postoperatively. Given the increasing proportion of T2DM patients referred for bariatric surgery, there is a need to review current practice on how to manage these patients in the short term and long term with a specific focus on improving end organ damage such as retinopathy, neuropathy and nephropathy.

  15. Glial cell ceruloplasmin and hepcidin differentially regulate iron efflux from brain microvascular endothelial cells.

    PubMed

    McCarthy, Ryan C; Kosman, Daniel J

    2014-01-01

    We have used an in vitro model system to probe the iron transport pathway across the brain microvascular endothelial cells (BMVEC) of the blood-brain barrier (BBB). This model consists of human BMVEC (hBMVEC) and C6 glioma cells (as an astrocytic cell line) grown in a transwell, a cell culture system commonly used to quantify metabolite flux across a cell-derived barrier. We found that iron efflux from hBMVEC through the ferrous iron permease ferroportin (Fpn) was stimulated by secretion of the soluble form of the multi-copper ferroxidase, ceruloplasmin (sCp) from the co-cultured C6 cells. Reciprocally, expression of sCp mRNA in the C6 cells was increased by neighboring hBMVEC. In addition, data indicate that C6 cell-secreted hepcidin stimulates internalization of hBMVEC Fpn but only when the end-feet projections characteristic of this glia-derived cell line are proximal to the endothelial cells. This hepcidin-dependent loss of Fpn correlated with knock-down of iron efflux from the hBMVEC; this result was consistent with the mechanism by which hepcidin regulates iron efflux in mammalian cells. In summary, the data support a model of iron trafficking across the BBB in which the capillary endothelium induce the underlying astrocytes to produce the ferroxidase activity needed to support Fpn-mediated iron efflux. Reciprocally, astrocyte proximity modulates the effective concentration of hepcidin at the endothelial cell membrane and thus the surface expression of hBMVEC Fpn. These results are independent of the source of hBMVEC iron (transferrin or non-transferrin bound) indicating that the model developed here is broadly applicable to brain iron homeostasis.

  16. Preserved Microvascular Endothelial Function in Young, Obese Adults with Functional Loss of Nitric Oxide Signaling

    PubMed Central

    Harrell, John W.; Johansson, Rebecca E.; Evans, Trent D.; Sebranek, Joshua J.; Walker, Benjamin J.; Eldridge, Marlowe W.; Serlin, Ronald C.; Schrage, William G.

    2015-01-01

    Data indicate endothelium-dependent dilation (EDD) may be preserved in the skeletal muscle microcirculation of young, obese adults. Preserved EDD might be mediated by compensatory mechanisms, impeding insight into preclinical vascular dysfunction. We aimed to determine the functional roles of nitric oxide synthase (NOS) and cyclooxygenase (COX) toward EDD in younger obese adults. We first hypothesized EDD would be preserved in young, obese adults. Further, we hypothesized a reduced contribution of NOS in young, obese adults would be replaced by increased COX signaling. Microvascular EDD was assessed with Doppler ultrasound and brachial artery infusion of acetylcholine (ACh) in younger (27 ± 1 year) obese (n = 29) and lean (n = 46) humans. Individual and combined contributions of NOS and COX were examined with intra-arterial infusions of l-NMMA and ketorolac, respectively. Vasodilation was quantified as an increase in forearm vascular conductance (ΔFVC). Arterial endothelial cell biopsies were analyzed for protein expression of endothelial nitric oxide synthase (eNOS). ΔFVC to ACh was similar between groups. After l-NMMA, ΔFVC to ACh was greater in obese adults (p < 0.05). There were no group differences in ΔFVC to ACh with ketorolac. With combined NOS-COX inhibition, ΔFVC was greater in obese adults at the intermediate dose of ACh. Surprisingly, arterial endothelial cell eNOS and phosphorylated eNOS were similar between groups. Younger obese adults exhibit preserved EDD and eNOS expression despite functional dissociation of NOS-mediated vasodilation and similar COX signaling. Compensatory NOS- and COX-independent vasodilatory mechanisms conceal reduced NOS contributions in otherwise healthy obese adults early in life, which may contribute to vascular dysfunction. PMID:26733880

  17. Action of Shiga Toxin Type-2 and Subtilase Cytotoxin on Human Microvascular Endothelial Cells

    PubMed Central

    Amaral, María M.; Sacerdoti, Flavia; Jancic, Carolina; Repetto, Horacio A.; Paton, Adrienne W.; Paton, James C.; Ibarra, Cristina

    2013-01-01

    The hemolytic uremic syndrome (HUS) associated with diarrhea is a complication of Shiga toxin (Stx)-producing Escherichia coli (STEC) infection. In Argentina, HUS is endemic and responsible for acute and chronic renal failure in children younger than 5 years old. The human kidney is the most affected organ due to the presence of very Stx-sensitive cells, such as microvascular endothelial cells. Recently, Subtilase cytotoxin (SubAB) was proposed as a new toxin that may contribute to HUS pathogenesis, although its action on human glomerular endothelial cells (HGEC) has not been described yet. In this study, we compared the effects of SubAB with those caused by Stx2 on primary cultures of HGEC isolated from fragments of human pediatric renal cortex. HGEC were characterized as endothelial since they expressed von Willebrand factor (VWF) and platelet/endothelial cell adhesion molecule 1 (PECAM-1). HGEC also expressed the globotriaosylceramide (Gb3) receptor for Stx2. Both, Stx2 and SubAB induced swelling and detachment of HGEC and the consequent decrease in cell viability in a time-dependent manner. Preincubation of HGEC with C-9 −a competitive inhibitor of Gb3 synthesis-protected HGEC from Stx2 but not from SubAB cytotoxic effects. Stx2 increased apoptosis in a time-dependent manner while SubAB increased apoptosis at 4 and 6 h but decreased at 24 h. The apoptosis induced by SubAB relative to Stx2 was higher at 4 and 6 h, but lower at 24 h. Furthermore, necrosis caused by Stx2 was significantly higher than that induced by SubAB at all the time points evaluated. Our data provide evidence for the first time how SubAB could cooperate with the development of endothelial damage characteristic of HUS pathogenesis. PMID:23936204

  18. Retinal microvascular caliber and chronic kidney disease in an Asian population.

    PubMed

    Sabanayagam, Charumathi; Shankar, Anoop; Koh, David; Chia, Kee Seng; Saw, Seang Mei; Lim, Su Chi; Tai, E Shyong; Wong, Tien Yin

    2009-03-01

    Retinal arteriolar narrowing is a marker of microvascular damage from elevated blood pressure. Between August 2004 and June 2006, the authors examined the association between retinal vascular diameter and chronic kidney disease in a population-based cohort of 3,280 community-dwelling adults of Malay ethnicity aged 40-80 years living in Singapore. Chronic kidney disease was defined as 1) an estimated glomerular filtration rate (eGFR) of <60 mL/minute/1.73 m(2) from serum creatinine or 2) the presence of micro/macroalbuminuria defined as urinary albumin:creatinine ratios of > or = 17 mg/g for men and > or = 25 mg/g for women. Retinal arteriolar and venular diameters were measured and summarized as central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). Individuals with reduced CRAE were more likely to have chronic kidney disease than those with increased CRAE. After controlling for age, gender, education, smoking, diabetes, hypertension, body mass index, and total and high density lipoprotein cholesterol, the authors found the odds ratio comparing the smallest with the largest CRAE quartile to be 1.42 (95% confidence interval: 1.03, 1.96; P(trend) = 0.02) for eGFR of <60 mL/minute/1.73 m(2) and 1.80 (95% confidence interval: 1.11, 2.91; P(trend) = 0.01) for micro/macroalbuminuria. Retinopathy was also found to be positively associated with both eGFR and micro/macroalbuminuria. Retinal venular diameter was not associated with chronic kidney disease. These data suggest that retinal arteriolar narrowing is associated with chronic kidney disease, independent of diabetes and hypertension. PMID:19092170

  19. A unique pulmonary microvascular endothelial cell niche revealed by Weibel-Palade bodies and Griffonia simplicifolia

    PubMed Central

    Stevens, Troy

    2014-01-01

    Abstract Pulmonary endothelium displays considerable heterogeneity along the vascular axis, from arteries to capillaries to veins. Griffonia simplicifolia is a lectin that recognizes pulmonary microvascular endothelium with preference over extra-alveolar endothelium in both arteries and veins, yet the precise vascular location where this phenotypic shift occurs is poorly resolved. We gelatin-filled the circulation and agarose-loaded the airways and then labeled the lung with Griffonia lectin to enable visualization of the endothelial transition zone. Endothelium in vessels with internal diameters less than 38 μm were uniformly Griffonia positive, whereas vessels with internal diameters greater than 60 μm were always Griffonia negative. Two populations of endothelium were identified in vessels ranging from 38 to 60 μm in diameter, including some that were positive and others that were negative for binding to G. simplicifolia. To better resolve this endothelial transition zone, we performed morphology studies to measure the distribution of Weibel-Palade bodies (WPbs), since WPbs are present in conduit vessel endothelium and absent in capillary endothelium. WPbs were found in endothelium with vascular dimensions as small as 18 μm in diameter but were not found in capillaries. Thus, we identify with precision that the endothelial phenotype transition from a cell that does not interact with Griffonia lectin to one that does occurs in blood vessels with internal diameters of approximately 38 μm, and we reveal an unappreciated vascular zone, between 18 and 38 μm in diameter, where endothelium both is Griffonia positive and possesses WPbs. PMID:25006426

  20. A unique pulmonary microvascular endothelial cell niche revealed by Weibel-Palade bodies and Griffonia simplicifolia.

    PubMed

    Wu, Songwei; Zhou, Chun; King, Judy A C; Stevens, Troy

    2014-03-01

    Pulmonary endothelium displays considerable heterogeneity along the vascular axis, from arteries to capillaries to veins. Griffonia simplicifolia is a lectin that recognizes pulmonary microvascular endothelium with preference over extra-alveolar endothelium in both arteries and veins, yet the precise vascular location where this phenotypic shift occurs is poorly resolved. We gelatin-filled the circulation and agarose-loaded the airways and then labeled the lung with Griffonia lectin to enable visualization of the endothelial transition zone. Endothelium in vessels with internal diameters less than 38 μm were uniformly Griffonia positive, whereas vessels with internal diameters greater than 60 μm were always Griffonia negative. Two populations of endothelium were identified in vessels ranging from 38 to 60 μm in diameter, including some that were positive and others that were negative for binding to G. simplicifolia. To better resolve this endothelial transition zone, we performed morphology studies to measure the distribution of Weibel-Palade bodies (WPbs), since WPbs are present in conduit vessel endothelium and absent in capillary endothelium. WPbs were found in endothelium with vascular dimensions as small as 18 μm in diameter but were not found in capillaries. Thus, we identify with precision that the endothelial phenotype transition from a cell that does not interact with Griffonia lectin to one that does occurs in blood vessels with internal diameters of approximately 38 μm, and we reveal an unappreciated vascular zone, between 18 and 38 μm in diameter, where endothelium both is Griffonia positive and possesses WPbs.

  1. Ghrelin protects musculocutaneous tissue from ischemic necrosis by improving microvascular perfusion.

    PubMed

    Rezaeian, F; Wettstein, R; Scheuer, C; Bäumker, K; Bächle, A; Vollmar, B; Menger, M D; Harder, Y

    2012-02-01

    Persistent ischemia in musculocutaneous tissue may lead to wound breakdown and necrosis. The objective of this experimental study was to analyze, whether the gastric peptide ghrelin prevents musculocutaneous tissue from necrosis and to elucidate underlying mechanisms. Thirty-two C57BL/6 mice equipped with a dorsal skinfold chamber containing ischemic musculocutaneous tissue were allocated to four groups: 1) ghrelin; 2) N(ω)-nitro-l-arginine methyl ester (l-NAME); 3) ghrelin and l-NAME; and 4) control. Microcirculation, inflammation, angiogenesis, and tissue survival were assessed by fluorescence microscopy. Inducible and endothelial nitric oxide synthase (iNOS I and eNOS), vascular endothelial growth factor (VEGF), as well as nuclear factor κB (NF-κB) were assessed by Western blot analysis. Ghrelin-treated animals showed an increased expression of iNOS and eNOS in critically perfused tissue compared with controls. This was associated with arteriolar dilation, increased arteriolar perfusion, and a sustained functional capillary density. Ghrelin further upregulated NF-κB and VEGF and induced angiogenesis. Finally, ghrelin reduced microvascular leukocyte-endothelial cell interactions, apoptosis, and overall tissue necrosis (P < 0.05 vs. control). Inhibition of nitric oxide by l-NAME did not affect the anti-inflammatory and angiogenic action of ghrelin but completely blunted the ghrelin-induced tissue protection by abrogating the arteriolar dilation, the improved capillary perfusion, and the increased tissue survival. Ghrelin prevents critically perfused tissue from ischemic necrosis. Tissue protection is the result of a nitric oxide synthase-mediated improvement of the microcirculation but not due to induction of angiogenesis or attenuation of inflammation. This might represent a promising, noninvasive, and clinically applicable approach to protect musculocutaneous tissue from ischemia. PMID:22159999

  2. Alternative erythropoietin-mediated signaling prevents secondary microvascular thrombosis and inflammation within cutaneous burns.

    PubMed

    Bohr, Stefan; Patel, Suraj J; Shen, Keyue; Vitalo, Antonia G; Brines, Michael; Cerami, Anthony; Berthiaume, Francois; Yarmush, Martin L

    2013-02-26

    Alternate erythropoietin (EPO)-mediated signaling via the heteromeric receptor composed of the EPO receptor and the β-common receptor (CD131) exerts the tissue-protective actions of EPO in various types of injuries. Herein we investigated the effects of the EPO derivative helix beta surface peptide (synonym: ARA290), which specifically triggers alternate EPO-mediated signaling, but does not bind the erythropoietic EPO receptor homodimer, on the progression of secondary tissue damage following cutaneous burns. For this purpose, a deep partial thickness cutaneous burn injury was applied on the back of mice, followed by systemic administration of vehicle or ARA290 at 1, 12, and 24 h postburn. With vehicle-only treatment, wounds exhibited secondary microvascular thrombosis within 24 h postburn, and subsequent necrosis of the surrounding tissue, thus converting to a full-thickness injury within 48 h. On the other hand, when ARA290 was systemically administered, patency of the microvasculature was maintained. Furthermore, ARA290 mitigated the innate inflammatory response, most notably tumor necrosis factor-alpha-mediated signaling. These findings correlated with long-term recovery of initially injured yet viable tissue components. In conclusion, ARA290 may be a promising therapeutic approach to prevent the conversion of partial- to full-thickness burn injuries. In a clinical setting, the decrease in burn depth and area would likely reduce the necessity for extensive surgical debridement as well as secondary wound closure by means of skin grafting. This use of ARA290 is consistent with its tissue-protective properties previously reported in other models of injury, such as myocardial infarction and hemorrhagic shock. PMID:23401545

  3. Altered long non-coding RNA transcriptomic profiles in brain microvascular endothelium after cerebral ischemia.

    PubMed

    Zhang, J; Yuan, L; Zhang, X; Hamblin, M H; Zhu, T; Meng, F; Li, Y; Chen, Y E; Yin, K J

    2016-03-01

    The brain endothelium is an important therapeutic target for the inhibition of cerebrovascular dysfunction in ischemic stroke. Previously, we documented the important regulatory roles of microRNAs in the cerebral vasculature, in particular the cerebral vascular endothelium. However, the functional significance and molecular mechanisms of other classes of non-coding RNAs in the regulation of cerebrovascular endothelial pathophysiology after stroke are completely unknown. Using RNA sequencing (RNA-seq) technology, we profiled long non-coding RNA (lncRNA) expressional signatures in primary brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation (OGD), an in vitro mimic of ischemic stroke conditions. After 16h of OGD exposure, the expression levels for 362 of the 10,677 lncRNAs analyzed changed significantly, including a total of 147 lncRNAs increased and 70 lncRNAs decreased by more than 2-fold. Among them, the most highly upregulated lncRNAs include Snhg12, Malat1, and lnc-OGD 1006, whereas the most highly downregulated lncRNAs include 281008D09Rik, Peg13, and lnc-OGD 3916. Alteration of the most highly upregulated/downregulated ODG-responsive lncRNAs was further confirmed in cultured BMECs after OGD as well as isolated cerebral microvessels in mice following transient middle cerebral artery occlusion (MCAO) and 24h reperfusion by the quantitative real-time PCR approach. Moreover, promoter analysis of altered ODG-responsive endothelial lncRNA genes by bioinformatics showed substantial transcription factor binding sites on lncRNAs, implying potential transcriptional regulation of those lncRNAs. These findings are the first to identify OGD-responsive brain endothelial lncRNAs, which suggest potential pathological roles for these lncRNAs in mediating endothelial responses to ischemic stimuli. Endothelial-selective lncRNAs may function as a class of novel master regulators in cerebrovascular endothelial pathologies after ischemic stroke.

  4. Galantamine and carbon monoxide protect brain microvascular endothelial cells by heme oxygenase-1 induction

    SciTech Connect

    Nakao, Atsunori; Kaczorowski, David J.; Zuckerbraun, Brian S.; Lei Jing; Faleo, Gaetano; Deguchi, Kentaro; McCurry, Kenneth R.; Billiar, Timothy R.; Kanno, Shinichi

    2008-03-14

    Galantamine, a reversible inhibitor of acetylcholine esterase (AChE), is a novel drug treatment for mild to moderate Alzheimer's disease and vascular dementia. Interestingly, it has been suggested that galantamine treatment is associated with more clinical benefit in patients with mild-to-moderate Alzheimer disease compared to other AChE inhibitors. We hypothesized that the protective effects of galantamine would involve induction of the protective gene, heme oxygenase-1 (HO-1), in addition to enhancement of the cholinergic system. Brain microvascular endothelial cells (mvECs) were isolated from spontaneous hypertensive rats. Galantamine significantly reduced H{sub 2}O{sub 2}-induced cell death of mvECs in association with HO-1 induction. These protective effects were completely reversed by nuclear factor-{kappa}B (NF-{kappa}B) inhibition or HO inhibition. Furthermore, galantamine failed to induce HO-1 in mvECs which lack inducible nitric oxide synthase (iNOS), supplementation of a nitric oxide (NO) donor or iNOS gene transfection on iNOS-deficient mvECs resulted in HO-1 induction with galantamine. These data suggest that the protective effects of galantamine require NF-{kappa}B activation and iNOS expression, in addition to HO-1. Likewise, carbon monoxide (CO), one of the byproducts of HO, up-regulated HO-1 and protected mvECs from oxidative stress in a similar manner. Our data demonstrate that galantamine mediates cytoprotective effects on mvECs through induction HO-1. This pharmacological action of galantamine may, at least in part, account for the superior clinical efficacy of galantamine in vascular dementia and Alzheimer disease.

  5. Visible light optical coherence tomography for microvascular oximetry in ocular circulation (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Chen, Siyu; Yi, Ji; Zhang, Hao F.

    2016-03-01

    Visible light optical coherence tomography (vis-OCT) is intrinsically capable of optical determination of blood oxygen saturation (sO2). Thanks to its 3D sectioning ability, confounding factors that plaque multi-wavelength fundus photography can be avoided. We further supplemented it with motion-enhanced angiography (vis-OCTA), which allowed us to resolve retinal micro vessels without losing spectral information. As a result, spectroscopic vis-OCTA can extract microvascular sO2 which are generally inaccessible. Here we extend the theoretical formulation of vis-OCTA oximetry to include optical attenuation, scattering and motion contrast. The model allows robust estimation of sO2, while also promising reduction of illuminating power to 1/3 of current value of ~1 mW. To demonstrate the capability of our approach, we performed oxygen challenge while taking vis-OCTA measurements on rat ocular circulation in vivo. We supplied the experiment animal with the following gas mixture: normal air, 5% CO2 air, pure O2 and 10% O2 air. For each inhalation gas, the OCTA measurements were compared with peripheral capillary sO2 (spO2) provided by a pulse oximeter. The retinal artery sO2 measurements corresponded well with spO2 reading as expected (R2 = 0.87). We found that both retinal and choroidal circulation sO2 moderately increased when we supplied 5% CO2 air. 100% O2 inhalation significantly increased both artery and vein oxygenation. On the contrary, 10% O2 air could deplete the oxygen reservoir in the circulation and lead to low sO2 readings.

  6. Influenza-Induced Priming and Leak of Human Lung Microvascular Endothelium upon Exposure to Staphylococcus aureus.

    PubMed

    Wang, Changsen; Armstrong, Susan M; Sugiyama, Michael G; Tabuchi, Arata; Krauszman, Adrienn; Kuebler, Wolfgang M; Mullen, Brendan; Advani, Suzanne; Advani, Andrew; Lee, Warren L

    2015-10-01

    A major cause of death after influenza virus infection is lung injury due to a bacterial superinfection, yet the mechanism is unknown. Death has been attributed to virus-induced immunosuppression and bacterial overgrowth, but this hypothesis is based on data from the preantibiotic era and animal models that omit antimicrobial therapy. Because of diagnostic uncertainty, most patients with influenza receive antibiotics, making bacterial overgrowth unlikely. Respiratory failure after superinfection presents as acute respiratory distress syndrome, a disorder characterized by lung microvascular leak and edema. The objective of this study was to determine whether the influenza virus sensitizes the lung endothelium to leak upon exposure to circulating bacterial-derived molecular patterns from Staphylococcus aureus. In vitro as well as in vivo models of influenza followed by S. aureus superinfection were used. Molecular mechanisms were explored using molecular biology, knockout mice, and human autopsy specimens. Influenza virus infection sensitized human lung endothelium to leak when challenged with S. aureus, even at low doses of influenza and even when the pathogens were given days apart. Influenza virus increased endothelial expression of TNFR1 both in vitro and in intact lungs, a finding corroborated by human autopsy specimens of patients with influenza. Leak was recapitulated with protein A, a TNFR1 ligand, and sequential infection caused protein A-dependent loss of IκB, cleavage of caspases 8 and 3, and lung endothelial apoptosis. Mice infected sequentially with influenza virus and S. aureus developed significantly increased lung edema that was protein A and TNFR1 dependent. Influenza virus primes the lung endothelium to leak, predisposing patients to acute respiratory distress syndrome upon exposure to S. aureus.

  7. Preserved Microvascular Endothelial Function in Young, Obese Adults with Functional Loss of Nitric Oxide Signaling.

    PubMed

    Harrell, John W; Johansson, Rebecca E; Evans, Trent D; Sebranek, Joshua J; Walker, Benjamin J; Eldridge, Marlowe W; Serlin, Ronald C; Schrage, William G

    2015-01-01

    Data indicate endothelium-dependent dilation (EDD) may be preserved in the skeletal muscle microcirculation of young, obese adults. Preserved EDD might be mediated by compensatory mechanisms, impeding insight into preclinical vascular dysfunction. We aimed to determine the functional roles of nitric oxide synthase (NOS) and cyclooxygenase (COX) toward EDD in younger obese adults. We first hypothesized EDD would be preserved in young, obese adults. Further, we hypothesized a reduced contribution of NOS in young, obese adults would be replaced by increased COX signaling. Microvascular EDD was assessed with Doppler ultrasound and brachial artery infusion of acetylcholine (ACh) in younger (27 ± 1 year) obese (n = 29) and lean (n = 46) humans. Individual and combined contributions of NOS and COX were examined with intra-arterial infusions of l-NMMA and ketorolac, respectively. Vasodilation was quantified as an increase in forearm vascular conductance (ΔFVC). Arterial endothelial cell biopsies were analyzed for protein expression of endothelial nitric oxide synthase (eNOS). ΔFVC to ACh was similar between groups. After l-NMMA, ΔFVC to ACh was greater in obese adults (p < 0.05). There were no group differences in ΔFVC to ACh with ketorolac. With combined NOS-COX inhibition, ΔFVC was greater in obese adults at the intermediate dose of ACh. Surprisingly, arterial endothelial cell eNOS and phosphorylated eNOS were similar between groups. Younger obese adults exhibit preserved EDD and eNOS expression despite functional dissociation of NOS-mediated vasodilation and similar COX signaling. Compensatory NOS- and COX-independent vasodilatory mechanisms conceal reduced NOS contributions in otherwise healthy obese adults early in life, which may contribute to vascular dysfunction. PMID:26733880

  8. Controlled human wood smoke exposure: oxidative stress, inflammation and microvascular function

    PubMed Central

    2012-01-01

    Background Exposure to wood smoke is associated with respiratory symptoms, whereas knowledge on systemic effects is limited. We investigated effects on systemic inflammation, oxidative stress and microvascular function (MVF) after controlled wood smoke exposure. Methods In a randomised, double-blinded, cross-over study 20 non-smoking atopic subjects were exposed at rest to 14, 220, or 354 μg/m3 of particles from a well-burning modern wood stove for 3 h in a climate controlled chamber with 2 week intervals. We investigated the level of oxidatively damaged DNA, inflammatory markers and adhesion molecules before and 0, 6 and 20 h after exposure. Six h after exposure we measured MVF non-invasively by digital peripheral artery tonometry following arm ischemia. Results The MVF score was unaltered after inhalation of clean air (1.58 ± 0.07; mean ± SEM), low (1.51 ± 0.07) or high (1.61 ± 0.09) concentrations of wood smoke particles in atopic subjects, whereas unexposed non-atopic subjects had higher score (1.91 ± 0.09). The level of oxidatively damaged DNA, mRNA of ITGAL, CCL2, TNF, IL6, IL8, HMOX1, and OGG1 and surface marker molecules ICAM1, ITGAL and L-selectin in peripheral blood mononuclear cells were not affected by inhalation of wood smoke particles. Conclusions Exposure to wood smoke had no effect on markers of oxidative stress, DNA damage, cell adhesion, cytokines or MVF in atopic subjects. PMID:22452928

  9. Recent advances in microvascular autologous breast reconstruction after ablative tumor surgery

    PubMed Central

    Pollhammer, Michael S; Duscher, Dominik; Schmidt, Manfred; Huemer, Georg M

    2016-01-01

    Breast cancer is a ubiquitous disease and one of the leading causes of death in women in western societies. With overall increasing survival rates, the number of patients who need post-mastectomy reconstruction is on the rise. Especially since its psychological benefits have been broadly recognized, breast reconstruction has become a key component of breast cancer treatment. Evolving from the early beginnings of breast reconstruction with synthetic implants in the 1960s, microsurgical tissue transfer is on the way to become the gold standard for post oncology restoration of the breast. Particularly since the advent of perforator based free flap surgery, free tissue transfer has become as safe option for breast reconstruction with low morbidity. The lower abdominal skin and subcutaneous fat tissue typically offer enough volume to create an aesthetically satisfying breast mound. Nowadays, the most commonly used flap from this donor site is the deep inferior epigastric artery perforator flap. If the lower abdomen is not available as a donor site, the gluteal area and thigh provide a number of flaps suitable for breast reconstruction. If the required breast volume is small, and there is enough tissue available on the upper medial thigh, then a transverse upper gracilis flap may be a practicable method to reconstruct the breast. In case of a higher amount of required volume, a gluteal artery perforator flap is the best choice. However, what is crucial in addition to selecting the best flap option for the individual patient is the timing of the operation. In patients with confirmed post-mastectomy radiation therapy, it is advisable to perform microvascular breast reconstruction only in a delayed fashion. PMID:26862495

  10. Decreased Neointimal Extracellular Matrix Formation in RAGE-Knockout Mice After Microvascular Denudation

    SciTech Connect

    Groezinger, Gerd Schmehl, Joerg Bantleon, Ruediger Kehlbach, Rainer; Mehra, Tarun; Claussen, Claus Wiesinger, Benjamin

    2012-12-15

    Purpose: To evaluate in vivo the role of RAGE (receptor for advanced glycated end products) in the development of restenosis and neointimal proliferation in RAGE-deficient knockout (KO) mice compared with wild-type (WT) mice in an animal model. Materials and Methods: Sixteen WT and 15 RAGE-deficient mice underwent microvascular denudation of the common femoral artery under general anaesthesia. Contralateral arteries underwent a sham operation and served as controls. Four weeks after the intervention, all animals were killed, and paraformaldehyde-fixed specimens of the femoral artery were analysed with different stains (hematoxylin and eosin and Elastica van Gieson) and several different types of immunostaining (proliferating cell nuclear antigen, {alpha}-actin, collagen, von Willebrand factor, RAGE). Luminal area, area of the neointima, and area of the media were measured in all specimens. In addition, colony-formation assays were performed, and collagen production by WT smooth muscle cells (SMCs) and RAGE-KO SMCs was determined. For statistical analysis, P < 0.05 was considered statistically significant. Results: Four weeks after denudation, WT mice showed a 49.6% loss of luminal area compared with 14.9% loss of luminal area in RAGE-deficient mice (sham = 0% loss) (P < 0.001). The neointima was 18.2 (*1000 {mu}m{sup 2} [n = 15) in the WT group compared with only 8.4 (*1000 {mu}m{sup 2} [n = 16]) in the RAGE-KO group. RAGE-KO SMCs showed significantly decreased proliferation activity and production of extracellular matrix protein. Conclusion: RAGE may be shown to play a considerable role in the formation of neointima leading to restenosis after vascular injury.

  11. Balamuthia mandrillaris interactions with human brain microvascular endothelial cells in vitro.

    PubMed

    Matin, Abdul; Siddiqui, Ruqaiyyah; Jung, Suk-Yul; Kim, Kwang Sik; Stins, Monique; Khan, Naveed Ahmed

    2007-08-01

    Balamuthia amoebic encephalitis (BAE) is a serious human disease almost always leading to death. An important step in BAE is amoebae invasion of the bloodstream, followed by their haematogenous spread. Balamuthia mandrillaris entry into the central nervous system most likely occurs at the blood-brain barrier sites. Using human brain microvascular endothelial cells (HBMECs), which constitute the blood-brain barrier, this study determined (i) the ability of B. mandrillaris to bind to HBMECs and (ii) the associated molecular mechanisms. Adhesion assays revealed that B. mandrillaris exhibited greater than 90 % binding to HBMECs in vitro. To determine whether recognition of carbohydrate moieties on the surface of the HBMECs plays a role in B. mandrillaris adherence to the target cells, adhesion assays were performed in the presence of the saccharides mannose, galactose, xylose, glucose and fucose. It was observed that adherence of B. mandrillaris was significantly reduced by galactose, whilst the other saccharides had no effect. Acetone fixation of amoebae, but not of HBMECs, abolished adhesion, suggesting that B. mandrillaris adhesin(s) bind to galactose-containing glycoproteins of HBMECs. B. mandrillaris also bound to microtitre wells coated with galactose-BSA. By affinity chromatography using a galactose-Sepharose column, a galactose-binding protein (GBP) was isolated from detergent extracts of unlabelled amoebae. The isolation of a GBP from cell-surface-biotin-labelled amoebae suggested its membrane association. One-dimensional SDS-PAGE confirmed the proteinaceous nature of the GBP and determined its molecular mass as approximately 100 kDa. This is the first report suggesting the role of a GBP in B. mandrillaris interactions with HBMECs. PMID:17644721

  12. [Pre-surgical simulation of microvascular decompression for hemifacial spasm using 3D-models].

    PubMed

    Mashiko, Toshihiro; Yang, Qiang; Kaneko, Naoki; Konno, Takehiko; Yamaguchi, Takashi; Watanabe, Eiju

    2015-01-01

    We have been performing pre-surgical simulations using custom-built patient-specific 3D-models. Here we report the advantageous use of 3D-models for simulating microvascular decompression(MVD)for hemifacial spasms. Seven cases of MVD surgery were performed. Two types of 3D-printers were used to fabricate the 3D-models:one using plaster as the modeling material(Z Printer®450, 3D systems, Rock Hill, SC, USA)and the other using acrylonitrile butadiene styrene(ABS)(UP! Plus 3D printer®, Beijing Tiertime Technology, Beijing). We tested three types of models. Type 1 was a plaster model of the brainstem, cerebellum, facial nerve, and the artery compressing the root exit zone of the facial nerve. Part of the cerebellum was digitally trimmed off to observe "the compressing point" from the same angle as that used during actual surgery. Type 2 was a modified Type 1 in which part of the skull was opened digitally to mimic a craniectomy. Type 3 was a combined model in which the cerebellum and the artery of the Type 2 model were replaced by a soft retractable cerebellum and an elastic artery. The cerebellum was made from polyurethane and cast from a plaster prototype. To fabricate elastic arteries, liquid silicone was painted onto the surface of an ABS artery and the inner ABS model was dissolved away using solvent. In all cases, the 3D-models were very useful. Although each type has advantages, the Type-3 model was judged extremely useful for training junior surgeons in microsurgical approaches.

  13. Reduced CSF leak in complete calvarial reconstructions of microvascular decompression craniectomies using calcium phosphate cement

    PubMed Central

    Eseonu, Chikezie I.; Goodwin, C. Rory; Zhou, Xin; Theodros, Debebe; Bender, Matthew T.; Mathios, Dimitrios; Bettegowda, Chetan; Lim, Michael

    2016-01-01

    OBJECT Calcium phosphate cement provides a biomaterial that can be used for calvarial reconstruction in a retrosigmoid craniectomy for microvascular decompression (MVD). This study evaluates the outcomes of postoperative CSF leak and wound infection for patients undergoing a complete cranioplasty using calcium phosphate cement versus incomplete cranioplasty using polyethylene titanium mesh following a retrosigmoid craniectomy for MVD. METHODS The authors evaluated 211 cases involving patients who underwent first-time retrosigmoid craniectomies performed by a single attending surgeon for trigeminal neuralgia from October 2008 to June 2014. From this patient population, 111 patients underwent calvarial reconstruction after retrosigmoid craniectomy using polyethylene titanium mesh, and 100 patients had reconstructions using calcium phosphate cement. A Pearson’s chi-square test was used to compare postoperative complications of CSF leak and wound infection in these 2 types of cranioplasties. RESULTS The polyethylene titanium mesh group included 5 patients (4.5%) with postoperative CSF leak or pseudomeningocele and 3 patients (2.7%) with wound infections. In the calcium phosphate cement group, no patients had a CSF leak, and 2 patients (2%) had wound infections. This represented a statistically significant reduction of postoperative CSF leak in patients who underwent calcium phosphate reconstructions of their calvarial defect compared with those who underwent polyethylene titanium mesh reconstructions (p = 0.03). No significant difference was seen between the 2 groups in the number of patients with postoperative wound infections. CONCLUSIONS Calcium phosphate cement provides a viable alternative biomaterial for calvarial reconstruction of retrosigmoid craniectomy defects in patients who have an MVD. The application of this material provides a biocompatible barrier that reduces the incidence of postoperative CSF leaks. http://thejns.org/doi/abs/10.3171/2015.1.JNS142102

  14. IL-17 Promotes Neutrophil-Mediated Immunity by Activating Microvascular Pericytes and Not Endothelium.

    PubMed

    Liu, Rebecca; Lauridsen, Holly M; Amezquita, Robert A; Pierce, Richard W; Jane-Wit, Dan; Fang, Caodi; Pellowe, Amanda S; Kirkiles-Smith, Nancy C; Gonzalez, Anjelica L; Pober, Jordan S

    2016-09-15

    A classical hallmark of acute inflammation is neutrophil infiltration of tissues, a multistep process that involves sequential cell-cell interactions of circulating leukocytes with IL-1- or TNF-activated microvascular endothelial cells (ECs) and pericytes (PCs) that form the wall of the postcapillary venules. The initial infiltrating cells accumulate perivascularly in close proximity to PCs. IL-17, a proinflammatory cytokine that acts on target cells via a heterodimeric receptor formed by IL-17RA and IL-17RC subunits, also promotes neutrophilic inflammation but its effects on vascular cells are less clear. We report that both cultured human ECs and PCs strongly express IL-17RC and, although neither cell type expresses much IL-17RA, PCs express significantly more than ECs. IL-17, alone or synergistically with TNF, significantly alters inflammatory gene expression in cultured human PCs but not ECs. RNA sequencing analysis identifies many IL-17-induced transcripts in PCs encoding proteins known to stimulate neutrophil-mediated immunity. Conditioned media from IL-17-activated PCs, but not ECs, induce pertussis toxin-sensitive neutrophil polarization, likely mediated by PC-secreted chemokines, and they also stimulate neutrophil production of proinflammatory molecules, including TNF, IL-1α, IL-1β, and IL-8. Furthermore, IL-17-activated PCs, but not ECs, can prolong neutrophil survival by producing G-CSF and GM-CSF, delaying the mitochondrial outer membrane permeabilization and caspase-9 activation. Importantly, neutrophils exhibit enhanced phagocytic capacity after activation by conditioned media from IL-17-treated PCs. We conclude that PCs, not ECs, are the major target of IL-17 within the microvessel wall and that IL-17-activated PCs can modulate neutrophil functions within the perivascular tissue space. PMID:27534549

  15. Thrombin enhances the barrier function of rat microvascular endothelium in a PAR-1-dependent manner.

    PubMed

    Troyanovsky, B; Alvarez, D F; King, J A; Schaphorst, K L

    2008-02-01

    Thrombin is a multifunctional coagulation protease with pro- and anti-inflammatory vascular effects. We questioned whether thrombin may have segmentally differentiated effects on pulmonary endothelium. In cultured rat endothelial cells, rat thrombin (10 U/ml) recapitulated the previously reported decrease in transmonolayer electrical resistance (TER), F-actin stress fiber formation, paracellular gap formation, and increased permeability. In contrast, in rat pulmonary microvascular endothelial cells (PMVEC), isolated on the basis of Griffonia simplicifolia lectin recognition, thrombin increased TER, induced fewer stress fibers, and decreased permeability. To assess for differential proteinase-activated receptor (PAR) expression as a basis for the different responses, PAR family expression was analyzed. Both pulmonary artery endothelial cells and PMVEC expressed PAR-1 and PAR-2; however, only PMVEC expressed PAR-3, as shown by both RT-PCR and Western analysis. PAR-1 activating peptides (PAR-APs: SFLLRN-NH(2) and TFLLRN-NH(2)) were used to confirm a role for the PAR-1 receptor. PAR-APs (25-250 muM) also increased TER, formed fewer stress fibers, and did not induce paracellular gaps in PMVEC in contrast to that shown in pulmonary artery endothelial cells. These results were confirmed in isolated perfused rat lung preparations. PAR-APs (100 mug/ml) induced a 60% increase in the filtration coefficient over baseline. However, by transmission electron microscopy, perivascular fluid cuffs were seen only along conduit veins and arteries without evidence of intra-alveolar edema. We conclude that thrombin exerts a segmentally differentiated effect on endothelial barrier function in vitro, which corresponds to a pattern of predominant perivascular fluid cuff formation in situ. This may indicate a distinct role for thrombin in the microcirculation. PMID:18083763

  16. Repression of retinal microvascular endothelial cells by transthyretin under simulated diabetic retinopathy conditions

    PubMed Central

    Shao, Jun; Yao, Yong

    2016-01-01

    AIM To investigate biological effects of transthyretin (TTR) on the development of neovascularization under simulated diabetic retinopathy (DR) condition associated with high glucose and hypoxia. METHODS Human retinal microvascular endothelial cells (hRECs) were cultured in normal and simulated DR environments with high glucose and hypoxia. The normal serum glucose concentration is approximately 5.5 mmol/L; thus, hyperglycemia was simulated with 25 mmol/L glucose, while hypoxia was induced using 200 µmol/L CoCl2. The influence of TTR on hRECs and human retinal pigment epithelial cells (hRPECs) was determined by incubating the cells with 4 µmol/L TTR in normal and abnormal media. A co-culture system was then employed to evaluate the effects of hRPECs on hRECs. RESULTS Decreased hRECs and hRPECs were observed under abnormal conditions, including high-glucose and hypoxic media. In addition, hRECs were significantly inhibited by 4 µmol/L exogenous TTR during hyperglycemic culture. During co-culture, hRPECs inhibited hRECs in both the normal and abnormal environments. CONCLUSION hREC growth is inhibited by exogenous TTR under simulated DR environments with high-glucose and hypoxic, particularly in the medium containing 25 mmol/L glucose. hRPECs, which manufacture TTR in the eye, also represses hRECs in the same environment. TTR is predicted to inhibit the proliferation of hRECs and neovascularization. PMID:27366679

  17. Pigment epithelium-derived factor regulates microvascular permeability through adipose triglyceride lipase in sepsis.

    PubMed

    He, Ting; Hu, Jiongyu; Yan, Guangning; Li, Lingfei; Zhang, Dongxia; Zhang, Qiong; Chen, Bing; Huang, Yuesheng

    2015-07-01

    The integrity of the vascular barrier, which is essential to blood vessel homoeostasis, can be disrupted by a variety of soluble permeability factors during sepsis. Pigment epithelium-derived factor (PEDF), a potent endogenous anti-angiogenic molecule, is significantly increased in sepsis, but its role in endothelial dysfunction has not been defined. To assess the role of PEDF in the vasculature, we evaluated the effects of exogenous PEDF in vivo using a mouse model of cecal ligation and puncture (CLP)-induced sepsis and in vitro using human dermal microvascular endothelial cells (HDMECs). In addition, PEDF was inhibited using a PEDF-monoclonal antibody (PEDF-mAb) or recombinant lentivirus vectors targeting PEDF receptors, including adipose triglyceride lipase (ATGL) and laminin receptor (LR). Our results showed that exogenous PEDF induced vascular hyperpermeability, as measured by extravasation of Evan's Blue (EB), dextran and microspheres in the skin, blood, trachea and cremaster muscle, both in a normal state and under conditions of sepsis. In control and LR-shRNA-treated HDMECs, PEDF alone or in combination with inflammatory mediators resulted in activation of RhoA, which was accompanied by actin rearrangement and disassembly of intercellular junctions, impairing endothelial barrier function. But in ATGL-shRNA-treated HDMECs, PEDF failed to induce the aforementioned alterations, suggesting that PEDF-induced hyperpermeability was mediated through the ATGL receptor. These results reveal a novel role for PEDF as a potential vasoactive substance in septic vascular hyperpermeability. Furthermore, our results suggest that PEDF and ATGL may serve as therapeutic targets for managing vascular hyperpermeability in sepsis. PMID:25700221

  18. Microvascular permeability to water is independent of shear stress, but dependent on flow direction

    PubMed Central

    Adamson, R. H.; Sarai, R. K.; Altangerel, A.; Clark, J. F.; Weinbaum, S.

    2013-01-01

    Endothelial cells in a cultured monolayer change from a “cobblestone” configuration when grown under static conditions to a more elongated shape, aligned with the direction of flow, after exposure to sustained uniform shear stress. Sustained blood flow acts to protect regions of large arteries from injury. We tested the hypothesis that the stable permeability state of individually perfused microvessels is also characteristic of flow conditioning. In individually perfused rat mesenteric venular microvessels, microvascular permeability, measured as hydraulic conductivity (Lp), was stable [mean 1.0 × 10−7 cm/(s × cmH2O)] and independent of shear stress (3–14 dyn/cm2) for up to 3 h. Vessels perfused opposite to the direction of normal blood flow exhibited a delayed Lp increase [ΔLp was 7.6 × 10−7 cm/(s × cmH2O)], but the increase was independent of wall shear stress. Addition of chondroitin sulfate and hyaluronic acid to perfusates increased the shear stress range, but did not modify the asymmetry in response to flow direction. Increased Lp in reverse-perfused vessels was associated with numerous discontinuities of VE-cadherin and occludin, while both proteins were continuous around the periphery of forward-perfused vessels. The results are not consistent with a general mechanism for graded shear-dependent permeability increase, but they are consistent with the idea that a stable Lp under normal flow contributes to prevention of edema formation and also enables physiological regulation of shear-dependent small solute permeabilities (e.g., glucose). The responses during reverse flow are consistent with reports that disturbed flows result in a less stable endothelial barrier in venular microvessels. PMID:23417864

  19. Evaluation of microvascular anastomosis using real-time ultrahigh resolution Fourier domain Doppler optical coherence tomography

    PubMed Central

    Huang, Yong; Tong, Dedi; Zhu, Shan; Wu, Lehao; Mao, Qi; Ibrahim, Zuhaib; Lee, WP Andrew; Brandacher, Gerald; Kang, Jin U.

    2014-01-01

    Background Evolution and improvements in microsurgical techniques and tools have paved the way for super-microsurgical anastomoses with vessel diameters often approaching below 0.8 mm in the clinical realm and even smaller (0.2–0.3 mm) in murine models. Several imaging and monitoring devices have been introduced for post-operative monitoring but intra-operative guidance, assessment and predictability have remained limited to binocular optical microscope and surgeon’s experience. We present a high-resolution real time 3D imaging modality for intra-operative evaluation of luminal narrowing, thrombus formation and flow alterations. Methods An imaging modality that provides immediate, in-depth high resolution 3D structure view and flow information of the anastomosed site called phase resolved Doppler optical coherence tomography (PRDOCT) was developed. 22 mouse femoral artery anastomoses and 17 mouse venous anastomoses were performed and evaluated with PRDOCT. Flow status, vessel inner lumen 3D structure, and early thrombus detection were analyzed based on PRDOCT imaging results. Initial PRDOCT based predictions were correlated with actual long term surgical outcomes. Eventually four cases of mouse orthotopic limb transplantation were carried out and PRDOCT predicted long term patency were confirmed by actual results. Results PRDOCT was able to provide high-resolution 3D visualization of the vessel flow status and vessel inner lumen. The assessments based on PRDOCT visualization shows a 92% sensitivity and 90% specificity for arterial anastomoses and 90% sensitivity and 86% specificity for venous anastomoses. Conclusions PRDOCT is an effective evaluation tool for microvascular anastomosis. It can predict the long term vessel patency with high sensitivity and specificity. PMID:25811583

  20. Metformin improves endothelial function in aortic tissue and microvascular endothelial cells subjected to diabetic hyperglycaemic conditions.

    PubMed

    Ghosh, Suparna; Lakshmanan, Arun P; Hwang, Mu Ji; Kubba, Haidar; Mushannen, Ahmed; Triggle, Chris R; Ding, Hong

    2015-12-01

    The cellular mechanisms whereby metformin, the first line drug for type 2 diabetes (T2DM), mediates its antidiabetic effects remain elusive, particularly as to whether metformin has a direct protective action on the vasculature. This study was designed to determine if a brief 3-h exposure to metformin protects endothelial function against the effects of hyperglycaemia. We investigated the protective effects of metformin on endothelial-dependent vasodilatation (EDV) in thoracic aortae from T2DM db/db mice and on high glucose (HG, 40 mM) induced changes in endothelial nitric oxide synthase (eNOS) signaling in mouse microvascular endothelial cells (MMECs) in culture. Exposure of aortae from db+/? non-diabetic control mice to high glucose (HG, 40 mM) containing Krebs for 3-h significantly (P<0.05) reduced acetylcholine (ACh)-induced EDV compared to ACh-induced EDV in aortae maintained in normal glucose (NG, 11 mM) Krebs. The reduction of EDV was partially reversed following a 3-h exposure to 50 μM metformin; metformin also improved ACh-induced EDV in aortae from diabetic db/db mice. Immunoblot analysis of MMECs cultured in HG versus NG revealed a significant reduction of the ratio of phosphorylated (p-eNOS)/eNOS and p-Akt/Akt, but not the expression of total eNOS or Akt. The 3-h exposure of MMECs to metformin significantly (P<0.05) reversed the HG-induced reduction in phosphorylation of both eNOS and Akt; however, no changes were detected for phosphorylation of AMPK or the expression of SIRT1. Our data indicate that a 3-h exposure to metformin can reverse/reduce the impact of HG on endothelial function, via mechanisms linked to increased phosphorylation of eNOS and Akt.

  1. Circulating platelet-leukocyte aggregates: a marker of microvascular injury in diabetic patients.

    PubMed

    Elalamy, I; Chakroun, T; Gerotziafas, G T; Petropoulou, A; Robert, F; Karroum, A; Elgrably, F; Samama, M-M; Hatmi, M

    2008-01-01

    Diabetes is associated with multiple disorders including metabolic, cellular and blood disturbances leading to vascular complications. Increased circulating levels of platelet-leukocyte aggregates (PLA) have been described in several thrombotic diseases. In this study, we have evaluated circulating PLA in diabetic patients and we have investigated whether they may be a marker of vascular complications. Using flow cytometry assay, we have quantified PLA percentages in 65 diabetics including 20 patients with type I and 45 with type II diabetes, and 25 healthy subjects. Specific labelling identified platelet-polymorphonuclear aggregates (PPA) and platelet-monocyte aggregates (PMA). We have observed a significant increase of PPA and PMA levels in diabetics (22+/-12% and 45+/-18%, respectively) compared to controls (7+/-4% and 19+/-10%, respectively) (p<0.01). However, both PPA and PMA values were similar in the two diabetes types. Circulating PPA and PMA were significantly enhanced in diabetics with vascular lesions (PPA: 24+/-13%; PMA: 50+/-18%) than in diabetics without vascular lesions (PPA: 18+/-8%; PMA: 38+/-15%) (p<0.05 and p<0.01). Patients with PPA>18% and/or PMA>38% showed a more important vascular injury (OR: 6; 95% CI: 1.6-23). Increased PMA circulating rate is particularly correlated to retinopathic injury (OR: 19; 95% CI: 2.3-154). Our findings established a relationship between increased circulating PLA levels, particularly PMA, and the incidence of microvascular complications in diabetes. They reinforce the concept of pro-inflammatory cells involvement in diabetic retinopathy pathogenesis and their link with thrombotic process. PMID:17825880

  2. Impaired microvascular response to cholinergic stimuli in primary Sjögren's syndrome

    PubMed Central

    Kovacs, L.; Torok, T.; Bari, F.; Keri, Z.; Kovacs, A.; Makula, E.; Pokorny, G.

    2000-01-01

    OBJECTIVE—Signs of a parasympathetic dysfunction have been revealed in primary Sjögren's syndrome (SS). Its role in the pathogenesis and the clinical picture of the disease is not clear. To investigate the responsiveness of SS patients to a cholinergic agonist, a model was used involving examination of the cutaneous microcirculation. The microvascular response to the administration of carbachol was measured, a muscarinic cholinergic agonist.
METHODS—Twenty two SS patients and 12 controls were examined. Carbachol and 0.9% saline solution were administered intracutaneously into the forearm skin at two distinct places. Skin blood flow (SBF) in the injected areas was measured continuously before and for 10 minutes after the injections by means of a laser Doppler perfusion monitor. The increase in SBF in response to carbachol (dSBF), reflecting vasodilatation, was calculated by a formula including the baseline and the maximum SBF values after the injections of carbachol and saline solution.
RESULTS—The vasodilatation was significantly lower in SS patients than in the controls (mean dSBF: 2.1 (range: 1.0-4.5) versus 3.3 (range: 1.7-7.6), p=0.02). With non-responder patients defined as those in whom a smaller response was observed than in any of the controls, 11 of the 22 SS patients proved to be non-responders to carbachol. Comparisons of demographic, clinical and laboratory characteristics and HLA class II genotypes between responder and non-responder SS patients did not show any significant differences.
CONCLUSIONS—A diminished or absent response to carbachol indicates a cholinergic dysfunction in SS patients. A disturbance in the neurotransmission at a receptorial or postreceptorial level is hypothesised. Unresponsiveness to cholinergic stimuli may contribute to exocrine insufficiency.

 PMID:10627427

  3. Adherence to human lung microvascular endothelial cells (HMVEC-L) of Plasmodium vivax isolates from Colombia

    PubMed Central

    2013-01-01

    Background For years Plasmodium vivax has been considered the cause of benign malaria. Nevertheless, it has been observed that this parasite can produce a severe disease comparable to Plasmodium falciparum. It has been suggested that some physiopathogenic processes might be shared by these two species, such as cytoadherence. Recently, it has been demonstrated that P. vivax-infected erythrocytes (Pv-iEs) have the capacity to adhere to endothelial cells, in which intercellular adhesion molecule-1 (ICAM-1) seems to be involved in this process. Methods Adherence capacity of 21 Colombian isolates, from patients with P. vivax mono-infection to a microvascular line of human lung endothelium (HMVEC-L) was assessed in static conditions and binding was evaluated at basal levels or in tumor necrosis factor (TNF) stimulated cells. The adherence specificity for the ICAM-1 receptor was determined through inhibition with an anti-CD54 monoclonal antibody. Results The majority of P. vivax isolates, 13 out of 21 (61.9%), adhered to the HMVEC-L cells, but P. vivax adherence was at least seven times lower when compared to the four P. falciparum isolates. Moreover, HMVEC-L stimulation with TNF led to an increase of 1.6-fold in P. vivax cytoadhesion, similar to P. falciparum isolates (1.8-fold) at comparable conditions. Also, blockage of ICAM-1 receptor with specific antibodies showed a significant 50% adherence reduction. Conclusions Plasmodium vivax isolates found in Colombia are also capable of adhering specifically in vitro to lung endothelial cells, via ICAM-1 cell receptor, both at basal state and after cell stimulation with TNF. Collectively, these findings reinforce the concept of cytoadherence for P. vivax, but here, to a different endothelial cell line and using geographical distinct isolates, thus contributing to understanding P. vivax biology. PMID:24080027

  4. Microvascular decompression for glossopharyngeal neuralgia through a microasterional approach: A case series

    PubMed Central

    Revuelta-Gutiérrez, Rogelio; Morales-Martínez, Andres Humberto; Mejías-Soto, Carolina; Martínez-Anda, Jaime Jesús; Ortega-Porcayo, Luis Alberto

    2016-01-01

    Background: Glossopharyngeal neuralgia (GPN) is an uncommon craniofacial pain syndrome. It is characterized by a sudden onset lancinating pain usually localized in the sensory distribution of the IX cranial nerve associated with excessive vagal outflow, which leads to bradycardia, hypotension, syncope, or cardiac arrest. This study aims to review our surgical experience performing microvascular decompression (MVD) in patients with GPN. Methods: Over the last 20 years, 14 consecutive cases were diagnosed with GPN. MVD using a microasterional approach was performed in all patients. Demographic data, clinical presentation, surgical findings, clinical outcome, complications, and long-term follow-up were reviewed. Results: The median age of onset was 58.7 years. The mean time from onset of symptoms to treatment was 8.8 years. Glossopharyngeal and vagus nerve compression was from the posterior inferior cerebellar artery in eleven cases (78.5%), vertebral artery in two cases (14.2%), and choroid plexus in one case (7.1%). Postoperative mean follow-up was 26 months (3–180 months). Pain analysis demonstrated long-term pain improvement of 114 ± 27.1 months and pain remission in 13 patients (92.9%) (P = 0.0001) two complications were documented, one patient had a cerebrospinal fluid leak, and another had bacterial meningitis. There was no surgical mortality. Conclusions: GPN is a rare entity, and secondary causes should be discarded. MVD through a retractorless microasterional approach is a safe and effective technique. Our series demonstrated an excellent clinical outcome with pain remission in 92.9%. PMID:27213105

  5. Analysis of 10-Year Training Results of Medical Students Using the Microvascular Research Center Training Program.

    PubMed

    Onoda, Satoshi; Kimata, Yoshihiro; Sugiyama, Narushi; Tokuyama, Eijiro; Matsumoto, Kumiko; Ota, Tomoyuki; Thuzar, Moe

    2016-06-01

    Background In this article, we reviewed the training results of medical students using the Microvascular Research Center Training Program (MRCP), and proposed an ideal microsurgical training program for all individuals by analyzing the training results of medical students who did not have any surgical experience. Methods As of 2015, a total of 29 medical students completed the MRCP. In the most recent 12 medical students, the number of trials performed for each training stage and the number of rats needed to complete the training were recorded. Additionally, we measured the operating time upon finishing stage 5 for the recent six medical students after it became a current program. Results The average operating time upon finishing stage 5 for the recent six medical students was 120 minutes ± 11 minutes (standard deviation [SD]). The average vascular anastomosis time (for the artery and vein) was 52 minutes ± 2 minutes (SD). For the most recent 12 medical students, there was a negative correlation between the number of trials performed in the non-rat stages (stages 1-3) and the number of rats used in the rat stages (stages 4-5). Conclusion Analysis of the training results of medical students suggests that performing microsurgery first on silicon tubes and chicken wings saves animals' lives later during the training program. We believe that any person can learn the technique of microsurgery by performing 7 to 8 hours of training per day over a period of 15 days within this program setting.

  6. Evaluation of the Microvascular Research Center Training Program for Assessing Microsurgical Skills in Trainee Surgeons

    PubMed Central

    Yamada, Kiyoshi; Yamashita, Shuji; Sugiyama, Narushi; Tokuyama, Eijiro; Matsumoto, Kumiko; Takara, Ayumi; Kimata, Yoshihiro

    2013-01-01

    Background We established the Microvascular Research Center Training Program (MRCP) to help trainee surgeons acquire and develop microsurgical skills. Medical students were recruited to undergo the MRCP to assess the effectiveness of the MRCP for trainee surgeons. Methods Twenty-two medical students with no prior microsurgical experience, who completed the course from 2005 to 2012, were included. The MRCP comprises 5 stages of training, each with specific passing requirements. Stages 1 and 2 involve anastomosing silicone tubes and blood vessels of chicken carcasses, respectively, within 20 minutes. Stage 3 involves anastomosing the femoral artery and vein of live rats with a 1-day patency rate of >80%. Stage 4 requires replantation of free superficial inferior epigastric artery flaps in rats with a 7-day success rate of >80%. Stage 5 involves successful completion of one case of rat replantation/transplantation. We calculated the passing rate for each stage and recorded the number of anastomoses required to pass stages 3 and 4. Results The passing rates were 100% (22/22) for stages 1 and 2, 86.4% (19/22) for stage 3, 59.1% (13/22) for stage 4, and 55.0% (11/20) for stage 5. The number of anastomoses performed was 17.2±12.2 in stage 3 and 11.3±8.1 in stage 4. Conclusions Majority of the medical students who undertook the MRCP acquired basic microsurgical skills. Thus, we conclude that the MRCP is an effective microsurgery training program for trainee surgeons. PMID:23730596

  7. Microvascular disease precedes the decline in renal function in the streptozotocin-induced diabetic rat

    PubMed Central

    Maric-Bilkan, Christine; Flynn, Elizabeth R.

    2012-01-01

    Diabetic nephropathy is a progressive and generalized vasculopathic condition associated with abnormal angiogenesis. We aim to determine whether changes in renal microvascular (MV) density correlate with and play a role in the progressive deterioration of renal function in diabetes. We hypothesize that MV changes represent the early steps of renal injury that worsen as diabetes progresses, initiating a vicious circle that leads to irreversible renal injury. Male nondiabetic (ND) or streptozotocin-induced diabetic (D) Sprague-Dawley rats were followed for 4 or 12 wk. Renal blood flow and glomerular filtration rate (GFR) were measured by PAH and 125I-[iothalamate], respectively. Renal MV density was quantified ex vivo using three-dimensional micro computed tomography and JG-12 immunoreactivity. Vascular endothelial growth factor (VEGF) levels (ELISA) and expression of VEGF receptors and factors involved in MV remodeling were quantified in renal tissue by Western blotting. Finally, renal morphology was investigated by histology. Four weeks of diabetes was associated with increased GFR, accompanied by a 34% reduction in renal MV density and augmented renal VEGF levels. However, at 12 wk, while GFR remained similarly elevated, reduction of MV density was more pronounced (75%) and associated with increased MV remodeling, renal fibrosis, but unchanged renal VEGF compared with ND at 12 wk. The damage, loss, and subsequent remodeling of the renal MV architecture in the diabetic kidney may represent the initiating events of progressive renal injury. This study suggests a novel concept of MV disease as an early instigator of diabetic kidney disease that may precede and likely promote the decline in renal function. PMID:22031855

  8. Association of Maternal Antiangiogenic Profile at Birth With Early Postnatal Loss of Microvascular Density in Offspring of Hypertensive Pregnancies

    PubMed Central

    Yu, Grace Z.; Aye, Christina Y.L.; Lewandowski, Adam J.; Davis, Esther F.; Khoo, Cheen P.; Newton, Laura; Yang, Cheng T.; Al Haj Zen, Ayman; Simpson, Lisa J.; O’Brien, Kathryn; Cook, David A.; Granne, Ingrid; Kyriakou, Theodosios; Channon, Keith M.; Watt, Suzanne M.

    2016-01-01

    Offspring of hypertensive pregnancies are more likely to have microvascular rarefaction and increased blood pressure in later life. We tested the hypothesis that maternal angiogenic profile during a hypertensive pregnancy is associated with fetal vasculogenic capacity and abnormal postnatal microvascular remodeling. Infants (n=255) born after either hypertensive or normotensive pregnancies were recruited for quantification of postnatal dermal microvascular structure at birth and 3 months of age. Vasculogenic cell potential was assessed in umbilical vein endothelial cells from 55 offspring based on in vitro microvessel tube formation and proliferation assays. Maternal angiogenic profile (soluble fms-like tyrosine kinase-1, soluble endoglin, vascular endothelial growth factor, and placental growth factor) was measured from postpartum plasma samples to characterize severity of pregnancy disorder. At birth, offspring born after hypertensive pregnancy had similar microvessel density to those born after a normotensive pregnancy, but during the first 3 postnatal months, they had an almost 2-fold greater reduction in total vessel density (−17.7±16.4% versus −9.9±18.7%; P=0.002). This postnatal loss varied according to the vasculogenic capacity of the endothelial cells of the infant at birth (r=0.49; P=0.02). The degree of reduction in both in vitro and postnatal in vivo vascular development was proportional to levels of antiangiogenic factors in the maternal circulation. In conclusion, our data indicate that offspring born to hypertensive pregnancies have reduced vasculogenic capacity at birth that predicts microvessel density loss over the first 3 postnatal months. Degree of postnatal microvessel reduction is proportional to levels of antiangiogenic factors in the maternal circulation at birth. PMID:27456522

  9. Association of Maternal Antiangiogenic Profile at Birth With Early Postnatal Loss of Microvascular Density in Offspring of Hypertensive Pregnancies.

    PubMed

    Yu, Grace Z; Aye, Christina Y L; Lewandowski, Adam J; Davis, Esther F; Khoo, Cheen P; Newton, Laura; Yang, Cheng T; Al Haj Zen, Ayman; Simpson, Lisa J; O'Brien, Kathryn; Cook, David A; Granne, Ingrid; Kyriakou, Theodosios; Channon, Keith M; Watt, Suzanne M; Leeson, Paul

    2016-09-01

    Offspring of hypertensive pregnancies are more likely to have microvascular rarefaction and increased blood pressure in later life. We tested the hypothesis that maternal angiogenic profile during a hypertensive pregnancy is associated with fetal vasculogenic capacity and abnormal postnatal microvascular remodeling. Infants (n=255) born after either hypertensive or normotensive pregnancies were recruited for quantification of postnatal dermal microvascular structure at birth and 3 months of age. Vasculogenic cell potential was assessed in umbilical vein endothelial cells from 55 offspring based on in vitro microvessel tube formation and proliferation assays. Maternal angiogenic profile (soluble fms-like tyrosine kinase-1, soluble endoglin, vascular endothelial growth factor, and placental growth factor) was measured from postpartum plasma samples to characterize severity of pregnancy disorder. At birth, offspring born after hypertensive pregnancy had similar microvessel density to those born after a normotensive pregnancy, but during the first 3 postnatal months, they had an almost 2-fold greater reduction in total vessel density (-17.7±16.4% versus -9.9±18.7%; P=0.002). This postnatal loss varied according to the vasculogenic capacity of the endothelial cells of the infant at birth (r=0.49; P=0.02). The degree of reduction in both in vitro and postnatal in vivo vascular development was proportional to levels of antiangiogenic factors in the maternal circulation. In conclusion, our data indicate that offspring born to hypertensive pregnancies have reduced vasculogenic capacity at birth that predicts microvessel density loss over the first 3 postnatal months. Degree of postnatal microvessel reduction is proportional to levels of antiangiogenic factors in the maternal circulation at birth.

  10. [Posterior fossa microvascular decompression for hemifacial spasm and trigeminal neuralgia--some improvements on operative devices and technique].

    PubMed

    Hongo, K; Kobayashi, S; Takemae, T; Sugita, K

    1985-12-01

    Microvascular decompression has been widely used as a method for the treatment of hemifacial spasm and trigeminal neuralgia. We have experienced 30 such cases in the last 2 years; 25 of them were hemifacial spasm and 5 trigeminal neuralgia. Excellent results were obtained in 26 cases; the remaining two cases, both hemifacial spasm, were partially cured. Mild facial paresis appeared several days after the operation in 3 patients. In all the cases, the facial paresis recovered completely within several weeks. The cause of the facial paresis was not known. In 2 cases a slight hearing deficits were noticed after surgery, which has been gradually improving over several months. As this operation is functional surgery, operative complications must be avoided as much as possible. It has been our policy that we first try medical treatment and/or some kinds of nerve block and if no effects are obtained, we recommend the microvascular decompression. For microvascular decompression, suboccipital craniectomy is performed in lateral position. From the point of view of surgical technique, we stress several important points as follows: The head is elevated about 30 degrees, and it is kept approximately horizontal and should not be excessively rotated. Craniectomy is made as far laterally as the sigmoid sinus; its shape is elongated oval. Retraction of the cerebellum should not be done in the direction of the cranial nerves to avoid post-operative hearing deficit. Two tapered retractors are effectively used for cerebellar retraction. A third slim, tapered retractor is useful for holding an offending artery when exploring the root exit zone or placing a sponge for decompression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:4088451

  11. Inhibition of cytokine-induced microvascular arrest of tumor cells by recombinant endostatin prevents experimental hepatic melanoma metastasis.

    PubMed

    Mendoza, Lorea; Valcárcel, María; Carrascal, Teresa; Egilegor, Eider; Salado, Clarisa; Sim, B Kim Lee; Vidal-Vanaclocha, Fernando

    2004-01-01

    We investigated effects of endostatin (ES) in the prometastatic microenvironment of inflammation occurring during the microvascular phase of cancer cell infiltration in the liver. We used a model of intrasplenic injection of B16 melanoma (B16M) cells leading to hepatic metastasis through vascular cell adhesion molecule-(VCAM-1)-mediated capillary arrest of cancer cells via interleukin-18 (IL-18)-dependent mechanism. We show that administration of 50 mg/kg recombinant human (rh) ES 30 min before B16M, plus repetition of same dose for 3 additional days decreased metastasis number by 60%. A single dose of rhES before B16M injection reduced hepatic microvascular retention of luciferase-transfected B16M by 40% and inhibited hepatic production of tumor necrosis factor alpha (TNF-alpha) and IL-18 and VCAM-1 expression by hepatic sinusoidal endothelia (HSE). Consistent with these data, rhES inhibited VCAM-1-dependent B16M cell adhesion to primary cultured HSE receiving B16M conditioned medium, and it abolished the HSE cell production of TNF-alpha and IL-18 induced by tumor-derived vascular endothelial cell growth factor (VEGF). rhES abrogated recombinant murine VEGF-induced tyrosine phosphorylation of KDR/flk-1 receptor in HSE cells, preventing the proinflammatory action of tumor-derived VEGF on HSE. rhES also abolished hepatic production of TNF-alpha, microvascular retention of luciferase-transfected B16M, and adhesion of B16M cells to isolated HSE cells, all of them induced in mice given 5 micro g/kg recombinant murine VEGF for 18 h. This capillary inflammation-deactivating capability constitutes a nonantiangiogenic antitumoral action of endostatin that decreases cancer cell arrest within liver microvasculature and prevents metastases promoted by proinflammatory cytokines induced by VEGF. PMID:14729638

  12. Identification of hepatic microvascular adhesion-related genes of human colon cancer cells using random homozygous gene perturbation.

    PubMed

    Márquez, Joana; Kohli, Manu; Arteta, Beatriz; Chang, Shaojing; Li, Wu-Bo; Goldblatt, Michael; Vidal-Vanaclocha, Fernando

    2013-11-01

    Random homozygous gene perturbation (RHGP), in combination with liver sinusoidal endothelial cell (LSEC) adhesion screening of clonal colon cancer cells with perturbed genes, was used to identify genes contributing to the hepatic microvascular adhesion of colon cancer cells. Plasmid vector encoding transactivator and gene search vector were transfected into HT-29 human colorectal cancer cells to create a HT-29 RHGP cell library; the adhesion of these library cells to primary cultured mouse LSEC significantly decreased in the presence of RSL1 ligand (inducer), indicating that most of the genes contributing to HT-29 adhesion to LSEC were altered. Next, HT-29 RHGP cell library fractions with upregulated or silenced LSEC adhesion-related genes were isolated. Around 160 clones having altered expression in LSEC adhesion-related genes were obtained, and nine relevant protein-coding genes were identified. Some were proadhesive genes detected because of their overexpression in adherent HT-29 cells (DGCR8 and EFEMP1 genes) and their silenced status in nonadherent HT-29 cells (DGKE, DPY19L1, KIAA0753, PVR and USP11 genes). Others were antiadhesive genes detected because of their overexpression in nonadherent HT-29 cells (ITPKC gene) and their silenced status in adherent HT-29 cells (PPP6R2 gene). Silencing of PVR, DGCR8 and EFEMP1 genes decreased adhesion to LSEC and hepatic microvascular retention of HT-29 cells. The results conclude that RHGP was a valuable strategy for the discovery of mechanisms regulating microvascular adhesion of circulating colon cancer cells before hepatic metastasis formation. Identified genes may contribute to understand the metastatic process of colon cancer and to discovering molecular targets for hepatic metastasis therapeutics.

  13. Association of Maternal Antiangiogenic Profile at Birth With Early Postnatal Loss of Microvascular Density in Offspring of Hypertensive Pregnancies.

    PubMed

    Yu, Grace Z; Aye, Christina Y L; Lewandowski, Adam J; Davis, Esther F; Khoo, Cheen P; Newton, Laura; Yang, Cheng T; Al Haj Zen, Ayman; Simpson, Lisa J; O'Brien, Kathryn; Cook, David A; Granne, Ingrid; Kyriakou, Theodosios; Channon, Keith M; Watt, Suzanne M; Leeson, Paul

    2016-09-01

    Offspring of hypertensive pregnancies are more likely to have microvascular rarefaction and increased blood pressure in later life. We tested the hypothesis that maternal angiogenic profile during a hypertensive pregnancy is associated with fetal vasculogenic capacity and abnormal postnatal microvascular remodeling. Infants (n=255) born after either hypertensive or normotensive pregnancies were recruited for quantification of postnatal dermal microvascular structure at birth and 3 months of age. Vasculogenic cell potential was assessed in umbilical vein endothelial cells from 55 offspring based on in vitro microvessel tube formation and proliferation assays. Maternal angiogenic profile (soluble fms-like tyrosine kinase-1, soluble endoglin, vascular endothelial growth factor, and placental growth factor) was measured from postpartum plasma samples to characterize severity of pregnancy disorder. At birth, offspring born after hypertensive pregnancy had similar microvessel density to those born after a normotensive pregnancy, but during the first 3 postnatal months, they had an almost 2-fold greater reduction in total vessel density (-17.7±16.4% versus -9.9±18.7%; P=0.002). This postnatal loss varied according to the vasculogenic capacity of the endothelial cells of the infant at birth (r=0.49; P=0.02). The degree of reduction in both in vitro and postnatal in vivo vascular development was proportional to levels of antiangiogenic factors in the maternal circulation. In conclusion, our data indicate that offspring born to hypertensive pregnancies have reduced vasculogenic capacity at birth that predicts microvessel density loss over the first 3 postnatal months. Degree of postnatal microvessel reduction is proportional to levels of antiangiogenic factors in the maternal circulation at birth. PMID:27456522

  14. Passive heat therapy improves cutaneous microvascular function in sedentary humans via improved nitric oxide-dependent dilation.

    PubMed

    Brunt, Vienna E; Eymann, Taylor M; Francisco, Michael A; Howard, Matthew J; Minson, Christopher T

    2016-09-01

    Passive heat therapy (repeated hot tub or sauna use) reduces cardiovascular risk, but its effects on the mechanisms underlying improvements in microvascular function have yet to be studied. We investigated the effects of heat therapy on microvascular function and whether improvements were related to changes in nitric oxide (NO) bioavailability using cutaneous microdialysis. Eighteen young, sedentary, otherwise healthy subjects participated in 8 wk of heat therapy (hot water immersion to maintain rectal temperature ≥38.5°C for 60 min/session; n = 9) or thermoneutral water immersion (sham, n = 9), and participated in experiments before and after the 8-wk intervention in which forearm cutaneous hyperemia to 39°C local heating was assessed at three microdialysis sites receiving 1) Lactated Ringer's (Control), 2) N(ω)-nitro-l-arginine (l-NNA; nonspecific NO synthase inhibitor), and 3) 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol), a superoxide dismutase mimetic. The arm used for microdialysis experiments remained out of the water at all times. Data are means ± SE cutaneous vascular conductance (CVC = laser Doppler flux/mean arterial pressure), presented as percent maximal CVC (% CVCmax). Heat therapy increased local heating plateau from 42 ± 6 to 53 ± 6% CVCmax (P < 0.001) and increased NO-dependent dilation (difference in plateau between Control and l-NNA sites) from 26 ± 6 to 38 ± 4% CVCmax (P < 0.01), while no changes were observed in the sham group. When data were pooled across all subjects at 0 wk, Tempol had no effect on the local heating response (P = 0.53 vs. Control). There were no changes at the Tempol site across interventions (P = 0.58). Passive heat therapy improves cutaneous microvascular function by improving NO-dependent dilation, which may have clinical implications. PMID:27418688

  15. Morphological and microvascular changes of the adrenal glands in streptozotocin-induced long-term diabetic rats.

    PubMed

    Sricharoenvej, Sirinush; Boonprasop, Surasak; Lanlua, Passara; Piyawinijwong, Sitha; Niyomchan, Apichaya

    2009-01-01

    It has been known that diabetes mellitus is associated with hyperfunction of the adrenal gland. However, the structural changes of adrenal gland in diabetes have rarely been studied. The aims of this study were to investigate the morphological and microvascular alterations in streptozotocin (STZ)-induced long-term diabetic rats. Twelve male Sprague-Dawley rats were divided into diabetic (n=8) and control (n=4) groups. Each diabetic rat was induced by an intraperitoneal injection of STZ (60 mg/kg) in citrate buffer (pH 4.5). Control rats were intraperitoneally injected with the same amounts of the buffer. These animals were sacrificed at 20 weeks after the injections. The adrenal glands were processed for the morphological and microvascular studies by using conventional light microscopy (LM) and vascular corrosion cast technique combined with scanning electron microscopy (SEM), respectively. In the diabetic group, the cells in zona glomeruloza (ZG) became atrophied and the thickness of this zone was found to be less than that of the controls. In the zona fasciculata (ZF) and zona reticularis (ZR), the hypertrophic cells were investigated in both layers. The degenerated chromaffin and hypertrophic sympathetic ganglion cells in the adrenal medulla were observed. Also some degenerated ganglion cells were found. Additionally, lymphocyte infiltration, macrophages and amyloidosis were found in the adrenal medulla of long-term diabetic rats with renal failure. Under the SEM observation, the luminal diameters of capillaries in the diabetic group were dilated in all zones. In addition, these capillaries in the ZF and ZR were arranged in tortuous courses. This study demonstrates morphological and microvascular changes in the adrenal gland of diabetic rats which are in accordance with the hormonal changes reported by previous investigators.

  16. Cyclosporin A differentially inhibits multiple steps in VEGF induced angiogenesis in human microvascular endothelial cells through altered intracellular signaling

    PubMed Central

    Rafiee, Parvaneh; Heidemann, Jan; Ogawa, Hitoshi; Johnson, Nathan A; Fisher, Pamela J; Li, Mona S; Otterson, Mary F; Johnson, Christopher P; Binion, David G

    2004-01-01

    The immunosuppressive agent cyclosporin A (CsA), a calcineurin inhibitor which blocks T cell activation has provided the pharmacologic foundation for organ transplantation. CsA exerts additional effects on non-immune cell populations and may adversely effect microvascular endothelial cells, contributing to chronic rejection, a long-term clinical complication and significant cause of mortality in solid-organ transplants, including patients with small bowel allografts. Growth of new blood vessels, or angiogenesis, is a critical homeostatic mechanism in organs and tissues, and regulates vascular populations in response to physiologic requirements. We hypothesized that CsA would inhibit the angiogenic capacity of human gut microvessels. Primary cultures of human intestinal microvascular endothelial cells (HIMEC) were used to evaluate CsA's effect on four in vitro measures of angiogenesis, including endothelial stress fiber assembly, migration, proliferation and tube formation, in response to the endothelial growth factor VEGF. We characterized the effect of CsA on intracellular signaling mechanisms following VEGF stimulation. CsA affected all VEGF induced angiogenic events assessed in HIMEC. CsA differentially inhibited signaling pathways which mediated distinct steps of the angiogenic process. CsA blocked VEGF induced nuclear translocation of the transcription factor NFAT, activation of p44/42 MAPK, and partially inhibited JNK and p38 MAPK. CsA differentially affected signaling cascades in a dose dependent fashion and completely blocked expression of COX-2, which was integrally linked to HIMEC angiogenesis. These data suggest that CsA inhibits the ability of microvascular endothelial cells to undergo angiogenesis, impairing vascular homeostatic mechanisms and contributing to the vasculopathy associated with chronic rejection. PMID:15175101

  17. Differential effects of topically applied formalin and aromatic compounds on neurogenic-mediated microvascular leakage in rat skin.

    PubMed

    Futamura, Masaki; Goto, Shiho; Kimura, Ryoko; Kimoto, Izumi; Miyake, Mio; Ito, Komei; Sakamoto, Tatsuo

    2009-01-01

    Various volatile organic compounds (VOCs) act as a causative agent of skin inflammation. We investigated the effect of topical application of several VOCs and formalin on microvascular leakage in rat skin. We tested capsaicin, which is a reagent that specifically causes the skin response via endogenously released tachykinins. Evans blue dye extravasation served as an index of the increase in skin vascular permeability. After shaving the abdomen, we applied formalin, m-xylene, toluene, styrene, benzene, ethylbenzene, acetone, diethyl ether, hexane, heptane, cyclohexane and capsaicin to the skin. At 40min after application, skin samples were collected. Among all of the VOCs tested, all of the aromatic compounds significantly produced skin microvascular leakage that was similar to formalin and capsaicin. We also investigated the skin responses seen after the intravenous administration of CP-99,994 (1.5 or 5mg/kg), which is a tachykinin NK1 receptor antagonist, ketotifen (1 or 3mg/kg), which is a histamine H1 receptor antagonist that stabilizes the mast cells, and the topical application of capsazepine (22.5 or 50mM), which is the transient receptor potential vanilloid 1 (TRPV1) antagonist. The response induced by formalin and capsaicin was completely inhibited by CP-99,994. On the other hand, the antagonist partially reduced the response induced by m-xylene, toluene and styrene by 39%, 50% and 46%, respectively. Capsazepine and ketotifen did not alter the response induced by formalin or any of the aromatic compounds. Like capsaicin, formalin and the aromatic compounds at least partially caused skin microvascular leakage, which was due to tachykinin NK1 receptor activation related to the release of tachykinins from the sensory nerve endings. However, it is unlikely that mast cells and TRPV1 play an important role in the skin response.

  18. Deleterious Effects of Intra-arterial Administration of Particulate Steroids on Microvascular Perfusion in a Mouse Model.

    PubMed

    Laemmel, Elisabeth; Segal, Nicolas; Mirshahi, Massoud; Azzazene, Dalel; Le Marchand, Sylvie; Wybier, Marc; Vicaut, Eric; Laredo, Jean-Denis

    2016-06-01

    Purpose To determine the in vivo effects of several particulate steroids on microvascular perfusion by using intravital microscopy in a mice model and to investigate the in vitro interactions between these particulate steroids and red blood cells (RBCs). Materials and Methods The study was conducted in agreement with the guidelines of the National Committee of Ethic Reflection on Animal Experimentation. By using intravital microscopy of mouse cremaster muscle, the in vivo effects of several particulate steroids on microvascular perfusion were assessed. Four to five mice were allocated to each of the following treatment groups: saline solution, dexamethasone sodium phosphate, a nonparticulate steroid, and the particulate steroids cortivazol, methylprednisolone, triamcinolone, and prednisolone. By using in vitro blood microcinematography and electron microscopy, the interactions between these steroids and human RBCs were studied. All results were analyzed by using nonparametric tests. Results With prednisolone, methylprednisolone, or triamcinolone, blood flow was rapidly and completely stopped in all the arterioles and venules (median RBC velocity in first-order arterioles, 5 minutes after administration was zero for these three groups) compared with a limited effect in mice treated with saline, dexamethasone, and cortivazol (20.3, 21.3, and 27.5 mm/sec, respectively; P < .003). This effect was associated with a large decrease in the functional capillary density (4.21, 0, and 0 capillaries per millimeter for methylprednisolone, triamcinolone, or prednisolone, respectively, vs 21.0, 21.4, and 19.1 capillaries per millimeter in mice treated with saline, dexamethasone, and cortivazol, respectively; P < .003). This was because of the rapid formation of RBC aggregates. However, no change in microvascular perfusion was associated with administration of cortivazol or dexamethasone. In vitro experiments confirmed the formation of RBC aggregates associated with the

  19. Effect of a Tibetan herbal mixture on microvascular endothelial function, heart rate variability and biomarkers of inflammation, clotting and coagulation.

    PubMed

    Schäfer, Daniela; Lambrecht, Julia; Radtke, Thomas; Wilhelm, Matthias; Saner, Hugo

    2015-08-01

    In this 6-week prospective, randomized, placebo-controlled and double-blind study, we investigated the effects of a natural herbal remedy based on a recipe from Tibet (Padma® 28), on microvascular endothelial function, heart rate variability and biomarkers of inflammation, clotting and coagulation in 80 coronary artery disease (CAD) patients (age 66 ± 8 years) on guideline-based medication for secondary prevention. We found no significant effects of Padma 28 and conclude that the addition of Padma 28 to guideline-based secondary prevention treatment of CAD did not lead to significant effects on important surrogate markers in elderly male CAD patients. PMID:25208904

  20. Ca2+ homeostasis in microvascular endothelial cells from an insulin-dependent diabetic model: role of endosomes/lysosomes

    NASA Astrophysics Data System (ADS)

    Sanka, Shankar C.; Bennett, David C.; Rojas, Jose D.; Tasby, Geraldine B.; Meininger, Cynthia J.; Wu, Guoyao; Wesson, Donald E.; Pfarr, Curtis M.; Martinez-Zaguilan, Raul

    2000-04-01

    Cytosolic Ca2+ ([Ca2+]cyt) regulates several cellular functions, e.g. cell growth, contraction, secretion, etc. In many cell types, ion homeostasis appears to be coupled with glucose metabolism. In certain cell types, a strict coupling between glycolysis and the activity of Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPases (SERCA) has been suggested. Glucose metabolism is altered in diabetes. We hypothesize that: (1) Ca2+ homeostasis is altered in microvascular endothelial cells from diabetic animals due to the dysfunction of glycolysis coupling the activity of SERCA; (2) endosomal/lysosomal compartments expressing SERCA are involved in the dysfunction associated with diabetes.

  1. Chemotherapeutic drug-specific alteration of microvascular blood flow in murine breast cancer as measured by diffuse correlation spectroscopy

    PubMed Central

    Ramirez, Gabriel; Proctor, Ashley R.; Jung, Ki Won; Wu, Tong Tong; Han, Songfeng; Adams, Russell R.; Ren, Jingxuan; Byun, Daniel K.; Madden, Kelley S.; Brown, Edward B.; Foster, Thomas H.; Farzam, Parisa; Durduran, Turgut; Choe, Regine

    2016-01-01

    The non-invasive, in vivo measurement of microvascular blood flow has the potential to enhance breast cancer therapy monitoring. Here, longitudinal blood flow of 4T1 murine breast cancer (N=125) under chemotherapy was quantified with diffuse correlation spectroscopy based on layer models. Six different treatment regimens involving doxorubicin, cyclophosphamide, and paclitaxel at clinically relevant doses were investigated. Treatments with cyclophosphamide increased blood flow as early as 3 days after administration, whereas paclitaxel induced a transient blood flow decrease at 1 day after administration. Early blood flow changes correlated strongly with the treatment outcome and distinguished treated from untreated mice individually for effective treatments. PMID:27699124

  2. TREATMENT OF MICROVASCULAR MICRO-EMBOLIZATION USING MICROBUBBLES AND LONG-TONE-BURST ULTRASOUND: AN IN VIVO STUDY

    PubMed Central

    Pacella, John J.; Brands, Judith; Schnatz, Frederick G.; Black, John J.; Chen, Xucai; Villanueva, Flordeliza S.

    2015-01-01

    Despite epicardial coronary artery reperfusion by percutaneous coronary intervention, distal micro-embolization into the coronary microcirculation limits myocardial salvage during acute myocardial infarction. Thrombolysis using ultrasound and microbubbles (sonothrombolysis) is an approach that induces microbubble oscillations to cause clot disruption and restore perfusion. We sought to determine whether this technique could restore impaired tissue perfusion caused by thrombotic microvascular obstruction. In 16 rats, an imaging transducer was placed on the biceps femoris muscle, perpendicular to a single-element 1-MHz treatment transducer. Ultrasound contrast perfusion imaging was performed at baseline and after micro-embolization. Therapeutic ultrasound (5000 cycles, pulse repetition frequency = 5 0.33 Hz, 1.5 MPa) was delivered to nine rats for two 10-min sessions during intra-arterial infusion of lipid-encapsulated microbubbles; seven control rats received no ultrasound–microbubble therapy. Ultrasound contrast perfusion imaging was repeated after each treatment or control period, and microvascular volume was measured as peak video intensity. There was a 90% decrease in video intensity after micro-embolization (from 8.6 ± 4.8 to 0.7 ± 0.8 dB, p < 0.01). The first and second ultrasound–microbubble sessions were respectively followed by video intensity increases of 5.8 ± 5.1 and 8.7 ± 5.7 dB (p < 0.01, compared with micro-embolization). The first and second control sessions, respectively, resulted in no significant increase in video intensity (2.4 ± 2.3 and 3.6 ± 4.9) compared with micro-embolization (0.6 ± 0.7 dB). We have developed an in vivo model that simulates the distal thrombotic microvascular obstruction that occurs after primary percutaneous coronary intervention. Long-pulse-length ultrasound with microbubbles has a therapeutic effect on microvascular perfusion and may be a valuable adjunct to reperfusion therapy for acute myocardial infarction

  3. Chemotherapeutic drug-specific alteration of microvascular blood flow in murine breast cancer as measured by diffuse correlation spectroscopy

    PubMed Central

    Ramirez, Gabriel; Proctor, Ashley R.; Jung, Ki Won; Wu, Tong Tong; Han, Songfeng; Adams, Russell R.; Ren, Jingxuan; Byun, Daniel K.; Madden, Kelley S.; Brown, Edward B.; Foster, Thomas H.; Farzam, Parisa; Durduran, Turgut; Choe, Regine

    2016-01-01

    The non-invasive, in vivo measurement of microvascular blood flow has the potential to enhance breast cancer therapy monitoring. Here, longitudinal blood flow of 4T1 murine breast cancer (N=125) under chemotherapy was quantified with diffuse correlation spectroscopy based on layer models. Six different treatment regimens involving doxorubicin, cyclophosphamide, and paclitaxel at clin