Assessment of microcirculation dynamics during cutaneous wound healing phases in vivo using optical microangiography

PubMed Central

Yousefi, Siavash; Qin, Jia; Dziennis, Suzan; Wang, Ruikang K.

2014-01-01

Abstract. Cutaneous wound healing consists of multiple overlapping phases starting with blood coagulation following incision of blood vessels. We utilized label-free optical coherence tomography and optical microangiography (OMAG) to noninvasively monitor healing process and dynamics of microcirculation system in a mouse ear pinna wound model. Mouse ear pinna is composed of two layers of skin separated by a layer of cartilage and because its total thickness is around 500 μm, it can be utilized as an ideal model for optical imaging techniques. These skin layers are identical to human skin structure except for sweat ducts and glands. Microcirculatory system responds to the wound injury by recruiting collateral vessels to supply blood flow to hypoxic region. During the inflammatory phase, lymphatic vessels play an important role in the immune response of the tissue and clearing waste from interstitial fluid. In the final phase of wound healing, tissue maturation, and remodeling, the wound area is fully closed while blood vessels mature to support the tissue cells. We show that using OMAG technology allows noninvasive and label-free monitoring and imaging each phase of wound healing that can be used to replace invasive tissue sample histology and immunochemistry technologies. PMID:25036212

Neutrophil-Mediated Delivery of Therapeutic Nanoparticles across Blood Vessel Barrier for Treatment of Inflammation and Infection.

PubMed

Chu, Dafeng; Gao, Jin; Wang, Zhenjia

2015-12-22

Endothelial cells form a monolayer in lumen of blood vessels presenting a great barrier for delivery of therapeutic nanoparticles (NPs) into extravascular tissues where most diseases occur, such as inflammation disorders and infection. Here, we report a strategy for delivering therapeutic NPs across this blood vessel barrier by nanoparticle in situ hitchhiking activated neutrophils. Using intravital microscopy of TNF-α-induced inflammation of mouse cremaster venules and a mouse model of acute lung inflammation, we demonstrated that intravenously (iv) infused NPs made from denatured bovine serum albumin (BSA) were specifically internalized by activated neutrophils, and subsequently, the neutrophils containing NPs migrated across blood vessels into inflammatory tissues. When neutrophils were depleted using anti-Gr-1 in a mouse, the transport of albumin NPs across blood vessel walls was robustly abolished. Furthermore, it was found that albumin nanoparticle internalization did not affect neutrophil mobility and functions. Administration of drug-loaded albumin NPs markedly mitigated the lung inflammation induced by LPS (lipopolysaccharide) or infection by Pseudomonas aeruginosa. These results demonstrate the use of an albumin nanoparticle platform for in situ targeting of activated neutrophils for delivery of therapeutics across the blood vessel barriers into diseased sites. This study demonstrates our ability to hijack neutrophils to deliver nanoparticles to targeted diseased sites.

INFLUENCE OF TOBACCO, ALCOHOL AND DIABETES ON THE COLLAGEN OF CREMASTER MUSCLE IN PATIENTS WITH INGUINAL HERNIAS.

PubMed

Módena, Sérgio Ferreira; Caldeira, Eduardo José; Peres, Marco Antonio O; Andreollo, Nelson Adami

2016-01-01

New findings point out that the mechanism of formation of the hernias can be related to the collagenous tissues, under activity of aggressive agents such as the tobacco, alcohol and diabetes. To analyze the collagen present in the cremaster muscle in patients with inguinal hernias, focusing the effect of tobacco, alcohol, and diabetes. Fifteen patients with inguinal hernia divided in three groups were studied: group I (n=5) was control; group II (n=5) were smokers and/or drinkers; and group III (n=5) had diabetes mellitus. All subjects were underwent to surgical repair of the inguinal hernias obeying the same pre, intra and postoperative conditions. During surgery, samples of the cremaster muscle were collected for analysis in polarized light microscopy, collagen morphometry and protein. The area occupied by the connective tissue was higher in groups II and III (p<0.05). The collagen tissue occupied the majority of the samples analyzed in comparison to the area occupied by muscle cells. The content of total protein was higher in groups II and III compared to the control group (p<0.05). The tobacco, alcohol and diabetes cause a remodel the cremaster muscle, leading to a loss of support or structural change in this region, which may enhance the occurrences and damage related to inguinal hernias. Estudos recentes sinalizam que o mecanismo de formação das hérnias pode estar relacionado aos tecidos colagenosos, sob a ação de agentes agressores como o tabaco, o álcool e o diabete. Avaliar o colágeno presente no músculo cremaster em pacientes com hérnias inguinais enfocando o efeito do tabaco, álcool e diabete. Foram estudados 15 pacientes com hérnias inguinais divididos em: grupo I (n=5) controles; grupo II (n=5) indivíduos fumantes e/ou etilistas; e grupo III (n=5) indivíduos que apresentavam diabete melito. Todos foram submetidos à correção cirúrgica das hérnias inguinais obedecendo às mesmas condições pré, intra e pós-operatórias. Durante o procedimento cirúrgico, amostras do músculo cremaster foram coletadas para análises em microscopia de luz polarizada, morfometria do colágeno e de proteínas. A área ocupada por tecido conjuntivo foi maior nos grupos II e III (p<0,05). O tecido colágeno ocupou a maior parte das amostras analisadas, em comparação à área ocupada pelas células musculares. O conteúdo de proteínas totais foi maior nos grupos II e III, quando comparado com o grupo controle (p<0,05). O tabaco, o álcool e o diabete ocasionam remodelação no músculo cremaster, levando à perda de suporte ou alteração estrutural nesta região, podendo intensificar as ocorrências e os danos relacionados às hérnias inguinais.

Inflamed phenotype of the mesenteric microcirculation of melanocortin type 3 receptor-null mice after ischemia-reperfusion

PubMed Central

Leoni, Giovanna; Patel, Hetal B.; Sampaio, André L. F.; Gavins, Felicity N. E.; Murray, Joanne F.; Grieco, Paolo; Getting, Stephen J.; Perretti, Mauro

2008-01-01

The existence of anti-inflammatory circuits centered on melanocortin receptors (MCRs) has been supported by the inhibitory properties displayed by melanocortin peptides in models of inflammation and tissue injury. Here we addressed the pathophysiological effect that one MCR, MCR type 3 (MC3R), might have on vascular inflammation. After occlusion (35 min) and reopening of the superior mesenteric artery, MC3R-null mice displayed a higher degree of plasma extravasation (45 min postreperfusion) and cell adhesion and emigration (90 min postreperfusion). These cellular alterations were complemented by higher expression of mesenteric tissue CCL2 and CXCL1 (mRNA and protein) and myeloperoxydase, as compared with wild-type animals. MC1R and MC3R mRNA and protein were both expressed in the inflamed mesenteric tissue; however, no changes in vascular responses were observed in a mouse colony bearing an inactive MC1R. Pharmacological treatment of animals with a selective MC3R agonist ([d-Trp8]-γ-melanocyte-stimulating hormone; 10 μg i.v.) produced marked attenuation of cell adhesion, emigration, and chemokine generation; such effects were absent in MC3R-null mice. These new data reveal the existence of a tonic inhibitory signal provided by MC3R in the mesenteric microcirculation of the mouse, acting to down-regulate cell trafficking and local mediator generation.—Leoni, G., Patel, H. B., Sampaio, A. L. F., Gavins, F. N. E., Murray, J. F., Grieco, P., Getting, S. J., Perretti, M. Inflamed phenotype of the mesenteric microcirculation of melanocortin type 3 receptor-null mice after ischemia-reperfusion. PMID:18757499

Label-free in vivo optical imaging of functional microcirculations within meninges and cortex in mice

PubMed Central

Jia, Yali; Wang, Ruikang K.

2010-01-01

Abnormal microcirculation within meninges is common in many neurological diseases. There is a need for an imaging method that is capable of monitoring dynamic meningeal microcirculations, preferably decoupled from cortical blood flow. Optical microangiography (OMAG) is a recently developed label-free imaging method capable of producing 3D images of dynamic blood perfusion within micro-circulatory tissue beds at an imaging depth up to ~2 mm, with an unprecedented imaging sensitivity to blood flow at ~4 µm/s. In this paper, we demonstrate the utility of OMAG in imaging the detailed blood flow distributions, at a capillary level resolution, within the meninges and cortex in mice with the cranium left intact. Using a thrombotic mouse model, we show that the OMAG can yield longitudinal measurements of meningeal vascular responses to the insult and can decouple these responses from those in the cortex, giving valuable information regarding the localized hemodynamics along with the dynamic formation of thrombotic event. The results indicate that OMAG can be a useful tool to study therapeutic strategies in preclinical animal models in order to mitigate various pathologies that are mainly related to the meningeal circulations. PMID:20933005

Crucial importance of the endothelial K+ channel SK3 and connexin40 in arteriolar dilations during skeletal muscle contraction.

PubMed

Milkau, Malte; Köhler, Ralf; de Wit, Cor

2010-09-01

Skeletal muscle activity requires substantial increases in blood flow, and the underlying vasodilation involves endothelial activity, but the contribution of the endothelium-dependent hyperpolarizing factor (EDHF) is only poorly defined. In EDHF signaling, endothelial hyperpolarization mediated by the Ca(2+)-activated K(+) channels SK3 and IK1 is a key step and also initiates gap junction-dependent conducted dilations. We assessed the role of SK3, IK1, and connexin40 (Cx40) in muscular contraction-induced dilations in the microcirculation in vivo. Hitherto, arterioles were observed in the electrically stimulated cremaster skeletal muscle of anesthetized mice lacking SK3, IK1, or Cx40 using intravital microscopy. Genetic deficiency of SK3, but not of IK1, strongly attenuated dilations to muscular contraction. Similarly, pharmacologic blockade of SK3 by the specific blocker UCL1684 impaired such dilations in wild-type and IK1-deficient mice. In contrast, IK1 was required for acetylcholine-induced dilations. Genetic deficiency of Cx40 also attenuated dilations induced by muscular contraction but not by acetylcholine. These data support the concept that endothelial hyperpolarization through activation of SK3 contributes to exercise hyperemia and the hyperpolarization ascends the vascular tree through gap junctions formed by Cx40 to orchestrate dilation. The differential impact of SK3- and IK1-deficiency on dilations to distinct stimuli suggests stimulus-dependent activation of these endothelial channels.

Short-term dietary copper deficiency does not inhibit angiogenesis in tumours implanted in striated muscle.

PubMed Central

Schuschke, D. A.; Reed, M. W.; Saari, J. T.; Olson, M. D.; Ackermann, D. M.; Miller, F. N.

1992-01-01

The effect of dietary copper deficiency on tumour growth, neovascularisation and microvascular integrity was studied in the rat cremaster muscle. Male, weanling Sprague-Dawley rats were fed purified diets which were copper deficient (< 0.5 micrograms g-1 of diet) or copper adequate (5 micrograms g-1 of diet). Seven days after initiation of diets, a chondrosarcoma was implanted in the cremaster muscle of each rat. Five, 10 or 20 days after tumour implantation, rats were anesthetised and their cremasters prepared for observation by intravital microscopy. Intraarterial injection of fluorescein isothiocyanate-conjugated albumin and subsequent observation of fluorescence in the perivascular space indicated no difference in microvascular albumin leakage between the tumour vasculature of copper deficient and copper adequate rats. Neither tumour growth (assessed by wet weight), vascular density (assessed by light microscopy), nor any ultrastructural characteristics of the tumour or its vasculature (assessed by electron microscopy) were affected by copper deficiency. In view of findings by others which indicate changes in tumour characteristics with copper deficiency, we conclude that the copper dependency of tumour growth and vascularisation is a function of the type of tumour, the host tissue, or the conditions of copper depletion. PMID:1280989

Label-free in vivo optical imaging of functional microcirculations within meninges and cortex in mice.

PubMed

Jia, Yali; Wang, Ruikang K

2010-12-15

Abnormal microcirculation within meninges is common in many neurological diseases. There is a need for an imaging method that is capable of monitoring dynamic meningeal microcirculations, preferably decoupled from cortical blood flow. Optical microangiography (OMAG) is a recently developed label-free imaging method capable of producing 3D images of dynamic blood perfusion within micro-circulatory tissue beds at an imaging depth up to ∼2 mm, with an unprecedented imaging sensitivity to blood flow at ∼4 μm/s. In this paper, we demonstrate the utility of OMAG in imaging the detailed blood flow distributions, at a capillary level resolution, within the meninges and cortex in mice with the cranium left intact. Using a thrombotic mouse model, we show that the OMAG can yield longitudinal measurements of meningeal vascular responses to the insult and can decouple these responses from those in the cortex, giving valuable information regarding the localized hemodynamics along with the dynamic formation of thrombotic event. The results indicate that OMAG can be a useful tool to study therapeutic strategies in preclinical animal models in order to mitigate various pathologies that are mainly related to the meningeal circulations. Copyright © 2010 Elsevier B.V. All rights reserved.

Citrulline Supplementation Improves Organ Perfusion and Arginine Availability under Conditions with Enhanced Arginase Activity

PubMed Central

Wijnands, Karolina A.P.; Meesters, Dennis M.; van Barneveld, Kevin W.Y.; Visschers, Ruben G.J.; Briedé, Jacob J.; Vandendriessche, Benjamin; van Eijk, Hans M.H.; Bessems, Babs A.F.M.; van den Hoven, Nadine; von Wintersdorff, Christian J.H.; Brouckaert, Peter; Bouvy, Nicole D.; Lamers, Wouter H.; Cauwels, Anje; Poeze, Martijn

2015-01-01

Enhanced arginase-induced arginine consumption is believed to play a key role in the pathogenesis of sickle cell disease-induced end organ failure. Enhancement of arginine availability with l-arginine supplementation exhibited less consistent results; however, l-citrulline, the precursor of l-arginine, may be a promising alternative. In this study, we determined the effects of l-citrulline compared to l-arginine supplementation on arginine-nitric oxide (NO) metabolism, arginine availability and microcirculation in a murine model with acutely-enhanced arginase activity. The effects were measured in six groups of mice (n = 8 each) injected intraperitoneally with sterile saline or arginase (1000 IE/mouse) with or without being separately injected with l-citrulline or l-arginine 1 h prior to assessment of the microcirculation with side stream dark-field (SDF)-imaging or in vivo NO-production with electron spin resonance (ESR) spectroscopy. Arginase injection caused a decrease in plasma and tissue arginine concentrations. l-arginine and l-citrulline supplementation both enhanced plasma and tissue arginine concentrations in arginase-injected mice. However, only the citrulline supplementation increased NO production and improved microcirculatory flow in arginase-injected mice. In conclusion, the present study provides for the first time in vivo experimental evidence that l-citrulline, and not l-arginine supplementation, improves the end organ microcirculation during conditions with acute arginase-induced arginine deficiency by increasing the NO concentration in tissues. PMID:26132994

The capillary bed offers the largest hemodynamic resistance to the cortical blood supply

PubMed Central

Gould, Ian Gopal; Tsai, Philbert; Kleinfeld, David

2016-01-01

The cortical angioarchitecture is a key factor in controlling cerebral blood flow and oxygen metabolism. Difficulties in imaging the complex microanatomy of the cortex have so far restricted insight about blood flow distribution in the microcirculation. A new methodology combining advanced microscopy data with large scale hemodynamic simulations enabled us to quantify the effect of the angioarchitecture on the cerebral microcirculation. High-resolution images of the mouse primary somatosensory cortex were input into with a comprehensive computational model of cerebral perfusion and oxygen supply ranging from the pial vessels to individual brain cells. Simulations of blood flow, hematocrit and oxygen tension show that the wide variation of hemodynamic states in the tortuous, randomly organized capillary bed is responsible for relatively uniform cortical tissue perfusion and oxygenation. Computational analysis of microcirculatory blood flow and pressure drops further indicates that the capillary bed, including capillaries adjacent to feeding arterioles (d < 10 µm), are the largest contributors to hydraulic resistance. PMID:27780904

Analysis of early thrombus dynamics in a humanized mouse laser injury model.

PubMed

Wang, Weiwei; Lindsey, John P; Chen, Jianchun; Diacovo, Thomas G; King, Michael R

2014-01-01

Platelet aggregation and thrombus formation at the site of injury is a dynamic process that involves the continuous addition of new platelets as well as thrombus rupture. In the early stages of hemostasis (within minutes after vessel injury) this process can be visualized by transfusing fluorescently labeled human platelets and observing their deposition and detachment. These two counterbalancing events help the developing thrombus reach a steady-state morphology, where it is large enough to cover the injured vessel surface but not too large to form a severe thrombotic occlusion. In this study, the spatial and temporal aspects of early stage thrombus dynamics which result from laser-induced injury on arterioles of cremaster muscle in the humanized mouse were visualized using fluorescent microscopy. It was found that rolling platelets show preference for the upstream region while tethering/detaching platelets were primarily found downstream. It was also determined that the platelet deposition rate is relatively steady, whereas the effective thrombus coverage area does not increase at a constant rate. By introducing a new method to graphically represent the real time in vivo physiological shear stress environment, we conclude that the thrombus continuously changes shape by regional growth and decay, and neither dominates in the high shear stress region.

Increase in endothelial cell Ca2+ in response to mouse cremaster muscle contraction

PubMed Central

Duza, Tasmia; Sarelius, Ingrid H

2004-01-01

We addressed the role of endothelial cells (ECs) in metabolic dilatation of skeletal muscle arterioles in anaesthetized mice in situ. Electrical field stimulation was used to contract the cremaster muscle for 15 s at 30 Hz. Diameter was observed using bright field microscopy. In controls, muscle contraction produced a 15.7 ± 1.5 μm dilatation from a baseline of 17.4 ± 1.6 μm. Endothelial denudation (−EC) via intraluminal perfusion of air abolished this response (1.6 ± 1.2 μm in −EC, P < 0.05), identifying endothelium as the primary vascular cell type initiating the dilatation. To investigate the role of EC Ca2+ in metabolic dilatation, arteriolar ECs were loaded with Fluo-4 AM or BAPTA AM by intraluminal perfusion, after which blood flow was re-established. Ca2+ activity of individual ECs was monitored as a function of change from baseline fluorescence using confocal microscopy. In ECs, whole cell Ca2+ increased (>10%, P < 0.05) during muscle contraction, and localized Ca2+ transients were increased (>20%, P < 0.05) during the first minute after contraction. Chelation of EC Ca2+ abolished the dilatations in response to muscle contraction (1.1 ± 0.7 μm, P < 0.05). Inhibition of P1 purinergic receptors (with xanthine amine congener) did not alter the rate of onset of the dilatation (P > 0.05) but decreased its magnitude immediately post stimulation (7.1 ± 0.9 μm, P < 0.05) and during recovery. These findings demonstrate obligatory roles for endothelium and EC Ca2+ during metabolic dilatation in intact arterioles. Furthermore, they suggest that at least two separate pathways mediate the local response, one of which involves stimulation of endothelial P1 purinergic receptors via endogenous adenosine produced during muscle activity. PMID:14694141

In vivo label-free quantification of liver microcirculation using dual-modality microscopy

NASA Astrophysics Data System (ADS)

Yan, Jie; Kang, Yuzhan; Xu, Shuoyu; Ong, Lee-Ling S.; Zhuo, Shuangmu; Bunte, Ralph M.; Chen, Nanguang; Asada, H. Harry; So, Peter T. C.; Wanless, Ian R.; Yu, Hanry

2014-11-01

Microcirculation lesion is a common symptom of chronic liver diseases in the form of vasculature deformation and circulation alteration. In acute to chronic liver diseases such as biliary atresia, microcirculation lesion can have an early onset. Detection of microcirculation lesion is meaningful for studying the progression of liver disease. We have combined wide-field fluorescence microscopy and a laser speckle contrast technique to characterize hepatic microcirculation in vivo without labeling in a bile-duct ligation rat fibrosis model of biliary atresia. Through quantitative image analysis of four microcirculation parameters, we observed significant microcirculation lesion in the early to middle stages of fibrosis. This bimodal imaging method is useful to assess hepatic microcirculation lesion for the study of liver diseases.

Ultrahigh sensitive optical microangiography reveals depth-resolved microcirculation and its longitudinal response to prolonged ischemic event within skeletal muscles in mice

NASA Astrophysics Data System (ADS)

Jia, Yali; Qin, Jia; Zhi, Zhongwei; Wang, Ruikang K.

2011-08-01

The primary pathophysiology of peripheral arterial disease is associated with impaired perfusion to the muscle tissue in the lower extremities. The lack of effective pharmacologic treatments that stimulate vessel collateralization emphasizes the need for an imaging method that can be used to dynamically visualize depth-resolved microcirculation within muscle tissues. Optical microangiography (OMAG) is a recently developed label-free imaging method capable of producing three-dimensional images of dynamic blood perfusion within microcirculatory tissue beds at an imaging depth of up to ~2 mm, with an unprecedented imaging sensitivity of blood flow at ~4 μm/s. In this paper, we demonstrate the utility of OMAG in imaging the detailed blood flow distributions, at a capillary-level resolution, within skeletal muscles of mice. By use of the mouse model of hind-limb ischemia, we show that OMAG can assess the time-dependent changes in muscle perfusion and perfusion restoration along tissue depth. These findings indicate that OMAG can represent a sensitive, consistent technique to effectively study pharmacologic therapies aimed at promoting the growth and development of collateral vessels.

Role of CD40 and ADAMTS13 in von Willebrand factor-mediated endothelial cell-platelet-monocyte interaction.

PubMed

Popa, Miruna; Tahir, Sibgha; Elrod, Julia; Kim, Su Hwan; Leuschner, Florian; Kessler, Thorsten; Bugert, Peter; Pohl, Ulrich; Wagner, Andreas H; Hecker, Markus

2018-06-12

Monocyte extravasation into the vessel wall is a key step in atherogenesis. It is still elusive how monocytes transmigrate through the endothelial cell (EC) monolayer at atherosclerosis predilection sites. Platelets tethered to ultra-large von Willebrand factor (ULVWF) multimers deposited on the luminal EC surface following CD40 ligand (CD154) stimulation may facilitate monocyte diapedesis. Human ECs grown in a parallel plate flow chamber for live-cell imaging or Transwell permeable supports for transmigration assay were exposed to fluid or orbital shear stress and CD154. Human isolated platelets and/or monocytes were superfused over or added on top of the EC monolayer. Plasma levels and activity of the ULVWF multimer-cleaving protease ADAMTS13 were compared between coronary artery disease (CAD) patients and controls and were verified by the bioassay. Two-photon intravital microscopy was performed to monitor CD154-dependent leukocyte recruitment in the cremaster microcirculation of ADAMTS13-deficient versus wild-type mice. CD154-induced ULVWF multimer-platelet string formation on the EC surface trapped monocytes and facilitated transmigration through the EC monolayer despite high shear stress. Two-photon intravital microscopy revealed CD154-induced ULVWF multimer-platelet string formation preferentially in venules, due to strong EC expression of CD40, causing prominent downstream leukocyte extravasation. Plasma ADAMTS13 abundance and activity were significantly reduced in CAD patients and strongly facilitated both ULVWF multimer-platelet string formation and monocyte trapping in vitro. Moderate ADAMTS13 deficiency in CAD patients augments CD154-mediated deposition of platelet-decorated ULVWF multimers on the luminal EC surface, reinforcing the trapping of circulating monocytes at atherosclerosis predilection sites and promoting their diapedesis.

Analysis of human microcirculation in weightlessness: Study protocol and pre-study experiments.

PubMed

Bimpong-Buta, Nana-Yaw; Jirak, Peter; Wernly, Bernhard; Lichtenauer, Michael; Masyuk, Maryna; Muessig, Johanna Maria; Braun, Kristina; Kaya, Sema; Kelm, Malte; Jung, Christian

2018-04-14

In weightlessness, alterations in organ systems have been reported. The microcirculation consists of a network of blood vessels with diameters of a few μm. It is considered the largest part of the circulatory system of the human body and essential for exchange of gas, nutrients and waste products. An investigation of the microcirculation in weightlessness seems warranted but has not yet been performed. In this paper, we outline a study in which we will investigate the possible interrelations between weightlessness and microcirculation. We will induce weightlessness in the course of parabolic flight maneuvers, which will be conducted during a parabolic flight campaign. In this study protocol also an evaluation of a possible influence of parabolic flight premedication on microcirculation will be described. The microcirculation will be investigated by sublingual intravital measurements applying sidestream darkfield microscopy. Parameters of macrocirculation such as heart rate, blood pressure and blood oxygenation will also be investigated. In our pre-study experiments, neither dimenhydrinate nor scopolamine altered microcirculation. As the application of motion sickness therapy did not alter microcirculation, it will be applied during the parabolic flight maneuvers of the campaign. Our results might deepen the understanding of microcirculation on space missions and on earth.

Monitoring blood-flow in the mouse cochlea using an endoscopic laser speckle contrast imaging system

PubMed Central

Yu, Sunkon; Jung, Byungjo; Choi, Jin Sil

2018-01-01

Laser speckle contrast imaging (LSCI) enables continuous high-resolution assessment of microcirculation in real-time. We applied an endoscope to LSCI to measure cochlear blood-flow in an ischemia–reperfusion mouse model. We also explored whether using xenon light in combination with LSCI facilitates visualization of anatomical position. Based on a previous preliminary study, the appropriate wavelength for penetrating the thin bony cochlea was 830 nm. A 2.7-mm-diameter endoscope was used, as appropriate for the size of the mouse cochlea. Our endoscopic LSCI system was used to illuminate the right cochlea after dissection of the mouse. We observed changes in the speckle signals when we applied the endoscopic LSCI system to the ischemia-reperfusion mouse model. The anatomical structure of the mouse cochlea and surrounding structures were clearly visible using the xenon light. The speckle signal of the cochlea was scattered, with an intensity that varied between that of the stapes (with the lowest signal), the negative control, and the stapedial artery (with the highest signal), the positive control. In the cochlear ischemia–reperfusion mouse model, the speckle signal of the cochlea decreased during the ischemic phase, and increased during the reperfusion phase, clearly reflecting cochlear blood-flow. The endoscopic LSCI system generates high-resolution images in real-time, allowing visualization of blood-flow and its changes in the mouse cochlea. Anatomical structures were clearly matched using LSCI along with visible light. PMID:29489849

Monitoring blood-flow in the mouse cochlea using an endoscopic laser speckle contrast imaging system.

PubMed

Kong, Tae Hoon; Yu, Sunkon; Jung, Byungjo; Choi, Jin Sil; Seo, Young Joon

2018-01-01

Laser speckle contrast imaging (LSCI) enables continuous high-resolution assessment of microcirculation in real-time. We applied an endoscope to LSCI to measure cochlear blood-flow in an ischemia-reperfusion mouse model. We also explored whether using xenon light in combination with LSCI facilitates visualization of anatomical position. Based on a previous preliminary study, the appropriate wavelength for penetrating the thin bony cochlea was 830 nm. A 2.7-mm-diameter endoscope was used, as appropriate for the size of the mouse cochlea. Our endoscopic LSCI system was used to illuminate the right cochlea after dissection of the mouse. We observed changes in the speckle signals when we applied the endoscopic LSCI system to the ischemia-reperfusion mouse model. The anatomical structure of the mouse cochlea and surrounding structures were clearly visible using the xenon light. The speckle signal of the cochlea was scattered, with an intensity that varied between that of the stapes (with the lowest signal), the negative control, and the stapedial artery (with the highest signal), the positive control. In the cochlear ischemia-reperfusion mouse model, the speckle signal of the cochlea decreased during the ischemic phase, and increased during the reperfusion phase, clearly reflecting cochlear blood-flow. The endoscopic LSCI system generates high-resolution images in real-time, allowing visualization of blood-flow and its changes in the mouse cochlea. Anatomical structures were clearly matched using LSCI along with visible light.

Role of T-type calcium channels in myogenic tone of skeletal muscle resistance arteries.

PubMed

VanBavel, Ed; Sorop, Oana; Andreasen, Ditte; Pfaffendorf, Martin; Jensen, Boye L

2002-12-01

T-type calcium channels may be involved in the maintenance of myogenic tone. We tested their role in isolated rat cremaster arterioles obtained after CO(2) anesthesia and decapitation. Total RNA was analyzed by RT-PCR and Southern blotting for calcium channel expression. We observed expression of voltage-operated calcium (Ca(V)) channels Ca(V)3.1 (T-type), Ca(V)3.2 (T-type), and Ca(V)1.2 (L-type) in cremaster arterioles (n = 3 rats). Amplification products were observed only in the presence of reverse transcriptase and cDNA. Concentration-response curves of the relatively specific L-type blocker verapamil and the relatively specific T-type blockers mibefradil and nickel were made on cannulated vessels with either myogenic tone (75 mmHg) or a similar level of constriction induced by 30 mM K(+) at 35 mmHg. Mibefradil and nickel were, respectively, 162-fold and 300-fold more potent in inhibiting myogenic tone compared with K(+)-induced constriction [log(IC(50), M): mibefradil, basal -7.3 +/- 0.2 (n = 9) and K(+) -5.1 +/- 0.1 (n = 5); nickel, basal -4.1 +/- 0.2 (n = 5) and K(+) -1.6 +/- 0.5 (n = 5); means +/- SE]. Verapamil had a 17-fold more potent effect [log(IC(50), M): basal -6.6 +/- 0.1 (n = 5); K(+) -5.4 +/- 0.3 (n = 4); all log(IC(50)) P < 0.05, basal vs. K(+)]. These data suggest that T-type calcium channels are expressed and involved in maintenance of myogenic tone in rat cremaster muscle arterioles.

Dynamin-related protein-1 controls fusion pore dynamics during platelet granule exocytosis.

PubMed

Koseoglu, Secil; Dilks, James R; Peters, Christian G; Fitch-Tewfik, Jennifer L; Fadel, Nathalie A; Jasuja, Reema; Italiano, Joseph E; Haynes, Christy L; Flaumenhaft, Robert

2013-03-01

Platelet granule exocytosis serves a central role in hemostasis and thrombosis. Recently, single-cell amperometry has shown that platelet membrane fusion during granule exocytosis results in the formation of a fusion pore that subsequently expands to enable the extrusion of granule contents. However, the molecular mechanisms that control platelet fusion pore expansion and collapse are not known. We identified dynamin-related protein-1 (Drp1) in platelets and found that an inhibitor of Drp1, mdivi-1, blocked exocytosis of both platelet dense and α-granules. We used single-cell amperometry to monitor serotonin release from individual dense granules and, thereby, measured the effect of Drp1 inhibition on fusion pore dynamics. Inhibition of Drp1 increased spike width and decreased prespike foot events, indicating that Drp1 influences fusion pore formation and expansion. Platelet-mediated thrombus formation in vivo after laser-induced injury of mouse cremaster arterioles was impaired after infusion of mdivi-1. These results demonstrate that inhibition of Drp1 disrupts platelet fusion pore dynamics and indicate that Drp1 can be targeted to control thrombus formation in vivo.

Pathophysiological levels of soluble P-selectin mediate adhesion of leukocytes to the endothelium through Mac-1 activation.

PubMed

Woollard, Kevin J; Suhartoyo, Andreas; Harris, Emma E; Eisenhardt, Steffen U; Jackson, Shaun P; Peter, Karlheinz; Dart, Anthony M; Hickey, Michael J; Chin-Dusting, Jaye P F

2008-11-07

Plasma soluble P-selectin (sP-selectin) levels are increased in pathologies associated with atherosclerosis, including peripheral arterial occlusive disease (PAOD). However, the role of sP-selectin in regulating leukocyte-endothelial adhesion is unclear. The aim of this study was to assess the ability of exogenous and endogenous sP-selectin to induce leukocyte responses that promote their adhesion to various forms of endothelium. In flow chamber assays, sP-selectin dose-dependently increased neutrophil adhesion to resting human iliac artery endothelial cells. Similarly, sP-selectin induced neutrophil adhesion to the endothelial surface of murine aortae and human radial venous segments in ex vivo flow chamber experiments. Using intravital microscopy to examine postcapillary venules in the mouse cremaster muscle, in vivo administration of sP-selectin was also found to significantly increase leukocyte rolling and adhesion in unstimulated postcapillary venules. Using a Mac-1-specific antibody and P-selectin knockout mouse, it was demonstrated that this finding was dependent on a contribution of Mac-1 to leukocyte rolling and endothelial P-selectin expression. This was confirmed in an ex vivo perfusion model using viable mouse aorta and human radial vessels. In contrast, with tumor necrosis factor-alpha-activated endothelial cells and intact endothelium, where neutrophil adhesion was already elevated, sP-selectin failed to further increase adhesion. Plasma samples from PAOD patients containing pathologically elevated concentrations of sP-selectin also increased neutrophil adhesion to the endothelium in a sP-selectin-dependent manner, as demonstrated by immunodepletion of sP-selectin. These studies demonstrate that raised plasma sP-selectin may influence the early progression of vascular disease by promoting leukocyte adhesion to the endothelium in PAOD, through Mac-1-mediated rolling and dependent on endothelial P-selectin expression.

Two-photon NADH imaging exposes boundaries of oxygen diffusion in cortical vascular supply regions

PubMed Central

Kasischke, Karl A; Lambert, Elton M; Panepento, Ben; Sun, Anita; Gelbard, Harris A; Burgess, Robert W; Foster, Thomas H; Nedergaard, Maiken

2011-01-01

Oxygen transport imposes a possible constraint on the brain's ability to sustain variable metabolic demands, but oxygen diffusion in the cerebral cortex has not yet been observed directly. We show that concurrent two-photon fluorescence imaging of endogenous nicotinamide adenine dinucleotide (NADH) and the cortical microcirculation exposes well-defined boundaries of tissue oxygen diffusion in the mouse cortex. The NADH fluorescence increases rapidly over a narrow, very low pO2 range with a p50 of 3.4±0.6 mm Hg, thereby establishing a nearly binary reporter of significant, metabolically limiting hypoxia. The transient cortical tissue boundaries of NADH fluorescence exhibit remarkably delineated geometrical patterns, which define the limits of tissue oxygen diffusion from the cortical microcirculation and bear a striking resemblance to the ideal Krogh tissue cylinder. The visualization of microvessels and their regional contribution to oxygen delivery establishes penetrating arterioles as major oxygen sources in addition to the capillary network and confirms the existence of cortical oxygen fields with steep microregional oxygen gradients. Thus, two-photon NADH imaging can be applied to expose vascular supply regions and to localize functionally relevant microregional cortical hypoxia with micrometer spatial resolution. PMID:20859293

Two-photon NADH imaging exposes boundaries of oxygen diffusion in cortical vascular supply regions.

PubMed

Kasischke, Karl A; Lambert, Elton M; Panepento, Ben; Sun, Anita; Gelbard, Harris A; Burgess, Robert W; Foster, Thomas H; Nedergaard, Maiken

2011-01-01

Oxygen transport imposes a possible constraint on the brain's ability to sustain variable metabolic demands, but oxygen diffusion in the cerebral cortex has not yet been observed directly. We show that concurrent two-photon fluorescence imaging of endogenous nicotinamide adenine dinucleotide (NADH) and the cortical microcirculation exposes well-defined boundaries of tissue oxygen diffusion in the mouse cortex. The NADH fluorescence increases rapidly over a narrow, very low pO(2) range with a p(50) of 3.4 ± 0.6 mm Hg, thereby establishing a nearly binary reporter of significant, metabolically limiting hypoxia. The transient cortical tissue boundaries of NADH fluorescence exhibit remarkably delineated geometrical patterns, which define the limits of tissue oxygen diffusion from the cortical microcirculation and bear a striking resemblance to the ideal Krogh tissue cylinder. The visualization of microvessels and their regional contribution to oxygen delivery establishes penetrating arterioles as major oxygen sources in addition to the capillary network and confirms the existence of cortical oxygen fields with steep microregional oxygen gradients. Thus, two-photon NADH imaging can be applied to expose vascular supply regions and to localize functionally relevant microregional cortical hypoxia with micrometer spatial resolution.

Arrest of B16 Melanoma Cells in the Mouse Pulmonary Microcirculation Induces Endothelial Nitric Oxide Synthase-Dependent Nitric Oxide Release that Is Cytotoxic to the Tumor Cells

PubMed Central

Qiu, Hongming; Orr, F.William; Jensen, Derrek; Wang, Hui Helen; McIntosh, Alan R.; Hasinoff, Brian B.; Nance, Dwight M.; Pylypas, Susan; Qi, Ke; Song, Chun; Muschel, Ruth J.; Al-Mehdi, Abu-Bakr

2003-01-01

Metastatic cancer cells seed the lung via blood vessels. Because endothelial cells generate nitric oxide (NO) in response to shear stress, we postulated that the arrest of cancer cells in the pulmonary microcirculation causes the release of NO in the lung. After intravenous injection of B16F1 melanoma cells, pulmonary NO increased sevenfold throughout 20 minutes and approached basal levels by 4 hours. NO induction was blocked by NG-nitro-l-arginine methyl ester (L-NAME) and was not observed in endothelial nitric oxide synthase (eNOS)-deficient mice. NO production, visualized ex vivo with the fluorescent NO probe diaminofluorescein diacetate, increased rapidly at the site of tumor cell arrest, and continued to increase throughout 20 minutes. Arrested tumor cells underwent apoptosis with apoptotic counts more than threefold over baseline at 8 and 48 hours. Neither the NO signals nor increased apoptosis were seen in eNOS knockout mice or mice pretreated with L-NAME. At 48 hours, 83% of the arrested cells had cleared from the lungs of wild-type mice but only ∼55% of the cells cleared from eNOS-deficient or L-NAME pretreated mice. eNOS knockout and L-NAME-treated mice had twofold to fivefold more metastases than wild-type mice, measured by the number of surface nodules or by histomorphometry. We conclude that tumor cell arrest in the pulmonary microcirculation induces eNOS-dependent NO release by the endothelium adjacent to the arrested tumor cells and that NO is one factor that causes tumor cell apoptosis, clearance from the lung, and inhibition of metastasis. PMID:12547699

[Microcirculation in patients with paranoid schizophrenia].

PubMed

Sakharov, A V; Ozornin, A S; Golygina, S E; Vinogradova, A O; Shvets, M S

2018-01-01

To study microcirculation in patients with paranoid schizophrenia by laser Doppler flowmetry. Fifty-three patients at the age from 18 to 38 years with a diagnosis of 'paranoid schizophrenia' (F20.0) were examined in the acute psychotic state and after 3 weeks of therapy. The control group consisted of 20 healthy volunteers. To assess microcirculation, the noninvasive technique of laser Doppler flowmetry using a laser blood flow analyzer was used. Significant changes in the microcirculation persisting even over three weeks of therapy in patients were identified. The total microcirculation index was increased by 1.4 times which indicated the acceleration of blood flow. An increase in the average fluctuations of perfusion by 3.7 times and in the coefficient of variation by 1.9 times, which reflect the excessive strengthening of local mechanisms of regulation of microcirculation, were found. There were an increase in the myogenic tone and neurogenic tone of metarteriole and precapillary sphincters as well as bypass index.

Anesthesia, Microcirculation and Wound Repair in Aging

PubMed Central

Bentov, Itay; Reed, May J.

2014-01-01

Age related changes in skin contribute to impaired wound healing after surgical procedures. Changes in skin with age include decline in thickness and composition, a decrease in the number of most cell types and diminished microcirculation. The microcirculation provides tissue perfusion, fluid homeostasis, and delivery of oxygen and other nutrients. It also controls temperature and the inflammatory response. Surgical incisions cause further disruption of the microvasculature of aged skin. Perioperative management can be modified to minimize insults to aged tissues. Judicious use of fluids, maintenance of normal body temperature, pain control and increased tissue oxygen tension are examples of adjustable variables that support the microcirculation. Anesthetic agents influence the microcirculation from a combination of effects on cardiac output, arterial pressure and local micro-vascular changes. We examine the role of anesthetic management in optimizing the microcirculation and potentially improving post-operative wound repair in older persons. PMID:24195972

Low Intensity Laser Therapy (LILT) Versus Transcutaneous Electrical Nerve Stimulation On Microcirculation In Diabetic Neuropathy

NASA Astrophysics Data System (ADS)

Battecha, Kadria H.; Atya, Azza M.

2011-09-01

Reduced microcirculation is a morbid element of neuropathy and one of the most common complications of uncontrolled diabetes. Many physical modalities have gained a considerable attention for enhancing cutaneous microcirculation in diabetic patients and prevent its serious complications. Accordingly, the present study was conducted to compare between the effect of low intensity laser therapy (LILT) and transcutaneous electrical nerve stimulation (TENS) on microcirculation in diabetic neuropathy. Thirty diabetic polyneuropathic patients ranged in age from 45-60 years participated in this study. They were randomly divided into two groups of equal number; patients in group (A) received LILT on plantar surface of foot with a dose of 3 J/cm2 and wavelength (904 nm), while those in group (B) received TENS on lower leg for 30 minutes with frequency (2 HZ). Treatment was conducted 3 times/week for 6 weeks. The cutaneous microcirculation was evaluated by Laser Doppler flowmetry at the baseline and at the end of treatment. Results revealed that group (A) showed statistically significant increase in the cutaneous microcirculation compared with group (B). So, it was concluded that LILT has to be more efficient than TENS in increasing cutaneous microcirculation in patients with diabetic neuropathy.

An encapsulated fruit and vegetable juice concentrate increases skin microcirculation in healthy women.

PubMed

De Spirt, S; Sies, H; Tronnier, H; Heinrich, U

2012-01-01

Microcirculation in the dermis of the skin is important for nutrient delivery to this tissue. In this study, the effects of a micronutrient concentrate (Juice Plus+®; 'active group'), composed primarily of fruit and vegetable juice powder, on skin microcirculation and structure were compared to placebo. This 12-week study had a monocentric, double-blind placebo and randomized controlled design with two treatment groups consisting of 26 healthy middle-aged women each. The 'oxygen to see' device was used to evaluate microcirculation. Skin density and thickness were measured using ultrasound. Measurements for skin hydration (Corneometer®), transepidermal water loss and serum analysis for carotenoids and α-tocopherol were also performed. By 12 weeks, microcirculation of the superficial plexus increased by 39%. Furthermore, skin hydration increased by 9% while skin thickness increased by 6% and skin density by 16% in the active group. In the placebo group, microcirculation decreased, and a slight increase in skin density was observed. Ingestion of a fruit- and vegetable-based concentrate increases microcirculation of the skin at 12 weeks of intervention and positively affects skin hydration, density and thickness. Copyright © 2011 S. Karger AG, Basel.

Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils

NASA Astrophysics Data System (ADS)

Wang, Zhenjia; Li, Jing; Cho, Jaehyung; Malik, Asrar B.

2014-03-01

Inflammatory diseases such as acute lung injury and ischaemic tissue injury are caused by the adhesion of a type of white blood cell--polymorphonuclear neutrophils--to the lining of the circulatory system or vascular endothelium and unchecked neutrophil transmigration. Nanoparticle-mediated targeting of activated neutrophils on vascular endothelial cells at the site of injury may be a useful means of directly inactivating neutrophil transmigration and hence mitigating vascular inflammation. Here, we report a method employing drug-loaded albumin nanoparticles, which efficiently deliver drugs into neutrophils adherent to the surface of the inflamed endothelium. Using intravital microscopy of tumour necrosis factor-α-challenged mouse cremaster post-capillary venules, we demonstrate that fluorescently tagged albumin nanoparticles are largely internalized by neutrophils adherent to the activated endothelium via cell surface Fcɣ receptors. Administration of albumin nanoparticles loaded with the spleen tyrosine kinase inhibitor, piceatannol, which blocks `outside-in' β2 integrin signalling in leukocytes, detached the adherent neutrophils and elicited their release into the circulation. Thus, internalization of drug-loaded albumin nanoparticles into neutrophils inactivates the pro-inflammatory function of activated neutrophils, thereby offering a promising approach for treating inflammatory diseases resulting from inappropriate neutrophil sequestration and activation.

Mast cells are dispensable for normal and activin-promoted wound healing and skin carcinogenesis.

PubMed

Antsiferova, Maria; Martin, Caroline; Huber, Marcel; Feyerabend, Thorsten B; Förster, Anja; Hartmann, Karin; Rodewald, Hans-Reimer; Hohl, Daniel; Werner, Sabine

2013-12-15

The growth and differentiation factor activin A is a key regulator of tissue repair, inflammation, fibrosis, and tumorigenesis. However, the cellular targets, which mediate the different activin functions, are still largely unknown. In this study, we show that activin increases the number of mature mast cells in mouse skin in vivo. To determine the relevance of this finding for wound healing and skin carcinogenesis, we mated activin transgenic mice with CreMaster mice, which are characterized by Cre recombinase-mediated mast cell eradication. Using single- and double-mutant mice, we show that loss of mast cells neither affected the stimulatory effect of overexpressed activin on granulation tissue formation and reepithelialization of skin wounds nor its protumorigenic activity in a model of chemically induced skin carcinogenesis. Furthermore, mast cell deficiency did not alter wounding-induced inflammation and new tissue formation or chemically induced angiogenesis and tumorigenesis in mice with normal activin levels. These findings reveal that mast cells are not major targets of activin during wound healing and skin cancer development and also argue against nonredundant functions of mast cells in wound healing and skin carcinogenesis in general.

Cre-mediated cell ablation contests mast cell contribution in models of antibody- and T cell-mediated autoimmunity.

PubMed

Feyerabend, Thorsten B; Weiser, Anne; Tietz, Annette; Stassen, Michael; Harris, Nicola; Kopf, Manfred; Radermacher, Peter; Möller, Peter; Benoist, Christophe; Mathis, Diane; Fehling, Hans Jörg; Rodewald, Hans-Reimer

2011-11-23

Immunological functions of mast cells remain poorly understood. Studies in Kit mutant mice suggest key roles for mast cells in certain antibody- and T cell-mediated autoimmune diseases. However, Kit mutations affect multiple cell types of both immune and nonimmune origin. Here, we show that targeted insertion of Cre-recombinase into the mast cell carboxypeptidase A3 locus deleted mast cells in connective and mucosal tissues by a genotoxic Trp53-dependent mechanism. Cre-mediated mast cell eradication (Cre-Master) mice had, with the exception of a lack of mast cells and reduced basophils, a normal immune system. Cre-Master mice were refractory to IgE-mediated anaphylaxis, and this defect was rescued by mast cell reconstitution. This mast cell-deficient strain was fully susceptible to antibody-induced autoimmune arthritis and to experimental autoimmune encephalomyelitis. Differences comparing Kit mutant mast cell deficiency models to selectively mast cell-deficient mice call for a systematic re-evaluation of immunological functions of mast cells beyond allergy. Copyright © 2011 Elsevier Inc. All rights reserved.

Analyzing Structure and Function of Vascularization in Engineered Bone Tissue by Video-Rate Intravital Microscopy and 3D Image Processing.

PubMed

Pang, Yonggang; Tsigkou, Olga; Spencer, Joel A; Lin, Charles P; Neville, Craig; Grottkau, Brian

2015-10-01

Vascularization is a key challenge in tissue engineering. Three-dimensional structure and microcirculation are two fundamental parameters for evaluating vascularization. Microscopic techniques with cellular level resolution, fast continuous observation, and robust 3D postimage processing are essential for evaluation, but have not been applied previously because of technical difficulties. In this study, we report novel video-rate confocal microscopy and 3D postimage processing techniques to accomplish this goal. In an immune-deficient mouse model, vascularized bone tissue was successfully engineered using human bone marrow mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) in a poly (D,L-lactide-co-glycolide) (PLGA) scaffold. Video-rate (30 FPS) intravital confocal microscopy was applied in vitro and in vivo to visualize the vascular structure in the engineered bone and the microcirculation of the blood cells. Postimage processing was applied to perform 3D image reconstruction, by analyzing microvascular networks and calculating blood cell viscosity. The 3D volume reconstructed images show that the hMSCs served as pericytes stabilizing the microvascular network formed by HUVECs. Using orthogonal imaging reconstruction and transparency adjustment, both the vessel structure and blood cells within the vessel lumen were visualized. Network length, network intersections, and intersection densities were successfully computed using our custom-developed software. Viscosity analysis of the blood cells provided functional evaluation of the microcirculation. These results show that by 8 weeks, the blood vessels in peripheral areas function quite similarly to the host vessels. However, the viscosity drops about fourfold where it is only 0.8 mm away from the host. In summary, we developed novel techniques combining intravital microscopy and 3D image processing to analyze the vascularization in engineered bone. These techniques have broad applicability for evaluating vascularization in other engineered tissues as well.

Monitoring microcirculation.

PubMed

Ocak, Işık; Kara, Atila; Ince, Can

2016-12-01

The clinical relevance of microcirculation and its bedside observation started gaining importance in the 1990s since the introduction of hand-held video microscopes. From then, this technology has been continuously developed, and its clinical relevance has been established in more than 400 studies. In this paper, we review the different types of video microscopes, their application techniques, the microcirculation of different organ systems, the analysis methods, and the software and scoring systems. The main focus of this review will be on the state-of-art technique, CytoCam-incident dark-field imaging, and the most recent technological and technical updates concerning microcirculation monitoring. Copyright © 2016 Elsevier Ltd. All rights reserved.

Correlation mapping: rapid method for retrieving microcirculation morphology from optical coherence tomography intensity images

NASA Astrophysics Data System (ADS)

Jonathan, E.; Enfield, J.; Leahy, M. J.

2011-03-01

The microcirculation plays a critical role is maintaining organ health and function by serving as a vascular are where trophic metabolism exchanges between blood and tissue takes place. To facilitate regular assessment in vivo, noninvasive microcirculation imagers are required in clinics. Among this group of clinical devices, are those that render microcirculation morphology such as nailfold capillaroscopy, a common device for early diagnosis and monitoring of microangiopathies. However, depth ambiguity disqualify this and other similar techniques in medical tomography where due to the 3-D nature of biological organs, imagers that support depth-resolved 2-D imaging and 3-D image reconstruction are required. Here, we introduce correlation map OCT (cmOCT), a promising technique for microcirculation morphology imaging that combines standard optical coherence tomography and an agile imaging analysis software based on correlation statistic. Promising results are presented of the microcirculation morphology images of the brain region of a small animal model as well as measurements of vessel geometry at bifurcations, such as vessel diameters, branch angles. These data will be useful for obtaining cardiovascular related characteristics such as volumetric flow, velocity profile and vessel-wall shear stress for circulatory and respiratory system.

Involvement of nitric oxide in the wound bed microcirculatory change during negative pressure wound therapy.

PubMed

Sano, Hitomi; Ichioka, Shigeru

2015-08-01

This study investigated the role of nitric oxide (NO) in the mechanism of blood flow increase in the wound bed during negative pressure wound therapy (NPWT). We developed an improved experimental model that allowed visualisation of the wound bed microcirculation under NPWT. Wounds were created on the mouse ear, taking care to preserve the subdermal vascular plexus, because the wound bed microcirculation was visualised using an intravital microscope system. We investigated whether application of a NO synthase inhibitor (N(G) -nitro-l-arginine methyl ester: L-NAME) might diminish the effect of the NPWT in increasing the wound blood flow. The experimental animals were divided into a negative pressure group (negative pressure of -125 mmHg applied to the wound for 5 minutes; n = 8), and a negative pressure plus L-NAME group (administration of L-NAME prior to application of the negative pressure; n = 8). In the negative pressure group, significant increase of blood flow was observed at 1 minute after the negative pressure application, which was sustained until 5 minutes. On the contrary, in the negative pressure plus L-NAME group, no significant changes were observed throughout the period of observation. These findings suggest that NO synthesis is involved in the wound bed microcirculatory change induced by NPWT. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Real-time acquisition and display of flow contrast using speckle variance optical coherence tomography in a graphics processing unit.

PubMed

Xu, Jing; Wong, Kevin; Jian, Yifan; Sarunic, Marinko V

2014-02-01

In this report, we describe a graphics processing unit (GPU)-accelerated processing platform for real-time acquisition and display of flow contrast images with Fourier domain optical coherence tomography (FDOCT) in mouse and human eyes in vivo. Motion contrast from blood flow is processed using the speckle variance OCT (svOCT) technique, which relies on the acquisition of multiple B-scan frames at the same location and tracking the change of the speckle pattern. Real-time mouse and human retinal imaging using two different custom-built OCT systems with processing and display performed on GPU are presented with an in-depth analysis of performance metrics. The display output included structural OCT data, en face projections of the intensity data, and the svOCT en face projections of retinal microvasculature; these results compare projections with and without speckle variance in the different retinal layers to reveal significant contrast improvements. As a demonstration, videos of real-time svOCT for in vivo human and mouse retinal imaging are included in our results. The capability of performing real-time svOCT imaging of the retinal vasculature may be a useful tool in a clinical environment for monitoring disease-related pathological changes in the microcirculation such as diabetic retinopathy.

Specimen preparation, imaging, and analysis protocols for knife-edge scanning microscopy.

PubMed

Choe, Yoonsuck; Mayerich, David; Kwon, Jaerock; Miller, Daniel E; Sung, Chul; Chung, Ji Ryang; Huffman, Todd; Keyser, John; Abbott, Louise C

2011-12-09

Major advances in high-throughput, high-resolution, 3D microscopy techniques have enabled the acquisition of large volumes of neuroanatomical data at submicrometer resolution. One of the first such instruments producing whole-brain-scale data is the Knife-Edge Scanning Microscope (KESM), developed and hosted in the authors' lab. KESM has been used to section and image whole mouse brains at submicrometer resolution, revealing the intricate details of the neuronal networks (Golgi), vascular networks (India ink), and cell body distribution (Nissl). The use of KESM is not restricted to the mouse nor the brain. We have successfully imaged the octopus brain, mouse lung, and rat brain. We are currently working on whole zebra fish embryos. Data like these can greatly contribute to connectomics research; to microcirculation and hemodynamic research; and to stereology research by providing an exact ground-truth. In this article, we will describe the pipeline, including specimen preparation (fixing, staining, and embedding), KESM configuration and setup, sectioning and imaging with the KESM, image processing, data preparation, and data visualization and analysis. The emphasis will be on specimen preparation and visualization/analysis of obtained KESM data. We expect the detailed protocol presented in this article to help broaden the access to KESM and increase its utilization.

Effect of hypokinesia on blood microcirculation

NASA Technical Reports Server (NTRS)

Chernukh, A. M.; Gazenko, O. G.; Fedorov, B. M.; Krupina, T. N.; Aleksandrov, P. N.; Shagal, D. I.; Ranferova, N. Y.; Proskurina, T. N.

1980-01-01

Blood microcirculation in the region of the scleral bulbar conjunctiva and the nail folds on the fingers and toes was studied in 18 practically healthy men during 182 day antiorthostatic hypokinesia and 30 day rehabilitation period. Marked changes in microcirculation in the sclera and feet and less evident changes on the hands was revealed. A complex of special prophylactic physical exercises had a distinctly favorable effect on circulation in the hands.

Association of locally produced IL10 and TGFb1 with tumor size, histological type and presence of metastases in patients with lung carcinoma.

PubMed

Karlicic, Vukoica; Vukovic, Jelena; Stanojevic, Ivan; Sotirovic, Jelena; Peric, Aleksandar; Jovic, Milena; Cvijanovic, Vlado; Djukic, Mirjana; Banovic, Tatjana; Vojvodic, Danilo

2016-01-01

Advanced lung carcinoma is charasterized with fast disease progression. Interleukin (IL)10 and transforming growth factor (TGF)b1 are immunosuppressive mediators and their role in lung carcinoma pathogenesis and in the antitumor response has not yet been elucidated. The purpose of this study was to correlate IL10 and TGFb1 levels in the serum and lung tumor microcirculation with clinical stage, disease extent, histological features and TNM stage. The study included 41 lung cancer patients in clinical stage III and IV. Histological type was determined immunohistochemically, while tumor size, localization and dissemination were determined radiologically by multislice computerized tomography (MSCT). IL10 and TGFb1 levels were quantified with commercial flow cytometric test in serum and lung tumor microcirculation samples. Non small cell lung cancer (NSCLC) patients had significantly elevated TGFb1 while small cell lung cancer (SCLC) patients had significantly increased IL10 in tumor microcirculation. IL10 was significantly elevated in patients with the largest tumors, as well as in patients with III clinical stage and without metastases, both in the serum and tumor microcirculation. TGFb1 was significantly increased in serum and tumor microcirculation in patients with larger tumors. We found significant correlation between these two immunosuppressive cytokines, IL10 and TGFb1, in tumor microcirculation but not in patient serum samples. IL10 and TGFb1 in systemic and tumor microcirculation are significantly associated with particular histological type of lung cancer, tumor size and degree of disease extent.

Cerebral Microcirculation during Experimental Normovolaemic Anemia

PubMed Central

Bellapart, Judith; Cuthbertson, Kylie; Dunster, Kimble; Diab, Sara; Platts, David G.; Raffel, O. Christopher; Gabrielian, Levon; Barnett, Adrian; Paratz, Jenifer; Boots, Rob; Fraser, John F.

2016-01-01

Anemia is accepted among critically ill patients as an alternative to elective blood transfusion. This practice has been extrapolated to head injury patients with only one study comparing the effects of mild anemia on neurological outcome. There are no studies quantifying microcirculation during anemia. Experimental studies suggest that anemia leads to cerebral hypoxia and increased rates of infarction, but the lack of clinical equipoise, when testing the cerebral effects of transfusion among critically injured patients, supports the need of experimental studies. The aim of this study was to quantify cerebral microcirculation and the potential presence of axonal damage in an experimental model exposed to normovolaemic anemia, with the intention of describing possible limitations within management practices in critically ill patients. Under non-recovered anesthesia, six Merino sheep were instrumented using an intracardiac transeptal catheter to inject coded microspheres into the left atrium to ensure systemic and non-chaotic distribution. Cytometric analyses quantified cerebral microcirculation at specific regions of the brain. Amyloid precursor protein staining was used as an indicator of axonal damage. Animals were exposed to normovolaemic anemia by blood extractions from the indwelling arterial catheter with simultaneous fluid replacement through a venous central catheter. Simultaneous data recording from cerebral tissue oxygenation, intracranial pressure, and cardiac output was monitored. A regression model was used to examine the effects of anemia on microcirculation with a mixed model to control for repeated measures. Homogeneous and normal cerebral microcirculation with no evidence of axonal damage was present in all cerebral regions, with no temporal variability, concluding that acute normovolaemic anemia does not result in short-term effects on cerebral microcirculation in the ovine brain. PMID:26869986

The Difference Between the Healing and the Nonhealing Diabetic Foot Ulcer: A Review of the Role of the Microcirculation.

PubMed

Lowry, Danielle; Saeed, Mujahid; Narendran, Parth; Tiwari, Alok

2017-09-01

Diabetic foot disease carries a high morbidity and is a leading cause of lower limb amputation. This may in part be due to the effect diabetes mellitus (DM) has on the microcirculation including in the skin. We conducted a review of studies that have examined the relationship between microcirculatory function and wound healing in patients with DM. A search of the Medline, Embase, and Web of Science databases was performed coupled with a review of references for the period 1946 to March 2015. Nineteen studies of diverse methodology and cohort selection were identified. Poor function of the microcirculation was related to poor outcome. Transcutaneous oxygen pressure (TcPO 2 ) was the most commonly used method to measure the microcirculation and thresholds for poor outcome proposed ranged from 10 mmHg to <34 mmHg. Two studies reexamined microcirculatory function following revascularization. Both found an increase in TcPO 2 , however only 1 reached statistical significance. No significant difference in the results of microcirculation tests was found between diabetic and nondiabetic patients. While it is not possible to draw firm conclusions from the evidence currently available there are clear areas that warrant research. Good microcirculation unsurprisingly appears to associate with better wound healing. The influence of DM is not clear, and neither is the degree of improvement required to achieve healing. Studies that examine a clearly defined cohort both with and without DM are urgently required. Accurate quantitative assessment of microcirculation will aid prediction of wound healing identifying those at greatest risk of amputation.

Functional preservation of vascular smooth muscle tissue

NASA Technical Reports Server (NTRS)

Alexander, W. C.; Hutchins, P. M.; Kimzey, S. L.

1973-01-01

The ionic and cellular feedback relationships operating to effect the vascular decompensatory modifications were examined to reveal procedures for implementing protective measures guarding against vascular collapse when returning from a weightless environment to that of the earth's gravity. The surgical procedures for preparing the rat cremaster, and the fixation methods are described. Abstracts of publications resulting from this research are included.

In vivo assessment of the human cerebral microcirculation and its glycocalyx: A technical report.

PubMed

Haeren, R H L; Rijkers, K; Schijns, O E M G; Dings, J; Hoogland, G; van Zandvoort, M A M J; Vink, H; van Overbeeke, J J

2018-06-01

The cerebral microcirculation and its glycocalyx, a matrix coating the luminal endothelium, are key regulators of capillary permeability and cerebral blood flow. Microvascular abnormalities are described in several neurological disorders. However, assessment of the cerebral microcirculation and glycocalyx has mainly been performed ex vivo. Here, the technical feasibility of in vivo assessment of the human cerebral microcirculation and its glycocalyx using sidestream dark field (SDF) imaging is discussed. Intraoperative assessment requires the application of a sterile drape covering the camera (slipcover). First, sublingual measurements with and without slipcover were performed in a healthy control to assess the impact of this slipcover. Subsequently, using SDF imaging, the sublingual (reference), cortical, and hippocampal microcirculation and glycocalyx were evaluated in patients who underwent resective brain surgery as treatment for drug-resistant temporal lobe epilepsy. Finally, vessel density, and the perfused boundary region (PBR), a validated gauge of glycocalyx health, were calculated using GlycoCheck © software. The addition of a slipcover affects vessel density and PBR values in a control subject. The cerebral measurements in five patients were more difficult to obtain than the sublingual ones. This was probably at least partly due to the introduction of a sterile slipcover. Results on vessel density and PBR showed similar patterns at all three measurement sites. This is the first report on in vivo assessment of the human cerebrovascular glycocalyx. Assessment of the glycocalyx is an additional application of in vivo imaging of the cerebral microcirculation using SDF technique. This method enables functional analysis of the microcirculation and glycocalyx, however the addition of a sterile slipcover affects the measurements. SDF imaging is a safe, quick, and straightforward technique to evaluate the functional cerebral microcirculation and glycocalyx. Because of their eminent role in cerebral homeostasis, this method may significantly add to research on the role of vascular pathophysiology underling various neurological disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Improvement of microcirculation and wound healing in vertical ridge augmentation after pre-treatment with self-inflating soft tissue expanders - a randomized study in dogs.

PubMed

Kaner, Dogan; Zhao, Han; Terheyden, Hendrik; Friedmann, Anton

2015-06-01

We investigated the effect of soft tissue expansion (STE) on vertical ridge augmentation with regard to the incidence of wound dehiscences and the impairment of microcirculation in dogs, and the applicability of laser Doppler flowmetry (LDF) to explore the relation between microcirculation and wound healing. Bone defects were created on both mandibular sides in ten beagle dogs by extraction of premolars and removal of bone. Six weeks later, self-filling tissue expanders were implanted in randomly assigned test sites. After 5 weeks of expansion, vertical augmentation was carried out in test and control sites using calvarial onlay grafts side by side with granular biphasic calcium phosphate covered with a resorbable polyethylene glycol membrane. Microcirculation was evaluated with laser Doppler flowmetry (LDF). The incidence of wound dehiscences was evaluated after 2 weeks. The validity of LDF to predict dehiscences was evaluated by construction of receiver operating characteristic (ROC) curves. After augmentation, test sites showed significantly better perfusion than control sites without preceding STE (P = 0.012). Three days after surgery, perfusion was still significantly decreased in control sites (P = 0.005), while microcirculation in test sites had returned to pre-surgical levels. After 2 weeks, healing in test sites was good, whereas eight dehiscences were found in control sites (P = 0.002). ROC curves showed that microcirculation levels immediately after augmentation surgery significantly predicted subsequent wound dehiscences (AUC = 0.799, CI 0.642-0.955, P = 0.006). Laser Doppler flowmetry is suitable for evaluation of soft tissue microcirculation after ridge augmentation. STE reduced the impairment of microcirculation caused by vertical ridge augmentation and decreased the incidence of wound dehiscences in the investigated animal model. © 2014 The Authors. Clinical Oral Implants Research Published by John Wiley & Sons Ltd.

A Targeting Microbubble for Ultrasound Molecular Imaging

PubMed Central

Yeh, James Shue-Min; Sennoga, Charles A.; McConnell, Ellen; Eckersley, Robert; Tang, Meng-Xing; Nourshargh, Sussan; Seddon, John M.; Haskard, Dorian O.; Nihoyannopoulos, Petros

2015-01-01

Rationale Microbubbles conjugated with targeting ligands are used as contrast agents for ultrasound molecular imaging. However, they often contain immunogenic (strept)avidin, which impedes application in humans. Although targeting bubbles not employing the biotin-(strept)avidin conjugation chemistry have been explored, only a few reached the stage of ultrasound imaging in vivo, none were reported/evaluated to show all three of the following properties desired for clinical applications: (i) low degree of non-specific bubble retention in more than one non-reticuloendothelial tissue; (ii) effective for real-time imaging; and (iii) effective for acoustic quantification of molecular targets to a high degree of quantification. Furthermore, disclosures of the compositions and methodologies enabling reproduction of the bubbles are often withheld. Objective To develop and evaluate a targeting microbubble based on maleimide-thiol conjugation chemistry for ultrasound molecular imaging. Methods and Results Microbubbles with a previously unreported generic (non-targeting components) composition were grafted with anti-E-selectin F(ab’)2 using maleimide-thiol conjugation, to produce E-selectin targeting microbubbles. The resulting targeting bubbles showed high specificity to E-selectin in vitro and in vivo. Non-specific bubble retention was minimal in at least three non-reticuloendothelial tissues with inflammation (mouse heart, kidneys, cremaster). The bubbles were effective for real-time ultrasound imaging of E-selectin expression in the inflamed mouse heart and kidneys, using a clinical ultrasound scanner. The acoustic signal intensity of the targeted bubbles retained in the heart correlated strongly with the level of E-selectin expression (|r|≥0.8), demonstrating a high degree of non-invasive molecular quantification. Conclusions Targeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described, may possess properties (i)–(iii) desired for clinical applications. PMID:26161541

Underlying chronic inflammation alters the profile and mechanisms of acute neutrophil recruitment.

PubMed

Ma, Bin; Whiteford, James R; Nourshargh, Sussan; Woodfin, Abigail

2016-11-01

Chronically inflamed tissues show altered characteristics that include persistent populations of inflammatory leukocytes and remodelling of the vascular network. As the majority of studies on leukocyte recruitment have been carried out in normal healthy tissues, the impact of underlying chronic inflammation on ongoing leukocyte recruitment is largely unknown. Here, we investigate the profile and mechanisms of acute inflammatory responses in chronically inflamed and angiogenic tissues, and consider the implications for chronic inflammatory disorders. We have developed a novel model of chronic ischaemia of the mouse cremaster muscle that is characterized by a persistent population of monocyte-derived cells (MDCs), and capillary angiogenesis. These tissues also show elevated acute neutrophil recruitment in response to locally administered inflammatory stimuli. We determined that Gr1 low MDCs, which are widely considered to have anti-inflammatory and reparative functions, amplified acute inflammatory reactions via the generation of additional proinflammatory signals, changing both the profile and magnitude of the tissue response. Similar vascular and inflammatory responses, including activation of MDCs by transient ischaemia-reperfusion, were observed in mouse hindlimbs subjected to chronic ischaemia. This response demonstrates the relevance of the findings to peripheral arterial disease, in which patients experience transient exercise-induced ischaemia known as claudication.These findings demonstrate that chronically inflamed tissues show an altered profile and altered mechanisms of acute inflammatory responses, and identify tissue-resident MDCs as potential therapeutic targets. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Dexamethasone-conjugated DNA nanotubes as anti-inflammatory agents in vivo.

PubMed

Sellner, Sabine; Kocabey, Samet; Zhang, Tao; Nekolla, Katharina; Hutten, Saskia; Krombach, Fritz; Liedl, Tim; Rehberg, Markus

2017-07-01

The biopolymer DNA allows to create nanoscale, biocompatible structures, which can be designed in a target-specific and stimuli-responsive manner. DNA carrier systems with these characteristics hold a great potential for nanomedical applications, such as for the treatment of inflammatory diseases. Here we used a DNA-based drug carrier system for the pH-dependent delivery of the glucocorticoid dexamethasone into macrophages, a cell type with a key role in the regulation of inflammation. Dexamethasone (Dex) nanotubes were internalized within minutes by MH-S macrophages in vitro and by tissue resident macrophages in the mouse cremaster muscle in vivo and localized in their endosomes. Treatment with Dex nanotubes in vitro significantly reduced the LPS-induced TNF secretion by macrophages, as compared to equivalent amounts of free dexamethasone without affecting cell viability. Microinjection of Dex nanotubes into postischemic muscle tissue of anesthetized mice resulted in a marked reduction of ischemia-reperfusion-elicited leukocyte transmigration and diminished vascular expression of the endothelial adhesion molecules VCAM-1 and ICAM-1. Taken together, our results demonstrate that DNA nanotubes can be used as a platform for the targeted delivery of glucocorticoids and could thus foster the development of nanomedical therapeutics with reduced off-target effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hemodynamic coherence and the rationale for monitoring the microcirculation.

PubMed

Ince, Can

2015-01-01

This article presents a personal viewpoint of the shortcoming of conventional hemodynamic resuscitation procedures in achieving organ perfusion and tissue oxygenation following conditions of shock and cardiovascular compromise, and why it is important to monitor the microcirculation in such conditions. The article emphasizes that if resuscitation procedures are based on the correction of systemic variables, there must be coherence between the macrocirculation and microcirculation if systemic hemodynamic-driven resuscitation procedures are to be effective in correcting organ perfusion and oxygenation. However, in conditions of inflammation and infection, which often accompany states of shock, vascular regulation and compensatory mechanisms needed to sustain hemodynamic coherence are lost, and the regional circulation and microcirculation remain in shock. We identify four types of microcirculatory alterations underlying the loss of hemodynamic coherence: type 1, heterogeneous microcirculatory flow; type 2, reduced capillary density induced by hemodilution and anemia; type 3, microcirculatory flow reduction caused by vasoconstriction or tamponade; and type 4, tissue edema. These microcirculatory alterations can be observed at the bedside using direct visualization of the sublingual microcirculation with hand-held vital microscopes. Each of these alterations results in oxygen delivery limitation to the tissue cells despite the presence of normalized systemic hemodynamic variables. Based on these concepts, we propose how to optimize the volume of fluid to maximize the oxygen-carrying capacity of the microcirculation to transport oxygen to the tissues.

In vivo assessment of the structure of skin microcirculation by reflectance confocal-laser-scanning microscopy

NASA Astrophysics Data System (ADS)

Sugata, Keiichi; Osanai, Osamu; Kawada, Hiromitsu

2012-02-01

One of the major roles of the skin microcirculation is to supply oxygen and nutrition to the surrounding tissue. Regardless of the close relationship between the microcirculation and the surrounding tissue, there are few non-invasive methods that can evaluate both the microcirculation and its surrounding tissue at the same site. We visualized microcapillary plexus structures in human skin using in vivo reflectance confocal-laser-scanning microscopy (CLSM), Vivascope 3000® (Lucid Inc., USA) and Image J software (National Institutes of Health, USA) for video image processing. CLSM is a non-invasive technique that can visualize the internal structure of the skin at the cellular level. In addition to internal morphological information such as the extracellular matrix, our method reveals capillary structures up to the depth of the subpapillary plexus at the same site without the need for additional optical systems. Video images at specific depths of the inner forearm skin were recorded. By creating frame-to-frame difference images from the video images using off-line video image processing, we obtained images that emphasize the brightness depending on changes of intensity coming from the movement of blood cells. Merging images from different depths of the skin elucidates the 3-dimensional fine line-structure of the microcirculation. Overall our results show the feasibility of a non-invasive, high-resolution imaging technique to characterize the skin microcirculation and the surrounding tissue.

Comparative evaluation of the effects of high-intensity and low-intensity laser radiation on microcirculation among patients with knee arthritis

NASA Astrophysics Data System (ADS)

Kulchitskaya, D. B.; Konchugova, T. V.; E Fedorova, N.

2017-04-01

Sixty patients with knee arthritis aged from 40 to 75 years old were examined. The patients were randomly divided into two groups: 1st group (30 patients) received high intensity laser radiation; 2nd group (20 patients) received low intensity laser radiation. As a result of the conducted research it was found that high intensity laser radiation is more efficient and leads to more vivid positive changes in the microcirculation of patients with knee arthritis. The changes in microcirculation were based on the normalization of the myogenic and neurogenic tonus of the arterioles, strengthening oscillation of the endothelial range. As a result of local mechanisms activation of tissue blood flow there occurs adequate modulation of the microcirculatory bloodstream, which is aimed at the elimination of congestive phenomena in the capillary and venular level of the microcirculation bloodstream. We should note that in the long-term more significant were the positive changes in the state of the venular level of the microcirculation bloodstream. in constructing both.

Prostaglandins induce vasodilatation of the microvasculature during muscle contraction and induce vasodilatation independent of adenosine

PubMed Central

Murrant, Coral L; Dodd, Jason D; Foster, Andrew J; Inch, Kristin A; Muckle, Fiona R; Ruiz, Della A; Simpson, Jeremy A; Scholl, Jordan H P

2014-01-01

Blood flow data from contracting muscle in humans indicates that adenosine (ADO) stimulates the production of nitric oxide (NO) and vasodilating prostaglandins (PG) to produce arteriolar vasodilatation in a redundant fashion such that when one is inhibited the other can compensate. We sought to determine whether these redundant mechanisms are employed at the microvascular level. First, we determined whether PGs were involved in active hyperaemia at the microvascular level. We stimulated four to five skeletal muscle fibres in the anaesthetized hamster cremaster preparation in situ and measured the change in diameter of 2A arterioles (maximum diameter 40 μm, third arteriolar level up from the capillaries) at a site of overlap with the stimulated muscle fibres before and after 2 min of contraction [stimulus frequencies: 4, 20 and 60 Hz at 15 contractions per minute (CPM) or contraction frequencies of 6, 15 or 60 CPM at 20 Hz; 250 ms train duration]. Muscle fibres were stimulated in the absence and presence of the phospholipase A2 inhibitor quinacrine. Further, we applied a range of concentrations of ADO (10−7–10−5 m) extraluminally, (to mimic muscle contraction) in the absence and presence of l-NAME (NO synthase inhibitor), indomethacin (INDO, cyclooxygenase inhibitor) and l-NAME + INDO and observed the response of 2A arterioles. We repeated the latter experiment on a different level of the cremaster microvasculature (1A arterioles) and on the microvasculature of a different skeletal muscle (gluteus maximus, 2A arterioles). We observed that quinacrine inhibited vasodilatation during muscle contraction at intermediate and high contraction frequencies (15 and 60 CPM). l-NAME, INDO and l-NAME + INDO were not effective at inhibiting vasodilatation induced by any concentration of ADO tested in 2A and 1A arterioles in the cremaster muscle or 2A arterioles in the gluteus maximus muscle. Our data show that PGs are involved in the vasodilatation of the microvasculature in response to muscle contraction but did not obtain evidence that extraluminal ADO causes vasodilatation through NO or PG or both. Thus, we propose that PG-induced microvascular vasodilation during exercise is independent of ADO. PMID:24469074

Prostaglandins induce vasodilatation of the microvasculature during muscle contraction and induce vasodilatation independent of adenosine.

PubMed

Murrant, Coral L; Dodd, Jason D; Foster, Andrew J; Inch, Kristin A; Muckle, Fiona R; Ruiz, Della A; Simpson, Jeremy A; Scholl, Jordan H P

2014-03-15

Blood flow data from contracting muscle in humans indicates that adenosine (ADO) stimulates the production of nitric oxide (NO) and vasodilating prostaglandins (PG) to produce arteriolar vasodilatation in a redundant fashion such that when one is inhibited the other can compensate. We sought to determine whether these redundant mechanisms are employed at the microvascular level. First, we determined whether PGs were involved in active hyperaemia at the microvascular level. We stimulated four to five skeletal muscle fibres in the anaesthetized hamster cremaster preparation in situ and measured the change in diameter of 2A arterioles (maximum diameter 40 μm, third arteriolar level up from the capillaries) at a site of overlap with the stimulated muscle fibres before and after 2 min of contraction [stimulus frequencies: 4, 20 and 60 Hz at 15 contractions per minute (CPM) or contraction frequencies of 6, 15 or 60 CPM at 20 Hz; 250 ms train duration]. Muscle fibres were stimulated in the absence and presence of the phospholipase A2 inhibitor quinacrine. Further, we applied a range of concentrations of ADO (10(-7)-10(-5) M) extraluminally, (to mimic muscle contraction) in the absence and presence of L-NAME (NO synthase inhibitor), indomethacin (INDO, cyclooxygenase inhibitor) and L-NAME + INDO and observed the response of 2A arterioles. We repeated the latter experiment on a different level of the cremaster microvasculature (1A arterioles) and on the microvasculature of a different skeletal muscle (gluteus maximus, 2A arterioles). We observed that quinacrine inhibited vasodilatation during muscle contraction at intermediate and high contraction frequencies (15 and 60 CPM). L-NAME, INDO and L-NAME + INDO were not effective at inhibiting vasodilatation induced by any concentration of ADO tested in 2A and 1A arterioles in the cremaster muscle or 2A arterioles in the gluteus maximus muscle. Our data show that PGs are involved in the vasodilatation of the microvasculature in response to muscle contraction but did not obtain evidence that extraluminal ADO causes vasodilatation through NO or PG or both. Thus, we propose that PG-induced microvascular vasodilation during exercise is independent of ADO.

Design of sensors for microcirculation investigation in pharyngeal mucosa

NASA Astrophysics Data System (ADS)

Mareew, Gleb O.; Mareew, Oleg V.; Fedosov, Ivan V.; Tuchin, Valery V.

2004-08-01

Sensors designed for research of blood microcirculation in pharyngeal mucosa by a laser Doppler flowmetry, are described and considered in view of anatomic and physiological features of objects of research. Two designs of sensors for laser Doppler flowmetry are described - non-contact and contact. The results of and clinical testing at norm and different pathologies of pharynx of on calibration of sensors, and also their comparative technical characteristics and materials of clinical researches of microcirculation are resulted at norm and at a various pathology.

Factors Affecting Tissue Oxygenation in Erythrocyte Transfusions

PubMed Central

Aykut, Güçlü; Yürük, Koray; İnce, Can

2014-01-01

Red blood cell transfusions are used to increase the oxygen-carrying capacity of blood in anemic states. But, because of the changes during storage of blood components and the specifics of preparation, erythrocytes may have controversial effects on tissue oxygenation and microcirculation. Also, the patient situation may play a role in the differing responses in oxygenation and microcirculation. In this review, the studies concerning the effects of banked blood and patient characteristics on microcirculation and tissue oxygenation are summarized. PMID:27366403

Monitoring peripheral perfusion and microcirculation.

PubMed

Dubin, Arnaldo; Henriquez, Elizabeth; Hernández, Glenn

2018-06-01

Microcirculatory alterations play a major role in the pathogenesis of shock. Monitoring tissue perfusion might be a relevant goal for shock resuscitation. The goal of this review was to revise the evidence supporting the monitoring of peripheral perfusion and microcirculation as goals of resuscitation. For this purpose, we mainly focused on skin perfusion and sublingual microcirculation. Although there are controversies about the reproducibility of capillary refill time in monitoring peripheral perfusion, it is a sound physiological variable and suitable for the ICU settings. In addition, observational studies showed its strong ability to predict outcome. Moreover, a preliminary study suggested that it might be a valuable goal for resuscitation. These results should be confirmed by the ongoing ANDROMEDA-SHOCK randomized controlled trial. On the other hand, the monitoring of sublingual microcirculation might also provide relevant physiological and prognostic information. On the contrary, methodological drawbacks mainly related to video assessment hamper its clinical implementation at the present time. Measurements of peripheral perfusion might be useful as goal of resuscitation. The results of the ANDROMEDA-SHOCK will clarify the role of skin perfusion as a guide for the treatment of shock. In contrast, the assessment of sublingual microcirculation mainly remains as a research tool.

PRotective Effect on the coronary microcirculation of patients with DIabetes by Clopidogrel or Ticagrelor (PREDICT): study rationale and design. A randomized multicenter clinical trial using intracoronary multimodal physiology.

PubMed

Cerrato, Enrico; Quirós, Alicia; Echavarría-Pinto, Mauro; Mejia-Renteria, Hernan; Aldazabal, Andres; Ryan, Nicola; Gonzalo, Nieves; Jimenez-Quevedo, Pilar; Nombela-Franco, Luis; Salinas, Pablo; Núñez-Gil, Iván J; Rumoroso, José Ramón; Fernández-Ortiz, Antonio; Macaya, Carlos; Escaned, Javier

2017-05-19

In diabetic patients a predisposed coronary microcirculation along with a higher risk of distal particulate embolization during primary percutaneous intervention (PCI) increases the risk of peri-procedural microcirculatory damage. However, new antiplatelet agents, in particular Ticagrelor, may protect the microcirculation through its adenosine-mediated vasodilatory effects. PREDICT is an original, prospective, randomized, multicenter controlled study designed to investigate the protective effect of Ticagrelor on the microcirculation during PCI in patient with diabetes mellitus type 2 or pre-diabetic status. The primary endpoints of this study aim to test (i) the decrease in microcirculatory resistance with antiplatelet therapy (Ticagrelor > Clopidogrel; mechanistic effect) and (ii) the relative microcirculatory protection of Ticagrelor compared to Clopidogrel during PCI (Ticagrelor < Clopidogrel; protective effect). PREDICT will be the first multicentre clinical trial to test the adenosine-mediated vasodilatory effect of Ticagrelor on the microcirculation during PCI in diabetic patients. The results will provide important insights into the prospective beneficial effect of this drug in preventing microvascular impairment related to PCI ( http://www.clinicaltrials.gov No. NCT02698618).

OXYGEN TRANSPORT IN THE MICROCIRCULATION AND ITS REGULATION

PubMed Central

Pittman, Roland N.

2012-01-01

Cells require energy to carry out their functions and they typically use oxidative phosphorylation to generate the needed ATP. Thus, cells have a continuous need for oxygen which they receive by diffusion from the blood through the interstitial fluid. The circulatory system pumps oxygen-rich blood through a network of increasingly minute vessels, the microcirculation. The structure of the microcirculation is such that all cells have at least one nearby capillary for diffusive exchange of oxygen and red blood cells release the oxygen bound to hemoglobin as they traverse capillaries. This review focuses first on the historical development of techniques to measure oxygen at various sites in the microcirculation, including the blood, interstitium and cells. Next, approaches are described as to how these techniques have been employed to make discoveries about different aspects of oxygen transport. Finally, ways in which oxygen might participate in the regulation of blood flow toward matching oxygen supply to oxygen demand is discussed. Overall, the transport of oxygen to the cells of the body is one of the most critical functions of the cardiovascular system and it is in the microcirculation where the final local determinants of oxygen supply, oxygen demand and their regulation are decided. PMID:23025284

In vivo Evaluation of Venular Glycocalyx during Hemorrhagic Shock in Rats using Intravital Microscopy

DTIC Science & Technology

2013-01-01

Brief Communication In vivo evaluation of venular glycocalyx during hemorrhagic shock in rats using intravital microscopy☆,☆☆ Ivo Torres Filho...pathophysiology and tested the hypothesis that hemorrhage causes glycocalyx degrada- tion in cremaster muscle microvessels. We utilized intravital microscopy...bound (Reitsma et al., 2007; Weinbaum et al., 2007). Intravital microscopy has been an invaluable resource for in vivo measurements of critically

Sensing of Vascular Permeability in Inflamed Vessel of Live Animal.

PubMed

Park, Sang A; Jeong, Soi; Choe, Young Ho; Hyun, Young-Min

2018-01-01

Increase in vascular permeability is a conclusive response in the progress of inflammation. Under controlled conditions, leukocytes are known to migrate across the vascular barriers to the sites of inflammation without severe vascular rupture. However, when inflammatory state becomes excessive, the leakage of blood components may occur and can be lethal. Basically, vascular permeability can be analyzed based on the intensity of blood outflow. To evaluate the amount and rate of leakage in live mice, we performed cremaster muscle exteriorization to visualize blood flow and neutrophil migration. Using two-photon intravital microscopy of the exteriorized cremaster muscle venules, we found that vascular barrier function is transiently and locally disrupted in the early stage of inflammatory condition induced by N-formylmethionyl-leucyl-phenylalanine (fMLP). Measurement of the concentration of intravenously (i.v.) injected Texas Red dextran inside and outside the vessels resulted in clear visualization of real-time increases in transient and local vascular permeability increase in real-time manner. We successfully demonstrated repeated leakage from a target site on a blood vessel in association with increasing severity of inflammation. Therefore, compared to other methods, two-photon intravital microscopy more accurately visualizes and quantifies vascular permeability even in a small part of blood vessels in live animals in real time.

Two alternative models concerning the perialveolar microcirculation in mammalian lungs.

PubMed

Günther, Bruno; Morgado, Enrique; Cociña, Manuela

2005-01-01

Despite the fact that the concept of sheet-flow in the pulmonary microcirculation of mammals was introduced more than three decades ago, the capillary circulatory model still prevails in the physiological literature. Since cardiac output is identical in the systemic and in pulmonary circulations, it is noteworthy that in the former, the resulting arterial pressure is five times higher than that of the latter, which means that the corresponding microcirculations must be radically different. The present study addresses this problem from both morphological and physiological perspectives.

Correlation mapping microscopy

NASA Astrophysics Data System (ADS)

McGrath, James; Alexandrov, Sergey; Owens, Peter; Subhash, Hrebesh M.; Leahy, Martin J.

2015-03-01

Changes in the microcirculation are associated with conditions such as Raynauds disease. Current modalities used to assess the microcirculation such as nailfold capillaroscopy are limited due to their depth ambiguity. A correlation mapping technique was recently developed to extend the capabilities of Optical Coherence Tomography to generate depth resolved images of the microcirculation. Here we present the extension of this technique to microscopy modalities, including confocal microscopy. It is shown that this correlation mapping microscopy technique can extend the capabilities of conventional microscopy to enable mapping of vascular networks in vivo with high spatial resolution.

Interrater Reliability and Diagnostic Performance of Subjective Evaluation of Sublingual Microcirculation Images by Physicians and Nurses: A Multicenter Observational Study.

PubMed

Lima, Alexandre; López, Alejandra; van Genderen, Michel E; Hurtado, Francisco Javier; Angulo, Martin; Grignola, Juan C; Shono, Atsuko; van Bommel, Jasper

2015-09-01

This was a cross-sectional multicenter study to investigate the ability of physicians and nurses from three different countries to subjectively evaluate sublingual microcirculation images and thereby discriminate normal from abnormal sublingual microcirculation based on flow and density abnormalities. Forty-five physicians and 61 nurses (mean age, 36 ± 10 years; 44 males) from three different centers in The Netherlands (n = 61), Uruguay (n = 12), and Japan (n = 33) were asked to subjectively evaluate a sample of 15 microcirculation videos randomly selected from an experimental model of endotoxic shock in pigs. All videos were first analyzed offline using the A.V.A. software by an independent, experienced investigator and were categorized as good, bad, or very bad microcirculation based on the microvascular flow index, perfused capillary density, and proportion of perfused capillaries. Then, the videos were randomly assigned to the examiners, who were instructed to subjectively categorize each image as good, bad, or very bad. An interrater analysis was performed, and sensitivity and specificity tests were calculated to evaluate the proportion of A.V.A. score abnormalities that the examiners correctly identified. The κ statistics indicated moderate agreement in the evaluation of microcirculation abnormalities using three categories, i.e., good, bad, or very bad (κ = 0.48), and substantial agreement using two categories, i.e., normal (good) and abnormal (bad or very bad) (κ = 0.66). There was no significant difference between the κ three and κ two statistics. We found that the examiner's subjective evaluations had good diagnostic performance and were highly sensitive (84%; 95% confidence interval, 81%-86%) and specific (87%; 95% confidence interval, 84%-90%) for sublingual microcirculatory abnormalities as assessed using the A.V.A. software. The subjective evaluations of sublingual microcirculation by physicians and nurses agreed well with a conventional offline analysis and were highly sensitive and specific for sublingual microcirculatory abnormalities.

Real-time digital imaging of leukocyte-endothelial interaction in ischemia-reperfusion injury (IRI) of the rat cremaster muscle.

PubMed

Thiele, Jan R; Goerendt, Kurt; Stark, G Bjoern; Eisenhardt, Steffen U

2012-08-05

Ischemia-reperfusion injury (IRI) has been implicated in a large array of pathological conditions such as cerebral stroke, myocardial infarction, intestinal ischemia as well as following transplant and cardiovascular surgery. Reperfusion of previously ischemic tissue, while essential for the prevention of irreversible tissue injury, elicits excessive inflammation of the affected tissue. Adjacent to the production of reactive oxygen species, activation of the complement system and increased microvascular permeability, the activation of leukocytes is one of the principle actors in the pathological cascade of inflammatory tissue damage during reperfusion. Leukocyte activation is a multistep process consisting of rolling, firm adhesion and transmigration and is mediated by a complex interaction between adhesion molecules in response to chemoattractants such as complement factors, chemokines, or platelet-activating factor. While leukocyte rolling in postcapillary venules is predominantly mediated by the interaction of selectins with their counter ligands, firm adhesion of leukocytes to the endothelium is selectin-controlled via binding to intercellular adhesion molecules (ICAM) and vascular cellular adhesion molecules (VCAM). Gold standard for the in vivo observation of leukocyte-endothelial interaction is the technique of intravital microscopy, first described in 1968. Though various models of IRI (ischemia-reperfusion injury) have been described for various organs, only few are suitable for direct visualization of leukocyte recruitment in the microvascular bed on a high level of image quality. We here promote the digital intravital epifluorescence microscopy of the postcapillary venule in the cremasteric microcirculation of the rat as a convenient method to qualitatively and quantitatively analyze leukocyte recruitment for IRI-research in striated muscle tissue and provide a detailed manual for accomplishing the technique. We further illustrate common pitfalls and provide useful tips which should enable the reader to truly appreciate, and safely perform the method. In a step by step protocol we depict how to get started with respiration controlled anesthesia under sufficient monitoring to keep the animal firmly anesthetized for longer periods of time. We then describe the cremasteric preparation as a thin flat sheet for outstanding optical resolution and provide a protocol for leukocyte imaging in IRI that has been well established in our laboratories.

The macro- and microcirculation of the kidney.

PubMed

Guerci, Philippe; Ergin, Bulent; Ince, Can

2017-09-01

Acute kidney injury (AKI) remains one of the main causes of morbidity and mortality in the intensive care medicine today. Its pathophysiology and progress to chronic kidney disease is still under investigation. In addition, the lack of techniques to adequately monitor renal function and microcirculation at the bedside makes its therapeutic resolution challenging. In this article, we review current concepts related to renal hemodynamics compromise as being the event underlying AKI. In doing so, we discuss the physiology of the renal circulation and the effects of alterations in systemic hemodynamics that lead to renal injury specifically in the context of reperfusion injury and sepsis. The ultimate key culprit of AKI leading to failure is the dysfunction of the renal microcirculation. The cellular and subcellular components of the renal microcirculation are discussed and how their injury contributes to AKI is described. Copyright © 2017. Published by Elsevier Ltd.

Dynamic Contrast-Enhanced Ultrasound Identifies Microcirculatory Alterations in Sepsis-Induced Acute Kidney Injury.

PubMed

Lima, Alexandre; van Rooij, Tom; Ergin, Bulent; Sorelli, Michele; Ince, Yasin; Specht, Patricia A C; Mik, Egbert G; Bocchi, Leonardo; Kooiman, Klazina; de Jong, Nico; Ince, Can

2018-05-15

We developed quantitative methods to analyze microbubble kinetics based on renal contrast-enhanced ultrasound imaging combined with measurements of sublingual microcirculation on a fixed area to quantify early microvascular alterations in sepsis-induced acute kidney injury. Prospective controlled animal experiment study. Hospital-affiliated animal research institution. Fifteen female pigs. The animals were instrumented with a renal artery flow probe after surgically exposing the kidney. Nine animals were given IV infusion of lipopolysaccharide to induce septic shock, and six were used as controls. Contrast-enhanced ultrasound imaging was performed on the kidney before, during, and after having induced shock. Sublingual microcirculation was measured continuously using the Cytocam on the same spot. Contrast-enhanced ultrasound effectively allowed us to develop new analytical methods to measure dynamic variations in renal microvascular perfusion during shock and resuscitation. Renal microvascular hypoperfusion was quantified by decreased peak enhancement and an increased ratio of the final plateau intensity to peak enhancement. Reduced intrarenal blood flow could be estimated by measuring the microbubble transit times between the interlobar arteries and capillary vessels in the renal cortex. Sublingual microcirculation measured using the Cytocam in a fixed area showed decreased functional capillary density associated with plugged sublingual capillary vessels that persisted during and after fluid resuscitation. In our lipopolysaccharide model, with resuscitation targeted at blood pressure, the contrast-enhanced ultrasound imaging can identify renal microvascular alterations by showing prolonged contrast enhancement in microcirculation during shock, worsened by resuscitation with fluids. Concomitant analysis of sublingual microcirculation mirrored those observed in the renal microcirculation.

High-sensitivity detection and monitoring of microcirculation using cutaneous and catheter probes for Doppler optical coherence tomography

NASA Astrophysics Data System (ADS)

Yang, Victor X.; Gordon, M. L.; Qi, B.; Yue, E. Seng; Tang, S.; Bisland, Stuart K.; Pekar, J.; Lo, S.; Marcon, Norman E.; Wilson, B.; Vitkin, Alex

2003-07-01

Background: Currently clinical Doppler ultrasound cannot detect microvascular blood flow and it is difficult to provide depth discrimination using laser Doppler flowmetry. Doppler optical coherence tomography (DOCT) is a novel technique for noninvasive subsurface imaging of microcirculation and tissue structure. Aims: To design handheld and catheter-based DOCT probes for clinical cutaneous and endoscopic imaging. To develop signal processing techniques for real-time detection and quantification of microvascular blood flow. Methods: A DOCT system, with interchangeable cutaneous and catheter probes, was developed. The axial spatial resolution was 10 μm, and the velocity resolution was 20 μm/s, using a 1300 nm broadband infrared light. The system achieved real-time imaging with frame rates up to 32 Hz at 512 x 256 pixels per frame. We used the system to detect microcirculation in human skin and rat esophagus, and to monitor microvascular responses to photodynamic therapy (PDT) in a rat tumor model. Results: We present experimental results from in vivo DOCT imaging of microcirculation in human skin arterio-venous malformations (AVM), normal rat esophagus, and a rat gliosarcoma PDT model. In the PDT model, we followed microvascular responses to PDT and observed differences in the microcirculation during and after therapy, which can have important implications for PDT dosimetry and treatment optimization. Conclusions: To our knowledge, this is the first demonstration of endoscopic catheter-based DOCT detection of microcirculation in vivo. In addition, AVM can be detected using handheld cutaneous DOCT probes under clinical settings. DOCT may serve as a real-time monitoring tool for PDT dosimetry, especially for vascular targeting photosensitizers.

Binge drinking disturbs hepatic microcirculation after transplantation: prevention with free radical scavengers.

PubMed

Zhong, Z; Arteel, G E; Connor, H D; Schemmer, P; Chou, S C; Raleigh, J A; Mason, R P; Lemasters, J J; Thurman, R G

1999-08-01

Disturbances in hepatic microcirculation increase graft injury and failure; therefore, this study evaluates the effects of ethanol on microcirculation after liver transplantation. Donor rats were given one dose of ethanol (5 g/kg) by gavage 20 h before explantation, and grafts were stored in University of Wisconsin solution for 24 h before implantation. Acute ethanol treatment decreased 7-day survival of grafts from about 90 to 30%, increased transaminase release nearly 4-fold, and decreased bile production by 60%. Moreover, portal pressure increased significantly and liver surface oxygen tension decreased about 50%, indicating that ethanol disturbs hepatic microcirculation. Pimonidazole, a 2-nitroimidazole hypoxia marker, was given i.v. to recipients 30 min after implantation, and grafts were harvested 1 h later. Ethanol increased hepatic pimonidazole binding about 3-fold, indicating that ethanol led to hypoxia in fatty grafts. Ethanol also significantly increased free radicals in bile. Catechin (30 mg/kg i.v. upon reperfusion), a free radical scavenger, and Carolina Rinse solution, which contains several agents that inhibit free radical formation, minimized disturbances in microcirculation and prevented pimonidazole adduct formation significantly. These treatments also blunted increases in transaminase release and improved survival of fatty grafts. Destruction of Kupffer cells with GdCl(3) (20 mg/kg i.v. 24 h before explantation) or inhibition of formation of leukotrienes with MK-886 (50 microM in University of Wisconsin or rinse solution) also minimized hypoxia and improved survival after transplantation. Taken together, these results demonstrate that ethanol disturbs hepatic microcirculation, leading to graft hypoxia after transplantation, most likely by activating Kupffer cells and increasing free radical production.

Application of LASCA imaging for detection of disorders of blood microcirculation in chicken embryo, infected by Chlamydia trachomatis

NASA Astrophysics Data System (ADS)

Ulianova, Onega; Subbotina, Irina; Filonova, Nadezhda; Zaitsev, Sergey; Saltykov, Yury; Polyanina, Tatiana; Lyapina, Anna; Ulyanov, Sergey; Larionova, Olga; Feodorova, Valentina

2018-04-01

Methods of t-LASCA and s-LASCA imaging have been firstly adapted to the problem of monitoring of blood microcirculation in chicken embryo model. Set-up for LASCA imaging of chicken embryo is mounted. Disorders of blood microcirculation in embryonated chicken egg, infected by Chlamydia trachomatis, are detected. Speckle-imaging technique is compared with white-light ovoscopy and new method of laser ovoscopy, based on the scattering of coherent light, advantages of LASCA imaging for the early detection of developmental process of chlamydial agent is demonstrated.

Physiopathology of the cochlear microcirculation.

PubMed

Shi, Xiaorui

2011-12-01

Normal blood supply to the cochlea is critically important for establishing the endocochlear potential and sustaining production of endolymph. Abnormal cochlear microcirculation has long been considered an etiologic factor in noise-induced hearing loss, age-related hearing loss (presbycusis), sudden hearing loss or vestibular function, and Meniere's disease. Knowledge of the mechanisms underlying the pathophysiology of cochlear microcirculation is of fundamental clinical importance. A better understanding of cochlear blood flow (CoBF) will enable more effective management of hearing disorders resulting from aberrant blood flow. This review focuses on recent discoveries and findings related to the physiopathology of the cochlear microvasculature. Published by Elsevier B.V.

Physiopathology of the Cochlear Microcirculation

PubMed Central

Shi, Xiaorui

2011-01-01

Normal blood supply to the cochlea is critically important for establishing the endocochlear potential and sustaining production of endolymph. Abnormal cochlear microcirculation has long been considered an etiologic factor in noise-induced hearing loss, age-related hearing loss (presbycusis), sudden hearing loss or vestibular function, and Meniere's disease. Knowledge of the mechanisms underlying the pathophysiology of cochlear microcirculation is of fundamental clinical importance. A better understanding of cochlear blood flow (CoBF) will enable more effective management of hearing disorders resulting from aberrant blood flow. This review focuses on recent discoveries and findings related to the physiopathology of the cochlear microvasculature. PMID:21875658

Effects of Mangifera indica (Careless) on Microcirculation and Glucose Metabolism in Healthy Volunteers.

PubMed

Buchwald-Werner, Sybille; Schön, Christiane; Frank, Sonja; Reule, Claudia

2017-07-01

A commercial Mangifera indica fruit powder (Careless) showed beneficial acute effects on microcirculation in a randomized, double-blind, crossover pilot study. Here, long-term effects on microcirculation and glucose metabolism were investigated in a double-blind, randomized, placebo-controlled, 3-arm parallel-design study in healthy individuals. A daily dose of 100 mg or 300 mg of the fruit powder was compared to placebo after supplementation for 4 weeks. Microcirculation and endothelial function were assessed by the Oxygen-to-see System and pulse amplitude tonometry, respectively. Glucose metabolism was assessed under fasting and postprandial conditions by capillary glucose and HbA1c values.Microcirculatory reactive hyperemia flow increased, especially in the 100 mg group (p = 0.025). The 300 mg of the M. indica fruit preparation reduced postprandial glucose levels by trend if compared to placebo (p = 0.0535) accompanied by significantly lower HbA1c values compared to baseline. Furthermore, 300 mg intake significantly improved postprandial endothelial function in individuals with decreased endothelial function after high-dose glucose intake (p = 0.0408; n = 11).In conclusion, the study suggests moderate beneficial effects of M. indica fruit preparation on microcirculation, endothelial function, and glucose metabolism. Georg Thieme Verlag KG Stuttgart · New York.

Blood microcirculation of ischemic pancreatitis

NASA Astrophysics Data System (ADS)

Dmitrieva, Irina V.; Arakelian, Sergei M.; Antonov, Olga V.

1998-06-01

Blood Microcirculation includes many of different components, which are joined by unique multiple system. Capillaries are one of the main link in this morpho-functional chain. Changes in any components of blood microcirculation are revealed by many of pathological processes in different organs and systems of the whole organism. We investigated 250 patients from 30 to 77 ages. Men included 149, women -- 101. The main diagnosis of all patients was the ischaemic pancreatitis. For verification of this diagnosis we used the whole spectrum of clinical, laboratorial and instrumental methods. These were the following: the definition of amylase of blood and urine, sonography and computer's tomography of pancreas, angiography of vessels of pancreas and Doppler's sonography of abdominal aorta and her branches: arteria mesenterica superior (AMS), truncus coeliacus (TC), arteria hepatica communis (AHC) and arteria lienalis (AL). We investigated the blood microcirculation of the mucous of the inferior lip, using Laser Dopplerography. The equipment for this research was LACC-01 with modified computer's program. The normal levels of blood microcirculation were from 120 to 180 Units. But patients with ischaemic pancreatitis had more lower level than in normal situation. This method are suggested as express diagnostic in the cases of abdominal ischaemic pathology. It can used as singel method or in combined with ultrasound Dopplerography.

Relationship between the Direction of Ophthalmic Artery Blood Flow and Ocular Microcirculation before and after Carotid Artery Stenting.

PubMed

Ishii, Masashi; Hayashi, Morito; Yagi, Fumihiko; Sato, Kenichiro; Tomita, Goji; Iwabuchi, Satoshi

2016-01-01

When internal carotid artery stenosis is accompanied by ocular ischemic syndrome, intervention is recommended to prevent irreversible visual loss. In this study, we used laser speckle flowgraphy to measure the ocular microcirculation in the optic nerve head before and after carotid artery stenting (CAS) of 40 advanced internal carotid stenosis lesions from 37 patients. The aim was to investigate the relationship between ocular microcirculation and the direction of ophthalmic artery blood flow obtained by angiography. We found that there was a significant increase in blood flow after CAS ( P = 0.003). Peak systolic velocity as an indicator of the rate of stenosis was also significantly higher in the group with retrograde/undetected flow of the ophthalmic artery than in the group with antegrade flow ( P = 0.002). In all cases where retrograde flow of the ophthalmic artery was observed before stenting, the flow changed to antegrade after stenting. Through the use of laser speckle flowgraphy, this study found that CAS can improve ocular microcirculation. Furthermore, while patients displaying retrograde flow of the ophthalmic artery before stenting have a poor prognosis, CAS corrected the flow to antegrade, suggesting that visual loss can be prevented by improving the ocular microcirculation.

[The relationship between ophthalmic nerve lesion in glaucoma and ocular and systemic haemodynamic disturbance].

PubMed

Liu, L; Yuan, S; Yang, W

1999-04-01

To explore the relationship between the optic nerve lesion in glaucoma and ocular and systemic haemodynamic disturbance. The color Doppler imaging was used to study blood velocity in the ophthalmic, the central retinal and the short posterior ciliary arteries in 34 patients with primary open angle glaucoma, 31 patients with low tension glaucoma and 90 healthy controls. The peak systolic velocity(PSV), the end diastolic velocity (EDV) and resistive index (RI) in each artery were measured, moreover the nailfold microcirculation and blood viscosity in each patient were examined. Compared with the control group, the PSV and EDV of the central retinal arteries were significantly lower while the RI of the central retinal arteries was significantly higher in both POAG and LTG patients. The RI of the short posterior ciliary arteries however was significantly higher in POAG. Nailfold microcirculation shows that some important parameters, including flow pattern, loop surrounding, morphological weighted value, total weighted value and capillary deformity rate in the two glaucoma groups were higher, whereas the flow velocity was lower than in the control group. The plasm viscosity and the whole blood viscosity (low spear) were higher than normal. According to our measurements, the nailfold microcirculation and blood viscosity was worse at the end stage of glaucoma than at early stage. The correlative analysis between measurement results of color doppler imaging and microcirculation and heamorrheology showed that nailfold microcirculation morphological weighted value was negatively correlated with the EDV of the central retinal artery and positively correlated with the RI of the central retinal artery in LTG patients. The abnormity of ocular haemodynamics and systemic microcirculation and blood viscosity is one important factor of optic nerve damage in glaucoma.

Chemotherapy impedes in vitro microcirculation and promotes migration of leukemic cells with impact on metastasis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prathivadhi-Bhayankaram, Sruti V.; Ning, Jianhao; Mimlitz, Michael

Although most cancer drugs target the proliferation of cancer cells, it is metastasis, the complex process by which cancer cells spread from the primary tumor to other tissues and organs of the body where they form new tumors, that leads to over 90% of all cancer deaths. Thus, there is an urgent need for anti-metastasis therapy. Surprisingly, emerging evidence suggests that certain anti-cancer drugs such as paclitaxel and doxorubicin can actually promote metastasis, but the mechanism(s) behind their pro-metastatic effects are still unclear. Here, we use a microfluidic microcirculation mimetic (MMM) platform which mimics the capillary constrictions of the pulmonarymore » and peripheral microcirculation, to determine if in-vivo-like mechanical stimuli can evoke different responses from cells subjected to various cancer drugs. In particular, we show that leukemic cancer cells treated with doxorubicin and daunorubicin, commonly used anti-cancer drugs, have over 100% longer transit times through the device, compared to untreated leukemic cells. Such delays in the microcirculation are known to promote extravasation of cells, a key step in the metastatic cascade. Furthermore, we report a significant (p < 0.01) increase in the chemotactic migration of the doxorubicin treated leukemic cells. Both enhanced retention in the microcirculation and enhanced migration following chemotherapy, are pro-metastatic effects which can serve as new targets for anti-metastatic drugs. - Highlights: • Doxorubicin enhances migration of leukemic cancer cells before cell death. • Doxorubicin and Daunorubicin stiffen and delay cells in mimicked microcirculation. • Some cancer drugs cause changes in cell mechanics that lead to pro-metastatic effects. • Cell mechanics becomes a new target for anti-metastatic drugs.« less

The effect of a cryotherapy gel wrap on the microcirculation of skin affected by chronic venous disorders.

PubMed

Kelechi, Teresa J; Mueller, Martina; Zapka, Jane G; King, Dana E

2011-11-01

The aim of this randomized clinical trial was to investigate a cryotherapy (cooling) gel wrap applied to lower leg skin affected by chronic venous disorders to determine whether therapeutic cooling improves skin microcirculation. Chronic venous disorders are under-recognized vascular health problems that result in severe skin damage and ulcerations of the lower legs. Impaired skin microcirculation contributes to venous leg ulcer development, thus new prevention therapies should address the microcirculation to prevent venous leg ulcers. Sixty participants (n = 30 per group) were randomized to receive one of two daily 30-minute interventions for four weeks. The treatment group applied the cryotherapy gel wrap around the affected lower leg skin, or compression and elevated the legs on a special pillow each evening at bedtime. The standard care group wore compression and elevated the legs only. Laboratory pre- and post-measures included microcirculation measures of skin temperature with a thermistor, blood flow with a laser Doppler flowmeter, and venous refill time with a photoplethysmograph. Data were collected between 2008 2009 and analysed using descriptive statistics, paired t-tests or Wilcoxon signed ranks tests, logistic regression analyses, and mixed model analyses. Fifty-seven participants (treatment = 28; standard care = 29) completed the study. The mean age was 62 years, 70% female, 50% African American. In the final adjusted model, there was a statistically significant decrease in blood flow between the two groups (-6.2[-11.8; -0.6], P = 0.03). No statistically significant differences were noted in temperature or venous refill time. Study findings suggest that cryotherapy improves blood flow by slowing movement within the microcirculation and thus might potentially provide a therapeutic benefit to prevent leg ulcers. © 2011 Blackwell Publishing Ltd.

The effect of a cryotherapy gel wrap on the microcirculation of skin affected by Chronic Venous Disorders

PubMed Central

Mueller, Martina; Zapka, Jane G.; King, Dana E.

2011-01-01

Aim This randomized clinical trial was conducted 2008 – 2009 to investigate a cryotherapy (cooling) gel wrap applied to lower leg skin affected by chronic venous disorders to determine whether therapeutic cooling improves skin microcirculation. Impaired skin microcirculation contributes to venous leg ulcer development, thus new prevention therapies should address the microcirculation to prevent venous leg ulcers. Data Sources Sixty participants (n = 30 per group) were randomized to receive one of two daily 30-minute interventions for four weeks. The treatment group applied the cryotherapy gel wrap around the affected lower leg skin, or compression and elevated the legs on a special pillow each evening at bedtime. The standard care group wore compression and elevated the legs only. Laboratory pre- and post-measures included microcirculation measures of skin temperature with a thermistor, blood flow with a laser Doppler flowmeter, and venous refill time with a photoplethysmograph. Review methods Data were analysed using descriptive statistics, paired t-tests or Wilcoxon signed ranks tests, logistic regression analyses, and mixed model analyses. Results Fifty-seven participants (treatment = 28; standard care = 29) completed the study. The mean age was 62 years, 70% female, 50% African American. In the final adjusted model, there was a statistically significant decrease in blood flow between the two groups (−6.2[−11.8; −0.6], P = 0.03). No statistically significant differences were noted in temperature or venous refill time. Conclusion Study findings suggest that cryotherapy improves blood flow by slowing movement within the microcirculation and thus might potentially provide a therapeutic benefit to prevent leg ulcers. PMID:21592186

Comparison of cerebral microcirculation of alloxan diabetes and healthy mice using laser speckle contrast imaging

NASA Astrophysics Data System (ADS)

Timoshina, Polina A.; Shi, Rui; Zhang, Yang; Zhu, Dan; Semyachkina-Glushkovskaya, Oxana V.; Tuchin, Valery V.; Luo, Qingming

2015-03-01

The study of blood microcirculation is one of the most important problems of the medicine. This paper presents results of experimental study of cerebral blood flow microcirculation in mice with alloxan-induced diabetes using Temporal Laser Speckle Imaging (TLSI). Additionally, a direct effect of glucose water solution (concentration 20% and 45%) on blood flow microcirculation was studied. In the research, 20 white laboratory mice weighing 20-30 g were used. The TLSI method allows one to investigate time dependent scattering from the objects with complex dynamics, since it possesses greater temporal resolution. Results show that in brain of animal diabetic group diameter of sagittal vein is increased and the speed of blood flow reduced relative to the control group. Topical application of 20%- or 45%-glucose solutions also causes increase of diameter of blood vessels and slows down blood circulation. The results obtained show that diabetes development causes changes in the cerebral microcirculatory system and TLSI techniques can be effectively used to quantify these alterations.

[Unintended cooling, active warming, and microcirculation in cardiosurgical patients].

PubMed

Aksel'rod, B A; Trekova, N A; Guleshov, V A; Tolstova, I A; Gus'kov, D A; Babaev, M A

2010-01-01

The study was undertaken to compare various methods to maintain a patient's body temperature and to evaluate their impact on microcirculation during myocardial revascularization under normothermal extracorporeal circulation (NTEC). The study enrolled 50 patients with NYHA Functional Classes III-IV coronary heart disease, who underwent aortocoronary bypass surgery under NTEC. A HICO-AQUATHERM 660 water-warming unit (Hirtz, Germany) was used in Group 1 patients (n=30). A Bair Hugger air-warming unit (Arizant, U.S.A.) with a mattress located under a patient was employed in Group 2 (n=20). Intraoperative microcirculation monitoring was carried out by a laser analyzer (Lazma, Moscow).

History and physical examination findings predictive of testicular torsion: an attempt to promote clinical diagnosis by house staff.

PubMed

Srinivasan, Arun; Cinman, Nadya; Feber, Kevin M; Gitlin, Jordan; Palmer, Lane S

2011-08-01

To standardize the history and physical examination of boys who present with acute scrotum and identify parameters that best predict testicular torsion. Over a 5-month period, a standardized history and physical examination form with 22 items was used for all boys presenting with scrotal pain. Management decisions for radiological evaluation and surgical intervention were based on the results. Data were statistically analyzed in correlation with the eventual diagnosis. Of the 79 boys evaluated, 8 (10.1%) had testicular torsion. On univariate analysis, age, worsening pain, nausea/vomiting, severe pain at rest, absence of ipsilateral cremaster reflex, abnormal testicular position and scrotal skin changes were statistically predictive of torsion. After multivariate analysis and adjusting for confounding effect of other co-existing variables, absence of ipsilateral cremaster reflex (P < 0.001), nausea/vomiting (P < 0.05) and scrotal skin changes (P < 0.001) were the only consistent predictive factors of testicular torsion. An accurate history and physical examination of boys with acute scrotum should be primary in deciding upon further radiographic or surgical evaluation. While several forces have led to less consistent overnight resident staffing, consistent and reliable clinical evaluation of the acute scrotum using a standardized approach should reduce error, improve patient care and potentially reduce health care costs. Copyright © 2011 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Cardiac frequency and cutaneous microcirculation during and after exercising in the view of physical condition.

PubMed

Saemann, Lars; Lachner, Karin; Wenzel, Folker

2017-01-01

In the field of cardiovascular diseases an ergometer test is a common diagnostical method in which a change in microcirculation can be reached. In this paper cardiac frequency and cutaneous microcirculation during and after exercising will be compared with each other. The cutaneous microcirculation of  6 healthy volunteers (2 females, 4 males) is measured. As an instrument the PeriFlux 5000 combined with a Laser-Doppler-Flow(LDF)-Probe (Perimed Instruments) is used. The cardiac frequency (CF) is measured by the POLAR T31 sensor and as an ergometer the ERGO-FIT ® 457 is used. The mean initial LDF (97,7±57,3 PU) decreases at the beginning (64,5±21,7 PU), increases during theexercise, reaches its maximum (247,8±82,1 PU) after the end of the exercise and drops to lower values (256,4±69,5 PU)after a few minutes. Contrasting to the LDF the mean initial CF (86±22/min) increases at the beginning (97±9/min),furthermore during the whole exercise (103±9/min) and then falls after having finished the exercise (96±3/min).Furthermore, during regeneration, one can see the CF decreasing towards its initial value, while LDF reaches its maximum. In further studies, realized with volunteers with well-known levels of physical condition, a directconnection between cutaneous microcirculation and physical condition might be found.

Low-Magnitude High-Frequency Vibration Accelerated the Foot Wound Healing of n5-streptozotocin-induced Diabetic Rats by Enhancing Glucose Transporter 4 and Blood Microcirculation.

PubMed

Yu, Caroline Oi-Ling; Leung, Kwok-Sui; Jiang, Jonney Lei; Wang, Tina Bai-Yan; Chow, Simon Kwoon-Ho; Cheung, Wing-Hoi

2017-09-14

Delayed wound healing is a Type 2 diabetes mellitus (DM) complication caused by hyperglycemia, systemic inflammation, and decreased blood microcirculation. Skeletal muscles are also affected by hyperglycemia, resulting in reduced blood flow and glucose uptake. Low Magnitude High Frequency Vibration (LMHFV) has been proven to be beneficial to muscle contractility and blood microcirculation. We hypothesized that LMHFV could accelerate the wound healing of n5-streptozotocin (n5-STZ)-induced DM rats by enhancing muscle activity and blood microcirculation. This study investigated the effects of LMHFV in an open foot wound created on the footpad of n5-STZ-induced DM rats (DM_V), compared with no-treatment DM (DM), non-DM vibration (Ctrl_V) and non-DM control rats (Ctrl) on Days 1, 4, 8 and 13. Results showed that the foot wounds of DM_V and Ctrl_V rats were significantly reduced in size compared to DM and Ctrl rats, respectively, at Day 13. The blood glucose level of DM_V rats was significantly reduced, while the glucose transporter 4 (GLUT4) expression and blood microcirculation of DM_V rats were significantly enhanced in comparison to those of DM rats. In conclusion, LMHFV can accelerate the foot wound healing process of n5-STZ rats.

Preliminary clinical evaluation of automated analysis of the sublingual microcirculation in the assessment of patients with septic shock: Comparison of automated versus semi-automated software.

PubMed

Sharawy, Nivin; Mukhtar, Ahmed; Islam, Sufia; Mahrous, Reham; Mohamed, Hassan; Ali, Mohamed; Hakeem, Amr A; Hossny, Osama; Refaa, Amera; Saka, Ahmed; Cerny, Vladimir; Whynot, Sara; George, Ronald B; Lehmann, Christian

2017-01-01

The outcome of patients in septic shock has been shown to be related to changes within the microcirculation. Modern imaging technologies are available to generate high resolution video recordings of the microcirculation in humans. However, evaluation of the microcirculation is not yet implemented in the routine clinical monitoring of critically ill patients. This is mainly due to large amount of time and user interaction required by the current video analysis software. The aim of this study was to validate a newly developed automated method (CCTools®) for microcirculatory analysis of sublingual capillary perfusion in septic patients in comparison to standard semi-automated software (AVA3®). 204 videos from 47 patients were recorded using incident dark field (IDF) imaging. Total vessel density (TVD), proportion of perfused vessels (PPV), perfused vessel density (PVD), microvascular flow index (MFI) and heterogeneity index (HI) were measured using AVA3® and CCTools®. Significant differences between the numeric results obtained by the two different software packages were observed. The values for TVD, PVD and MFI were statistically related though. The automated software technique successes to show septic shock induced microcirculation alterations in near real time. However, we found wide degrees of agreement between AVA3® and CCTools® values due to several technical factors that should be considered in the future studies.

Time Evolution of Sublingual Microcirculatory Changes in Recreational Marathon Runners

PubMed Central

Arstikyte, Justina; Vaitkaitiene, Egle; Vaitkaitis, Dinas

2017-01-01

We aimed to evaluate changes in sublingual microcirculation induced by a marathon race. Thirteen healthy male controls and 13 male marathon runners volunteered for the study. We performed sublingual microcirculation, using a Cytocam-IDF device (Braedius Medical, Huizen, Netherlands), and systemic hemodynamic measurements four times: 24 hours prior to their participation in the Kaunas Marathon (distance: 41.2 km), directly after finishing the marathon, 24 hours after the marathon, and one week after the marathon. The marathon runners exhibited a higher functional capillary density (FCD) and total vascular density of small vessels at the first visit compared with the controls. Overall, we did not find any changes in sublingual microcirculation of the marathon runners at any of the other visits. However, in a subgroup of marathon runners with a decreased FCD compared to the subgroup with increased FCD, the subgroup with decreased FCD had shorter running time (190.37 ± 30.2 versus 221.80 ± 23.4 min, p = 0.045), ingested less fluids (907 ± 615 versus 1950 ± 488 mL, p = 0.007) during the race, and lost much more weight (−2.4 ± 1.3 versus −1.0 ± 0.8 kg, p = 0.041). Recreational marathon running is not associated with an alteration of sublingual microcirculation. However, faster running and dehydration may be crucial for further impairing microcirculation. PMID:28828386

Basal sympathetic activity to the microcirculation in tetraplegic man revealed by wavelet transform of laser Doppler flowmetry.

PubMed

Bernjak, A; Deitrick, G A; Bauman, W A; Stefanovska, A; Tuckman, J

2011-05-01

The 1984/86 published neurogram results showing only rare sympathetic nerve activity (SNA) to the muscles and skin in tetraplegia are still accepted. The present study by a different method attempted to confirm or deny those findings. The effect of basal SNA to the microcirculation of the feet and calf in 10 complete (AIS A) traumatic tetraplegic and 10 healthy age matched subjects were evaluated by wavelet transform of laser Doppler flowmetry (LDF) recordings. The results clearly indicated there is significant basal SNA from the decentralized spinal cord in tetraplegia. In addition, wavelet analysis allowed a study of other influences on the microcirculation besides SNA. Collectively, in tetraplegia compared with controls, the powers of the low frequency oscillations in blood flow were reduced; in that the endothelium caused less vasodilatation while the SNA and intrinsic vascular smooth muscles induced smaller degrees of vasoconstriction. However, the high frequency and especially the cardiac powers were greater. The latter presenting an obvious important factor for the preservation of blood flow in the microcirculation. It is suggested that basal SNA to the cutaneous microcirculation occurs in complete tetraplegia, and the significant levels of circulating noradrenaline reported by others indicate this is also true in other parts of the body. This may explain the usual absence of severe, incapacitating, autonomic deficiency in this condition. Published by Elsevier Inc.

Thin and open vessel windows for intra-vital fluorescence imaging of murine cochlear blood flow

PubMed Central

Shi, Xiaorui; Zhang, Fei; Urdang, Zachary; Dai, Min; Neng, Lingling; Zhang, Jinhui; Chen, Songlin; Ramamoorthy, Sripriya; Nuttall, Alfred L.

2014-01-01

Normal microvessel structure and function in the cochlea is essential for maintaining the ionic and metabolic homeostasis required for hearing function. Abnormal cochlear microcirculation has long been considered an etiologic factor in hearing disorders. A better understanding of cochlear blood flow (CoBF) will enable more effective amelioration of hearing disorders that result from aberrant blood flow. However, establishing the direct relationship between CoBF and other cellular events in the lateral wall and response to physio-pathological stress remains a challenge due to the lack of feasible interrogation methods and difficulty in accessing the inner ear. Here we report on new methods for studying the CoBF in a mouse model using a thin or open vessel-window in combination with fluorescence intra-vital microscopy (IVM). An open vessel-window enables investigation of vascular cell biology and blood flow permeability, including pericyte (PC) contractility, bone marrow cell migration, and endothelial barrier leakage, in wild type and fluorescent protein-labeled transgenic mouse models with high spatial and temporal resolution. Alternatively, the thin vessel-window method minimizes disruption of the homeostatic balance in the lateral wall and enables study CoBF under relatively intact physiological conditions. A thin vessel-window method can also be used for time-based studies of physiological and pathological processes. Although the small size of the mouse cochlea makes surgery difficult, the methods are sufficiently developed for studying the structural and functional changes in CoBF under normal and pathological conditions. PMID:24780131

Colloids and the Microcirculation.

PubMed

He, Huaiwu; Liu, Dawei; Ince, Can

2018-05-01

Colloid solutions have been advocated for use in treating hypovolemia due to their expected effect on improving intravascular retention compared with crystalloid solutions. Because the ultimate desired effect of fluid resuscitation is the improvement of microcirculatory perfusion and tissue oxygenation, it is of interest to study the effects of colloids and crystalloids at the level of microcirculation under conditions of shock and fluid resuscitation, and to explore the potential benefits of using colloids in terms of recruiting the microcirculation under conditions of hypovolemia. This article reviews the physiochemical properties of the various types of colloid solutions (eg, gelatin, dextrans, hydroxyethyl starches, and albumin) and the effects that they have under various conditions of hypovolemia in experimental and clinical scenarios.

Renovascular disease, microcirculation, and the progression of renal injury: role of angiogenesis

PubMed Central

2011-01-01

Emerging evidence supports the pivotal role of renal microvascular disease as a determinant of tubulo-interstitial and glomerular fibrosis in chronic kidney disease. An intact microcirculation is vital to restore blood flow to the injured tissues, which is a crucial step to achieve a successful repair response. The purpose of this review is to discuss the impact and mechanisms of the functional and structural changes of the renal microvascular network, as well as the role of these changes in the progression and irreversibility of renal injury. Damage of the renal microcirculation and deterioration of the angiogenic response may constitute early steps in the complex pathways involved in progressive renal injury. There is limited but provocative evidence that stimulation of vascular proliferation and repair may stabilize renal function and slow the progression of renal disease. The feasibility of novel potential therapeutic interventions for stabilizing the renal microvasculature is also discussed. Targeted interventions to enhance endogenous renoprotective mechanisms focused on the microcirculation, such as cell-based therapy or the use of angiogenic cytokines have shown promising results in some experimental and clinical settings. PMID:21307362

Heart-rate sensitive optical coherence angiography for measuring vascular changes due to posttraumatic brain injury in mice

NASA Astrophysics Data System (ADS)

Tremoleda, Jordi L.; Alvarez, Karl; Aden, Abdirahman; Donnan, Robert; Michael-Titus, Adina T.; Tomlins, Peter H.

2017-12-01

Traumatic brain injury (TBI) results in direct vascular disruption, triggering edema, and reduction in cerebral blood flow. Therefore, understanding the pathophysiology of brain microcirculation following TBI is important for the development of effective therapies. Optical coherence angiography (OCA) is a promising tool for evaluating TBI in rodent models. We develop an approach to OCA that uses the heart-rate frequency to discriminate between static tissue and vasculature. This method operates on intensity data and is therefore not phase sensitive. Furthermore, it does not require spatial overlap of voxels and thus can be applied to pre-existing datasets for which oversampling may not have been explicitly considered. Heart-rate sensitive OCA was developed for dynamic assessment of mouse microvasculature post-TBI. Results show changes occurring at 5-min intervals within the first 50 min of injury.

In Vitro Activation of eNOS by Mangifera indica (Careless™) and Determination of an Effective Dosage in a Randomized, Double-Blind, Human Pilot Study on Microcirculation.

PubMed

Gerstgrasser, Alexandra; Röchter, Sigrid; Dressler, Dirk; Schön, Christiane; Reule, Claudia; Buchwald-Werner, Sybille

2016-03-01

Mangifera indica fruit preparation (Careless™) activates the evolutionary conserved metabolic sensors sirtuin 1 and adenosine monophosphate-activated protein kinase, which have been identified as playing a key role in microcirculation and endothelial function. Here, an acute effect of a single dose of 100 mg or 300 mg Careless™ on microcirculation was investigated in a randomized, double-blind, crossover pilot study in ten healthy women to determine the effective dosage. Microcirculation and endothelial function were assessed by the Oxygen-to-see system and pulse amplitude tonometry (EndoPAT™), respectively. Cutaneous blood flow was increased over time by 100 mg (54% over pre-values, p = 0.0157) and 300 mg (35% over pre-value, p = 0.209) Careless™. The EndoPAT™ reactive hyperemia response was slightly improved 3 h after intake compared to pretesting with 300 mg Careless™. Furthermore, activation of endothelial nitric oxide synthase, as an important regulator for endothelial function, was tested in vitro in primary human umbilical vein endothelial cells. Careless™, after simulation of digestion, increased the activated form of endothelial nitric oxide synthase dose-dependently by 23% (300 µg/mL), 42% (1500 µg/mL), and 60% (3000 µg/mL) compared to the untreated control. In conclusion, the study suggests moderate beneficial effects of Careless™ on microcirculation, which is at least partly mediated by endothelial nitric oxide synthase activation. Georg Thieme Verlag KG Stuttgart · New York.

[Does autonomic diabetic neuropathy influence microcirculation reactivity in adolescents with diabetes type 1?].

PubMed

Urban, Mirosława; Peczyńska, Jadwiga; Kowalewski, Marek; Głowińska-Olszewska, Barbara

2007-01-01

Microcirculation is known to be disturbed in many organs of diabetic patients. Retinopathy, nephropathy and neuropathy might be considered as the cause of the functional and morphological changes at the level of microcirculation. The aim of the study was to assess by means of dynamic capillaroscopy the influence of autonomic diabetic nephropathy (CAN) in adolescents with type 1 diabetes mellitus on capillary blood flow (CBV) in skin microcirculation. The study group consisted of 18 patients with type 1 diabetes mellitus (mean age 15+/-2 years). In 9 of them the diagnosis of CAN was made on the basis of Ewing tests. The control group consisted of 10 healthy persons aged 15+/-1.5 years. CBV was measured in capillars of the nailfold of the fourth finger during rest and after 2 minutes of arterial occlusion (the occlusion pressure - above 20 mmHg systolic blood pressure - was obtained by the occlusion of brachial artery using sphygnomanometer cuff). The resting CBV did not differ between patients with CAN, without CAN and healthy controls (0.39+/-0.06, 0.41+0.05 i 0.42+/-0.07). The values of the peak CBV significantly differ between the examined groups (CAN: 0.75+0.1; without CAN: 0.86+/-0.11; control group: 0.98+/-0.09, p<0.01). The obtained results indicate that the presence of the autonomic diabetic neuropathy significantly influences the regulatory function of microcirculation, which may predispose to occurrence of different late diabetic complications.

In situ assessment of the renal microcirculation in mechanically ventilated rats using sidestream dark-field imaging.

PubMed

Astapenko, D; Jor, O; Lehmann, C; Cerny, V

2015-02-01

For microcirculation research there is a need for baseline data and feasibility protocols describing microcirculation of various organs. The aim of our study was to examine the reliability and reproducibility of sidestream dark-field (SDF) imaging within the renal cortical microcirculation in rats. Renal microcirculation was observed using SDF probe placed on the exposed renal surface via the upper midline laparotomy. Video sequences recorded intermittently in short apneic pauses were analyzed off-line by using AVA 3.0 software (MicroVision Medical, Amsterdam, the Netherlands). Results are expressed as mean (SD) or median (25-75% percentiles). We obtained 60 clear sequences from all recorded analyzable videos from all the animals. The total small vessel and all vessel density (in mm.mm(-2) ) were (28.79 ± 0.40) and (28.95 ± 0.40), respectively. The perfused small and all vessel density were (28.79 ± 0.40) and (28.95 ± 0.40), respectively. The DeBacker Score was (19.14 ± 0.43), the proportion of perfused vessels was 100% (100-100%) and the microvascular flow index was 3.49 (3-3.75). We conclude SDF imaging provides a reliable method to examine the renal microvascular bed in vivo and thus can be used for the study of the renal cortical vascular network in various experimental diseases models and clinical settings. © 2014 The Authors Journal of Microscopy © 2014 Royal Microscopical Society.

In vivo microcirculation imaging of the sub surface fingertip using correlation mapping optical coherence tomography (cmOCT)

NASA Astrophysics Data System (ADS)

Dsouza, Roshan I.; Zam, Azhar; Subhash, Hrebesh M.; Larin, Kirill V.; Leahy, Martin

2013-02-01

We describe a novel application of correlation mapping optical coherence tomography (cmOCT) for sub-surface fingerprint biometric identification. Fingerprint biometrics including automated fingerprint identification systems, are commonly used to recognise the fingerprint, since they constitute simple, effective and valuable physical evidence. Spoofing of biometric fingerprint devices can be easily done because of the limited information obtained from the surface topography. In order to overcome this limitation a potentially more secure source of information is required for biometric identification applications. In this study, we retrieve the microcirculation map of the subsurface fingertip by use of the cmOCT technique. To increase probing depth of the sub surface microcirculation, an optical clearing agent composed of 75% glycerol in aqueous solution was applied topically and kept in contact for 15 min. OCT intensity images were acquired from commercial research grade swept source OCT system (model OCT1300SS, Thorlabs Inc. USA). A 3D OCT scan of the fingertip was acquired over an area of 5x5 mm using 1024x1024 A-scans in approximately 70 s. The resulting volume was then processed using the cmOCT technique with a 7x7 kernel to provide a microcirculation map. We believe these results will demonstrate an enhanced security level over artificial fingertips. To the best of our knowledge, this is the first demonstration of imaging microcirculation map of the subsurface fingertip.

[Comparison of bulbar conjunctival microcirculation in rabbits of five subtypes of blood stasis syndrome].

PubMed

Hu, Wen-Juan; Zhang, Bing-Tao; Wu, Rui

2013-09-01

To observe changes of bulbar conjunctival microcirculation in rabbits of five kinds subtypes of blood stasis syndrome (BSS), and to analyze their different properties. Totally 60 Japanese big-ear rabbits were randomly divided into six groups, i.e., qi deficiency blood stasis group, qi stagnation blood stasis group, cold coagulation blood stasis group, heat toxin blood stasis group, external injury blood stasis group, and the normal control group, 10 in each group. Changes of rabbit bulbar conjunctiva microcirculation were observed before and after modeling. Compared with the normal control group, the total integral of bulbar conjunctiva microcirculation obviously increased in the 5 BSS groups (P < 0.05). There was no statistical difference among the 5 BSS groups (P > 0.05). But there was statistical difference in any concrete integral among the 5 BSS groups (P < 0.05). Thickening blood vessels and errhysis of vascular walls were dominant in the heat toxin blood stasis group. Ischemia, partial cystic dilatation, vascular engorgement and twist were dominant in the qi deficiency blood stasis group. Partial vascular buckling, aneurysmal changes, flow velocity slowed down were dominant in the qi stagnation blood stasis group. Vascular buckling, hyperemia, vascular engorgement, blood flow slowed down were dominant in the external injury blood stasis group. Vascular buckling, ischemia, dark color were dominant in the cold coagulation blood stasis group. Changes of bulbar conjunctival microcirculation were different in 5 kinds of BSS types, which could reflect their various features.

[Minimal work-up for Raynaud syndrome: a consensus report. Microcirculation working group of the Société française de médecine vasculaire].

PubMed

Pistorius, M-A; Carpentier, P-H

2013-01-01

About ten to fifteen percent of the French population suffer from Raynaud's phenomenon. Most of the time, it is considered as primary Raynaud's phenomenon, without underlying disease. The aim of this expert consensus from the "microcirculation group" for the French Society of Vascular Medicine and the French Society for Microcirculation, was to define clinical guidelines in patients consulting for Raynaud's phenomenon. The recommended minimal screening includes clinical examination, nailfold capillaroscopy and antinuclear antibodies. In particular, the aim of this screening is to identify patients with a significant risk for scleroderma, who would need a careful follow up. Copyright © 2013. Published by Elsevier Masson SAS.

The C-terminal CGHC motif of protein disulfide isomerase supports thrombosis

PubMed Central

Zhou, Junsong; Wu, Yi; Wang, Lu; Rauova, Lubica; Hayes, Vincent M.; Poncz, Mortimer; Essex, David W.

2015-01-01

Protein disulfide isomerase (PDI) has two distinct CGHC redox-active sites; however, the contribution of these sites during different physiologic reactions, including thrombosis, is unknown. Here, we evaluated the role of PDI and redox-active sites of PDI in thrombosis by generating mice with blood cells and vessel wall cells lacking PDI (Mx1-Cre Pdifl/fl mice) and transgenic mice harboring PDI that lacks a functional C-terminal CGHC motif [PDI(ss-oo) mice]. Both mouse models showed decreased fibrin deposition and platelet accumulation in laser-induced cremaster arteriole injury, and PDI(ss-oo) mice had attenuated platelet accumulation in FeCl3-induced mesenteric arterial injury. These defects were rescued by infusion of recombinant PDI containing only a functional C-terminal CGHC motif [PDI(oo-ss)]. PDI infusion restored fibrin formation, but not platelet accumulation, in eptifibatide-treated wild-type mice, suggesting a direct role of PDI in coagulation. In vitro aggregation of platelets from PDI(ss-oo) mice and PDI-null platelets was reduced; however, this defect was rescued by recombinant PDI(oo-ss). In human platelets, recombinant PDI(ss-oo) inhibited aggregation, while recombinant PDI(oo-ss) potentiated aggregation. Platelet secretion assays demonstrated that the C-terminal CGHC motif of PDI is important for P-selectin expression and ATP secretion through a non-αIIbβ3 substrate. In summary, our results indicate that the C-terminal CGHC motif of PDI is important for platelet function and coagulation. PMID:26529254

ICAM-1-expressing neutrophils exhibit enhanced effector functions in murine models of endotoxemia.

PubMed

Woodfin, Abigail; Beyrau, Martina; Voisin, Mathieu-Benoit; Ma, Bin; Whiteford, James R; Hordijk, Peter L; Hogg, Nancy; Nourshargh, Sussan

2016-02-18

Intracellular adhesion molecule-1 (ICAM-1) is a transmembrane glycoprotein expressed on the cell surface of numerous cell types such as endothelial and epithelial cells, vascular smooth muscle cells, and certain leukocyte subsets. With respect to the latter, ICAM-1 has been detected on neutrophils in several clinical and experimental settings, but little is known about the regulation of expression or function of neutrophil ICAM-1. In this study, we report on the de novo induction of ICAM-1 on the cell surface of murine neutrophils by lipopolysaccharide (LPS), tumor necrosis factor, and zymosan particles in vitro. The induction of neutrophil ICAM-1 was associated with enhanced phagocytosis of zymosan particles and reactive oxygen species (ROS) generation. Conversely, neutrophils from ICAM-1-deficient mice were defective in these effector functions. Mechanistically, ICAM-1-mediated intracellular signaling appeared to support neutrophil ROS generation and phagocytosis. In vivo, LPS-induced inflammation in the mouse cremaster muscle and peritoneal cavity led to ICAM-1 expression on intravascular and locally transmigrated neutrophils. The use of chimeric mice deficient in ICAM-1 on myeloid cells demonstrated that neutrophil ICAM-1 was not required for local neutrophil transmigration, but supported optimal intravascular and extravascular phagocytosis of zymosan particles. Collectively, the present results shed light on regulation of expression and function of ICAM-1 on neutrophils and identify it as an additional regulator of neutrophil effector responses in host defense. © 2016 by The American Society of Hematology.

Mast cells are dispensable in a genetic mouse model of chronic dermatitis.

PubMed

Sulcova, Jitka; Meyer, Michael; Guiducci, Eva; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Werner, Sabine

2015-06-01

Chronic inflammatory skin diseases, such as atopic dermatitis, affect a large percentage of the population, but the role of different immune cells in the pathogenesis of these disorders is largely unknown. Recently, we found that mice lacking fibroblast growth factor receptor 1 (Fgfr1) and Fgfr2 (K5-R1/R2 mice) in the epidermis have a severe impairment in the epidermal barrier, which leads to the development of a chronic inflammatory skin disease that shares many features with human atopic dermatitis. Using Fgfr1-/Fgfr2-deficient mice, we analyzed the consequences of the loss of mast cells. Mast cells accumulated and degranulated in the skin of young Fgfr1-/Fgfr2-deficient mice, most likely as a consequence of increased expression of the mast cell chemokine Ccl2. The increase in mast cells occurred before the development of histological abnormalities, indicating a functional role of these cells in the inflammatory skin phenotype. To test this hypothesis, we mated the Fgfr1-/Fgfr2-deficient mice with mast cell-deficient CreMaster mice. Surprisingly, loss of mast cells did not or only mildly affect keratinocyte proliferation, epidermal thickness, epidermal barrier function, accumulation and activation of different immune cells, or expression of different proinflammatory cytokines in the skin. These results reveal that mast cells are dispensable for the development of chronic inflammation in response to a defect in the epidermal barrier. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

A separate role for ICAM-1 and fluid shear in regulating leukocyte interactions with straight regions of venular wall and venular convergences

PubMed Central

Sumagin, Ronen; Lamkin-Kennard, Kathleen A.; Sarelius, Ingrid H

2011-01-01

Objective Variation in expression of adhesion molecules plays a key role in regulating leukocyte behavior, but the contribution of fluid shear to these interactions cannot be ignored. Here we dissected the effects of each of these factors on leukocyte behavior in different venular regions. Methods Leukocyte behavior was quantified in blood perfused microvascular networks in anesthetized mouse cremaster muscle using intravital confocal microscopy. ICAM-1 expression and fluid shear rate were quantified using ICAM-1 fluorescent labeling, fluorescent particle tracking, and computational fluid dynamics. Results TNFα-induced an increase in ICAM-1 expression, and abolished the differences observed among control venules of different sizes. Consequently, leukocyte adhesion was increased to a similar level across all vessel sizes (5.1±0.46 leukocytes/100μm vs. 2.1±0.47 [control]), but remained significantly higher in venular convergences (7.8±0.4). Leukocyte transmigration occurred primarily in the smallest venules and venular convergences (23.9±5.1 and 31.9±2.7 leukocytes/10,000μm2 tissue, respectively). In venular convergences the two inlet vessels are predicted to create a region of low velocity, increasing leukocyte adhesion probability. Conclusions In straight regions of different sized venules the variability in ICAM-1 expression accounts for the differences in leukocyte behavior; in converging regions, fluid shear potentially has a greater effect on leukocyte-EC interactions. PMID:19468960

Impact of antibiotics on the microcirculation in local and systemic inflammation.

PubMed

Al-Banna, N A; Pavlovic, D; Gründling, M; Zhou, J; Kelly, M; Whynot, S; Hung, O; Johnston, B; Issekutz, T B; Kern, H; Cerny, V; Lehmann, Ch

2013-01-01

The main function of antibiotics is related to their capacity to eliminate a microorganism. In addition to the antimicrobial function of antibiotics, they are known to have anti-inflammatory and vasomodulatory effects on the microcirculation. The ability of non-antimicrobial derivatives of antibiotics to control inflammation illustrates the distinct anti-microbial and anti-inflammatory roles of antibiotics. In this review, we discuss the impact of antibiotics on leukocyte recruitment and the state of the microcirculation. Literature reporting the effect of antibiotics in non-infectious inflammatory conditions is reviewed as well as the studies demonstrating the anti-inflammatory effects of antibiotics in animal models of infection. In addition, the effect of the antibiotics on the immune system is summarized in this review, in order to postulate some mechanisms of action for the proand anti-inflammatory contribution of antibiotics. Literature reported the effect of antibiotics on the production of cytokines, chemotaxis and recruitment of leukocytes, production of reactive oxygen species, process of phagocytosis and autophagy, and apoptosis of leukocytes. Yet, all antibiotics may not necessarily exert an anti-inflammatory effect on the microcirculation. Thus, we suggest a model for spectrum of anti-inflammatory and vasomodulatory effects of antibiotics in the microcirculation of animals in local and systemic inflammation. Although the literature suggests the ability of antibiotics to modulate leukocyte recruitment and microperfusion, the process and the mechanism of action are not fully characterized. Studying this process will expand the knowledge base that is required for the selection of antibiotic treatment based on its anti-inflammatory functions, which might be particularly important for critically ill patients.

Ultra-high-sensitive optical micro-angiography provides depth resolved visualization of microcirculations within human skin under psoriatic conditions

NASA Astrophysics Data System (ADS)

Qin, Jia; An, Lin; Wang, Ruikang

2011-03-01

Adequate functioning of the peripheral micro vascular in human skin is necessary to maintain optimal tissue perfusion and preserve normal hemodynamic function. There is a growing body of evidence suggests that vascular abnormalities may directly related to several dermatologic diseases, such as psoriasis, port-wine stain, skin cancer, etc. New in vivo imaging modalities to aid volumetric microvascular blood perfusion imaging are there for highly desirable. To address this need, we demonstrate the capability of ultra-high sensitive optical micro angiography to allow blood flow visualization and quantification of vascular densities of lesional psoriasis area in human subject in vivo. The microcirculation networks of lesion and non-lesion skin were obtained after post processing the data sets captured by the system. With our image resolution (~20 μm), we could compare these two types of microcirculation networks both qualitatively and quantitatively. The B-scan (lateral or x direction) cross section images, en-face (x-y plane) images and the volumetric in vivo perfusion map of lesion and non-lesion skin areas were obtained using UHS-OMAG. Characteristic perfusion map features were identified between lesional and non-lesional skin area. A statistically significant difference between vascular densities of lesion and non-lesion skin area was also found using a histogram based analysis. UHS-OMAG has the potential to differentiate the normal skin microcirculation from abnormal human skin microcirculation non-invasively with high speed and sensitivity. The presented data demonstrates the great potential of UHS-OMAG for detecting and diagnosing skin disease such as psoriasis in human subjects.

Thin and open vessel windows for intra-vital fluorescence imaging of murine cochlear blood flow.

PubMed

Shi, Xiaorui; Zhang, Fei; Urdang, Zachary; Dai, Min; Neng, Lingling; Zhang, Jinhui; Chen, Songlin; Ramamoorthy, Sripriya; Nuttall, Alfred L

2014-07-01

Normal microvessel structure and function in the cochlea is essential for maintaining the ionic and metabolic homeostasis required for hearing function. Abnormal cochlear microcirculation has long been considered an etiologic factor in hearing disorders. A better understanding of cochlear blood flow (CoBF) will enable more effective amelioration of hearing disorders that result from aberrant blood flow. However, establishing the direct relationship between CoBF and other cellular events in the lateral wall and response to physio-pathological stress remains a challenge due to the lack of feasible interrogation methods and difficulty in accessing the inner ear. Here we report on new methods for studying the CoBF in a mouse model using a thin or open vessel-window in combination with fluorescence intra-vital microscopy (IVM). An open vessel-window enables investigation of vascular cell biology and blood flow permeability, including pericyte (PC) contractility, bone marrow cell migration, and endothelial barrier leakage, in wild type and fluorescent protein-labeled transgenic mouse models with high spatial and temporal resolution. Alternatively, the thin vessel-window method minimizes disruption of the homeostatic balance in the lateral wall and enables study CoBF under relatively intact physiological conditions. A thin vessel-window method can also be used for time-based studies of physiological and pathological processes. Although the small size of the mouse cochlea makes surgery difficult, the methods are sufficiently developed for studying the structural and functional changes in CoBF under normal and pathological conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of a new piezoelectric device on periosteal microcirculation after subperiosteal preparation.

PubMed

Stoetzer, Marcus; Felgenträger, Dörthe; Kampmann, Andreas; Schumann, Paul; Rücker, Martin; Gellrich, Nils-Claudius; von See, Constantin

2014-07-01

Subperiosteal preparation using a periosteal elevator leads to disturbances of local periosteal microcirculation. Soft-tissue damage can usually be considerably reduced using piezoelectric technology. For this reason, we investigated the effects of a novel piezoelectric device on local periosteal microcirculation and compared this approach with the conventional preparation of the periosteum using a periosteal elevator. A total of 20 Lewis rats were randomly assigned to one of two groups. Subperiosteal preparation was performed using either a piezoelectric device or a periosteal elevator. Intravital microscopy was performed immediately after the procedure as well as three and eight days postoperatively. Statistical analysis of microcirculatory parameters was performed offline using analysis of variance (ANOVA) on ranks (p<0.05). At all time points investigated, intravital microscopy demonstrated significantly higher levels of periosteal perfusion in the group of rats that underwent piezosurgery than in the group of rats that underwent treatment with a periosteal elevator. The use of a piezoelectric device for subperiosteal preparation is associated with better periosteal microcirculation than the use of a conventional periosteal elevator. As a result, piezoelectric devices can be expected to have a positive effect on bone metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

Quantification of video-taped images in microcirculation research using inexpensive imaging software (Adobe Photoshop).

PubMed

Brunner, J; Krummenauer, F; Lehr, H A

2000-04-01

Study end-points in microcirculation research are usually video-taped images rather than numeric computer print-outs. Analysis of these video-taped images for the quantification of microcirculatory parameters usually requires computer-based image analysis systems. Most software programs for image analysis are custom-made, expensive, and limited in their applicability to selected parameters and study end-points. We demonstrate herein that an inexpensive, commercially available computer software (Adobe Photoshop), run on a Macintosh G3 computer with inbuilt graphic capture board provides versatile, easy to use tools for the quantification of digitized video images. Using images obtained by intravital fluorescence microscopy from the pre- and postischemic muscle microcirculation in the skinfold chamber model in hamsters, Photoshop allows simple and rapid quantification (i) of microvessel diameters, (ii) of the functional capillary density and (iii) of postischemic leakage of FITC-labeled high molecular weight dextran from postcapillary venules. We present evidence of the technical accuracy of the software tools and of a high degree of interobserver reliability. Inexpensive commercially available imaging programs (i.e., Adobe Photoshop) provide versatile tools for image analysis with a wide range of potential applications in microcirculation research.

Laser speckle contrast imaging of cerebral autoregulation in rats at a macro- and microcirculation level

NASA Astrophysics Data System (ADS)

Semyachkina-Glushkovskaya, O. V.; Abdurashitov, A. S.; Sindeev, S. S.; Tuchin, V. V.

2016-06-01

Using the method of laser speckle imaging for the simultaneous study of macro- and microcirculation in cerebral vessels of healthy rats, we show that the mechanisms underlying cerebral autoregulation depend on the initial condition of the organism and the sex of individual animals. The pharmacological dose-dependent stimulation of the peripheral arterial pressure increase is not accompanied by the cerebral circulation responses of analogous intensity, but manifests itself as 'compensating' reactions, namely, the redistribution of the blood flow at the level of macro- (in females) and microcirculation (in females and males). The obtained results extend our understanding of the capabilities of laser speckle imaging technique in neurophysiological studies of reserve abilities of cerebral circulation autoregulation under the conditions of hypertensive status formation.

Laser speckle-imaging of blood microcirculation in the brain cortex of laboratory rats in stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vilensky, M A; Semyachkina-Glushkovskaya, Oxana V; Timoshina, P A

2012-06-30

The results of experimental approbation of the method of laser full-field speckle-imaging for monitoring the changes in blood microcirculation state of the brain cortex of laboratory rats under the conditions of developing stroke and administration of vasodilating and vasoconstrictive agents are presented. The studies aimed at the choice of the optimal conditions of speckle-image formation and recording were performed and the software implementing an adaptive algorithm for processing the data of measurements was created. The transfer of laser radiation to the probed region of the biotissue was implemented by means of a silica-polymer optical fibre. The problems and prospects ofmore » speckle-imaging of cerebral microcirculation of blood in laboratory and clinical conditions are discussed.« less

Intravital Fluorescence Videomicroscopy to Study Tumor Angiogenesis and Microcirculation1

PubMed Central

Vajkoczy, Peter; Ullrich, Axel; Meager, Michael D

2000-01-01

Abstract Angiogenesis and microcirculation play a central role in growth and metastasis of human neoplasms, and, thus, represent a major target for novel treatment strategies. Mechanistic analysis of processes involved in tumor vascularization, however, requires sophisticated in vivo experimental models and techniques. Intravital microscopy allows direct assessment of tumor angiogenesis, microcirculation and overall perfusion. Its application to the study of tumor-induced neovascularization further provides information on molecular transport and delivery, intra- and extravascular cell-to-cell and cell-to-matrix interaction, as well as tumor oxygenation and metabolism. With the recent advances in the field of bioluminescence and fluorescent reporter genes, appropriate for in vivo imaging, the intravital fluorescent microscopic approach has to be considered a powerful tool to study microvascular, cellular and molecular mechanisms of tumor growth. PMID:10933068

The laser Doppler flowmeter for measuring microcirculation in human nasal mucosa.

PubMed

Olsson, P; Bende, M; Ohlin, P

1985-01-01

A new technique, based on the laser doppler principle, for measuring nasal mucosal microcirculation in humans, is presented. With this technique the relation between the blood flow and the temperature of the nasal mucosa was evaluated in healthy subjects exposed to peripheral cold stimulus. A decrease in blood flow and in mucosal temperature was found in all subjects when the feet were exposed to cold water for 5 min. The decrease in blood flow occurred almost momentarily and was restored to normal within the 5 min of exposure, while the drop in mucosal temperature was more gradual and persisted for a longer time. The implication of this study is that the laser doppler flowmeter seems to be a useful tool for estimation of changes in nasal mucosal microcirculation.

Endothelial NOS is required for SDF-1alpha/CXCR4-mediated peripheral endothelial adhesion of c-kit+ bone marrow stem cells.

PubMed

Kaminski, Alexander; Ma, Nan; Donndorf, Peter; Lindenblatt, Nicole; Feldmeier, Gregor; Ong, Lee-Lee; Furlani, Dario; Skrabal, Christian A; Liebold, Andreas; Vollmar, Brigitte; Steinhoff, Gustav

2008-01-01

In the era of intravascular approaches for regenerative cell therapy, the underlying mechanisms of stem cell migration to non-marrow tissue have not been clarified. We hypothesized that next to a local inflammatory response implying adhesion molecule expression, endothelial nitric oxide synthase (eNOS)-dependent signaling is required for stromal- cell-derived factor-1 alpha (SDF-1alpha)-induced adhesion of c-kit+ cells to the vascular endothelium. SDF-1alpha/tumor necrosis factor-alpha (TNF-alpha)-induced c-kit+-cell shape change and migration capacity was studied in vitro using immunohistochemistry and Boyden chamber assays. In vivo interaction of c-kit+ cells from bone marrow with the endothelium in response to SDF-1alpha/TNF-alpha stimulation was visualized in the cremaster muscle microcirculation of wild-type (WT) and eNOS (-/-) mice using intravital fluorescence microscopy. In addition, NOS activity was inhibited with N-nitro-L-arginine-methylester-hydrochloride in WT mice. To reveal c-kit+-specific adhesion behavior, endogenous leukocytes (EL) and c-kit+ cells from peripheral blood served as control. Moreover, intercellular adhesion molecule-1 (ICAM-1) and CXCR4 were blocked systemically to determine their role in inflammation-related c-kit+-cell adhesion. In vitro, SDF-1alpha enhanced c-kit+-cell migration. In vivo, SDF-1alpha alone triggered endothelial rolling-not firm adherence-of c-kit+ cells in WT mice. While TNF-alpha alone had little effect on adhesion of c-kit+ cells, it induced maximum endothelial EL adherence. However, after combined treatment with SDF-1alpha+TNF-alpha, endothelial adhesion of c-kit+ cells increased independent of their origin, while EL adhesion was not further incremented. Systemic treatment with anti-ICAM-1 and anti-CXCR4-monoclonal antibody completely abolished endothelial c-kit+-cell adhesion. In N-nitro-L-arginine-methylester-hydrochloride-treated WT mice as well as in eNOS (-/-) mice, firm endothelial adhesion of c-kit+ cells was entirely abrogated, while EL adhesion was significantly increased. The chemokine SDF-1alpha mediates firm adhesion c-kit+ cells only in the presence of TNF-alpha stimulation via an ICAM-1- and CXCR4-dependent mechanism. The presence of eNOS appears to be a crucial and specific factor for firm c-kit+-cell adhesion to the vascular endothelium.

[The characteristics of the geroprotective action of magnetotherapy in elderly patients with combined cardiovascular pathology].

PubMed

Abramovich, S G; Fedotchenko, A A; Koriakina, A V; Pogodin, K V; Smirnov, S N

1999-01-01

Central hemodynamics, diastolic and pumping functions of the heart, myocardial reactivity, microcirculation and biological age of cardiovascular system were studied in 66 elderly patients suffering from hypertension and ischemic heart disease. The patients received systemic magnetotherapy which produced a geroprotective effect as shown by improved microcirculation, myocardial reactivity, central hemodynamics reducing biological age of cardiovascular system and inhibiting its ageing.

Life and death in the microcirculation: a role for angiotensin II

NASA Technical Reports Server (NTRS)

Greene, A. S.; Cowley, A. W. (Principal Investigator)

1998-01-01

OBJECTIVE: Angiotensin II (ANGII) plays a critical role in the maintenance of the microcirculation and in the anatomical loss of microvessels (rarefaction) that occurs in low renin forms of hypertension and in animals fed a high-salt diet. Elevations in sodium intake can trigger a series of hemodynamic and hormonal responses culminating in a substantial rarefaction of small arterioles and capillaries in both normal and reduced renal mass hypertensive rats. METHODS: Immunohistochemistry, Northern blot, and reverse transcription-polymerase chain reaction (RT-PCR) analysis of microdissected blood vessels were used to localize ANGII receptors in the microcirculation. Chronic infusion of ANGII and other physiologic and pharmacologic manipulations of the reninangiotensin system in rats was combined with morphologic and mathematical analysis of the network architecture. RESULTS: We have shown that rarefaction of the microcirculation can cause an increase in total peripheral resistance, reduced tissue perfusion, decreased oxygen delivery, and impaired organ function. Although the mechanisms by which this occurs are not well understood, a number of key observations point to a role for the renin-angiotensin system in this effect. First, ANGII infused systemically at subpressor levels, or locally into the skeletal muscle interstitium, can induce significant microvessel growth. Second, localization of ANGII receptor proteins by immunohistochemistry and Western blotting and RNA localization by RT-PCR confirm the presence of AT1 receptors, which are growth-stimulatory, and AT2 receptors, which are growth-inhibitory in the microcirculation. Third, maintenance of ANGII at normal levels during periods of hypertension or high-salt diet completely eliminates rarefaction. CONCLUSIONS: Taken together, these results support the hypothesis that ANGII acting through AT1- and AT2-receptor mechanisms modulate vessel density during high-salt diet and hypertension.

Inhibition of glycogen synthase kinase (GSK)-3-β improves liver microcirculation and hepatocellular function after hemorrhagic shock.

PubMed

Jellestad, Lena; Fink, Tobias; Pradarutti, Sascha; Kubulus, Darius; Wolf, Beate; Bauer, Inge; Thiemermann, Chris; Rensing, Hauke

2014-02-05

Ischemia and reperfusion may cause liver injury and are characterized by hepatic microperfusion failure and a decreased hepatocellular function. Inhibition of glycogen synthase kinase (GSK)-3β, a serine-threonine kinase that has recently emerged as a key regulator in the modulation of the inflammatory response after stress events, may be protective in conditions like sepsis, inflammation and shock. Therefore, aim of the study was to assess the role of GSK-3β in liver microcirculation and hepatocellular function after hemorrhagic shock and resuscitation (H/R). Anesthetized male Sprague-Dawley rats underwent pretreatment with Ringer´s solution, vehicle (DMSO) or TDZD-8 (1 mg/kg), a selective GSK-3β inhibitor, 30 min before induction of hemorrhagic shock (mean arterial pressure 35±5 mmHg for 90 min) and were resuscitated with shed blood and Ringer´s solution (2h). 5h after resuscitation hepatic microcirculation was assessed by intravital microscopy. Propidium iodide (PI) positive cells, liver enzymes and alpha-GST were measured as indicators of hepatic injury. Liver function was estimated by assessment of indocyanine green plasma disappearance rate. H/R led to a significant decrease in sinusoidal diameters and impairment of liver function compared to sham operation. Furthermore, the number of PI positive cells in the liver as well as serum activities of liver enzymes and alpha-GST increased significantly after H/R. Pretreatment with TDZD-8 prevented the changes in liver microcirculation, hepatocellular injury and liver function after H/R. A significant rise in the plasma level of IL-10 was observed. Thus, inhibition of GSK-3β before hemorrhagic shock modulates the inflammatory response and improves hepatic microcirculation and hepatocellular function. Copyright © 2013 Elsevier B.V. All rights reserved.

Why Rudolph’s nose is red: observational study

PubMed Central

van Kuijen, Anne-Marije; Milstein, Dan M J; Yürük, Koray; Folkow, Lars P; Fokkens, Wytske J; Blix, Arnoldus S

2012-01-01

Objective To characterise the functional morphology of the nasal microcirculation in humans in comparison with reindeer as a means of testing the hypothesis that the luminous red nose of Rudolph, one of the most well known reindeer pulling Santa Claus’s sleigh, is due to the presence of a highly dense and rich nasal microcirculation. Design Observational study. Setting Tromsø, Norway (near the North Pole), and Amsterdam, the Netherlands. Participants Five healthy human volunteers, two adult reindeer, and a patient with grade 3 nasal polyposis. Main outcome measures Architecture of the microvasculature of the nasal septal mucosa and head of the inferior turbinates, kinetics of red blood cells, and real time reactivity of the microcirculation to topical medicines. Results Similarities between human and reindeer nasal microcirculation were uncovered. Hairpin-like capillaries in the reindeers’ nasal septal mucosa were rich in red blood cells, with a perfused vessel density of 20 (SD 0.7) mm/mm2. Scattered crypt or gland-like structures surrounded by capillaries containing flowing red blood cells were found in human and reindeer noses. In a healthy volunteer, nasal microvascular reactivity was demonstrated by the application of a local anaesthetic with vasoconstrictor activity, which resulted in direct cessation of capillary blood flow. Abnormal microvasculature was observed in the patient with nasal polyposis. Conclusions The nasal microcirculation of reindeer is richly vascularised, with a vascular density 25% higher than that in humans. These results highlight the intrinsic physiological properties of Rudolph’s legendary luminous red nose, which help to protect it from freezing during sleigh rides and to regulate the temperature of the reindeer’s brain, factors essential for flying reindeer pulling Santa Claus’s sleigh under extreme temperatures. PMID:23247980

Active nitric oxide produced in the red cell under hypoxic conditions by deoxyhemoglobin-mediated nitrite reduction.

PubMed

Nagababu, Enika; Ramasamy, Somasundaram; Abernethy, Darrell R; Rifkind, Joseph M

2003-11-21

Recent studies have generated a great deal of interest in a possible role for red blood cells in the transport of nitric oxide (NO) to the microcirculation and the vascular effect of this nitric oxide in facilitating the flow of blood through the microcirculation. Many questions have, however, been raised regarding such a mechanism. We have instead identified a completely new mechanism to explain the role of red cells in the delivery of NO to the microcirculation. This new mechanism results in the production of NO in the microcirculation where it is needed. Nitrite produced when NO reacts with oxygen in arterial blood is reutilized in the arterioles when the partial pressure of oxygen decreases and the deoxygenated hemoglobin formed reduces the nitrite regenerating NO. Nitrite reduction by hemoglobin results in a major fraction of the NO generated retained in the intermediate state where NO is bound to Hb(III) and in equilibrium with the nitrosonium cation bound to Hb(II). This pool of NO, unlike Hb(II)NO, is weakly bound and can be released from the heme. The instability of Hb(III)NO in oxygen and its displacement when flushed with argon requires that reliable determinations of red blood cell NO must be performed on freshly lysed samples without permitting the sample to be oxygenated. In fresh blood samples Hb(III)NO accounts for 75% of the red cell NO with appreciably higher values in venous blood than arterial blood. These findings confirm that nitrite reduction at reduced oxygen pressures is a major source for red cell NO. The formation and potential release from the red cell of this NO could have a major impact in regulating the flow of blood through the microcirculation.

Facial microcirculatory and biomechanical skin properties after single high energy (Er):YAG laser application.

PubMed

Medved, Fabian; Wurm, Antonia; Held, Manuel

2017-12-01

Owing to skin aging and the growing demand for skin rejuvenation, minimal invasive aesthetic treatments such as laser procedures are increasingly coming into focus. However, until now, little has been known about the objective effects of these procedures with respect to skin microcirculation or changes in skin elasticity. Facial skin rejuvenation was performed on 32 volunteers using ablative Erbium: YAG laser. Skin microcirculation and skin elasticity have then been evaluated objectively. Microcirculation (flow, SO 2 , velocity, and rHB) has been analyzed before and directly after the laser session by using the O2C device. Skin elasticity has been evaluated by using the Cutometer device (Uf, Ua, Ur, and Ue) before and directly after the laser treatment, as well as 1 week and then 1, 3, and 6 months post treatment. Further, the outcome for the volunteers regarding their satisfactory level after laser treatment was evaluated. Twenty volunteers were available for a complete follow-up. Microcirculation displayed statistically significant increase in all values to 2 mm depth. The biomechanical skin parameter of firmness of skin displayed statistically significant improvement in superficial skin layer after 6 months. Concerning microcirculation and skin elasticity the ablative Erbium: YAG laser treatment revealed similar effects on the skin like a superficial burn injury. In contrast to the determined skin elasticity parameters, firmness of skin objectively revealed a skin tightening effect after 6 months. Along with the important epidermal effect, the suitability of ablative laser treatment for skin rejuvenation has been proved in a long-term follow-up. Lasers Surg. Med. 49:891-898, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Impairment of skin blood flow during post-occlusive reactive hyperhemy assessed by laser Doppler flowmetry correlates with renal resistive index.

PubMed

Coulon, P; Constans, J; Gosse, P

2012-01-01

We lack non-invasive tools for evaluating the coronary and renal microcirculations. Since cutaneous Doppler laser exploration has evidenced impaired cutaneous microvascular responses in coronary artery disease and in impaired renal function, we wanted to find out if there was a link between the impairments in the cutaneous and renal microcirculations. To specify the significance of the rise in the renal resistive index (RI), which is still unclear, we also sought relations between RI and arterial stiffness. We conducted a cross-sectional controlled study in a heterogeneous population including hypertensive patients of various ages with or without a history of cardiovascular disease along with a healthy control group. The cutaneous microcirculation was evaluated by laser Doppler flowmetry of the post-occlusive reactive hyperhemy (PORH) and of the hyperhemy to heat. The renal microcirculation was evaluated by measurement of the RI. Arterial stiffness was evaluated from an ambulatory measurement of the corrected QKD(100-60) interval. We included 22 hypertensives and 11 controls of mean age 60.6 vs 40.8 years. In this population, there was a correlation between RI and basal zero to peak flow variation (BZ-PF) (r=-0.42; P=0.02) and a correlation between RI and rest flow to peak flow variation (RF-PF) (r=-0.44; P=0.01). There was also a significant correlation between RI and the corrected QKD(100-60) (r=-0.47; P=0.01). The significant correlation between PORH parameters and RI indicates that the functional modifications of the renal and cutaneous microcirculations tend to evolve in parallel during ageing or hypertension. The relation between RI and arterial stiffness shows that RI is a compound index of both renal microvascular impairment and the deterioration of macrovascular mechanics.

MuSIC report III: tumour microcirculation patterns and development of metastasis in long-term follow-up of melanocytic uveal tumours.

PubMed

Klingenstein, Annemarie; Schaumberger, Markus M; Freeman, William R; Folberg, Robert; Mueller, Arthur J; Schaller, Ulrich C

2016-03-01

To statistically determine differences in microcirculation patterns between nevi and uveal melanomas and the influence of these patterns on metastatic potential in the long-term follow-up of 112 patients with melanocytic uveal tumours. In vivo markers indicating malignancy and metastatic potential have implications for treatment decision. Primary diagnosis and work-up included clinical examination, fundus photography, standardized A and B scan echography as well as evaluation of tumour microcirculation patterns via confocal fluorescein and indocyanine green angiography (ICGA). Patient data were collected from the patient files, the tumour registry or personal contact. Statistical analysis was performed with spss 22.0 using chi-square, Fisher's exact test and Kaplan-Meier survival analysis. Forty-three uveal melanocytic lesions remained untreated and were retrospectively classified as benign nevi, whereas 69 lesions were malignant melanomas (T1: 32, T2: 28, T3: 6 and T4: 3). 'Silent' and 'arcs without branching' were found significantly more often in nevi (p = 0.001 and p = 0.010), whereas 'parallel with cross-linking' and 'networks' were significantly more frequent in melanomas (p = 0.022 and p = 0.029). The microcirculation pattern 'parallel with cross-linking' proved significantly more frequent in patients who developed metastases (p = 0.001). Certain microcirculation patterns may guide us in differentiating uveal nevi from malignant melanomas. A non-invasive prognostic marker can be of great value for borderline lesions in which cytology is less likely taken. 'Parallel with cross-linking' did not only indicate malignancy, but it was also associated with later tumour metastasis. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Evaluation of peripheral microcirculation improvement of foot after tarsal tunnel release in diabetic patients by transcutaneous oximetry.

PubMed

Trignano, Emilio; Fallico, Nefer; Chen, Hung-Chi; Faenza, Mario; Bolognini, Alfonso; Armenti, Andrea; Santanelli Di Pompeo, Fabio; Rubino, Corrado; Campus, Gian Vittorio

2016-01-01

According to recent studies, peripheral nerve decompression in diabetic patients seems to not only improve nerve function, but also to increase microcirculation; thus decreasing the incidence of diabetic foot wounds and amputations. However, while the postoperative improvement of nerve function is demonstrated, the changes in peripheral microcirculation have not been demonstrated yet. The aim of this study is to assess the degree of microcirculation improvement of foot after the tarsal tunnel release in the diabetic patients by using transcutaneous oximetry. Twenty diabetic male patients aged between 43 and 72 years old (mean age 61.2 years old) suffering from diabetic peripheral neuropathy with superimposed nerve compression underwent transcutaneous oximetry (PtcO2) before and after tarsal tunnel release by placing an electrode on the skin at the level of the dorsum of the foot. Eight lower extremities presented diabetic foot wound preoperatively. Thirty-six lower extremities underwent surgical release of the tibialis posterior nerve only, whereas four lower extremities underwent the combined release of common peroneal nerve, anterior tibialis nerve, and posterior tibialis nerve. Preoperative values of transcutaneous oximetry were below the critical threshold, that is, lower than 40 mmHg (29.1 ± 5.4 mmHg). PtcO2 values at one month after surgery (45.8 ± 6.4 mmHg) were significantly higher than the preoperative ones (P = 0.01). The results of postoperative increase in PtcO2 values demonstrate that the release of the tarsal tunnel determines a relevant increase in microcirculation in the feet of diabetic patients. © 2015 Wiley Periodicals, Inc.

The Effect of Aging on the Cutaneous Microvasculature

PubMed Central

Bentov, Itay; Reed, May J

2015-01-01

Aging is associated with a progressive loss of function in all organs. Under normal conditions the physiologic compensation for age-related deficits is sufficient, but during times of stress the limitations of this reserve become evident. Explanations for this reduction in reserve include the changes in the microcirculation that occur during the normal aging process. The microcirculation is defined as the blood flow through arterioles, capillaries and venules, which are the smallest vessels in the vasculature and are embedded within organs and tissues. Optimal strategies to maintain the microvasculature following surgery and other stressors must use multifactorial approaches. Using skin as the model organ, we will review the anatomical and functional changes in the microcirculation with aging, and some of the available clinical strategies to potentially mitigate the effect of these changes on important clinical outcomes. PMID:25917013

Wavelet-based analysis of gastric microcirculation in rats with ulcer bleedings

NASA Astrophysics Data System (ADS)

Pavlov, A. N.; Rodionov, M. A.; Pavlova, O. N.; Semyachkina-Glushkovskaya, O. V.; Berdnikova, V. A.; Kuznetsova, Ya. V.; Semyachkin-Glushkovskij, I. A.

2012-03-01

Studying of nitric oxide (NO) dependent mechanisms of regulation of microcirculation in a stomach can provide important diagnostic markers of the development of stress-induced ulcer bleedings. In this work we use a multiscale analysis based on the discrete wavelet-transform to characterize a latent stage of illness formation in rats. A higher sensitivity of stomach vessels to the NO-level in ill rats is discussed.

[Using combined magnetotherapy in patients with acne].

PubMed

Kul'chitskaia, D B; Orekhova, E M; Vasil'eva, E S

2004-01-01

Laser Doppler flowmetry discovered microcirculatory disorders in acne patients. Affected are arterioles as well as capillaries and venules. Combination of magnetotherapy with medication improves microcirculation in acne patients. More marked positive changes occurred in the microcirculatory system due to combined treatment compared to medication therapy only. Thus, laser Doppler flowmetry is a new, noninvasive method of assessing microcirculation in acne patients and can serve an objective criterion of treatment efficacy.

Remodeling of the skeletal muscle microcirculation increases resistance to perfusion in obese Zucker rats.

PubMed

Frisbee, Jefferson C

2003-07-01

Whereas previous studies have demonstrated that the development of syndrome X in obese Zucker rats (OZR) is associated with impaired arteriolar reactivity to vasoactive stimuli, additional results from these studies indicate that the passive diameter of skeletal muscle arterioles is reduced in OZR versus lean Zucker rats (LZR). On the basis of these prior observations, the present study evaluated structural alterations to the skeletal muscle microcirculation as potential contributors to an elevated vascular resistance. Isolated skeletal muscle resistance arterioles exhibited a reduced passive diameter at all levels of intralumenal pressure and a left-shifted stress-strain curve in OZR versus LZR, indicative of structural remodeling of individual arterioles. Histological analyses using Griffonia simplicifolia I lectin-stained sections of skeletal muscle demonstrated reduced microvessel density (rarefaction) in OZR versus LZR, suggesting remodeling of entire microvascular networks. Finally, under maximally dilated conditions, constant flow-perfused skeletal muscle of OZR exhibited significant elevations in perfusion pressure versus LZR, indicative of an increased resistance to perfusion within the microcirculation. These data suggest that developing structural alterations to the skeletal muscle microcirculation in OZR result in elevated vascular resistance, which may, acting in concert with impaired arteriolar reactivity, contribute to blunted active hyperemic responses and compromised performance of in situ skeletal muscle with elevated metabolic demand.

The effect of three different surgical techniques for colon anastomosis on regional postoperative microperfusion: Laser Doppler Flowmetry study in pigs.

PubMed

Kaska, Milan; Blazej, Slavomir; Turek, Zdenek; Ryska, Ales; Jegorov, Boris; Radochova, Vera; Bezouska, Jan; Paral, Jiri

2018-01-01

The optimal surgical approach to reconnecting bowel ends safely after resection is of great importance. This project is focused on assessment of the perianastomotic microcirculation quality in the short postoperative period when using three different anastomosis techniques in experimental animal. The experimental study involved 27 young female domestic pigs divided into three subgroups of 9 animals according to each surgical method of anastomosis construction in the sigmoid colon region: by manual suture, by stapler, or by gluing. Blood microcirculation in the anastomosis region was monitored using Laser Doppler Flowmetry (LDF). Anastomosis healing was evaluated by macroscopic and histological examination. Evaluation of the microcirculation in the anastomosis region showed the smallest decrease in perfusion values in animals reconstructed by suturing (Δ= -38.01%). A significantly more profound drop was observed postoperatively after stapling or gluing (Δ= -52.42% and Δ= -59.53%, respectively). All performed anastomoses healed without any signs of tissue and function pathology. Sewing, stapling, and gluing techniques for bowel anastomosis each have a different effect on regional microcirculation during 120 min. postoperatively. Nevertheless, the final results of anastomosis healing were found without of any pathology in all experimental animals managed by above mentioned anastomotic techniques.

TNF-α inhibition using etanercept prevents noise-induced hearing loss by improvement of cochlear blood flow in vivo.

PubMed

Arpornchayanon, Warangkana; Canis, Martin; Ihler, Friedrich; Settevendemie, Claudia; Strieth, Sebastian

2013-08-01

Exposure to loud noise can impair cochlear microcirculation and cause noise-induced hearing loss (NIHL). TNF-α signaling has been shown to be activated in NIHL and to control spiral modiolar artery vasoconstriction that regulates cochlear microcirculation. It was the aim of this experimental study to analyse the effects of the TNF-α inhibitor etanercept on cochlear microcirculation and hearing threshold shift in NIHL in vivo. After assessment of normacusis using ABR, loud noise (106 dB SPL, 30 minutes) was applied on both ears in guinea pigs. Etanercept was administered systemically after loud noise exposure while control animals received a saline solution. In vivo fluorescence microscopy of strial capillaries was performed after surgical exposure of the cochlea for microcirculatory analysis. ABR measurements were derived from the contralateral ear. Guinea pigs (n = 6, per group). Compared to controls, cochlear blood flow in strial capillary segments was significantly increased in etanercept-treated animals. Additionally, hearing threshold was preserved in animals receiving the TNF-α inhibitor in contrast to a significant threshold raising in controls. TNF-α inhibition using etanercept improves cochlear microcirculation and protects hearing levels after loud noise exposure and appears as a promising treatment strategy for human NIHL.

Disturbance of microcirculation due to unhealthy lifestyle: Cause of type 2 diabetes.

PubMed

Matsumoto, Yukihiro; Ohno, Hideki; Noguchi, Izumi; Kikuchi, Yuji; Kurihara, Takeshi

2006-01-01

Recently, type 2 diabetes seems to be increasing annually in all developed countries. The outcome of type 2 diabetes is often tragic due to succession of complications including renal disorders requiring hemodialysis, blindness, and limb amputation. The expenses for the care of diabetic patients are also a large burden on the society. These circumstances strongly indicate the necessity of prevention. For satisfactory prevention, the clarification of the etiology related to lifestyle is important, but it remains insufficient to date. In this paper, we present a hypothesis of the etiology of type 2 diabetes from the viewpoint of microcirculation. As mentioned later, an unhealthy lifestyle first causes disturbance of the microcirculation, and a portion of the blood is considered to bypass the capillaries via arteriovenous shunts. This prevents the delivery of glucose and insulin to cells of peripheral tissues, causing hyperglycemia unrelated to the cell insulin sensitivity or the endocrine state, i.e., apparent reduction of insulin sensitivity. Disturbance of the microcirculation also causes oxidative stress in peripheral tissues by inducing ischemia and hypoxia. This oxidative stress is considered to further exacerbate reduction of insulin sensitivity. This hypothesis is supported by the well-known fact that insulin sensitivity recovers with improvement in lifestyle including moderate exercise.

Functional Integrity of the Chimeric (Humanized) Mouse Liver: Enzyme Zonation, Physiologic Spaces, and Hepatic Enzymes and Transporters.

PubMed

Chow, Edwin C Y; Wang, Jason Z Ya; Quach, Holly P; Tang, Hui; Evans, David C; Li, Albert P; Silva, Jose; Pang, K Sandy

2016-09-01

Chimeric mouse liver models are useful in vivo tools for human drug metabolism studies; however, liver integrity and the microcirculation remain largely uninvestigated. Hence, we conducted liver perfusion studies to examine these attributes in FRGN [Fah(-/-), Rag2(-/-), and Il2rg(-/-), NOD strain] livers (control) and chimeric livers repopulated with mouse (mFRGN) or human (hFRGN) hepatocytes. In single-pass perfusion studies (2.5 ml/min), outflow dilution profiles of noneliminated reference indicators ((51)Cr-RBC, (125)I-albumin, (14)C-sucrose, and (3)H-water) revealed preservation of flow-limited distribution and reduced water and albumin spaces in hFRGN livers compared with FRGN livers, a view supported microscopically by tightly packed sinusoids. With prograde and retrograde perfusion of harmol (50 µM) in FRGN livers, an anterior sulfation (Sult1a1) over the posterior distribution of glucuronidation (Ugt1a1) activity was preserved, evidenced by the 42% lower sulfation-to-glucuronidation ratio (HS/HG) and 14% higher harmol extraction ratio (E) upon switching from prograde to retrograde flow. By contrast, zonation was lost in mFRGN and hFRGN livers, with HS/HG and E for both flows remaining unchanged. Remnant mouse genes persisted in hFRGN livers (10%-300% those of FRGN). When hFRGN livers were compared with human liver tissue, higher UGT1A1 and MRP2, lower MRP3, and unchanged SULT1A1 and MRP4 mRNA expression were observed. Total Sult1a1/SULT1A1 protein expression in hFRGN livers was higher than that of FRGN livers, consistent with higher harmol sulfate formation. The composite data on humanized livers suggest a loss of zonation, lack of complete liver humanization, and persistence of murine hepatocyte activities leading to higher sulfation. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

Microvascular injury and the kidney in hypertension.

PubMed

Ruiz-Hurtado, G; Ruilope, L M

Renal macrocirculation participates in the development of arterial hypertension. The elevation in systemic blood pressure (BP) can damage the kidney starting in the microcirculation. Established arterial hypertension impinge upon the large arteries and stiffness develops. As a consequence central BP raises and BP pulsatility appear and contribute to further damage renal microcirculation by direct transmission of the elevated BP. Copyright © 2017 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.

Vasodilation by in vivo activation of astrocyte endfeet via two-photon calcium uncaging as a strategy to prevent brain ischemia

NASA Astrophysics Data System (ADS)

Chen, Yuanxin; Mancuso, James; Zhao, Zhen; Li, Xuping; Cheng, Jie; Roman, Gustavo; Wong, Stephen T. C.

2013-12-01

Decreased cerebral blood flow causes brain ischemia and plays an important role in the pathophysiology of many neurodegenerative diseases, including Alzheimer's disease and vascular dementia. In this study, we photomodulated astrocytes in the live animal by a combination of two-photon calcium uncaging in the astrocyte endfoot and in vivo imaging of neurovasculature and astrocytes by intravital two-photon microscopy after labeling with cell type specific fluorescent dyes. Our study demonstrates that photomodulation at the endfoot of a single astrocyte led to a 25% increase in the diameter of a neighboring arteriole, which is a crucial factor regulating cerebral microcirculation in downstream capillaries. Two-photon uncaging in the astrocyte soma or endfoot near veins does not show the same effect on microcirculation. These experimental results suggest that infrared photomodulation on astrocyte endfeet may be a strategy to increase cerebral local microcirculation and thus prevent brain ischemia.

Peripapillary Retinal Nerve Fiber Layer Vascular Microcirculation in Eyes With Glaucoma and Single-Hemifield Visual Field Loss.

PubMed

Chen, Chieh-Li; Bojikian, Karine D; Wen, Joanne C; Zhang, Qinqin; Xin, Chen; Mudumbai, Raghu C; Johnstone, Murray A; Chen, Philip P; Wang, Ruikang K

2017-05-01

Understanding the differences in vascular microcirculation of the peripapillary retinal nerve fiber layer (RNFL) between the hemispheres in eyes with glaucoma with single-hemifield visual field (VF) defects may provide insight into the pathophysiology of glaucoma. To investigate the changes in the microcirculation of the peripapillary RNFL of eyes with glaucoma by using optical microangiography. Eyes with glaucoma and single-hemifield VF defect and normal eyes underwent scanning using an optical microangiography system covering a 6.7 × 6.7-mm2 area centered at the optic nerve head. The RNFL microcirculation was measured within an annulus region centered at the optic nerve head divided into superior and inferior hemispheres. Blood flux index (the mean flow signal intensity in the vessels) and vessel area density (the percentage of the detected vessels in the annulus) were measured. Differences in microcirculation between the hemispheres in eyes with glaucoma and normal eyes and correlations among blood flow metrics, VF thresholds, and clinical optical coherence tomography structural measurements were assessed. Twenty-one eyes from 21 patients with glaucoma (7 men and 14 women; mean [SD] age, 63.7 [9.9] years) and 20 eyes from 20 healthy control individuals (9 men and 11 women; mean [SD] age, 68.3 [10.7] years) were studied. In eyes with glaucoma, the abnormal hemisphere showed a thinner RNFL (mean [SE] difference, 23.5 [4.5] μm; 95% CI, 15.1-32.0 µm; P < .001), lower RNFL blood flux index (mean [SE] difference, 0.04 [0.01]; 95% CI, 0.02-0.05; P < .001), and less vessel area density (mean [SE] difference, 0.08% [0.02%]; 95% CI, 0.05%-0.10%; P < .001) than did the normal hemisphere. Compared with normal eyes, reduced RNFL microcirculation was found in the normal hemisphere of eyes with glaucoma, measured by mean [SE] differences in blood flux index (0.06 [0.01]; 95% CI, 0.04-0.09; P < .001) and vessel area density (0.04% [0.02%]; 95% CI, 0.02%-0.08%; P = .003) but not in RNFL thickness (3.4 [4.7] μm; 95% CI, -6.2 to 12.9 µm; P = .48). Strong correlations were found between the blood flux index and VF mean deviation (Spearman ρ = 0.44; P = .045) and RNFL thickness (Spearman ρ = 0.65; P = .001) in the normal hemisphere of the eye with glaucoma. Reduced RNFL microcirculation was detected in the normal hemisphere of eyes with glaucoma, with strong correspondence with VF loss and RNFL thinning. Although the results suggest that vascular dysfunction precedes structural changes seen in glaucoma, longitudinal studies would be needed to confirm this finding.

The recovery time course of the endothelial-cell glycocalyx in vivo and its implications in vitro

PubMed Central

Potter, Daniel R.; Jiang, John; Damiano, Edward R.

2009-01-01

Compelling evidence continues to emerge suggesting that the glycocalyx surface layer on vascular endothelial cells plays a determining role in numerous physiological processes including inflammation, microvascular permeability, and endothelial mechanotransduction. Previous research has shown that enzymes degrade the glycocalyx, while inflammation causes shedding of the layer. To track the endogenous recovery of the glycocalyx in vivo, we used fluorescent micro-particle image velocimetry (µ-PIV) in mouse cremaster-muscle venules to estimate the hydrodynamically relevant glycocalyx thickness 1, 3, 5, and 7 days after enzymatic or cytokine-mediated degradation of the layer. Results indicate that after acute degradation of the glycocalyx, 5–7 days are required for the layer to endogenously restore itself to its native hydrodynamically relevant thickness in vivo. In light of these findings, and since demonstrable evidence has emerged that standard cell-culture conditions are not conducive to providing the environment and/or cellular conditions necessary to produce and maintain a physiologically relevant cell-surface glycocalyx in vitro, we sought to determine if merely the passage of time would be sufficient to promote the production of a hydrodynamically relevant glycocalyx on a confluent monolayer of human umbilical vein endothelial cells (HUVECs). Using µ-PIV, we found that the hydrodynamically relevant glycocalyx was substantially absent 7 days post-confluence on HUVEC-lined cylindrical collagen microchannels maintained under standard culture conditions. Thus it remains to be determined how a hydrodynamically relevant glycocalyx surface layer can be synthesized and maintained in culture before the endothelial-cell culture model can be used to elucidate glycocalyx-mediated mechanisms of endothelial-cell function. PMID:19443840

Effects of different cooling treatments on water diffusion, microcirculation, and water content within exercised muscles: evaluation by magnetic resonance T2-weighted and diffusion-weighted imaging.

PubMed

Yanagisawa, Osamu; Takahashi, Hideyuki; Fukubayashi, Toru

2010-09-01

In this study, we determined the effects of different cooling treatments on exercised muscles. Seven adults underwent four post-exercise treatments (20-min ice-bag application, 60-min gel-pack application at 10 degrees C and 17 degrees C, and non-cooling treatment) with at least 1 week between treatments. Magnetic resonance diffusion- and T2-weighted images were obtained to calculate the apparent diffusion coefficients (apparent diffusion coefficient 1, which reflects intramuscular water diffusion and microcirculation, and apparent diffusion coefficient 2, which is approximately equal to the true diffusion coefficient that excludes as much of the effect of intramuscular microcirculation as possible) and the T2 values (intramuscular water content level) of the ankle dorsiflexors, respectively, before and after ankle dorsiflexion exercise and after post-exercise treatment. The T2 values increased significantly after exercise and returned to pre-exercise values after each treatment; no significant differences were observed among the four post-exercise treatments. Both apparent diffusion coefficients also increased significantly after exercise and decreased significantly after the three cooling treatments; no significant difference was detected among the three cooling treatments. Local cooling suppresses both water diffusion and microcirculation within exercised muscles. Moreover, although the treatment time was longer, adequate cooling effects could be achieved using the gel-pack applications at relatively mild cooling temperatures.

Prototype of an in vitro model of the microcirculation.

PubMed

Shevkoplyas, Sergey S; Gifford, Sean C; Yoshida, Tatsuro; Bitensky, Mark W

2003-03-01

We have used microfabrication technology to construct a network of microchannels, patterned after the dimensions and architecture of the mammalian microcirculation. The network is cast in transparent silicone elastomer and the channels are coated with silanated mPEG to provide lubrication. Flow of red and white blood cells through the network is readily visualized by the use of high-speed digital image acquisition. The acquired sequences of high-quality images are used to calculate hematocrits and rates of red cell movement in the microchannels. Our prototype system has significant advantages over scaled-up room-size experimental systems in that it permits experimentation with actual human blood cells. Experiments can be carried out under well-controlled conditions in a network of microchannels with precisely known dimensions using cell suspensions of defined composition. Moreover, there is no need to counteract or anticipate the host's adaptive responses that may confound live animal experiments. Notwithstanding its limitations, the current prototype demonstrates certain features characteristic of the microcirculation, such as parachute and bullet shapes of red cells deformed in capillary channels, rouleaux formation, plasma skimming, and the utilization of collateral flow pathways due to flow obstruction caused by a white cell blocking a microchannel. We present this device as a prototype scale-to-scale model of the mammalian microcirculation. Limitations of the system as well as a variety of possible applications are described.

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 transformation of RBCs into spiculated RBCs with the same steroids. Conclusion Several particulate steroids have an immediate and massive effect on microvascular perfusion because of formation of RBC aggregates associated with the transformation of RBCs into spiculated RBCs. (©) RSNA, 2016 Online supplemental material is available for this article.

Decreased Reactivity of Skin Microcirculation in Response to l-Arginine in Later-Onset Type 1 Diabetes

PubMed Central

Neubauer-Geryk, Jolanta; Kozera, Grzegorz M.; Wolnik, Bogumil; Szczyrba, Sebastian; Nyka, Walenty M.; Bieniaszewski, Leszek

2013-01-01

OBJECTIVE The aim of our study was to evaluate the vasodilatory effect of l-arginine infusion on the skin microcirculation and to assess the relationship between this effect and the presence of microangiopathy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Capillaroscopy was performed before and after l-arginine infusion in 48 diabetic patients (26 women and 22 men; age, 39.8 ± 6.3 years) and 24 volunteers free of any chronic disease (13 women and 11 men; age, 38.0 ± 6.7 years). The skin microcirculation reactivity, as expressed by the percentage of area covered by capillaries (coverage) and the distance between capillaries (distance), and the relationship between microcirculation reactivity and the presence of microangiopathic complications were assessed. RESULTS The distance before l-arginine infusion was significantly lower in patients than in controls (221 [153–311] vs. 240 [185–356] µm; P = 0.02) and did not differ after l-arginine infusion (223.5 [127–318] vs. 242.5 [181–341] µm; P = 0.27). The difference between the coverage values obtained before and after l-arginine infusion (Δcoverage) was significantly different from zero in the control group but not in the diabetes group. Patients with later onset of diabetes were characterized by decreased skin microcirculation reactivity when compared with patients with earlier onset of diabetes (−1.18 [−5.07 to 11.60] vs. 1.36 [−6.00 to 8.06]; P = 0.02) despite the higher prevalence of retinopathy in patients with earlier onset of diabetes (64% vs. 26%; P = 0.02). CONCLUSIONS Skin microvascular reactivity is impaired in patients with later onset of type 1 diabetes. Capillaroscopy with l-arginine infusion is useful for the identification of skin microangiopathy in type 1 diabetes. PMID:23150282

Endothelial dysfunction in the microcirculation of patients with obstructive sleep apnea.

PubMed

Patt, Brian T; Jarjoura, David; Haddad, Diane N; Sen, Chandan K; Roy, Sashwati; Flavahan, Nicholas A; Khayat, Rami N

2010-12-15

Obstructive sleep apnea (OSA) is a risk factor for cardiovascular disease. We hypothesized that patients with OSA and no cardiovascular disease have oxidant-related microcirculatory endothelial dysfunction. To evaluate the microcirculation in OSA. This study included seven patients with OSA and seven age- and weight-matched control subjects (mean age, 38 yr; mean body mass index, 32.5 kg/m²). All participants were free of cardiovascular risk factors. Participants received measurement of brachial artery flow-mediated dilation and forearm subcutaneous biopsy. Patients underwent repeated tests 12 weeks after treatment. Microcirculatory endothelial cells were isolated, and immunohistochemistry staining for peroxynitrite in the microcirculation was performed. Flow-mediated dilation was lower in patients than in control subjects at baseline (mean ± SEM: 5.7 ± 0.5 vs. 9.5 ± 0.6; P = 0.02) and increased after treatment (5.7-7.3; change, 1.7 ± 0.6; P = 0.04). Microcirculatory peroxynitrite deposit was higher in patients compared with control subjects (44.0 ± 1.6 vs. 21.8 ± 1.9 stain density units; P < 0.001) and decreased after treatment from 44.0 to 30.5 stain density units (change, -13.5 ± 2.9; P = 0.009). In patients, transcription of endothelial nitric oxide synthase decreased from 5.2 to -1.3 after treatment (change, 6.5 ± 2.5; P = 0.05), and transcription of superoxide dismutase1 decreased from -4.0 to -12.3 after treatment (change, -8.3 ± 2.1; P = 0.01). These changes persisted after adjustment for weight and underlying severity of OSA. This is the first direct evaluation of the microcirculation in OSA. Patients with OSA with low cardiovascular risk status had increased oxidant production in the microcirculation and endothelial dysfunction, both of which improved with treatment. Endothelial nitric oxide synthase transcription decreased with treatment.

Endothelial Dysfunction in the Microcirculation of Patients with Obstructive Sleep Apnea

PubMed Central

Patt, Brian T.; Jarjoura, David; Haddad, Diane N.; Sen, Chandan K.; Roy, Sashwati; Flavahan, Nicholas A.; Khayat, Rami N.

2010-01-01

Rationale: Obstructive sleep apnea (OSA) is a risk factor for cardiovascular disease. We hypothesized that patients with OSA and no cardiovascular disease have oxidant-related microcirculatory endothelial dysfunction. Objectives: To evaluate the microcirculation in OSA. Methods: This study included seven patients with OSA and seven age- and weight-matched control subjects (mean age, 38 yr; mean body mass index, 32.5 kg/m2). All participants were free of cardiovascular risk factors. Participants received measurement of brachial artery flow-mediated dilation and forearm subcutaneous biopsy. Patients underwent repeated tests 12 weeks after treatment. Microcirculatory endothelial cells were isolated, and immunohistochemistry staining for peroxynitrite in the microcirculation was performed. Measurements and Main Results: Flow-mediated dilation was lower in patients than in control subjects at baseline (mean ± SEM: 5.7 ± 0.5 vs. 9.5 ± 0.6; P = 0.02) and increased after treatment (5.7–7.3; change, 1.7 ± 0.6; P = 0.04). Microcirculatory peroxynitrite deposit was higher in patients compared with control subjects (44.0 ± 1.6 vs. 21.8 ± 1.9 stain density units; P < 0.001) and decreased after treatment from 44.0 to 30.5 stain density units (change, −13.5 ± 2.9; P = 0.009). In patients, transcription of endothelial nitric oxide synthase decreased from 5.2 to −1.3 after treatment (change, 6.5 ± 2.5; P = 0.05), and transcription of superoxide dismutase1 decreased from −4.0 to −12.3 after treatment (change, −8.3 ± 2.1; P = 0.01). These changes persisted after adjustment for weight and underlying severity of OSA. Conclusions: This is the first direct evaluation of the microcirculation in OSA. Patients with OSA with low cardiovascular risk status had increased oxidant production in the microcirculation and endothelial dysfunction, both of which improved with treatment. Endothelial nitric oxide synthase transcription decreased with treatment. PMID:20656942

Comparison of an automatic analysis and a manual analysis of conjunctival microcirculation in a sheep model of haemorrhagic shock.

PubMed

Arnemann, Philip-Helge; Hessler, Michael; Kampmeier, Tim; Morelli, Andrea; Van Aken, Hugo Karel; Westphal, Martin; Rehberg, Sebastian; Ertmer, Christian

2016-12-01

Life-threatening diseases of critically ill patients are known to derange microcirculation. Automatic analysis of microcirculation would provide a bedside diagnostic tool for microcirculatory disorders and allow immediate therapeutic decisions based upon microcirculation analysis. After induction of general anaesthesia and instrumentation for haemodynamic monitoring, haemorrhagic shock was induced in ten female sheep by stepwise blood withdrawal of 3 × 10 mL per kilogram body weight. Before and after the induction of haemorrhagic shock, haemodynamic variables, samples for blood gas analysis, and videos of conjunctival microcirculation were obtained by incident dark field illumination microscopy. Microcirculatory videos were analysed (1) manually with AVA software version 3.2 by an experienced user and (2) automatically by AVA software version 4.2 for total vessel density (TVD), perfused vessel density (PVD) and proportion of perfused vessels (PPV). Correlation between the two analysis methods was examined by intraclass correlation coefficient and Bland-Altman analysis. The induction of haemorrhagic shock decreased the mean arterial pressure (from 87 ± 11 to 40 ± 7 mmHg; p < 0.001); stroke volume index (from 38 ± 14 to 20 ± 5 ml·m -2 ; p = 0.001) and cardiac index (from 2.9 ± 0.9 to 1.8 ± 0.5 L·min -1 ·m -2 ; p < 0.001) and increased the heart rate (from 72 ± 9 to 87 ± 11 bpm; p < 0.001) and lactate concentration (from 0.9 ± 0.3 to 2.0 ± 0.6 mmol·L -1 ; p = 0.001). Manual analysis showed no change in TVD (17.8 ± 4.2 to 17.8 ± 3.8 mm*mm -2 ; p = 0.993), whereas PVD (from 15.6 ± 4.6 to 11.5 ± 6.5 mm*mm -2 ; p = 0.041) and PPV (from 85.9 ± 11.8 to 62.7 ± 29.6%; p = 0.017) decreased significantly. Automatic analysis was not able to identify these changes. Correlation analysis showed a poor correlation between the analysis methods and a wide spread of values in Bland-Altman analysis. As characteristic changes in microcirculation during ovine haemorrhagic shock were not detected by automatic analysis and correlation between automatic and manual analyses (current gold standard) was poor, the use of the investigated software for automatic analysis of microcirculation cannot be recommended in its current version at least in the investigated model. Further improvements in automatic vessel detection are needed before its routine use.

New Insights into the Microvascular Mechanisms of Drag Reducing Polymers: Effect on the Cell-Free Layer

PubMed Central

Brands, Judith; Kliner, Dustin; Lipowsky, Herbert H.; Kameneva, Marina V.; Villanueva, Flordeliza S.; Pacella, John J.

2013-01-01

Drag-reducing polymers (DRPs) significantly increase blood flow, tissue perfusion, and tissue oxygenation in various animal models. In rectangular channel microfluidic systems, DRPs were found to significantly reduce the near-wall cell-free layer (CFL) as well as modify traffic of red blood cells (RBC) into microchannel branches. In the current study we further investigated the mechanism by which DRP enhances microvascular perfusion. We studied the effect of various concentrations of DRP on RBC distribution in more relevant round microchannels and the effect of DRP on CFL in the rat cremaster muscle in vivo. In round microchannels hematocrit was measured in parent and daughter branch at baseline and after addition of DRP. At DRP concentrations of 5 and 10 ppm, the plasma skimming effect in the daughter branch was eliminated, as parent and daughter branch hematocrit were equivalent, compared to a significantly lowered hematocrit in the daughter branch without DRPs. In anesthetized rats (N=11) CFL was measured in the cremaster muscle tissue in arterioles with a diameter of 32.6 ± 1.7 µm. In the control group (saline, N=6) there was a significant increase in CFL in time compared to corresponding baseline. Addition of DRP at 1 ppm (N=5) reduced CFL significantly compared to corresponding baseline and the control group. After DRP administration the CFL reduced to about 85% of baseline at 5, 15, 25 and 35 minutes after DRP infusion was complete. These in vivo and in vitro findings demonstrate that DRPs induce a reduction in CFL width and plasma skimming in the microvasculature. This may lead to an increase of RBC flux into the capillary bed, and thus explain previous observations of a DRP mediated enhancement of capillary perfusion. PMID:24124610

New insights into the microvascular mechanisms of drag reducing polymers: effect on the cell-free layer.

PubMed

Brands, Judith; Kliner, Dustin; Lipowsky, Herbert H; Kameneva, Marina V; Villanueva, Flordeliza S; Pacella, John J

2013-01-01

Drag-reducing polymers (DRPs) significantly increase blood flow, tissue perfusion, and tissue oxygenation in various animal models. In rectangular channel microfluidic systems, DRPs were found to significantly reduce the near-wall cell-free layer (CFL) as well as modify traffic of red blood cells (RBC) into microchannel branches. In the current study we further investigated the mechanism by which DRP enhances microvascular perfusion. We studied the effect of various concentrations of DRP on RBC distribution in more relevant round microchannels and the effect of DRP on CFL in the rat cremaster muscle in vivo. In round microchannels hematocrit was measured in parent and daughter branch at baseline and after addition of DRP. At DRP concentrations of 5 and 10 ppm, the plasma skimming effect in the daughter branch was eliminated, as parent and daughter branch hematocrit were equivalent, compared to a significantly lowered hematocrit in the daughter branch without DRPs. In anesthetized rats (N=11) CFL was measured in the cremaster muscle tissue in arterioles with a diameter of 32.6 ± 1.7 µm. In the control group (saline, N=6) there was a significant increase in CFL in time compared to corresponding baseline. Addition of DRP at 1 ppm (N=5) reduced CFL significantly compared to corresponding baseline and the control group. After DRP administration the CFL reduced to about 85% of baseline at 5, 15, 25 and 35 minutes after DRP infusion was complete. These in vivo and in vitro findings demonstrate that DRPs induce a reduction in CFL width and plasma skimming in the microvasculature. This may lead to an increase of RBC flux into the capillary bed, and thus explain previous observations of a DRP mediated enhancement of capillary perfusion.

First Selective 12-LOX Inhibitor, ML355, Impairs Thrombus Formation and Vessel Occlusion In Vivo With Minimal Effects on Hemostasis.

PubMed

Adili, Reheman; Tourdot, Benjamin E; Mast, Katherine; Yeung, Jennifer; Freedman, John C; Green, Abigail; Luci, Diane K; Jadhav, Ajit; Simeonov, Anton; Maloney, David J; Holman, Theodore R; Holinstat, Michael

2017-10-01

Adequate platelet reactivity is required for maintaining hemostasis. However, excessive platelet reactivity can also lead to the formation of occlusive thrombi. Platelet 12(S)-lipoxygenase (12-LOX), an oxygenase highly expressed in the platelet, has been demonstrated to regulate platelet function and thrombosis ex vivo, supporting a key role for 12-LOX in the regulation of in vivo thrombosis. However, the ability to pharmacologically target 12-LOX in vivo has not been established to date. Here, we studied the effect of the first highly selective 12-LOX inhibitor, ML355, on in vivo thrombosis and hemostasis. ML355 dose-dependently inhibited human platelet aggregation and 12-LOX oxylipin production, as confirmed by mass spectrometry. Interestingly, the antiplatelet effects of ML355 were reversed after exposure to high concentrations of thrombin in vitro. Ex vivo flow chamber assays confirmed that human platelet adhesion and thrombus formation at arterial shear over collagen were attenuated in whole blood treated with ML355 comparable to aspirin. Oral administration of ML355 in mice showed reasonable plasma drug levels by pharmacokinetic assessment. ML355 treatment impaired thrombus growth and vessel occlusion in FeCl 3 -induced mesenteric and laser-induced cremaster arteriole thrombosis models in mice. Importantly, hemostatic plug formation and bleeding after treatment with ML355 was minimal in mice in response to laser ablation on the saphenous vein or in a cremaster microvasculature laser-induced rupture model. Our data strongly support 12-LOX as a key determinant of platelet reactivity in vivo, and inhibition of platelet 12-LOX with ML355 may represent a new class of antiplatelet therapy. © 2017 American Heart Association, Inc.

2-D Model for Normal and Sickle Cell Blood Microcirculation

NASA Astrophysics Data System (ADS)

Tekleab, Yonatan; Harris, Wesley

2011-11-01

Sickle cell disease (SCD) is a genetic disorder that alters the red blood cell (RBC) structure and function such that hemoglobin (Hb) cannot effectively bind and release oxygen. Previous computational models have been designed to study the microcirculation for insight into blood disorders such as SCD. Our novel 2-D computational model represents a fast, time efficient method developed to analyze flow dynamics, O2 diffusion, and cell deformation in the microcirculation. The model uses a finite difference, Crank-Nicholson scheme to compute the flow and O2 concentration, and the level set computational method to advect the RBC membrane on a staggered grid. Several sets of initial and boundary conditions were tested. Simulation data indicate a few parameters to be significant in the perturbation of the blood flow and O2 concentration profiles. Specifically, the Hill coefficient, arterial O2 partial pressure, O2 partial pressure at 50% Hb saturation, and cell membrane stiffness are significant factors. Results were found to be consistent with those of Le Floch [2010] and Secomb [2006].

Simulations of the Microcirculation in the Human Conjunctiva

NASA Astrophysics Data System (ADS)

Dow, William; Jacobitz, Frank; Chen, Peter

2012-11-01

The microcirculation in the conjunctiva of a healthy human subject is analyzed using a simulation approach. A comparison between healthy and diseased states may lead to early diagnosis for a variety of vascular related disorders. Previous work suggests that hypertension, arteriosclerosis, and diabetes mellitus have noticeable very early changes in the microvasculature (Davis and Landau, 1957; Ditzel, 1968; Kunitomo, 1974) and the vessels of the conjunctiva are specifically useful for this research because they can be studied non-invasively. The microcirculation in the conjunctiva has been documented over the course of disease treatments, providing both still images and video footage for information on vessel length, diameter, and connectivity as well as the direction of blood flow. The numerical method is based on a Hagen-Poiseuille balance in the microvessels and a sparse matrix solver is used to obtain the solution. The simulations use realistic vessel topology for the microvasculature, reconstructed from microscope images of tissue samples, and consider blood rheology as well as passive and active vessel properties.

A new fluorescent imaging procedure in vivo for evaluation of the retinal microcirculation in rats.

PubMed

Kimura, H; Kiryu, J; Nishiwaki, H; Ogura, Y

1995-03-01

We investigated a new method for in vivo evaluation of the retinal microcirculation in rats using a cell-permeant fluorescent dye, acridine orange (AO), which stains cell nuclei and cytoplasm, and a scanning laser ophthalmoscope (SLO). AO, which binds and interacts with DNA and RNA, and thus stains cell nuclei and cytoplasm, was administered intravenously to rats. Fluorescein angiography was performed after administration of the AO, and fundus images were recorded on S-VHS videotape by means of an SLO. Argon laser was used as an exciter of the dye. The retinal vessels were stained with the dye, rendering the retinal microvasculature clearly visible. Cell nuclei and vessel walls were observed as greater fluorescence and lesser fluorescence, respectively. Leukocytes were also observed as highly fluorescent dots moving through the vessels. The results suggest that SLO visualization of AO uptake by cells may be a useful procedure for the evaluation of retinal microcirculation in vivo in rats.

High sensitive volumetric imaging of renal microcirculation in vivo using ultrahigh sensitive optical microangiography

NASA Astrophysics Data System (ADS)

Zhi, Zhongwei; Jung, Yeongri; Jia, Yali; An, Lin; Wang, Ruikang K.

2011-03-01

We present a non-invasive, label-free imaging technique called Ultrahigh Sensitive Optical Microangiography (UHSOMAG) for high sensitive volumetric imaging of renal microcirculation. The UHS-OMAG imaging system is based on spectral domain optical coherence tomography (SD-OCT), which uses a 47000 A-line scan rate CCD camera to perform an imaging speed of 150 frames per second that takes only ~7 seconds to acquire a 3D image. The technique, capable of measuring slow blood flow down to 4 um/s, is sensitive enough to image capillary networks, such as peritubular capillaries and glomerulus within renal cortex. We show superior performance of UHS-OMAG in providing depthresolved volumetric images of rich renal microcirculation. We monitored the dynamics of renal microvasculature during renal ischemia and reperfusion. Obvious reduction of renal microvascular density due to renal ischemia was visualized and quantitatively analyzed. This technique can be helpful for the assessment of chronic kidney disease (CKD) which relates to abnormal microvasculature.

Blood flow and blood cell interactions and migration in microvessels

NASA Astrophysics Data System (ADS)

Fedosov, Dmitry; Fornleitner, Julia; Gompper, Gerhard

2011-11-01

Blood flow in microcirculation plays a fundamental role in a wide range of physiological processes and pathologies in the organism. To understand and, if necessary, manipulate the course of these processes it is essential to investigate blood flow under realistic conditions including deformability of blood cells, their interactions, and behavior in the complex microvascular network which is characteristic for the microcirculation. We employ the Dissipative Particle Dynamics method to model blood as a suspension of deformable cells represented by a viscoelastic spring-network which incorporates appropriate mechanical and rheological cell-membrane properties. Blood flow is investigated in idealized geometries. In particular, migration of blood cells and their distribution in blood flow are studied with respect to various conditions such as hematocrit, flow rate, red blood cell aggregation. Physical mechanisms which govern cell migration in microcirculation and, in particular, margination of white blood cells towards the vessel wall, will be discussed. In addition, we characterize blood flow dynamics and quantify hemodynamic resistance. D.F. acknowledges the Humboldt Foundation for financial support.

Nitric oxide bioavailability in the microcirculation: insights from mathematical models.

PubMed

Tsoukias, Nikolaos M

2008-11-01

Over the last 30 years nitric oxide (NO) has emerged as a key signaling molecule involved in a number of physiological functions, including in the regulation of microcirculatory tone. Despite significant scientific contributions, fundamental questions about NO's role in the microcirculation remain unanswered. Mathematical modeling can assist in investigations of microcirculatory NO physiology and address experimental limitations in quantifying vascular NO concentrations. The number of mathematical models investigating the fate of NO in the vasculature has increased over the last few years, and new models are continuously emerging, incorporating an increasing level of complexity and detail. Models investigate mechanisms that affect NO availability in health and disease. They examine the significance of NO release from nonendothelial sources, the effect of transient release, and the complex interaction of NO with other substances, such as heme-containing proteins and reactive oxygen species. Models are utilized to test and generate hypotheses for the mechanisms that regulate NO-dependent signaling in the microcirculation.

Repeatability of Bolus Kinetics Ultrasound Perfusion Imaging for the Quantification of Cerebral Blood Flow.

PubMed

Vinke, Elisabeth J; Eyding, Jens; de Korte, Chris L; Slump, Cornelis H; van der Hoeven, Johannes G; Hoedemaekers, Cornelia W E

2017-12-01

Ultrasound perfusion imaging (UPI) can be used for the quantification of cerebral perfusion. In a neuro-intensive care setting, repeated measurements are required to evaluate changes in cerebral perfusion and monitor therapy. The aim of this study was to determine the repeatability of UPI in quantification of cerebral perfusion. UPI measurement of cerebral perfusion was performed three times in healthy patients. The coefficients of variation of the three bolus injections were calculated for both time- and volume-derived perfusion parameters in the macro- and microcirculation. The UPI time-dependent parameters had overall the lowest CVs in both the macro- and microcirculation. The volume-related parameters had poorer repeatability, especially in the microcirculation. Both intra-observer variability and inter-observer variability were low. Although UPI is a promising tool for the bedside measurement of cerebral perfusion, improvement of the technique is required before implementation in routine clinical practice. Copyright © 2017 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Circulating IGF-1 deficiency exacerbates hypertension-induced microvascular rarefaction in the mouse hippocampus and retrosplenial cortex: implications for cerebromicrovascular and brain aging.

PubMed

Tarantini, Stefano; Tucsek, Zsuzsanna; Valcarcel-Ares, M Noa; Toth, Peter; Gautam, Tripti; Giles, Cory B; Ballabh, Praveen; Wei, Jeanne Y; Wren, Jonathan D; Ashpole, Nicole M; Sonntag, William E; Ungvari, Zoltan; Csiszar, Anna

2016-08-01

Strong epidemiological and experimental evidence indicate that both age and hypertension lead to significant functional and structural impairment of the cerebral microcirculation, predisposing to the development of vascular cognitive impairment (VCI) and Alzheimer's disease. Preclinical studies establish a causal link between cognitive decline and microvascular rarefaction in the hippocampus, an area of brain important for learning and memory. Age-related decline in circulating IGF-1 levels results in functional impairment of the cerebral microvessels; however, the mechanistic role of IGF-1 deficiency in impaired hippocampal microvascularization remains elusive. The present study was designed to characterize the additive/synergistic effects of IGF-1 deficiency and hypertension on microvascular density and expression of genes involved in angiogenesis and microvascular regression in the hippocampus. To achieve that goal, we induced hypertension in control and IGF-1 deficient mice (Igf1 f/f  + TBG-Cre-AAV8) by chronic infusion of angiotensin II. We found that circulating IGF-1 deficiency is associated with decreased microvascular density and exacerbates hypertension-induced microvascular rarefaction both in the hippocampus and the neocortex. The anti-angiogenic hippocampal gene expression signature observed in hypertensive IGF-1 deficient mice in the present study provides important clues for subsequent studies to elucidate mechanisms by which hypertension may contribute to the pathogenesis and clinical manifestation of VCI. In conclusion, adult-onset, isolated endocrine IGF-1 deficiency exerts deleterious effects on the cerebral microcirculation, leading to a significant decline in cortical and hippocampal capillarity and exacerbating hypertension-induced cerebromicrovascular rarefaction. The morphological impairment of the cerebral microvasculature induced by IGF-1 deficiency and hypertension reported here, in combination with neurovascular uncoupling, increased blood-brain barrier disruption and neuroinflammation reported in previous studies likely contribute to the pathogenesis of vascular cognitive impairment in elderly hypertensive humans.

Local microcirculation disorders in uterus under laser tissue welding and their influence in the healing process

NASA Astrophysics Data System (ADS)

Kozlov, Valentine I.; Skobelkin, Oleg K.; Fatkullin, Ildar; Terman, Oleg A.; Chizhov, Gennadii; Gabidullina, Rushania

1994-12-01

To study the possibility of using Nd:YAG laser to weld the tissues of the uterus experiments in rats and dogs have been conducted. With the biomicroscopy and the laser Doppler flowmetry we have evaluated the microcirculation in the uterus wall under traditional suture and laser welding suture. As a model of the wound, the dissection of serosa and muscles of the organ wall have been used. In laser welding suture we have welded the zone of tissue about 1 mm3 with the laser (power density 270 W/cm2). Histological control has been fulfilled on various phases of the healing process. The investigation of the uterus wall demonstrates that there are zones of microcirculation disorders in tissues: (1) the zone of coagulation of microvessels and adjacent tissues (about 100 micrometers ); (2) the zone of stasis (150 - 200 micrometers ); (3) the zone of reactive-destructive changes of microvessels (300 micrometers ), (4) the zone of malfunctional microcirculatory changes (600 micrometers ). The coagulation of microvessels changes the character of inflammation and the healing process, decreases the exudation phase and the leucocyte infiltration of tissues, and accelerates the capillary growth. In contrast with traditional suture, in the case of laser welding suture the edema and hemorrhagic signs are less expressed. The complete restoration of microcirculation under laser welding suture has been observed by the fourteenth day of the healing process. Under the traditional suture method normalization of tissue nutritious blood flow has been achieved by 21 days.

Deterioration of endothelial function of micro- and macrocirculation in patients with diabetes type 1 and 2.

PubMed

Besic, Hana; Jeraj, Luka; Spirkoska, Ana; Jezovnik, Mateja K; Poredoš, Pavel

2017-08-01

Vascular complications are an important cause of morbidity in patients with diabetes mellitus (DM). Endothelial dysfunction is an early marker of atherosclerosis and has already been shown in macrocirculation of diabetic patients; however, data on endothelial function of microcirculation is scarce. Our aim was to evaluate endothelial function in macro- and microcirculation and their interrelationship in patients with type 1 and 2 DM. The study included 30 patients with type 1 DM, 30 patients with type 2 DM and 25 healthy controls. The endothelial function of large arteries was studied measuring flow-mediated dilation (FMD). Peripheral arterial tonometry was used for investigation of the endothelial function of microcirculation, measuring Reactive Hyperemia Index (RHI) and Augmentation Index (AI). In comparison to controls, both DM groups had decreased FMD: type 1 (4.0±5.0% vs. 10.0±7.8%, P=0.005) and type 2 (5.0±0.6% vs. 10.0±7.8%, P=0.007). However, only type 2 DM group had a lower RHI (1.71±0.44 vs. 2.05±0.54, P=0.017) in comparison to controls. Patients with type 1 and 2 DM had deteriorated functional capability of macrocirculation. However, endothelial dysfunction of microcirculation was present only in type 2 DM patients. Type 2 DM patients were also at higher risk for atherosclerosis because of the more frequent presence of risk factors.

The blood perfusion and NADH/FAD content combined analysis in patients with diabetes foot

NASA Astrophysics Data System (ADS)

Dremin, Victor V.; Sidorov, Victor V.; Krupatkin, Alexander I.; Galstyan, Gagik R.; Novikova, Irina N.; Zherebtsova, Angelina I.; Zherebtsov, Evgeny A.; Dunaev, Andrey V.; Abdulvapova, Zera N.; Litvinova, Karina S.; Rafailov, Ilya E.; Sokolovski, Sergei G.; Rafailov, Edik U.

2016-03-01

Skin blood microcirculation and the metabolism activity of tissue were examined on the patients with type 2 diabetes. Laser Doppler flowmetry (LDF) with 1064 nm laser light source and fluorescence spectroscopy (FS) with excitation light of 365 nm and 450 nm have been used to monitor the blood perfusion and the content of coenzymes NADH and FAD. Concluding, the proposed combined LDF and tissue FS approach allows to identify the significant violations in the blood microcirculation and metabolic activity for type 2 diabetes patients.

Quantitative laser speckle flowmetry of the in vivo microcirculation using sidestream dark field microscopy

PubMed Central

Nadort, Annemarie; Woolthuis, Rutger G.; van Leeuwen, Ton G.; Faber, Dirk J.

2013-01-01

We present integrated Laser Speckle Contrast Imaging (LSCI) and Sidestream Dark Field (SDF) flowmetry to provide real-time, non-invasive and quantitative measurements of speckle decorrelation times related to microcirculatory flow. Using a multi exposure acquisition scheme, precise speckle decorrelation times were obtained. Applying SDF-LSCI in vitro and in vivo allows direct comparison between speckle contrast decorrelation and flow velocities, while imaging the phantom and microcirculation architecture. This resulted in a novel analysis approach that distinguishes decorrelation due to flow from other additive decorrelation sources. PMID:24298399

Quantitative depth resolved microcirculation imaging with optical coherence tomography angiography (Part ΙΙ): Microvascular network imaging.

PubMed

Gao, Wanrong

2017-04-17

In this work, we review the main phenomena that have been explored in OCT angiography to image the vessels of the microcirculation within living tissues with the emphasis on how the different processing algorithms were derived to circumvent specific limitations. Parameters are then discussed that can quantitatively describe the depth-resolved microvascular network for possible clinic diagnosis applications. Finally,future directions in continuing OCT development are discussed. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[Temperature-dependent changes in the microcirculation of the dental pulp].

PubMed

Raab, W H; Müller, H

1989-07-01

Laser Doppler flowmetry was used to study the changes in the blood flow within the dental pulp as a reaction to thermal stimuli between 17 degrees C and 57 degree C. Temperatures below 31 degrees C resulted in a reduction, temperatures above 43 degrees C in an increase in blood flow. Temperatures higher than 49 degrees C caused irreversible damage to the pulp's microcirculation. Experimental nerve blocks showed that the reactive increase is linked to the afferent rather than the sympathetic innervation of the tooth pulp.

Investigation of Doppler spectra of laser radiation scattered inside hand skin during occlusion test

NASA Astrophysics Data System (ADS)

Kozlov, I. O.; Zherebtsov, E. A.; Zherebtsova, A. I.; Dremin, V. V.; Dunaev, A. V.

2017-11-01

Laser Doppler flowmetry (LDF) is a method widely used in diagnosis of microcirculation diseases. It is well known that information about frequency distribution of Doppler spectrum of the laser radiation scattered by moving red blood cells (RBC) usually disappears after signal processing procedure. Photocurrent’s spectrum distribution contains valuable diagnostic information about velocity distribution of the RBC. In this research it is proposed to compute the indexes of microcirculation in the sub-ranges of the Doppler spectrum as well as investigate the frequency distribution of the computed indexes.

[Rehabilitative medical technology for the correction of microcirculatory disorders in patients with arterial hypertension].

PubMed

Kul'chitskaia, D B

2009-01-01

The study with the use of laser Doppler flowmetry has revealed pathological changes in the microcirculatory system of patients with arterial hypertension. Their treatment with a low-frequency magnetic field showed that its effect on microcirculation depends on the regime and site of application of magnetotherapy as well as its combination with other physical factors. Frontal application of the magnetic field had the most pronounced beneficial effect on dynamic characteristics of microcirculation. Pulsed regime of magnetotherapy was more efficacious than conventional one. Amplipulse magnetotherapy produced better results than monotherapy.

Citrulline a More Suitable Substrate than Arginine to Restore NO Production and the Microcirculation during Endotoxemia

PubMed Central

Wijnands, Karolina A. P.; Vink, Hans; Briedé, Jacob J.; van Faassen, Ernst E.; Lamers, Wouter H.; Buurman, Wim A.; Poeze, Martijn

2012-01-01

Background Impaired microcirculation during endotoxemia correlates with a disturbed arginine-nitric oxide (NO) metabolism and is associated with deteriorating organ function. Improving the organ perfusion in endotoxemia, as often seen in patients with severe infection or systemic inflammatory response syndrome (SIRS) is, therefore, an important therapeutic target. We hypothesized that supplementation of the arginine precursor citrulline rather than arginine would specifically increase eNOS-induced intracellular NO production and thereby improve the microcirculation during endotoxemia. Methodology/Principal Findings To study the effects of L-Citrulline and L-Arginine supplementation on jejunal microcirculation, intracellular arginine availability and NO production in a non-lethal prolonged endotoxemia model in mice. C57/Bl6 mice received an 18 hrs intravenous infusion of endotoxin (LPS, 0.4 µg•g bodyweight−1•h−1), combined with either L-Citrulline (6.25 mg•h-1), L-Arginine (6.25 mg•h−1), or L-Alanine (isonitrogenous control; 12.5 mg•h−1) during the last 6 hrs. The control group received an 18 hrs sterile saline infusion combined with L-Alanine or L-Citrulline during the last 6 hrs. The microcirculation was evaluated at the end of the infusion period using sidestream dark-field imaging of jejunal villi. Plasma and jejunal tissue amino-acid concentrations were measured by HPLC, NO tissue concentrations by electron-spin resonance spectroscopy and NOS protein concentrations using Western blot. Conclusion/Significance L-Citrulline supplementation during endotoxemia positively influenced the intestinal microvascular perfusion compared to L-Arginine-supplemented and control endotoxemic mice. L-Citrulline supplementation increased plasma and tissue concentrations of arginine and citrulline, and restored intracellular NO production in the intestine. L-Arginine supplementation did not increase the intracellular arginine availability. Jejunal tissues in the L-Citrulline-supplemented group showed, compared to the endotoxemic and L-Arginine-supplemented endotoxemic group, an increase in degree of phosphorylation of eNOS (Ser 1177) and a decrease in iNOS protein level. In conclusion, L-Citrulline supplementation during endotoxemia and not L-Arginine reduced intestinal microcirculatory dysfunction and increased intracellular NO production, likely via increased intracellular citrulline and arginine availability. PMID:22666356

Characteristics of Intratendinous Microcirculation Shortly After an Achilles Rupture and Subsequent Treatment Outcomes.

PubMed

Chang, Yi-Ping; Shih, Kao-Shang; Chiang, Hongsen; Ma, Hsiao-Li; Lin, Leou-Chyr; Peng, Wei-Chen; Wen, Che-Sheng; Wang, Hsing-Kuo

2017-01-01

Early microcirculatory responses after experimental tenotomy are critical to the healing of tendons and their ultimate tensile strength. The effects of changes in microcirculation on the outcomes of tendon healing, however, have not been determined. To assess microcirculation values in injured Achilles tendons in the first 3 months after surgical repair and to correlate the inter-limb microcirculatory changes with functional outcomes at 3 and 6 months after surgery. Case-control study. A university sports physiotherapy laboratory. Thirteen subjects (median age: 45 years; range: 34.8-51.9 years) with a repaired Achilles tendon were recruited. Surgical repair. Measurements were obtained at 1, 2, 3, and 6 months after surgery. Bilateral measurements of tendon microcirculation (total hemoglobin [THb] and oxygen saturation [StO 2 ]) were recorded at the first 3 time points, whereas outcome measures of a Taiwan Chinese version of the Victorian Institute of Sport Assessment Scale-Achilles questionnaire, one-leg hopping distance, the star excursion balance test, and the heel raise index were conducted at the third and fourth time points. Correlations between the inter-limb microcirculatory changes, eg, between the measurements at 2 months and 1 month (2-1) after surgery, at 3 months and 2 months (3-2) after surgery, and at 3 months and 1 month (3-1) after surgery, and the outcome measures were investigated. Compared with the noninjured tendons, the repaired Achilles demonstrated greater THb (at 1, 2, and 3 months; P = .017, .008, and .012 respectively) and StO 2 (at 3 months; P = .017). Furthermore, the THb2-1 and THb3-2, StO 2 2-1, and StO 2 3-2 showed correlations with the heel raise index, differences in the star excursion balance test and one-leg hopping distance between the noninjured leg and injured leg, and Taiwan Chinese version of the Victorian Institute of Sport Assessment Scale-Achilles questionnaire scores (rho -0.921 to 0.855). Changes in the inter-limb microcirculation shortly after Achilles repair were correlated with subsequent symptoms and functional symmetry. III. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Conjunctival microcirculatory blood flow is altered but not abolished in brain dead patients: a prospective observational study.

PubMed

Tamosuitis, Tomas; Pranskunas, Andrius; Balciuniene, Neringa; Pilvinis, Vidas; Boerma, E Christiaan

2016-07-11

The conjunctival microcirculation has potential as a window to cerebral perfusion due to related blood supply, close anatomical proximity and easy accessibility for microcirculatory imaging technique, such as sidestream dark field (SDF) imaging. Our study aims to evaluate conjunctival and sublingual microcirculation in brain dead patients and to compare it with healthy volunteers in two diametrically opposed conditions: full stop versus normal arterial blood supply to the brain. In a prospective observational study we analyzed conjunctival and sublingual microcirculation using SDF imaging in brain dead patients after reaching systemic hemodynamic targets to optimize perfusion of donor organs, and in healthy volunteers. All brain death diagnoses were confirmed by cerebral angiography. Microcirculatory images were obtained and analyzed using standardized published recommendations. Study registered at ClinicalTrials.gov, number NCT02483273. Eleven brain dead patients and eleven apparently healthy controls were enrolled in the study. Microvascular flow index (MFI) of small vessels was significantly lower in brain dead patients in comparison to healthy controls in ocular conjunctiva (2.7 [2.4-2.9] vs. 3.0 [2.9-3.0], p = 0.01) and in sublingual mucosa (2.8 [2.6-2.9] vs. 3.0 [2.9-3.0], p = 0.02). Total vessel density (TVD) and perfused vessel density (PVD) of small vessels were significantly lower in brain dead patients in comparison to healthy controls in ocular conjunctiva (10.2 [6.6-14.8] vs. 18.0 [18.0-25.4] mm/mm(2), p = 0.001 and 5.0 [3.5-7.3] vs. 10.9 [10.9-13.5] 1/mm, p = 0.001), but not in sublingual mucosa. In comparison to healthy controls brain dead patients had a significant reduction in conjunctival microvascular blood flow and density. However, the presence of conjunctival flow in case general cerebral flow is completely absent makes it impossible to use the conjunctival microcirculation as a substitute for brain flow, and further research should focus on the link between the ocular microcirculation, intracranial pressure and alternative ocular circulation.

Microcirculation and its relation to continuous subcutaneous glucose sensor accuracy in cardiac surgery patients in the intensive care unit.

PubMed

Siegelaar, Sarah E; Barwari, Temo; Hermanides, Jeroen; van der Voort, Peter H J; Hoekstra, Joost B L; DeVries, J Hans

2013-11-01

Continuous glucose monitoring could be helpful for glucose regulation in critically ill patients; however, its accuracy is uncertain and might be influenced by microcirculation. We investigated the microcirculation and its relation to the accuracy of 2 continuous glucose monitoring devices in patients after cardiac surgery. The present prospective, observational study included 60 patients admitted for cardiac surgery. Two continuous glucose monitoring devices (Guardian Real-Time and FreeStyle Navigator) were placed before surgery. The relative absolute deviation between continuous glucose monitoring and the arterial reference glucose was calculated to assess the accuracy. Microcirculation was measured using the microvascular flow index, perfused vessel density, and proportion of perfused vessels using sublingual sidestream dark-field imaging, and tissue oxygenation using near-infrared spectroscopy. The associations were assessed using a linear mixed-effects model for repeated measures. The median relative absolute deviation of the Navigator was 11% (interquartile range, 8%-16%) and of the Guardian was 14% (interquartile range, 11%-18%; P = .05). Tissue oxygenation significantly increased during the intensive care unit admission (maximum 91.2% [3.9] after 6 hours) and decreased thereafter, stabilizing after 20 hours. A decrease in perfused vessel density accompanied the increase in tissue oxygenation. Microcirculatory variables were not associated with sensor accuracy. A lower peripheral temperature (Navigator, b = -0.008, P = .003; Guardian, b = -0.006, P = .048), and for the Navigator, also a higher Acute Physiology and Chronic Health Evaluation IV predicted mortality (b = 0.017, P < .001) and age (b = 0.002, P = .037) were associated with decreased sensor accuracy. The results of the present study have shown acceptable accuracy for both sensors in patients after cardiac surgery. The microcirculation was impaired to a limited extent compared with that in patients with sepsis and healthy controls. This impairment was not related to sensor accuracy but the peripheral temperature for both sensors and patient age and Acute Physiology and Chronic Health Evaluation IV predicted mortality for the Navigator were. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Blood-filled cerebrospinal fluid-enhanced pericyte microvasculature contraction in rat retina: A novel in vitro study of subarachnoid hemorrhage

PubMed Central

Liu, Zhi; Li, Qiang; Cui, Gaoyu; Zhu, Gang; Tang, Weihua; Zhao, Hengli; Zhang, John H.; Chen, Yujie; Feng, Hua

2016-01-01

Previously, it was widely accepted that the delayed ischemic injury and poor clinical outcome following subarachnoid hemorrhage (SAH) was caused by cerebral vasospasm. This classical theory was challenged by a clazosentan clinical trial, which failed to improve patient outcome, despite reversing angiographic vasospasm. One possible explanation for the results of this trial is the changes in microcirculation following SAH, particularly in pericytes, which are the primary cell type controlling microcirculation in the brain parenchyma. However, as a result of technical limitations and the lack of suitable models, there was no direct evidence of microvessel dysfunction following SAH. In the present study, whole-mount retinal microvasculature has been introduced to study microcirculation in the brain following experimental SAH in vitro. Artificial blood-filled cerebrospinal fluid (BSCF) was applied to the retinal microvasculature to test the hypothesis that the presence of subarachnoid blood affects the contractile properties of the pericytes containing cerebral microcirculation during the early phase of SAH. It was observed that BCSF induced retina microvessel contraction and that this contraction could be resolved by BCSF wash-out. Furthermore, BCSF application accelerated pericyte-populated collagen gel contraction and increased the expression of α-smooth muscle actin. In addition, BCSF induced an influx of calcium in cultured retinal pericytes. In conclusion, the present study demonstrates increased contractility of retinal microvessels and pericytes in the presence of BCSF in vitro. These findings suggest that pericyte contraction and microvascular dysfunction is induced following SAH, which could lead to greater susceptibility to SAH-induced ischemia. PMID:27698742

Oxygen gradients in the microcirculation.

PubMed

Pittman, R N

2011-07-01

Early in the last century August Krogh embarked on a series of seminal studies to understand the connection between tissue metabolism and mechanisms by which the cardiovascular system supplied oxygen to meet those needs. Krogh recognized that oxygen was supplied from blood to the tissues by passive diffusion and that the most likely site for oxygen exchange was the capillary network. Studies of tissue oxygen consumption and diffusion coefficient, coupled with anatomical studies of capillarity in various tissues, led him to formulate a model of oxygen diffusion from a single capillary. Fifty years after the publication of this work, new methods were developed which allowed the direct measurement of oxygen in and around microvessels. These direct measurements have confirmed the predictions by Krogh and have led to extensions of his ideas resulting in our current understanding of oxygenation within the microcirculation. Developments during the last 40 years are reviewed, including studies of oxygen gradients in arterioles, capillaries, venules, microvessel wall and surrounding tissue. These measurements were made possible by the development and use of new methods to investigate oxygen in the microcirculation, so mention is made of oxygen microelectrodes, microspectrophotometry of haemoglobin and phosphorescence quenching microscopy. Our understanding of oxygen transport from the perspective of the microcirculation has gone from a consideration of oxygen gradients in capillaries and tissue to the realization that oxygen has the ability to diffuse from any microvessel to another location under the conditions that there exists a large enough PO(2) gradient and that the permeability for oxygen along the intervening pathway is sufficient. © 2011 The Author. Acta Physiologica © 2011 Scandinavian Physiological Society.

Micro- and Macrocirculatory Changes During Sepsis and Septic Shock in a Rat Model.

PubMed

Hua, Tianfeng; Wu, Xiaobo; Wang, Wei; Li, Hao; Bradley, Jennifer; Peberdy, Mary A; Ornato, Joseph P; Tang, Wanchun

2018-05-01

Microcirculation is the motor of sepsis. In the present study, we investigated whether microcirculatory alterations occur before changes of systemic hemodynamics in a rat model of cecum ligation and puncture (CLP)-induced sepsis. We further investigated renal microcirculatory changes during sepsis and compared those with buccal microcirculation. Twelve male Sprague-Dawley rats were randomized into a sham control group (n = 6) and a CLP group (n = 6). Perfused microvessel density (PVD) and microvascular flow index (MFI) were evaluated using sidestream dark field (SDF) video microscopy at baseline-60, 120, 180, 240, 300, and 360 min following CLP. A semiquantitative score was calculated for vessels of less than 20 μm, primarily representing the capillaries. Hemodynamic measurements such as cardiac output (CO), aortic pressure (AP), heart rate (HR), end-tidal CO2 (ETCO2), blood pH, and lactate were measured simultaneously. The serum cytokine interleukin 6 (IL-6) was measured at baseline-120, 240, and 360 min. In the CLP group, buccal PVD and MFI were reduced at 180 min (P < 0.05 vs. baseline); renal PVD and MFI were reduced at 180 min (P < 0.05 vs. baseline), but MAP and CO did not change until 300 min after CLP. In the rat model of peritonitis-induced sepsis, microcirculatory alterations of both peripheral mucosa and kidney occurred earlier than global hemodynamics. Monitoring the microcirculation may provide a means of early detection of circulatory failure during sepsis. The changes of renal microcirculation correlate with that of buccal during sepsis and septic shock.

Compliance with dietary guidelines affects capillary recruitment in healthy middle-aged men and women.

PubMed

Govoni, Virginia; Sanders, Thomas A B; Reidlinger, Dianne P; Darzi, Julia; Berry, Sarah E E; Goff, Louise M; Seed, Paul T; Chowienczyk, Philip J; Hall, Wendy L

2017-04-01

Healthy microcirculation is important to maintain the health of tissues and organs, most notably the heart, kidney and retina. Single components of the diet such as salt, lipids and polyphenols may influence microcirculation, but the effects of dietary patterns that are consistent with current dietary guidelines are uncertain. It was hypothesized that compliance to UK dietary guidelines would have a favourable effect on skin capillary density/recruitment compared with a traditional British diet (control diet). A 12-week randomized controlled trial in men and women aged 40-70 years was used to test whether skin microcirculation, measured by skin video-capillaroscopy on the dorsum of the finger, influenced functional capillary density (number of capillaries perfused under basal conditions), structural capillary density (number of anatomical capillaries perfused during finger cuff inflation) and capillary recruitment (percentage difference between structural and functional capillary density). Microvascular measures were available for 137 subjects out of the 165 participants randomized to treatment. There was evidence of compliance to the dietary intervention, and participants randomized to follow dietary guidelines showed significant falls in resting supine systolic, diastolic and mean arterial pressure of 3.5, 2.6 and 2.9 mmHg compared to the control diet. There was no evidence of differences in capillary density, but capillary recruitment was 3.5 % (95 % CI 0.2, 6.9) greater (P = 0.04) on dietary guidelines compared with control. Adherence to dietary guidelines may help maintain a healthy microcirculation in middle-aged men and women. This study is registered at www.isrctn.com as ISRCTN92382106.

Verification and calibration of laser Doppler flowmetry (LDF) prototype for measurement of microcirculation

NASA Astrophysics Data System (ADS)

Li, Yung-Hui; Hu, Chia-Ming; Tsai, Ming-Lun

2017-10-01

Laser Doppler Flowmetry (LDF), a non-invasive microcirculation measurement equipment, is designed to be used in measuring microcirculation and perfusion in the skin. LDF is very applicable to healthcare. However, the cost of commercial LDF prevents its prevalence and popularity. In this paper, continuing previous researches, a LDF prototype was built from the combination of the off-the-shelf electronic components. The raw signals acquired from the proposed LDF prototype is validated to be relevant to the microcirculation flux. Furthermore, we would like to verify the consistency between the signals measured from both model, and find an implicit transformation rule to transform the LDF prototype signals. For the purpose of verification and calibration of the LDF prototype signal feature, we first collected a parallel database consisting of flux signals measured by commercial and prototype LDF at the same time. Second, we extract signals with specific frequency of normalized signals as features and use these features to establish a model to allow us to map signals measured by LDF prototype to the commercial model. The result of the experiment showed that after we used the linear regression models to calibrate physiological feature, the correlation coefficient reached nearly 0.9999, which is close to a perfect positive correlation. The overall evaluation results showed that the proposed method can verify and ensure the validity of the LDF prototype. Through the proposed transformation, the flux signals measured by the proposed LDF prototype can successfully be transformed to its parallel form as if it is measured by commercial LDF.

Oxygen Gradients in the Microcirculation

PubMed Central

Pittman, Roland N.

2010-01-01

Early in the last century August Krogh embarked on a series of seminal studies to understand the connection between tissue metabolism and mechanisms by which the cardiovascular system supplied oxygen to meet those needs. Krogh recognized that oxygen was supplied from blood to the tissues by passive diffusion and that the most likely site for oxygen exchange was the capillary network. Studies of tissue oxygen consumption and diffusion coefficient, coupled with anatomical studies of capillarity in various tissues, led him to formulate a model of oxygen diffusion from a single capillary. Fifty years after the publication of this work, new methods were developed which allowed the direct measurement of oxygen in and around microvessels. These direct measurements have confirmed the predictions by Krogh and have led to extensions of his ideas resulting in our current understanding of oxygenation within the microcirculation. Developments during the last 40 years are reviewed, including studies of oxygen gradients in arterioles, capillaries, venules, microvessel wall and surrounding tissue. These measurements were made possible by the development and use of new methods to investigate oxygen in the microcirculation, so mention is made of oxygen microelectrodes, microspectrophotometry of haemoglobin and phosphorescence quenching microscopy. Our understanding of oxygen transport from the perspective of the microcirculation has gone from a consideration of oxygen gradients in capillaries and tissue to the realization that oxygen has the ability to diffuse from any microvessel to another location under the conditions that there exists a large enough PO2 gradient and that the permeability for oxygen along the intervening pathway is sufficient. PMID:21281453

Is there a stimulation of blood microcirculation at low level laser irradiation

NASA Astrophysics Data System (ADS)

Rogatkin, Dmitry; Dunaev, Andrey

2014-05-01

In 1980-2000 besides the laser surgery an intensive evolution of Low Level Laser Therapy (LLLT) had started in medicine, especially in Russia as well as in several other East-European countries. At the same time the biophysical mechanisms of LLLT are still the subject of disputes. One of the most popular clinical effects at Low Level Laser Irradiation (LLLI) being mentioned in medical publications for justification of the LLLT healing outcome is a stimulation of blood microcirculation in irradiated area. It was declared a priori at a dawn of LLLT and is now a basis of medical interpretation of healing mechanisms of LLLT at least in Russia. But in past 20 years a lot of investigation was carried out on optical registration of microhaemodynamic parameters in vivo as well as a number of noninvasive diagnostic tools was created for that. So, today it is possible to experimentally check the blood microcirculation stimulation hypothesis. Our study was aimed on that during the past 10 years. The most precision and accurate experiments we have carried out recently using simultaneously three different noninvasive diagnostic techniques: Laser Doppler Flowmetry, Tissue Reflectance Oximetry and Infrared Thermography. All these methods didn't confirm the effect on the blood microcirculation stimulation in skin or mucosa at irradiation with the power density below 50 mW/cm2 and irradiation time up to 5-6 minutes. Above this threshold the heating on 0,8…1 °C of tissue in the field of irradiation and the corresponding synchronous increase of all parameters of microhemodynamics were observed.

Choroidal microcirculation in patients with rotary cardiac assist device.

PubMed

Polska, Elzbieta; Schima, Heinrich; Wieselthaler, Georg; Schmetterer, Leopold

2007-06-01

In recent years, fully implanted rotary blood pumps have been used for long-term cardiac assist in patients with end-stage heart failure. With these pumps, the pulsatility of arterial blood flow and arterial pressure pulse is considerably reduced. Effects on end-organ perfusion, particularly microcirculation, have been assessed. The ocular choroid offers a unique opportunity to study the pulsatile component of blood flow by measurement of fundus pulsation amplitude (FPA) as well as the microcirculation by laser Doppler flowmetry. Both techniques were applied in three male patients with rotary pumps (MicroMed DeBakey VAD), in whom pump velocity was adjusted to four levels of flow between individual minimal need and maximal support. In addition, blood flow velocities in the ophthalmic artery (peak, end-diastolic and mean flow velocity--PSV, EDV and MFV, respectively) were measured using color Doppler imaging. Systolic blood pressure increased by 6 to 22 mm Hg with increasing support. At maximal support FPA was reduced by -60% to -52% as compared with minimal pump support. Blood flow in the choroidal microvasculature, however, did not show relevant changes. A reduction in PSV (-31%, range -47% to -21%) and a pronounced rise in EDV (+93%, range +28% to +147%) was observed, whereas MFV was independent of pump flow. Our data indicate that mean choroidal blood flow is maintained when pump support is varied within therapeutic values, whereas the ratio of pulsatile to non-pulsatile choroidal flow changes. This study shows that, in patients with ventricular assist devices, a normal perfusion rate in the ocular microcirculation is maintained over a wide range of support conditions.

Tracking neutrophil intraluminal crawling, transendothelial migration and chemotaxis in tissue by intravital video microscopy.

PubMed

Xu, Najia; Lei, Xi; Liu, Lixin

2011-09-24

The recruitment of circulating leukocytes from blood stream to the inflamed tissue is a crucial and complex process of inflammation(1,2). In the postcapillary venules of inflamed tissue, leukocytes initially tether and roll on the luminal surface of venular wall. Rolling leukocytes arrest on endothelium and undergo firm adhesion in response to chemokine or other chemoattractants on the venular surface. Many adherent leukocytes relocate from the initial site of adhesion to the junctional extravasation site in endothelium, a process termed intraluminal crawling(3). Following crawling, leukocytes move across endothelium (transmigration) and migrate in extravascular tissue toward the source of chemoattractant (chemotaxis)(4). Intravital microscopy is a powerful tool for visualizing leukocyte-endothelial cell interactions in vivo and revealing cellular and molecular mechanisms of leukocyte recruitment(2,5). In this report, we provide a comprehensive description of using brightfield intravital microscopy to visualize and determine the detailed processes of neutrophil recruitment in mouse cremaster muscle in response to the gradient of a neutrophil chemoattractant. To induce neutrophil recruitment, a small piece of agarose gel (~1-mm(3) size) containing neutrophil chemoattractant MIP-2 (CXCL2, a CXC chemokine) or WKYMVm (Trp-Lys-Tyr-Val-D-Met, a synthetic analog of bacterial peptide) is placed on the muscle tissue adjacent to the observed postcapillary venule. With time-lapsed video photography and computer software ImageJ, neutrophil intraluminal crawling on endothelium, neutrophil transendothelial migration and the migration and chemotaxis in tissue are visualized and tracked. This protocol allows reliable and quantitative analysis of many neutrophil recruitment parameters such as intraluminal crawling velocity, transmigration time, detachment time, migration velocity, chemotaxis velocity and chemotaxis index in tissue. We demonstrate that using this protocol, these neutrophil recruitment parameters can be stably determined and the single cell locomotion conveniently tracked in vivo.

Low-volume binary drug therapy for the treatment of hypovolemia.

PubMed

Bhattacharjee, Himanshu; Nadipuram, Asha; Kosanke, Stanley; Kiani, Mohammad F; Moore, Bob M

2011-06-01

The selective regulation of total peripheral circulation in hypovolemic crisis offers a unique approach for treating and preventing hemorrhagic shock. Ideally, such a therapeutic intervention would require targeting of the striated muscle vascular beds without altering the vascular resistance in vital organ vascular beds. We discovered that a combination of cannabinoid receptor agonist, THC (Δ-tetrahydrocannabinol), and cyclooxygenase 2 inhibitor, NS-398, caused selective microvascular constriction in the mouse cremaster muscle manifested by a pronounced and significant 27.4% ± 7.9% decrease in vessel diameter relative to control (P < 0.01). This observation, and the reported lack of microvascular response in the mesentery and brain, led us to hypothesize that the drug combination could favorably redistribute blood volume in hypovolemia and prolong survival. To test the hypothesis, male Sprague-Dawley rats were subjected to a pressure-controlled hemorrhage (mean arterial pressure reduced to 30 ± 13.73 mmHg) then randomly assigned to one of six treatment groups (n = 6 per group). The untreated, NS-398-treated, and THC-treated groups manifested an insignificant difference in survival between groups after shock. The group treated with a combination of THC and NS-398 manifested a significant increase in mean survival from 53 ± 12 to 227 ± 23 min after shock (P < 0.001). The drug combination significantly reduced IL-1α, IL-1β, IFN-γ, and IL-10 production compared with the group resuscitated with normal saline. In addition, histological evaluation indicated that the therapy protects the lungs and liver against hemorrhagic shock-induced damage. The combination of cannabinoid receptor agonist and cyclooxygenase 2 inhibitor represents a potentially new approach to low-volume therapeutic intervention for hypovolemia.

Interleukin-35 Inhibits Endothelial Cell Activation by Suppressing MAPK-AP-1 Pathway.

PubMed

Sha, Xiaojin; Meng, Shu; Li, Xinyuan; Xi, Hang; Maddaloni, Massimo; Pascual, David W; Shan, Huimin; Jiang, Xiaohua; Wang, Hong; Yang, Xiao-feng

2015-07-31

Vascular response is an essential pathological mechanism underlying various inflammatory diseases. This study determines whether IL-35, a novel responsive anti-inflammatory cytokine, inhibits vascular response in acute inflammation. Using a mouse model of LPS-induced acute inflammation and plasma samples from sepsis patients, we found that IL-35 was induced in the plasma of mice after LPS injection as well as in the plasma of sepsis patients. In addition, IL-35 decreased LPS-induced proinflammatory cytokines and chemokines in the plasma of mice. Furthermore, IL-35 inhibited leukocyte adhesion to the endothelium in the vessels of lung and cremaster muscle and decreased the numbers of inflammatory cells in bronchoalveolar lavage fluid. Mechanistically, IL-35 inhibited the LPS-induced up-regulation of endothelial cell (EC) adhesion molecule VCAM-1 through IL-35 receptors gp130 and IL-12Rβ2 via inhibition of the MAPK-activator protein-1 (AP-1) signaling pathway. We also found that IL-27, which shares the EBI3 subunit with IL-35, promoted LPS-induced VCAM-1 in human aortic ECs and that EBI3-deficient mice had similar vascular response to LPS when compared with that of WT mice. These results demonstrated for the first time that inflammation-induced IL-35 inhibits LPS-induced EC activation by suppressing MAPK-AP1-mediated VCAM-1 expression and attenuates LPS-induced secretion of proinflammatory cytokines/chemokines. Our results provide insight into the control of vascular inflammation by IL-35 and suggest that IL-35 is an attractive novel therapeutic reagent for sepsis and cardiovascular diseases. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

S-nitrosation of β-catenin and p120 catenin: a novel regulatory mechanism in endothelial hyperpermeability

PubMed Central

Marín, N.; Zamorano, P.; Carrasco, R.; Mujica, P.; González, FG.; Quezada, C.; Meininger, CJ.; Boric, MP.; Durán, WN.; Sánchez, FA.

2014-01-01

Rationale Endothelial adherens junction proteins constitute an important element in the control of microvascular permeability. Platelet-activating factor (PAF) increases permeability to macromolecules via translocation of eNOS to cytosol and stimulation of eNOS-derived NO signaling cascade. The mechanisms by which NO signaling regulates permeability at adherens junctions are still incompletely understood. Objective We explored the hypothesis that PAF stimulates hyperpermeability via S-nitrosation (SNO) of adherens junction proteins. Methods and Results We measured PAF-stimulated S-nitrosation of β-catenin and p120-catenin (p120) in three cell lines: ECV-eNOSGFP, EAhy926 (derived from human umbilical vein) and CVEC (derived from bovine heart endothelium) and in the mouse cremaster muscle in vivo. SNO correlated with diminished abundance of β-catenin and p120 at the adherens junction and with hyperpermeability. TNF-α increased NO production and caused similar increase in S-nitrosation as PAF. To ascertain the importance of eNOS subcellular location in this process, we used ECV-304 cells transfected with cytosolic eNOS (GFPeNOSG2A) and plasma membrane eNOS (GFPeNOSCAAX). PAF induced S-nitrosation of β-catenin and p120 and significantly diminished association between these proteins in cells with cytosolic eNOS but not in cells wherein eNOS is anchored to the cell membrane. Inhibitors of NO production and of S-nitrosation blocked PAF-induced S-nitrosation and hyperpermeability whereas inhibition of the cGMP pathway had no effect. Mass spectrometry analysis of purified p120 identified cysteine 579 as the main S-nitrosated residue in the region that putatively interacts with VE-cadherin. Conclusions Our results demonstrate that agonist-induced SNO contributes to junctional membrane protein changes that enhance endothelial permeability. PMID:22777005

A systems approach to hemostasis: 4. How hemostatic thrombi limit the loss of plasma-borne molecules from the microvasculature

PubMed Central

Welsh, John D.; Muthard, Ryan W.; Stalker, Timothy J.; Taliaferro, Joshua P.; Diamond, Scott L.

2016-01-01

Previous studies have shown that hemostatic thrombi formed in response to penetrating injuries have a core of densely packed, fibrin-associated platelets overlaid by a shell of less-activated, loosely packed platelets. Here we asked, first, how the diverse elements of this structure combine to stem the loss of plasma-borne molecules and, second, whether antiplatelet agents and anticoagulants that perturb thrombus structure affect the re-establishment of a tight vascular seal. The studies combined high-resolution intravital microscopy with a photo-activatable fluorescent albumin marker to simultaneously track thrombus formation and protein transport following injuries to mouse cremaster muscle venules. The results show that protein loss persists after red cell loss has ceased. Blocking platelet deposition with an αIIbβ3 antagonist delays vessel sealing and increases extravascular protein accumulation, as does either inhibiting adenosine 5′-diphosphate (ADP) P2Y12 receptors or reducing integrin-dependent signaling and retraction. In contrast, sealing was unaffected by introducing hirudin to block fibrin accumulation or a Gi2α gain-of-function mutation to expand the thrombus shell. Collectively, these observations describe a novel approach for studying vessel sealing after injury in real time in vivo and show that (1) the core/shell architecture previously observed in arterioles also occurs in venules, (2) plasma leakage persists well beyond red cell escape and mature thrombus formation, (3) the most critical events for limiting plasma extravasation are the stable accumulation of platelets, ADP-dependent signaling, and the emergence of a densely packed core, not the accumulation of fibrin, and (4) drugs that affect platelet accumulation and packing can delay vessel sealing, permitting protein escape to continue. PMID:26738537

A novel approach to prevent endothelial hyperpermeability: the Crataegus extract WS® 1442 targets the cAMP/Rap1 pathway.

PubMed

Bubik, Martin F; Willer, Elisabeth A; Bihari, Peter; Jürgenliemk, Guido; Ammer, Hermann; Krombach, Fritz; Zahler, Stefan; Vollmar, Angelika M; Fürst, Robert

2012-01-01

Endothelial hyperpermeability followed by edema formation is a hallmark of many severe disorders. Effective drugs directly targeting endothelial barrier function are widely lacking. We hypothesized that the hawthorn (Crataegus spp.) extract WS® 1442, a proven multi-component drug against moderate forms of heart failure, would prevent vascular leakage by affecting endothelial barrier-regulating systems. In vivo, WS® 1442 inhibited the histamine-evoked extravasation of FITC-dextran from mouse cremaster muscle venules. In cultured human endothelial cells, WS® 1442 blocked the thrombin-induced FITC-dextran permeability. By applying biochemical and microscopic techniques, we revealed that WS® 1442 abrogates detrimental effects of thrombin on adherens junctions (vascular endothelial-cadherin), the F-actin cytoskeleton, and the contractile apparatus (myosin light chain). Mechanistically, WS® 1442 inhibited the thrombin-induced rise of intracellular calcium (ratiometric measurement), followed by an inactivation of PKC and RhoA (pulldown assay). Moreover, WS® 1442 increased endothelial cAMP levels (ELISA), which consequently activated PKA and Rap1 (pulldown assay). Utilizing pharmacological inhibitors or siRNA, we found that PKA is not involved in barrier protection, whereas Epac1, Rap1, and Rac1 play a crucial role in the WS® 1442-induced activation of cortactin, which triggers a strong cortical actin rearrangement. In summary, WS® 1442 effectively protects against endothelial barrier dysfunction in vitro and in vivo. It specifically interacts with endothelial permeability-regulating systems by blocking the Ca(2+)/PKC/RhoA and activating the cAMP/Epac1/Rap1 pathway. As a proven safe herbal drug, WS® 1442 opens a novel pharmacological approach to treat hyperpermeability-associated diseases. This in-depth mechanistic work contributes to a better acceptance of this herbal remedy. Copyright © 2011 Elsevier Ltd. All rights reserved.

ARQ 092, an orally-available, selective AKT inhibitor, attenuates neutrophil-platelet interactions in sickle cell disease

PubMed Central

Kim, Kyungho; Li, Jing; Barazia, Andrew; Tseng, Alan; Youn, Seock-Won; Abbadessa, Giovanni; Yu, Yi; Schwartz, Brian; Andrews, Robert K.; Gordeuk, Victor R.; Cho, Jaehyung

2017-01-01

Previous studies identified the Ser/Thr protein kinase, AKT, as a therapeutic target in thrombo-inflammatory diseases. Here we report that specific inhibition of AKT with ARQ 092, an orally-available AKT inhibitor currently in phase Ib clinical trials as an anti-cancer drug, attenuates the adhesive function of neutrophils and platelets from sickle cell disease patients in vitro and cell-cell interactions in a mouse model of sickle cell disease. Studies using neutrophils and platelets isolated from sickle cell disease patients revealed that treatment with 50–500 nM ARQ 092 significantly blocks αMβ2 integrin function in neutrophils and reduces P-selectin exposure and glycoprotein Ib/IX/V-mediated agglutination in platelets. Treatment of isolated platelets and neutrophils with ARQ 092 inhibited heterotypic cell-cell aggregation under shear conditions. Intravital microscopic studies demonstrated that short-term oral administration of ARQ 092 or hydroxyurea, a major therapy for sickle cell disease, diminishes heterotypic cell-cell interactions in venules of sickle cell disease mice challenged with tumor necrosis factor-α. Co-administration of hydroxyurea and ARQ 092 further reduced the adhesive function of neutrophils in venules and neutrophil transmigration into alveoli, inhibited expression of E-selectin and intercellular adhesion molecule-1 in cremaster vessels, and improved survival in these mice. Ex vivo studies in sickle cell disease mice suggested that co-administration of hydroxyurea and ARQ 092 efficiently blocks neutrophil and platelet activation and that the beneficial effect of hydroxyurea results from nitric oxide production. Our results provide important evidence that ARQ 092 could be a novel drug for the prevention and treatment of acute vaso-occlusive complications in patients with sickle cell disease. PMID:27758820

Angiotensin II-mediated microvascular thrombosis

PubMed Central

Senchenkova, Elena Y.; Russell, Janice; Almeida-Paula, Lidiana D.; Harding, Joseph W.; Granger, D. Neil

2010-01-01

Hypertension is associated with an increased risk of thrombosis that appears to involve an interaction between the renin-angiotensin system and hemostasis. In this study we determined whether angiotensin II-mediatedthrombosis occurs in arterioles and/or venules, and assessed the involvement of type-1 (AT1), type-2 (AT2) and type 4 (AT4) angiotensin II receptors, as well as receptors for endothelin-1 (ET-1) and bradykinin (BK-1, BK-2) in angiotensin II-enhanced microvascular thrombosis. Thrombus development in mouse cremaster microvessels was quantified after light/dye injury using the time of onset of the thrombus and time to blood flow cessation. Wild type and AT1-receptor deficient mice were implanted with an angiotensin II-loaded Alzet pump for 2 wks. Angiotensin II administration in both wild type and AT1-receptor deficient mice significantly accelerated thrombosis in arterioles. Genetic deficiency and pharmacological antagonism of AT1-receptors did not alter the thrombosis response to angiotensin II. Isolated murine platelets aggregated in response to low (pM), but not high (nM), concentrations of angiotensin II. The platelet aggregation response to angiotensin II was dependent on AT1-receptors. Antagonism of AT2-receptors in vivo significantly prolonged the onset of angiotensin II enhanced thrombosis, while an AT4-receptor antagonist prolonged the time to flow cessation. Selective antagonism of either ET-1 or BK-1 receptors largely prevented both the onset and flow cessation responses to chronic angiotensin II infusion. Our findings indicate that angiotensin II-induced hypertension is accompanied by enhanced thrombosis in arterioles and this response is mediated by a mechanism that involves AT2, AT4, BK-1 and ET-1 receptor-mediated signaling. PMID:20975035

Capillary pericytes express α-smooth muscle actin, which requires prevention of filamentous-actin depolymerization for detection.

PubMed

Alarcon-Martinez, Luis; Yilmaz-Ozcan, Sinem; Yemisci, Muge; Schallek, Jesse; Kılıç, Kıvılcım; Can, Alp; Di Polo, Adriana; Dalkara, Turgay

2018-03-21

Recent evidence suggests that capillary pericytes are contractile and play a crucial role in the regulation of microcirculation. However, failure to detect components of the contractile apparatus in capillary pericytes, most notably α-smooth muscle actin (α-SMA), has questioned these findings. Using strategies that allow rapid filamentous-actin (F-actin) fixation (i.e. snap freeze fixation with methanol at -20°C) or prevent F-actin depolymerization (i.e. with F-actin stabilizing agents), we demonstrate that pericytes on mouse retinal capillaries, including those in intermediate and deeper plexus, express α-SMA. Junctional pericytes were more frequently α-SMA-positive relative to pericytes on linear capillary segments. Intravitreal administration of short interfering RNA (α-SMA-siRNA) suppressed α-SMA expression preferentially in high order branch capillary pericytes, confirming the existence of a smaller pool of α-SMA in distal capillary pericytes that is quickly lost by depolymerization. We conclude that capillary pericytes do express α-SMA, which rapidly depolymerizes during tissue fixation thus evading detection by immunolabeling. © 2018, Alarcon-Martinez et al.

Processing of CXCL12 impedes the recruitment of endothelial progenitor cells in diabetic wound healing.

PubMed

Feng, Guang; Hao, Daifeng; Chai, Jiake

2014-11-01

High blood sugar levels result in defective wound healing processes in diabetic patients. Endothelial progenitor cells (EPCs) play an important role in vasculogenesis, and thereby contribute to reconstitution of the microcirculation and healing. This study aimed to determine the possible mechanism by which the numbers of circulating EPCs are regulated in response to tissue wounding. In the streptozotocin-induced diabetic mouse model, we found that phagocytes activated by local inflammatory cytokines in the wound interfere with the mobilization and recruitment of EPCs to the lesion area. Specifically, the activated macrophages inactivate CXCL12, the major chemokine for EPC recruitment, via matrix metalloproteinases (MMPs), and thereby prevent local chemotaxis and subsequent homing of EPCs to the wound. The wound healing process is delayed by local administration of inflammatory cytokines, and its rate is increased by MMP inhibitors. This study indicates that local inhibition of MMPs is beneficial for regeneration of damaged vessels, and may explain poor wound healing in diabetic patients, thus demonstrating its potential utility as a local treatment therapy to promote diabetic wound healing. © 2014 FEBS.

Robust optimal design of diffusion-weighted magnetic resonance experiments for skin microcirculation

NASA Astrophysics Data System (ADS)

Choi, J.; Raguin, L. G.

2010-10-01

Skin microcirculation plays an important role in several diseases including chronic venous insufficiency and diabetes. Magnetic resonance (MR) has the potential to provide quantitative information and a better penetration depth compared with other non-invasive methods such as laser Doppler flowmetry or optical coherence tomography. The continuous progress in hardware resulting in higher sensitivity must be coupled with advances in data acquisition schemes. In this article, we first introduce a physical model for quantifying skin microcirculation using diffusion-weighted MR (DWMR) based on an effective dispersion model for skin leading to a q-space model of the DWMR complex signal, and then design the corresponding robust optimal experiments. The resulting robust optimal DWMR protocols improve the worst-case quality of parameter estimates using nonlinear least squares optimization by exploiting available a priori knowledge of model parameters. Hence, our approach optimizes the gradient strengths and directions used in DWMR experiments to robustly minimize the size of the parameter estimation error with respect to model parameter uncertainty. Numerical evaluations are presented to demonstrate the effectiveness of our approach as compared to conventional DWMR protocols.

Evaluation of three inverse problem models to quantify skin microcirculation using diffusion-weighted MRI

NASA Astrophysics Data System (ADS)

Cordier, G.; Choi, J.; Raguin, L. G.

2008-11-01

Skin microcirculation plays an important role in diseases such as chronic venous insufficiency and diabetes. Magnetic resonance imaging (MRI) can provide quantitative information with a better penetration depth than other noninvasive methods, such as laser Doppler flowmetry or optical coherence tomography. Moreover, successful MRI skin studies have recently been reported. In this article, we investigate three potential inverse models to quantify skin microcirculation using diffusion-weighted MRI (DWI), also known as q-space MRI. The model parameters are estimated based on nonlinear least-squares (NLS). For each of the three models, an optimal DWI sampling scheme is proposed based on D-optimality in order to minimize the size of the confidence region of the NLS estimates and thus the effect of the experimental noise inherent to DWI. The resulting covariance matrices of the NLS estimates are predicted by asymptotic normality and compared to the ones computed by Monte-Carlo simulations. Our numerical results demonstrate the effectiveness of the proposed models and corresponding DWI sampling schemes as compared to conventional approaches.

Evaluation of gingival vascularisation using laser Doppler flowmetry

NASA Astrophysics Data System (ADS)

Vitez, B.; Todea, C.; Velescu, A.; Şipoş, C.

2016-03-01

Aim: The present study aims to assess the level of vascularisation of the lower frontal gingiva of smoker patients, in comparison with non-smokers by using Laser Doppler Flowmetry (LDF), in order to determine the changes in gingival microcirculation. Material & methods: 16 volunteers were included in this study and separated into 2 equal groups: non-smoker subjects in Group I and smoker subjects in Group II. All patients were submitted to a visual examination and professional cleaning The gingival bloodflow of each patient was recorded in 5 zones using LDF, resulting in a total of 80 recordings. LDF was done with the Moor Instruments Ltd. "moorLAB" Laser Doppler. All data were collected as graphs, raw values and statistically analyzed. Results: After strict analysis results show that Group II presents a steady level of gingival microcirculation with even patterns in the graph, while Group I shows many signs of damage to it`s microvascular system through many irregularities in the microcirculation level and graph patterns. Conclusion: The results suggest that prolonged smoking has a definitive effect on the gingival vascularisation making it a key factor in periodontal pathology.

High-Efficiency Multiscale Modeling of Cell Deformations in Confined Microenvironments in Microcirculation and Microfluidic Devices

NASA Astrophysics Data System (ADS)

Lu, Huijie; Peng, Zhangli

2017-11-01

Our goal is to develop a high-efficiency multiscale modeling method to predict the stress and deformation of cells during the interactions with their microenvironments in microcirculation and microfluidic devices, including red blood cells (RBCs) and circulating tumor cells (CTCs). There are more than 1 billion people in the world suffering from RBC diseases, e.g. anemia, sickle cell diseases, and malaria. The mechanical properties of RBCs are changed in these diseases due to molecular structure alternations, which is not only important for understanding the disease pathology but also provides an opportunity for diagnostics. On the other hand, the mechanical properties of cancer cells are also altered compared to healthy cells. This can lead to acquired ability to cross the narrow capillary networks and endothelial gaps, which is crucial for metastasis, the leading cause of cancer mortality. Therefore, it is important to predict the deformation and stress of RBCs and CTCs in microcirculations. We are developing a high-efficiency multiscale model of cell-fluid interaction to study these two topics.

Wavelet-analysis of gastric microcirculation in rats with ulcer bleedings

NASA Astrophysics Data System (ADS)

Pavlov, A. N.; Semyachkina-Glushkovskaya, O. V.; Pavlova, O. N.; Bibikova, O. A.; Kurths, J.

2013-10-01

Nitric oxide (NO) plays an important role in regulation of central and peripheral circulation in normal state and during hemorrhagic stress. Because the impaired gastric mucosal blood flow is the major cause of gastroduodenal lesions including ulcer bleeding (UB), we study in this work the NO-ergic mechanism responsible for regulation of this blood flow. Our study is performed in rats with a model of stress-induced UB using laser Doppler flowmetry (LDF) that characterizes the rate of blood flow by measuring a Doppler shift of the laser beam scattered by the moving red blood cells. Numerical analysis of LDF-data is based on the discrete wavelet-transform (DWT) using Daubechies wavelets aiming to quantify influences of NO on the gastric microcirculation. We show that the stress-induced UB is associated with an increased level of NO in the gastric tissue and a stronger vascular sensitivity to pharmacological modulation of NO-production by L-NAME. We demonstrate that wavelet-based analyses of NO-dependent regulation of gastric microcirculation can provide an effective endoscopic diagnostics of a risk of UB.

Parameters of Microcirculation in the Broad Ligament of the Uterus in Wistar Rats after Injection of Autologous Biomedical Cell Product.

PubMed

Dergacheva, T I; Lykov, A P; Shurlygina, A V; Starkova, E V; Poveshchenko, O V; Bondarenko, N A; Kim, I I; Tenditnik, M V; Borodin, Yu I; Konenkov, V I

2015-10-01

We studied the effects of autologous biomedical cell product (bone marrow multipotent mesenchymal stromal cells and their conditioned media) on the parameters of the microcirculatory bed in the broad ligament of the uterus of normal Wistar rats were studied. The parameters of microcirculation and lymph drainage in the broad ligament changed in opposite directions in response to injection of autologous biomedical cell product via different routes. This fact should be taken into consideration when prescribing cell therapy for inflammatory degenerative processes in the pelvic organs.

Impaired cerebral microcirculation induced by ammonium chloride in rats is due to cortical adenosine release.

PubMed

Bjerring, Peter Nissen; Bjerrum, Esben Jannik; Larsen, Fin Stolze

2018-06-01

Liver failure results in hyperammonaemia, impaired regulation of cerebral microcirculation, encephalopathy, and death. However, the key mediator that alters cerebral microcirculation remains unidentified. In this study we show that topically applied ammonium significantly increases periarteriolar adenosine tone on the brain surface of healthy rats and is associated with a disturbed microcirculation. Cranial windows were prepared in anaesthetized Wistar rats. The flow velocities were measured by speckle contrast imaging and compared before and after 30 min of exposure to 10 mM ammonium chloride applied on the brain surface. These flow velocities were compared with those for control groups exposed to artificial cerebrospinal fluid or ammonium plus an adenosine receptor antagonist. A flow preservation curve was obtained by analysis of flow responses to a haemorrhagic hypotensive challenge and during stepwise exsanguination. The periarteriolar adenosine concentration was measured with enzymatic biosensors inserted in the cortex. After ammonium exposure the arteriolar flow velocity increased by a median (interquartile range) of 21.7% (23.4%) vs. 7.2% (10.2%) in controls (n = 10 and n = 6, respectively, p <0.05), and the arteriolar surface area increased. There was a profound rise in the periarteriolar adenosine concentration. During the hypotensive challenge the flow decreased by 27.8% (14.9%) vs. 9.2% (14.9%) in controls (p <0.05). The lower limit of flow preservation remained unaffected, 27.7 (3.9) mmHg vs. 27.6 (6.4) mmHg, whereas the autoregulatory index increased, 0.29 (0.33) flow units per millimetre of mercury vs. 0.03 (0.21) flow units per millimetre of mercury (p <0.05). When ammonium exposure was combined with topical application of an adenosine receptor antagonist, the autoregulatory index was normalized. Vasodilation of the cerebral microcirculation during exposure to ammonium chloride is associated with an increase in the adenosine tone. Application of a specific adenosine receptor antagonist restores the regulation of the microcirculation. This indicates that adenosine could be a key mediator of the brain dysfunction seen during hyperammonaemia and is a potential therapeutic target. In patients with liver failure, disturbances in brain function are caused in part by ammonium toxicity. In our project we studied how ammonia, through adenosine release, affects the blood flow in the brain of rats. In our experimental model we demonstrated that the detrimental effect of ammonia on blood flow regulation was counteracted by blocking the adenosine receptors in the brain. With this observation we identified a novel potential treatment target. If we can confirm our findings in a future clinical study, this might help patients with liver failure and the severe condition called hepatic encephalopathy. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Noninvasive Imaging of Retinal Morphology and Microvasculature in Obese Mice Using Optical Coherence Tomography and Optical Microangiography

PubMed Central

Zhi, Zhongwei; Chao, Jennifer R.; Wietecha, Tomasz; Hudkins, Kelly L.; Alpers, Charles E.; Wang, Ruikang K.

2014-01-01

Purpose. To evaluate early diabetes-induced changes in retinal thickness and microvasculature in a type 2 diabetic mouse model by using optical coherence tomography (OCT)/optical microangiography (OMAG). Methods. Twenty-two-week-old obese (OB) BTBR mice (n = 10) and wild-type (WT) control mice (n = 10) were imaged. Three-dimensional (3D) data volumes were captured with spectral domain OCT using an ultrahigh-sensitive OMAG scanning protocol for 3D volumetric angiography of the retina and dense A-scan protocol for measurement of the total retinal blood flow (RBF) rate. The thicknesses of the nerve fiber layer (NFL) and that of the NFL to the inner plexiform layer (IPL) were measured and compared between OB and WT mice. The linear capillary densities within intermediate and deep capillary layers were determined by the number of capillaries crossing a 500-μm line. The RBF rate was evaluated using an en face Doppler approach. These quantitative measurements were compared between OB and WT mice. Results. The retinal thickness of the NFL to IPL was significantly reduced in OB mice (P < 0.01) compared to that in WT mice, whereas the NFL thickness between the two was unchanged. 3D depth-resolved OMAG angiography revealed the first in vivo 3D model of mouse retinal microcirculation. Although no obvious differences in capillary vessel densities of the intermediate and deep capillary layers were detected between normal and OB mice, the total RBF rate was significantly lower (P < 0.05) in OB mice than in WT mice. Conclusions. We conclude that OB BTBR mice have significantly reduced NFL–IPL thicknesses and total RBF rates compared with those of WT mice, as imaged by OCT/OMAG. OMAG provides an unprecedented capability for high-resolution depth-resolved imaging of mouse retinal vessels and blood flow that may play a pivotal role in providing a noninvasive method for detecting early microvascular changes in patients with diabetic retinopathy. PMID:24458155

Development and Application of Multifunctional Optical Coherence Tomography

NASA Astrophysics Data System (ADS)

Zhi, Zhongwei

Microcirculation refers to the functions of capillaries and the neighboring lymphatic vessels. It plays a vital role in the pathophysiology of disorders in many clinical areas including cardiology, dermatology, neurology and ophthalmology, and so forth. It is crucial to develop imaging technologies that can provide both qualitative and quantitative information as to how microcirculation responds to certain injury and/or disease, and its treatment. Optical coherence tomography (OCT) is a non-invasive optical imaging technique for high-resolution cross-sectional imaging of specimens, with many applications in clinical medicine. Current state-of-the-art OCT systems operate in the Fourier domain, using either a broadband light source with a spectrometer, known as spectral domain OCT (SDOCT), or a rapidly tunable laser, known as swept source OCT (SSOCT). The current Fourier domain OCT systems have dramatically improvement in sensitivity, resolution and speed compared to time domain OCT. In addition to the improvement in the OCT system hardware, different methods for functional measurements of tissue beds have been developed and demonstrated. This includes but not limited to, i) Phase-resolved Doppler OCT for quantifying the blood flow, ii) OCT angiography for visualization of microvasculature, iii) Polarization sensitive OCT for measuring the intrinsic optical property/ birefringence of tissue, iv) spectroscopic OCT for measuring blood oxygenation, etc. Functional OCT can provide important clinical information that is not available in the typical intensity based structural OCT images. Among these functional OCT modalities, Doppler OCT and OCT angiography attract great interests as they show high capability for in vivo study of microvascular pathology. By analyzing the Doppler effect of a flowing particle on light frequency, Doppler OCT allows the quantification of the blood flow speed and blood flow rate. The most popular approach for Doppler OCT is achieved through analysis of the phase term in complex OCT signal which termed as Phase-resolved Doppler OCT. However, as limited by the phase noise and motion, Phase-resolved Doppler OCT can only be applied for relative large blood vessels, such as arterioles and venules. On the other hand, in order to visualize the microcirculation network, a number of strategies to enable better contrast of microvasculature components, which we termed OCT angiography, have been introduced during recent years. As a variation of Fourier domain OCT, optical microangiography (OMAG) is one of earliest proposed OCT angiography technique which is capable of generating 3D images of dynamic blood perfusion distribution within microcirculatory tissue beds. The OMAG algorithm works by separating the static and moving elements by high pass filtering on complex valued interferometric data after Fourier transform. Based on the conventional OMAG algorithm, we further developed ultra-high sensitive OMAG (UHS-OMAG) by switching the high-pass filtering from fast scan direction (adjacent A-lines within one B-frame) to slow scan direction (adjacent B-frames), which has a dramatically improved performance for capillary network imaging and analysis. Apart from the microvascular study with current available functional OCT for, visualization of the lymphatic system (lymph nodes and lymphatic vessels) plays a significant role in assessing patients with various malignancies and lymphedema. However, there is a lack of label-free and noninvasive method for lymphangiography. Hence, a cutting edge research to investigate the capability of OCT as a tool for non-invasive and label-free lymphangiography would be highly desired. The objective of my thesis is to develop a multiple-functional SDOCT system to image the microcirculation and quantify the several important parameters of microcirculation within microcirculatory tissue beds, and further apply it for pre-clinical research applications. The multifunctional OCT system provides modalities including structural OCT, OCT angiography, Doppler OCT and Optical lymphangiography, for multi-parametric study of tissue microstructure, blood vessel morphology, blood flow and lymphatic vessel all together. The thesis mainly focus on two parts: first, development of multi-functional OCT/optical microangiography (OMAG) system and methods for volumetric imaging of microvasculature and quantitative measurement of blood flow, and its application for pathological research in ophthalmology on rodent eye models; second, development of ultra-high resolution OCT system and algorithm for simultaneous label free imaging of blood and lymphatic vessel, and its application in wound healing study on mouse ear flap model. Objectives of my research are achieved through the following specific aims: Aim 1: Improve the sensitivity of OMAG for microvasculature imaging; perform volumetric and quantitative imaging of vasculature with combined OMAG and Phase-resolved Doppler OCT for in vivo study of vascular physiology. Aim 2: Develop high speed high resolution OCT system and method for rodent eye imaging. Apply the combined OMAG and Phase-resolved Doppler OCT approach to investigate the impact of elevated intraocular pressure on retinal, choroidal and optic nerve head blood flow in rat eye model, which aids to the better understanding of the mechanism and development of glaucoma. Aim 3: Apply the developed OCT system and ultra-high sensitive OMAG algorithm for noninvasive imaging of retinal morphology and microvasculature in obese mice, which may play an important role in early diagnosis of Diabetic retinopathy. Aim 4: Developing an ultra-high resolution SDOCT system using broadband Supercontinuum light source to achieve ultra-high resolution microvasculature imaging of biological tissue. Aim 5: Develop methods for simultaneous label free optical imaging of blood and lymphatic vessel and demonstrate its capability by monitoring the blood and lymph response to wound healing on mouse ear pinna model.

Effect of different dialyzer membranes on cutaneous microcirculation during hemodialysis.

PubMed

Sato, M; Morita, H; Ema, H; Yamaguchi, S; Amano, I

2006-12-01

Biocompatibility profiles of synthetic membranes may vary. In this prospective crossover study, we examined the effect of various membranes on cutaneous microcirculation during HD. 11 HD patients without cardiovascular complications were enrolled in this study. They were dialyzed using three types of membrane in a randomized order: ethylene-vinyl alcohol copolymer (EVAL), vitamin E-bonded cellulose (VE-C) and polysulfone (PS). The transcutaneous oxygen tension (TcPO2) was examined on the dorsum of foot to assess the cutaneous microcirculation. Serum biochemical parameters were also measured. The TcPO2 as a percentage of the predialysis level decreased from the beginning of HD, and significant differences were observed after 15 min of HD between EVAL and the other 2 membranes (98 +/- 6% (mean +/- SD) for EVAL versus 89 +/- 7% for VE-C (p < 0.01) and 88 +/- 10% for PS (p < 0.01)). Furthermore, there were significant differences at 30 and 60 min between EVAL and PS (30 min: 93 +/- 9% for EVAL versus 85 +/- 7% for PS (p < 0.05); 60 min: 92 +/- 10% for EVAL versus 79 +/- 10% for PS (p < 0.01)). The serum level of thiobarbituric acid reactants (TBARs), a marker of lipid peroxidation, increased significantly at the end of HD relative to that at the beginning of HD when using a PS membrane (from 1.9 +/- 0.5 to 2.1 +/- 0.5 nmol/ml, p < 0.05). Our results indicate that an EVAL membrane is superior to PS and VE-C membranes in terms of its smaller influence on cutaneous microcirculation. The repeated occurrence of microcirculatory disturbance during HD sessions may cause chronic endothelial dysfunction and even cardiovascular complications in HD patients.

Inhalation of methane preserves the epithelial barrier during ischemia and reperfusion in the rat small intestine.

PubMed

Mészáros, András T; Büki, Tamás; Fazekas, Borbála; Tuboly, Eszter; Horváth, Kitti; Poles, Marietta Z; Szűcs, Szilárd; Varga, Gabriella; Kaszaki, József; Boros, Mihály

2017-06-01

Methane is part of the gaseous environment of the intestinal lumen. The purpose of this study was to elucidate the bioactivity of exogenous methane on the intestinal barrier function in an antigen-independent model of acute inflammation. Anesthetized rats underwent sham operation or 45-min occlusion of the superior mesenteric artery. A normoxic methane (2.2%)-air mixture was inhaled for 15 min at the end of ischemia and at the beginning of a 60-min or 180-min reperfusion. The integrity of the epithelial barrier of the ileum was assessed by determining the lumen-to-blood clearance of fluorescent dextran, while microvascular permeability changes were detected by the Evans blue technique. Tissue levels of superoxide, nitrotyrosine, myeloperoxidase, and endothelin-1 were measured, the superficial mucosal damage was visualized and quantified, and the serosal microcirculation and mesenteric flow was recorded. Erythrocyte deformability and aggregation were tested in vitro. Reperfusion significantly increased epithelial permeability, worsened macro- and microcirculation, increased the production of proinflammatory mediators, and resulted in a rapid loss of the epithelium. Exogenous normoxic methane inhalation maintained the superficial mucosal structure, decreased epithelial permeability, and improved local microcirculation, with a decrease in reactive oxygen and nitrogen species generation. Both the deformability and aggregation of erythrocytes improved with incubation of methane. Normoxic methane decreases the signs of oxidative and nitrosative stress, improves tissue microcirculation, and thus appears to modulate the ischemia-reperfusion-induced epithelial permeability changes. These findings suggest that the administration of exogenous methane may be a useful strategy for maintaining the integrity of the mucosa sustaining an oxido-reductive attack. Copyright © 2017 Elsevier Inc. All rights reserved.

Calf Muscle Oxygen Saturation During Six-Minute Walk Test And Its Relationship With Walking Impairment In Symptomatic Peripheral Artery Disease.

PubMed

Andrade-Lima, Aluísio; Cucato, Gabriel G; Domingues, Wagner J R; Germano-Soares, Antônio H; Cavalcante, Bruno R; Correia, Marilia A; Saes, Glauco F; Wolosker, Nelson; Gardner, Andrew W; Zerati, Antônio E; Ritti-Dias, Raphael M

2018-05-21

Impaired microcirculation is associated with poor walking capacity in symptomatic peripheral artery disease (PAD) patients during treadmill test, however, this test does not simulate the efforts of daily walking of these patients. Thus, the aim of the study was to describe the microcirculation responses during six-minute walk test (6MWT) and to analyze the relationship between microcirculation indicators and walking impairment in symptomatic PAD patients. Thirty-four patients were included (mean age = 67.6 ± 11.2). The clinical characteristics were collected and they performed a 6MWT in which initial claudication distance (ICD) and total walking distance (TWD) were recorded. During and after the 6MWT, calf muscle oxygen saturation (StO 2 ) parameters were monitored continuously to measure microcirculation behavior. The association between calf muscle StO 2 parameters and walking impairment was analyzed by Pearson or Spearman correlations. Walking impairment was not associated with any StO 2 parameters during exercise. In contrast, after 6MWT, recovery time of StO 2 (r = -0.472, P = .008) and recovery time to maximal StO 2 (r= -0.402, P = .019) were negatively correlated with ICD. Furthermore, the distance walked under claudication symptoms (ΔTWD - ICD) was positively correlated with recovery time to maximal StO 2 (r = 0.347, P = .048). In symptomatic PAD patients, shorter ICD values during a 6MWT are associated with a delayed recovery in calf muscle StO 2 after exercise. Calf muscle StO 2 parameters decrease subtly during 6MWT, suggesting that the degree of ischemia in the calf muscle during ground walking, simulating efforts of the daily walking, is relatively low. Copyright © 2018 Elsevier Inc. All rights reserved.

Early Healing Events after Periodontal Surgery: Observations on Soft Tissue Healing, Microcirculation, and Wound Fluid Cytokine Levels.

PubMed

Kaner, Doğan; Soudan, Mouaz; Zhao, Han; Gaßmann, Georg; Schönhauser, Anna; Friedmann, Anton

2017-01-27

Early wound healing after periodontal surgery with or without enamel matrix derivative/biphasic calcium phosphate (EMD/BCP) was characterized in terms of soft tissue closure, changes of microcirculation, and expression of pro- and anti-inflammatory cytokines in gingival crevicular fluid/wound fluid (GCF/WF). Periodontal surgery was carried out in 30 patients (18 patients: application of EMD/BCP for regeneration of bony defects; 12 patients: surgical crown lengthening (SCL)). Healthy sites were observed as untreated controls. GCF/WF samples were collected during two post-surgical weeks. Flap microcirculation was measured using laser Doppler flowmetry (LDF). Soft tissue healing was evaluated after two weeks. GCF/WF levels of interleukin 1β (IL-1β), tumour necrosis factor (TNF-α), IL-6, and IL-10 were determined using a multiplex immunoassay. Surgery caused similar reductions of flap microcirculation followed by recovery within two weeks in both EMD/BCP and SCL groups. GCF/WF and pro-inflammatory cytokine levels were immediately increased after surgery, and returned only partially to baseline levels within the two-week observation period. Levels of IL-10 were temporarily reduced in all surgical sites. Flap dehiscence caused prolonged elevated levels of GCF/WF, IL-1β, and TNF-α. These findings show that periodontal surgery triggers an immediate inflammatory reaction corresponding to the early inflammatory phase of wound healing, and these inflammation measures are temporary in case of maintained closure of the flap. However, flap dehiscence causes prolonged inflammatory exudation from the periodontal wound. If the biological pre-conditions for periodontal wound healing are considered important for the clinical outcome, care should be taken to maintain primary closure of the flap.

Thermodiffusion for continuous quantification of hepatic microcirculation--validation and potential in liver transplantation.

PubMed

Klar, E; Kraus, T; Bleyl, J; Newman, W H; Bowman, H F; Hofmann, W J; Kummer, R; Bredt, M; Herfarth, C

1999-09-01

Hepatic microcirculation is a main determinant of reperfusion injury and graft quality in liver transplantation. Methods available for the quantification of hepatic microcirculation are indirect, are invasive, or preclude postoperative application. The aim of this study was the validation of thermodiffusion in a new modification allowing long-term use in the clinical setting. In six pigs Doppler flowmeters were positioned around the hepatic artery and portal vein for the measurement of total liver blood flow. Liver perfusion was quantified by thermodiffusion and compared to H(2) clearance as an established technique under baseline conditions, during different degrees of portal venous obstruction and during occlusion of the hepatic artery. Thermodiffusion measurements were recorded for five days postoperatively followed by histological evaluation of the hepatic puncture site. Perfusion data obtained by thermodiffusion were significantly correlated to H(2) clearance (r = 0.94, P < 0. 001) and to liver blood flow (r = 0.9, P < 0.05). The agreement between thermodiffusion and H(2) clearance was excellent (mean difference -2.1 ml/100 g/min; limits of agreement -12.5 and 8.3 ml/100 g/min). Occlusion of the portal vein or hepatic artery was immediately detected by thermodiffusion, indicating a decrease of perfusion by 64 +/- 7% or 27 +/- 5% of baseline, respectively. Perfusion values at baseline and during vascular occlusion were reproducible during the entire observation period. Histological changes of the liver tissue adjacent to the thermodiffusion probes were minute and did not influence long-term measurements. In vivo validation proved that enhanced thermodiffusion is a minimally invasive technique for the continuous, real-time quantification of hepatic microcirculation. Changes in liver perfusion can be safely detected over several days postoperatively. The implication for liver transplantation has led to the clinical application of thermodiffusion. Copyright 1999 Academic Press.

Comparative Evaluation of Enalapril and Losartan in Pharmacological Correction of Experimental Osteoporosis and Fractures of Its Background

PubMed Central

Rajkumar, D. S. R.; Faitelson, A. V.; Gudyrev, O. S.; Dubrovin, G. M.; Pokrovski, M. V.; Ivanov, A. V.

2013-01-01

In the experiment on the white Wistar female rats (222 animals), the osteoprotective effect of enalapril and losartan was studied on experimental models of osteoporosis and osteoporotic fractures. It was revealed that in rats after ovariectomy, the endothelial dysfunction of microcirculation vessels of osteal tissue develops, resulting in occurrence of osteoporosis and delay of consolidation of experimental fractures. Enalapril and losartan prevented the reduction of microcirculation in bone, which was reflected in slowing the thinning of bone trabeculae and in preventing the occurrence of these microfractures, as well as increasing quality of experimental fractures healing. PMID:23401845

Skin microcirculation and vasopressin infusion: a laser Doppler study

PubMed Central

Bernard, Francis; Vinet, Alain; Verdant, Colin

2006-01-01

Use of arginine vasopressin in the management of refractory vasodilatory shock has been associated with development of ischaemic skin lesions. Because of the increasing popularity of arginine vasopressin, it is important to evaluate its effects on microcirculatory blood flow. Such studies are crucial if we are to appreciate the microcirculatory consequences of our various resuscitation strategies. However, methodological issues must always be considered because they can significantly influence interpretation of the results. Some aspects of use of laser Doppler to evaluate the microcirculation are reviewed within the context of recent findings presented by Luckner and coworkers in this issue of Critical Care. PMID:16594988

Effect of zero magnetic field on cardiovascular system and microcirculation

NASA Astrophysics Data System (ADS)

Gurfinkel, Yu. I.; At'kov, O. Yu.; Vasin, A. L.; Breus, T. K.; Sasonko, M. L.; Pishchalnikov, R. Yu.

2016-02-01

The effects of zero magnetic field conditions on cardiovascular system of healthy adults have been studied. In order to generate zero magnetic field, the facility for magnetic fields modeling ;ARFA; has been used. Parameters of the capillary blood flow, blood pressure, and the electrocardiogram (ECG) monitoring were measured during the study. All subjects were tested twice: in zero magnetic field and, for comparison, in sham condition. The obtained results during 60 minutes of zero magnetic field exposure demonstrate a clear effect on cardiovascular system and microcirculation. The results of our experiments can be used in studies of long-term stay in hypo-magnetic conditions during interplanetary missions.

Structural and functional bases of laser-microvessels interaction

NASA Astrophysics Data System (ADS)

Kozlov, Valentine I.; Terman, Oleg A.; Builin, Vitalij; Lebedeva, Natalia A.; Samoilov, Nickolai

1993-07-01

Structural and functional microcirculatory changes in tissues and organs (muscles, liver, derma, epinephros, brain cortex) under various dosages and powers of laser irradiation in the red (633 nm) and near infrared (890 nm) spectrum regions have been studied in experiments and clinic. In case of nonsensitized tissues the `photoactivation' range of power densities and doses of laser irradiation has been established. We have identified a short-term reaction of microvessels and a long-term reaction (adaptation). The former consists of intensification of microcirculation and metabolism rise in parenchymatous cells; the latter is connected with neoangiogenesis acceleration. The intensification of the blood microcirculation includes a dilation of microvessels of all orders, an amplification of arteriolar vasomotions and an opening of `reserved' capillaries. Data on the structural reconstruction of myocytes and endotheliocytes have shown that the high differential parenchymatous cells and its membrane structures are sensitive to low energy laser irradiation and, on the other hand, under low energy laser irradiation there is an activation of synthetic processes in the cells. Thus, during the laser-tissue interaction in such complex system as human organism the microcirculation plays the key role among the other systems.

Diffusing wave spectroscopy and its application for monitoring of skin blood microcirculation

NASA Astrophysics Data System (ADS)

Meglinski, Igor V.

2003-10-01

Diffusing Wave Spectroscopy (DWS) is a novel modern technique uniquely suited for the non-invasive measurements of the particles size and their motion within the randomly inhomogeneous highly scattering and absorbing media, including biological tissues as a human skin. The technique is based on the illuminating the media (tissues) with a coherent laser light, and analyzing the loss of coherence of the scattered field arises from motion of the scattering particles with respect to each other. Both theoretical and experimental results has shown the potentialities and viability of DWS application for the express non-invasive quantitative monitoring and functional diagnostics of skin blood microcirculation, with down to 1 μm/sec resolution. This is likely lead to quantitative monitoring in general diagnostics, diabetes studies, pharmacological intervention for the failing surgical skin flaps or replants, blood microcirculation monitoring during sepsis, assess burn depth, diagnose atherosclerotic disease, and investigate mechanisms of photodynamic therapy for cancer treatment. In frame of current report we describe the recent developments of DWS further to the point that skin blood micro-flow can be routinely and accurately obtained in a separate skin vascular bed on normal skin tissues.

Anatomical evaluation of oral microcirculation: capillary characteristics associated with sex or age group.

PubMed

Scardina, Giuseppe Alessandro; Giuseppe Alessandro, Scardina; Cacioppo, Antonino; Antonino, Cacioppo; Messina, Pietro

2009-10-01

There are various types of oral mucosa specific to different parts of the mouth and each of these has a unique histological structure. The variations in the epithelial structure are consistently related to observable differences in the underlying microcirculation: i.e. differences in the course, conformation, and density of capillaries. The aim of this research has been to investigate oral microcirculatory differences between men and women as well as between various age groups, in order to map the oral mucosa, and to highlight changes occurring during aging. A total of 45 healthy subjects were enrolled for this study (12 men and 33 women; mean age 60.37; range 30-82). A complete in-vivo videocapillaroscopic mapping of the oral mucosa was done on each subject. The capillaroscopic patterns of the various areas differ particularly in the course of the loops in relation to the mucosal surface. On the basis of statistical analysis of the collected data, it emerges that there are many differences in capillary loop density between men and women and between different age groups. This study demonstrates the necessity of approaching the investigation of patient microcirculation in different ways depending on sex or age.

Imaging photoplethysmography for clinical assessment of cutaneous microcirculation at two different depths

NASA Astrophysics Data System (ADS)

Marcinkevics, Zbignevs; Rubins, Uldis; Zaharans, Janis; Miscuks, Aleksejs; Urtane, Evelina; Ozolina-Moll, Liga

2016-03-01

The feasibility of bispectral imaging photoplethysmography (iPPG) system for clinical assessment of cutaneous microcirculation at two different depths is proposed. The iPPG system has been developed and evaluated for in vivo conditions during various tests: (1) topical application of vasodilatory liniment on the skin, (2) skin local heating, (3) arterial occlusion, and (4) regional anesthesia. The device has been validated by the measurements of a laser Doppler imager (LDI) as a reference. The hardware comprises four bispectral light sources (530 and 810 nm) for uniform illumination of skin, video camera, and the control unit for triggering of the system. The PPG signals were calculated and the changes of perfusion index (PI) were obtained during the tests. The results showed convincing correlations for PI obtained by iPPG and LDI at (1) topical liniment (r=0.98) and (2) heating (r=0.98) tests. The topical liniment and local heating tests revealed good selectivity of the system for superficial microcirculation monitoring. It is confirmed that the iPPG system could be used for assessment of cutaneous perfusion at two different depths, morphologically and functionally different vascular networks, and thus utilized in clinics as a cost-effective alternative to the LDI.

Imaging photoplethysmography for clinical assessment of cutaneous microcirculation at two different depths.

PubMed

Marcinkevics, Zbignevs; Rubins, Uldis; Zaharans, Janis; Miscuks, Aleksejs; Urtane, Evelina; Ozolina-Moll, Liga

2016-03-01

The feasibility of bispectral imaging photoplethysmography (iPPG) system for clinical assessment of cutaneous microcirculation at two different depths is proposed. The iPPG system has been developed and evaluated for in vivo conditions during various tests: (1) topical application of vasodilatory liniment on the skin, (2) skin local heating, (3) arterial occlusion, and (4) regional anesthesia. The device has been validated by the measurements of a laser Doppler imager (LDI) as a reference. The hardware comprises four bispectral light sources (530 and 810 nm) for uniform illumination of skin, video camera, and the control unit for triggering of the system. The PPG signals were calculated and the changes of perfusion index (PI) were obtained during the tests. The results showed convincing correlations for PI obtained by iPPG530 nm and LDI at (1) topical liniment (r = 0.98) and (2) heating (r = 0.98) tests. The topical liniment and local heating tests revealed good selectivity of the system for superficial microcirculation monitoring. It is confirmed that the iPPG system could be used for assessment of cutaneous perfusion at two different depths, morphologically and functionally different vascular networks, and thus utilized in clinics as a cost-effective alternative to the LDI.

[Angina pectoris and coronary insufficiency with a normal coronary angiogram: pathophysiological principles, diagnosis and therapeutic consequences].

PubMed

Strauer, B E

1988-01-01

The clinical syndrome "coronary insufficience at normal coronary arteriogram" is found in approximately 10-20% of patients with exercise-induced coronary insufficience. In most of these cases disturbances of coronary microcirculation are present. They can appear in vascular diseases (arterial hypertension, systemic immunopathies, immune complex vasculitis, etc.), in rheological diseases (paraproteinemia, hyperlipoproteinemia, polyglobulia, etc.), and in disturbances of transport and diffusion of oxygen (carbon monoxide intoxication, methemoglobinemia, hyperlipoproteinemia). The clinical diagnosis is based on usual diagnostic programs (electrocardiogram, exercise electrocardiogram, responsiveness to nitroglycerin, etc.), as well as on newer, functionally orientated diagnostic procedures (determinations of coronary blood flow and of coronary vascular reserve, production of lactate, serological findings, histology and immune histology of peripheral arteries, measurements of viscosities in both plasma and blood, etc.). Many clinically relevant disturbances in coronary microcirculation can thus be detected and treated on a rational basis by the management of the internal main disease, that is, by the treatment of the vascular, rheological, and metabolic disorders. Persistent angina pectoris in the presence of normal coronary arteriogram represents no termination of coronary diagnostics, but moreover implies the clinical task for using diagnostic possibilities to enable functional and therapeutical assessment of coronary microcirculation.

Quantification of Macrocirculation and Microcirculation in Brain Using Ultrasound Perfusion Imaging.

PubMed

Vinke, Eline J; Eyding, Jens; de Korte, Chris; Slump, Cornelis H; van der Hoeven, Johannes G; Hoedemaekers, Cornelia W E

2018-01-01

The aim of this study was to investigate the feasibility of simultaneous visualization of the cerebral macrocirculation and microcirculation, using ultrasound perfusion imaging (UPI). In addition, we studied the sensitivity of this technique for detecting changes in cerebral blood flow (CBF). We performed an observational study in ten healthy volunteers. Ultrasound contrast was used for UPI measurements during normoventilation and hyperventilation. For the data analysis of the UPI measurements, an in-house algorithm was used to visualize the DICOM files, calculate parameter images and select regions of interest (ROIs). Next, time intensity curves (TIC) were extracted and perfusion parameters calculated. Both volume- and velocity-related perfusion parameters were significantly different between the macrocirculation and the parenchymal areas. Hyperventilation-induced decreases in CBF were detectable by UPI in both the macrocirculation and microcirculation, most consistently by the volume-related parameters. The method was safe, with no adverse effects in our population. Bedside quantification of CBF seems feasible and the technique has a favourable safety profile. Adjustment of current method is required to improve its diagnostic accuracy. Validation studies using a 'gold standard' are needed to determine the added value of UPI in neurocritical care monitoring.

Protective effects of a selective neutrophil elastase inhibitor (sivelestat) on lipopolysaccharide-induced acute dysfunction of the pulmonary microcirculation.

PubMed

Inoue, Yoshiaki; Seiyama, Akitoshi; Tanaka, Hiroshi; Ukai, Isao; Akimau, Pavel; Nishino, Masato; Shimazu, Takeshi; Sugimoto, Hisashi

2005-08-01

The purpose of this study was to evaluate the effect of a neutrophil elastase inhibitor, sivelestat, on lipopolysaccharide-induced acute lung injury through analysis of hemodynamic changes in the pulmonary microcirculation. Randomized animal study. Medical school laboratory. Twenty-seven Wistar rats (15 rats for microspectroscopic observations, 12 rats for measurements of neutrophil elastase activity and wet-to-dry ratio). Thoracosternotomy was performed on male Wistar rats under continuous anesthesia and mechanical ventilation. Rats were divided into three groups (n = 5 each groups) on the basis of the reagent used: lipopolysaccharide group (100 microg/kg lipopolysaccharide intravenously), sivelestat group (10 mg/kg sivelestat; 100 microg/kg lipopolysaccharide intravenously), and control group (saline only, intravenously). We measured morphologic changes and hemodynamic variables, including tissue blood flow, erythrocyte velocity, erythrocyte count, thickness of interalveolar septa, and leukocyte adhesion in the pulmonary microcirculation, with a video-rate (33 msec/frame) dual-spot microspectroscopy system (DSMSS) and a laser-Doppler flowmeter. Blood-free wet-to-dry ratio and neutrophil elastase activity in bronchoalveolar lavage fluid, serum, and supernatant of lung homogenate were measured in another set of experiments (n = 4 for each group). Sixty minutes after lipopolysaccharide administration, severe thickening of the interalveolar septa was observed in the lipopolysaccharide but not the sivelestat group. In the lipopolysaccharide group, DSMSS measurements of erythrocyte velocity and hemoglobin oxygenation in single capillaries were decreased significantly (vs. control p < .05, vs. sivelestat p < .01), whereas tissue blood flow and erythrocyte velocity measurements from laser-Doppler flowmeter were increased significantly (vs. control p < .05, vs. sivelestat p < .01). The number of adherent leukocytes was increased significantly in the lipopolysaccharide group at 30, 45, and 60 mins after lipopolysaccharide administration (vs. control p < .01, vs. sivelestat p < .05). The number of adherent leukocytes did not increase in the sivelestat group. The wet-to-dry ratio was significantly higher in the lipopolysaccharide group than in control (p < .05) and sivelestat (p < .05) groups. Neutrophil elastase activities in the bronchoalveolar lavage fluid, serum, and lung tissue were all significantly lower in the sivelestat group than in the lipopolysaccharide group (p < .05). Lipopolysaccharide induces leukocyte adhesion in the pulmonary microcirculation, resulting in decreased tissue hemoglobin oxygen and alveolar and interstitial edema. The selective neutrophil elastase inhibitor sivelestat reduces neutrophil elastase activity and attenuates acute changes in the pulmonary microcirculation.

EFFECTS OF LOW-FREQUENCY ULTRASOUND ON MICROCIRCULATION IN VENOUS LEG ULCERS

PubMed Central

Wollina, Uwe; Heinig, Birgit; Naumann, Gunther; Scheibe, Armin; Schmidt, Wolf-Dieter; Neugebauer, Reimund

2011-01-01

Background: Therapeutic low-frequency ultrasound (US) has been used for many years to improve wound healing in chronic wounds like venous leg ulcers. No human data are available for the possible effects of single US applications on microcirculation and their frequency-dependency. Aims: To investigated the role of therapeutic low-frequency US on microcirculation of venous leg ulcers in vivo. Patients and Methods: This is a pilot study on an inpatient basis. We use a newly developed low-frequency continuous-wave US-equipment composed of a US transducer based on piezo-fiber composites that allow the change of frequency. In this study, we apply US of 34 kHz, 53.5 kHz, and 75 kHz respectively. Twelve patients with chronic venous leg ulcers are analyzed. As an adjunct to good ulcer care, therapeutic US is applied, non-contacting, once a day, in a subaqual position for 10 minutes. Microcirculation is assessed in the ulcers adjacent to skin before US-therapy, immediately after the treatment and 30 minutes later. We use a micro-light guide spectrophotometer (O2C, LEA Medizintechnik GmbH, Gieίen, Germany) for calculation of blood flow velocity, hemoglobin oxygen saturation (SCO2) and relative hemoglobin concentration (rHb) in 2 and 8 mm depth. Contact-free remission spectroscopy (SkinREM3, Color Control Chemnitz GmbH, Chemnitz, Germany) allows contact free measurements in the VIS-NIR range of the spectrum (400 ± 1600 nm). Results: It is seen that therapeutic US is well tolerated. One patient dropped out from a treatment series since he developed erysipelas responding to standard antibiotic. Effects were seen at 34 kHz only. The SO2 values increased after single US application. The values for rHb were higher in the superficial layer of the wound bed (depth 2 mm) compared to deeper parts (8 mm depth). US treatment did not result in significant changes of rHb and blood cell velocity. The data obtained by remission spectroscopy disclose an increase of oxygenized hemoglobin. Conclusions: The major findings are that continuous-wave low-frequency US of 34 kHz, but not, 53.5 kHz or 75 kHz, has a temporary stimulatory effect on microcirculation mainly due to an improved oxygenation. Further studies with treatment series are necessary. PMID:21716543

Numerical modeling of fluid and oxygen exchanges through microcirculation for the assessment of microcirculation alterations caused by type 2 diabetes.

PubMed

Tang, Yuanliang; He, Ying

2018-05-01

Type 2 diabetes mellitus (DM2) is frequently accompanied by microcirculation complications, including structural and functional alterations, which may have serious effects on substance exchanges between blood and interstitial tissue and the health of organs. In this paper, we aim to study the influence of microcirculation alterations in DM2 patients on fluid and oxygen exchanges through a model analysis. A fluid flow and oxygen transport model were developed by considering the interplay between blood in capillary network and interstitial tissue. The two regions were separately represented by 1D network model and 3D volume model, and the immersed boundary method (IBM) was adopted to solve fluid and mass transfer between these two regions. By using the model, the steady flow field and the distributions of oxygen in capillary network and surrounding tissue were firstly simulated. In the interstitial volume, fluid pressure and oxygen tension decreased with the increase of distance from the network; in the network, oxygen tension in blood plasma dropped from 100 mm Hg at the entrance to about 40 mm Hg at the exit. We further tested several structural and functional disorders related to diabetic pathological conditions. Simulated results show that the impaired connectivity of the network could result in poor robustness in maintaining blood flow and perfused surface; under high fluid permeability conditions of capillary walls, the pressure gradient was much larger around the capillary bed, and this alteration led to a saturation level of the interstitial pressure when lymphatic flow drainage can't work effectively; the variations in network connectivity and permeability of capillary wall also had unfavorable influence on oxygen distributions in interstitial tissue. In addition, when the oxygen releasing capacity of hemoglobin was confined by glycosylated hemoglobin (HbA1) in the case of diabetes, the plasma could not be complemented with adequate oxygen and thus the hypoxic tissue range will be extended. This study illustrates that when microcirculation disturbances, including the structure of capillary network, the wall osmosis property and the capacity of blood binding oxygen occur in DM2, some negative impacts are raised on microvascular hemodynamics and metabolism circumstance of interstitial tissue. Copyright © 2018 Elsevier Inc. All rights reserved.

ENDOTHELIAL CONTRACTION INDUCED BY HISTAMINE-TYPE MEDIATORS

PubMed Central

Majno, Guido; Shea, Stephen M.; Leventhal, Monika

1969-01-01

Previous work has shown that endogenous chemical mediators, of which histamine is the prototype, increase the permeability of blood vessels by causing gaps to appear between endothelial cells. In the present paper, morphologic and statistical evidence is presented, to suggest that endothelial cells contract under the influence of mediators, and that this contraction causes the formation of intercellular gaps. Histamine, serotonin, and bradykinin were injected subcutaneously into the scrotum of the rat, and the vessels of the underlying cremaster muscle were examined by electron microscopy. To eliminate the vascular collapse induced by routine fixation, in one series of animals (including controls) the root of the cremaster was constricted for 2–4 min prior to sacrifice, and the tissues were fixed under conditions of mild venous congestion. Electron micrographs were taken of 599 nuclei from the endothelium of small blood vessels representing the various experimental situations. Nuclear deformations were classified into four types of increasing tightness (notches, foldsl closing folds, and pinches. In the latter the apposed surfaces of the nuclear membrane are in contact). It was found that: (1) venous congestion tends to straighten the nuclei in al groups; (2) mediators cause a highly significant increase in the number of pinches (P < 0.001), also if the vessels are distended by venous congestion; (3) fixation without venous congestion causes vascular collapse. The degree of endothelial recoil, as measured by nuclear pinches, is very different from that caused by mediators (P < 0.001). (4) Pinched nuclei are more frequent in leaking vessels, and in cells adjacent to gaps (P < 0.001); (5) mediators also induce, in the endothelium, cytoplasmic changes suggestive of contraction, and similar to those of contracted smooth muscle; (6) there is no evidence of pericyte contraction under the conditions tested. Occasional pericytes appeared to receive fine nerve endings. Various hypotheses to explain nuclear pinching are discussed; the only satisfactory explanation is that which requires endothelial contraction. PMID:5801425

Extracellular adenosine initiates rapid arteriolar vasodilation induced by a single skeletal muscle contraction in hamster cremaster muscle.

PubMed

Ross, G A; Mihok, M L; Murrant, C L

2013-05-01

Recent studies suggest that adenosine (ADO) can be produced extracellularly in response to skeletal muscle contraction. We tested the hypothesis that a single muscle contraction produces extracellular ADO rapidly enough and in physiologically relevant concentrations to be able to contribute to the rapid vasodilation that occurs at the onset of muscle contraction. We stimulated four to five skeletal muscle fibres in the anaesthetized hamster cremaster preparation in situ and measured the change in diameter of arterioles at a site of overlap with the stimulated muscle fibres before and after a single contraction (stimulus frequencies: 4, 20 and 60 Hz; 250 ms train duration). Muscle fibres were stimulated in the absence and presence of non-specific ADO membrane receptor antagonists 8-phenyltheophylline (8-PT, 10(-6) M) or xanthine amine congener (XAC, 10(-6) M) or an inhibitor of an extracellular source of ADO, ecto-5'-nucleotidase inhibitor α,β-methylene adenosine 5'-diphosphate (AMPCP, 10(-5) M). We observed that the dilatory event at 4 s following a single contraction was significantly inhibited at all stimulus frequencies by an average of 63.9 ± 2.6% by 8-PT. The 20-s dilatory event that occurred at 20 and 60 Hz was significantly inhibited by 53.6 ± 2.6 and 73.8 ± 2.3% by 8-PT and XAC respectively. Further, both the 4- and 20-s dilatory events were significantly inhibited by AMPCP by 78.6 ± 6.6 and 67.1 ± 1.5%, respectively, at each stimulus frequency tested. Our data show that ADO is produced extracellularly during a single muscle contraction and that it is produced rapidly enough and in physiologically relevant concentrations to contribute to the rapid vasodilation in response to muscle contraction. © 2013 The Authors Acta Physiologica © 2013 Scandinavian Physiological Society.

Optical coherence tomography angiography offers comprehensive evaluation of skin optical clearing in vivo by quantifying optical properties and blood flow imaging simultaneously

NASA Astrophysics Data System (ADS)

Guo, Li; Shi, Rui; Zhang, Chao; Zhu, Dan; Ding, Zhihua; Li, Peng

2016-08-01

Tissue optical clearing (TOC) is helpful for reducing scattering and enhancing the penetration depth of light, and shows promising potential in optimizing optical imaging performances. A mixture of fructose with PEG-400 and thiazone (FPT) is used as an optical clearing agent in mouse dorsal skin and evaluated with OCT angiography (Angio-OCT) by quantifying optical properties and blood flow imaging simultaneously. It is observed that FPT leads to an improved imaging performance for the deeper tissues. The imaging performance improvement is most likely caused by the FPT-induced dehydration of skin, and the reduction of scattering coefficient (more than ˜40.5%) and refractive-index mismatching (more than ˜25.3%) in the superficial (epidermal, dermal, and hypodermal) layers. A high correlation (up to ˜90%) between the relative changes in refractive-index mismatching and Angio-OCT signal strength is measured. The optical clearing rate is ˜5.83×10-5 cm/s. In addition, Angio-OCT demonstrates enhanced performance in imaging cutaneous hemodynamics with satisfactory spatiotemporal resolution and contrast when combined with TOC, which exhibits a powerful practical application in studying microcirculation.

Lactate stimulates angiogenesis and accelerates the healing of superficial and ischemic wounds in mice.

PubMed

Porporato, Paolo E; Payen, Valéry L; De Saedeleer, Christophe J; Préat, Véronique; Thissen, Jean-Paul; Feron, Olivier; Sonveaux, Pierre

2012-12-01

Wounds notoriously accumulate lactate as a consequence of both anaerobic and aerobic glycolysis following microcirculation disruption, immune activation, and increased cell proliferation. Several pieces of evidence suggest that lactate actively participates in the healing process through the activation of several molecular pathways that collectively promote angiogenesis. Lactate indeed stimulates endothelial cell migration and tube formation in vitro, as well as the recruitment of circulating vascular progenitor cells and vascular morphogenesis in vivo. In this study, we examined whether the pro-angiogenic potential of lactate may be exploited therapeutically to accelerate wound healing. We show that lactate delivered from a Matrigel matrix improves reperfusion and opposes muscular atrophy in ischemic hindlimb wounds in mice. Both responses involve lactate-induced reparative angiogenesis. Using microdialysis and enzymatic measurements, we found that, contrary to poly-L-lactide (PLA), a subcutaneous implant of poly-D,L-lactide-co-glycolide (PLGA) allows sustained local and systemic lactate release. PLGA promoted angiogenesis and accelerated the closure of excisional skin wounds in different mouse strains. This polymer is FDA-approved for other applications, emphasizing the possibility of exploiting PLGA therapeutically to improve wound healing.

Modeling and Measurement of Correlation between Blood and Interstitial Glucose Changes

PubMed Central

Shi, Ting; Li, Dachao; Li, Guoqing; Zhang, Yiming; Xu, Kexin; Lu, Luo

2016-01-01

One of the most effective methods for continuous blood glucose monitoring is to continuously measure glucose in the interstitial fluid (ISF). However, multiple physiological factors can modulate glucose concentrations and affect the lag phase between blood and ISF glucose changes. This study aims to develop a compensatory tool for measuring the delay in ISF glucose variations in reference to blood glucose changes. A theoretical model was developed based on biophysics and physiology of glucose transport in the microcirculation system. Blood and interstitial fluid glucose changes were measured in mice and rats by fluorescent and isotope methods, respectively. Computer simulation mimicked curves were fitted with data resulting from fluorescent measurements of mice and isotope measurements of rats, indicating that there were lag times for ISF glucose changes. It also showed that there was a required diffusion distance for glucose to travel from center of capillaries to interstitial space in both mouse and rat models. We conclude that it is feasible with the developed model to continuously monitor dynamic changes of blood glucose concentration through measuring glucose changes in ISF with high accuracy, which requires correct parameters for determining and compensating for the delay time of glucose changes in ISF. PMID:27239479

Evaluation of Laser Speckle Contrast Imaging for the Assessment of Oral Mucosal Blood Flow following Periodontal Plastic Surgery: An Exploratory Study

PubMed Central

Molnár, Eszter; Molnár, Bálint; Lohinai, Zsolt; Tóth, Zsuzsanna; Benyó, Zoltán; Hricisák, Laszló; Windisch, Péter

2017-01-01

The laser speckle contrast imaging (LSCI) is proved to be a reliable tool in flap monitoring in general surgery; however, it has not been evaluated in oral surgery yet. We applied the LSCI to compare the effect of a xenogeneic collagen matrix (Geistlich Mucograft®) to connective tissue grafts (CTG) on the microcirculation of the modified coronally advanced tunnel technique (MCAT) for gingival recession coverage. Gingival microcirculation and wound fluid were measured before and after surgery for six months at twenty-seven treated teeth. In males, the flap microcirculation was restored within 3 days for both grafts followed by a hyperemic response. During the first 8 days the blood flow was higher at xenogeneic graft comparing to the CTG. In females, the ischemic period lasted for 7–12 days depending on the graft and no hyperemic response was observed. Females had more intense and prolonged wound fluid production. The LSCI method is suitable to capture the microcirculatory effect of the surgical intervention in human oral mucosa. The application of xenogeneic collagen matrices as a CTG substitute does not seem to restrain the recovery of graft bed circulation. Gender may have an effect on postoperative circulation and inflammation. PMID:28232940

Impact of different antithrombotics on the microcirculation and viability of perforator-based ischaemic skin flaps in a small animal model.

PubMed

Fichter, Andreas M; Ritschl, Lucas M; Robitzky, Luisa K; Wagenpfeil, Stefan; Mitchell, David A; Wolff, Klaus-Dietrich; Mücke, Thomas

2016-10-21

The effects of antithrombotic drugs on random and free flap survival have been investigated in the past, but the experimental and clinical results are not in agreement. A perforator-based critical ischaemia model was used to evaluate the effects of different perioperatively administered pharmaceutical agents on tissue ischaemia and to assess the potential additional haemorheological or vasodilative effects of antithrombotics on flap microcirculation. Combined laser Doppler flowmetry and remission spectroscopy revealed an increase in certain microcirculation parameters in most groups in comparison with saline controls, and these changes correlated with flap survival. Clopidogrel and hirudin significantly improved the amount of viable flap tissue in comparison with controls, while unfractioned heparin had a negative effect on flap survival. Low molecular weight heparin, aspirin, pentoxifylline, and hydroxyethyl starch had no impact on the amount of viable flap tissue. A higher complication rate was observed in all experimental groups, but only clopidogrel had a negative impact on the flap viability. Our results add to the body of evidence supporting the conclusion that perioperative antithrombotic treatment improves flap survival. Clopidogrel and hirudin are effective pharmacological agents that significantly increased the viability of perforator-based skin flaps in rats, but at a higher risk of postoperative bleeding.

Evaluation of Laser Speckle Contrast Imaging for the Assessment of Oral Mucosal Blood Flow following Periodontal Plastic Surgery: An Exploratory Study.

PubMed

Molnár, Eszter; Molnár, Bálint; Lohinai, Zsolt; Tóth, Zsuzsanna; Benyó, Zoltán; Hricisák, Laszló; Windisch, Péter; Vág, János

2017-01-01

The laser speckle contrast imaging (LSCI) is proved to be a reliable tool in flap monitoring in general surgery; however, it has not been evaluated in oral surgery yet. We applied the LSCI to compare the effect of a xenogeneic collagen matrix (Geistlich Mucograft®) to connective tissue grafts (CTG) on the microcirculation of the modified coronally advanced tunnel technique (MCAT) for gingival recession coverage. Gingival microcirculation and wound fluid were measured before and after surgery for six months at twenty-seven treated teeth. In males, the flap microcirculation was restored within 3 days for both grafts followed by a hyperemic response. During the first 8 days the blood flow was higher at xenogeneic graft comparing to the CTG. In females, the ischemic period lasted for 7-12 days depending on the graft and no hyperemic response was observed. Females had more intense and prolonged wound fluid production. The LSCI method is suitable to capture the microcirculatory effect of the surgical intervention in human oral mucosa. The application of xenogeneic collagen matrices as a CTG substitute does not seem to restrain the recovery of graft bed circulation. Gender may have an effect on postoperative circulation and inflammation.

Anethole and eugenol reduce in vitro and in vivo leukocyte migration induced by fMLP, LTB4, and carrageenan.

PubMed

Estevão-Silva, Camila Fernanda; Kummer, Raquel; Fachini-Queiroz, Fernanda Carolina; Grespan, Renata; Nogueira de Melo, Gessilda Alcântara; Baroni, Silmara; Cuman, Roberto Kenji Nakamura; Bersani-Amado, Ciomar Aparecida

2014-07-01

The aim of this study was to investigate the effect of anethole (AN) and eugenol (EUG) on leukocyte migration using in vitro chemotaxis and in situ microcirculation assays. BALB/c mice were used for the in vitro chemotaxis assay, and Wistar rats for the in situ microcirculation assay. We evaluated (a) the in vitro leukocyte migration in response to chemotactic factors (formyl-methionyl-leucyl-phenylalanine [fMLP] and leukotriene B4 [LTB4]) and (b) the rolling, adhesion, and migration of leukocytes induced by an injection of carrageenan (100 µg/cavity) into the scrotum of the animal. In the in vitro chemotaxis assay, AN and EUG at doses of 1, 3, 9, and 27 µg/ml significantly inhibited leukocyte migration when stimulated by the chemotactic agents fMLP and LTB4. In the in situ microcirculation assay, AN at doses of 125 and 250 mg/kg and EUG at a dose of 250 mg/kg significantly decreased the number of leukocytes that rolled, adhered, and migrated to perivascular tissue. The results indicate that AN and EUG exert inhibitory effects on leukocyte migration, highlighting their possible use to diminish excessive leukocyte migration in the inflammatory process.

Optical monitoring of cerebral microcirculation in neurointensive care.

PubMed

Rejmstad, Peter; Haj-Hosseini, Neda; Åneman, Oscar; Wårdell, Karin

2017-12-08

Continuous optical monitoring of local cerebral microcirculation could benefit neurointensive care patients treated for subarachnoid hemorrhage (SAH). The aim of the study was to evaluate laser Doppler flowmetry (LDF) and diffuse reflectance spectroscopy (DRS) for long-term monitoring of brain microcirculation and oxygen saturation (SO 2 ) in the neurointensive care unit (NICU). A fiber optic probe was designed for intraparenchymal use and connected to LDF and DRS for assessment of the local blood flow (perfusion and tissue reflectance (TLI)) and SO 2 in the brain. The optically monitored parameters were compared with conventional NICU monitors and Xe-CT. The LDF signals were low with median and 25 to 75% interquartiles of perfusion = 70 (59 to 83) a.u. and TLI = 2.0 (1.0 to 2.4) a.u. and showed correlation with the NICU monitors in terms of heart rate. Median and interquartiles of SO 2 were 17.4 (15.7 to 19.8) %. The lack of correlation between local perfusion and cerebral perfusion pressure indicated intact cerebral autoregulation. The systems were capable of monitoring both local perfusion and SO 2 with stable signals in the NICU over 4 days. Further clinical studies are required to evaluate the optical systems' potential for assessing the onset of secondary brain injury.

Improvement of small intestinal microcirculation by postconditioning after lower limb ischemia.

PubMed

Turóczi, Zsolt; Fülöp, András; Czigány, Zoltán; Varga, Gabriella; Rosero, Oliver; Tökés, Tünde; Kaszaki, József; Lotz, Gábor; Harsányi, László; Szijártó, Attila

2015-03-01

Major lower limb vascular surgeries may result in severe, remote injury of the gastrointestinal system, which has high mortality rates. Postconditioning is a technique with potential capability of reducing remote gastrointestinal complications. Our aim was to assess the remote macro- and micro-hemodynamic changes of the small intestine following an infrarenal aortic occlusion and to evaluate the effects of postconditioning on these alterations. Rats underwent 3h of infrarenal aortic occlusion followed by 4h of reperfusion. In one group, postconditioning was applied. Blood pressure, superior mesenteric artery flow and mucosal microcirculation of the duodenum, jejunum and ileum were assessed. Samples were taken from each intestinal segment for histological examinations. Superior mesenteric artery flow, as well as microcirculation of the duodenum, jejunum and ileum showed significant impairment in the IR group, while histological damage was significantly worsened. Postconditioning was able to limit flow reduction in all three small bowel segments and in the superior mesenteric artery, and was able to significantly reduce histological damage. Strong negative correlation was found between microcirculatory values and histological damage. Microcirculatory impairment might be responsible for remote intestinal injury following infrarenal aortic occlusion. Postconditioning was able to reduce this remote intestinal damage. Copyright © 2015 Elsevier Inc. All rights reserved.

Monitoring of small lymphatics function under different impact on animal model by integrated optical imaging

NASA Astrophysics Data System (ADS)

Galanzha, Ekaterina I.; Tuchin, Valery V.; Chowdhury, Parimal; Zharov, Vladimir P.

2004-08-01

The digital transmission microscopy is very informative, noninvasive for vessels, simple and available method for studying and measuring lymph microvessels function in vivo. Rat mesentery can use as promising animal model of lymph microvessels in vivo. Such imaging system allowed visualizing the entire lymphangion (with input and output valves), its wall, lymphatic valves, lymph flow as well as single cells in flow; obtaining anew basic information on lymph microcirculation and quantitative data on lymphatic function including indexes of phasic contractions and valve function, the quantitative parameters of lymph-flow velocity. Rat mesentery is good model to create different types of lymphedemas in acute and chronic experiments. The obtained data revealed that significant edema started immediately after lymph node dissection in one-half of cases and was accompanied by lymphatic disturbances. The greatest degree of edema was found after 1 week. After 4 weeks, the degree of edema sometimes decreased, but functional lymphatic disturbances progressed. Nicotine had significant direct dose-dependent effect on microlymphatic function at the acute local application, but the same dose of this drug was not effect on microcirculation in chronic intoxication. Despite yielding interesting data, transmittance microscopy had some limitations when applied to microcirculation studies. The problems could be solved at the application of integrated measuring technique.

Effect of Tea Theaflavins and Catechins on Microvascular Function

PubMed Central

Fuchs, Dagmar; de Graaf, Young; van Kerckhoven, Roeland; Draijer, Richard

2014-01-01

Beneficial effects of flavonoid-rich black and green tea on macrocirculation have been well established. Theaflavins are unique to black tea as they are formed from catechins during the enzymatic oxidation of tea leaves. The study was performed to gain more insight into the effects of theaflavins on microcirculation and to compare effects with another important flavonoid class, the green tea derived catechins, which have been reported to improve vascular function. Twenty-four healthy subjects were included in a double-blind, placebo-controlled, randomised, cross-over study. On six different days, subjects received capsules with a single dose of catechins (500 mg), four varying doses of theaflavins (100 to 500 mg) or placebo. Microcirculation was assessed after each treatment by Pulse Amplitude Tonometry (EndoPAT) at baseline and 2, 4 and 6 h after test product intake. The EndoPAT reactive hyperemia response was improved by 500 mg catechins (reactive hyperemia index (RHI): 0.2; p = 0.04) and by 500 mg theaflavins (RHI: 0.19; p = 0.06) compared to placebo. Also, 300 mg theaflavins increased the RHI (0.28; p = 0.02), but no effects were observed at lower doses. The study suggests moderate effects of single doses of catechins and theaflavins on peripheral microcirculation. PMID:25514559

Evaluation of a pointwise microcirculation assessment method using liquid and multilayered tissue simulating phantoms

NASA Astrophysics Data System (ADS)

Fredriksson, Ingemar; Saager, Rolf B.; Durkin, Anthony J.; Strömberg, Tomas

2017-11-01

A fiber-optic probe-based instrument, designed for assessment of parameters related to microcirculation, red blood cell tissue fraction (fRBC), oxygen saturation (S), and speed resolved perfusion, has been evaluated using state-of-the-art tissue phantoms. The probe integrates diffuse reflectance spectroscopy (DRS) at two source-detector separations and laser Doppler flowmetry, using an inverse Monte Carlo method for identifying the parameters of a multilayered tissue model. Here, we characterize the accuracy of the DRS aspect of the instrument using (1) liquid blood phantoms containing yeast and (2) epidermis-dermis mimicking solid-layered phantoms fabricated from polydimethylsiloxane, titanium oxide, hemoglobin, and coffee. The root-mean-square (RMS) deviations for fRBC for the two liquid phantoms were 11% and 5.3%, respectively, and 11% for the solid phantoms with highest hemoglobin signatures. The RMS deviation for S was 5.2% and 2.9%, respectively, for the liquid phantoms, and 2.9% for the solid phantoms. RMS deviation for the reduced scattering coefficient (μs‧), for the solid phantoms was 15% (475 to 850 nm). For the liquid phantoms, the RMS deviation in average vessel diameter (D) was 1 μm. In conclusion, the skin microcirculation parameters fRBC and S, as well as, μs‧ and D are estimated with reasonable accuracy.

[Microcirculatory blood and lymph flow examination in eyelid skin by laser Doppler flowmetry].

PubMed

Safonova, T N; Kintyukhina, N P; Sidorov, V V; Gladkova, O V; Reyn, E S

to study normal blood and lymph microcirculation of the upper and lower eyelids in different age groups. The study included 108 volunteers (216 eyes) aged from 20 to 80 years with no signs of changes in anterior segment structures, who were grouped by age ranges (20-30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years, and 71-80 years) into 6 groups equal in gender and quantitative composition. In all volunteers, microcirculation of the upper and lower eyelids was examined by laser Doppler flowmetry (LDF) ('LASMA MC-1' peripheral blood and lymph flow analyzer and 'LASMA MC' laser diagnostic complex, LASMA LLC). The average perfusion changes in blood and lymph flow as well as blood and lymph flow oscillations were analyzed. Blood and lymph flow in the microvasculature of the upper and lower eyelids is variable and depends on neither the age, nor gender of the test subject. On LDF-gram, every increase in amplitude of blood flow corresponds to a decrease in that of lymph flow. The non-invasive method of LDF expands our diagnostic capabilities as it enables assessment of not only blood, but also lymph flow. The data obtained can serve as a starting point for exploring microcirculation in different age groups in the presence of different pathological processes.

Effects of carbogen on cochlear blood flow and hearing function following acute acoustic trauma in guinea pigs.

PubMed

Zhao, Jing; Sun, Jianjun; Liu, Yang

2012-10-01

Disturbances of microcirculation and hemorheological changes in the inner ear are the results of noise-induced hearing loss (NIHL). Both the disturbances of microcirculation and hemorheological changes are the etiologies of NIHL development, but they are also the results. Although previous reports that inhalation of high concentration of CO(2) may increase cochlear blood flow (CoBF), the effects of carbogen on the cochlear microcirculation and NIHL remain unclear. Changes induced by noise, carbogen and pure oxygen within the cochlear lateral wall microvasculature and in hearing thresholds were observed in guinea pigs using intravital microscopy and the auditory brainstem response. At the same time, arterial oxygen saturation and morphologic changes of cochlear hair cells were observed. Carbogen inhalation increased vessel diameters and blood flow velocities. Hearing thresholds elevation in the carbogen group was smaller than those in the control and oxygen group (p <0.05). Carbogen inhalation produced a trend toward less threshold shift after noise exposure, which reached statistical significance after day 3 (p <0.01). Respiratory acidosis was not found in our study. The segmented basal membranes of Corti in three groups indicated that no losses or discorders of hair cells were found. Carbogen inhalation can preserve hearing in animal models after acute acoustic trauma. Copyright © 2012 IMSS. All rights reserved.

Cerebral Microcirculation and Oxygen Tension in the Human Secondary Cortex

PubMed Central

Linninger, A. A.; Gould, I. G.; Marinnan, T.; Hsu, C.-Y.; Chojecki, M.; Alaraj, A.

2013-01-01

The three-dimensional spatial arrangement of the cortical microcirculatory system is critical for understanding oxygen exchange between blood vessels and brain cells. A three-dimensional computer model of a 3 × 3 × 3 mm3 subsection of the human secondary cortex was constructed to quantify oxygen advection in the microcirculation, tissue oxygen perfusion, and consumption in the human cortex. This computer model accounts for all arterial, capillary and venous blood vessels of the cerebral microvascular bed as well as brain tissue occupying the extravascular space. Microvessels were assembled with optimization algorithms emulating angiogenic growth; a realistic capillary bed was built with space filling procedures. The extravascular tissue was modeled as a porous medium supplied with oxygen by advection–diffusion to match normal metabolic oxygen demand. The resulting synthetic computer generated network matches prior measured morphometrics and fractal patterns of the cortical microvasculature. This morphologically accurate, physiologically consistent, multi-scale computer network of the cerebral microcirculation predicts the oxygen exchange of cortical blood vessels with the surrounding gray matter. Oxygen tension subject to blood pressure and flow conditions were computed and validated for the blood as well as brain tissue. Oxygen gradients along arterioles, capillaries and veins agreed with in vivo trends observed recently in imaging studies within experimental tolerances and uncertainty. PMID:23842693

High-Efficiency Multiscale Modeling of Cell Deformations in Confined Microenvironments in Microcirculation and Microfluidics

NASA Astrophysics Data System (ADS)

Lu, Huijie; Peng, Zhangli

2017-11-01

We developed a high-efficiency multiscale modeling method to predict the stress and deformation of cells during the interactions with their microenvironments in microcirculation and microfluidics, including red blood cells (RBCs) and circulating tumor cells (CTCs). There are more than 1 billion people in the world suffering from RBC diseases. The mechanical properties of RBCs are changed in these diseases due to molecular structure alternations, which is not only important for understanding the disease pathology but also provides an opportunity for diagnostics. On the other hand, the mechanical properties of cancer cells are also altered compared to healthy cells. This can lead to acquired ability to cross the narrow capillary networks and endothelial gaps, which is crucial for metastasis, the leading cause of cancer mortality. Therefore, it is important to predict the deformation and stress of RBCs and CTCs in microcirculations. We develop a high-efficiency multiscale model of cell-fluid interaction. We pass the information from our molecular scale models to the cell scale to study the effect of molecular mutations. Using our high-efficiency boundary element methods of fluids, we will be able to run 3D simulations using a single CPU within several hours, which will enable us to run extensive parametric studies and optimization.

Dynamic Flow Velocity Mapping from Fluorescent Dye Transit Times in the Brain Surface Microcirculation of Anesthetized Rats and Mice.

PubMed

Hoshikawa, Ryo; Kawaguchi, Hiroshi; Takuwa, Hiroyuki; Ikoma, Yoko; Tomita, Yutaka; Unekawa, Miyuki; Suzuki, Norihiro; Kanno, Iwao; Masamoto, Kazuto

2016-08-01

This study aimed to develop a new method for mapping blood flow velocity based on the spatial evolution of fluorescent dye transit times captured with CLSFM in the cerebral microcirculation of anesthetized rodents. The animals were anesthetized with isoflurane, and a small amount of fluorescent dye was intravenously injected to label blood plasma. The CLSFM was conducted through a closed cranial window to capture propagation of the dye in the cortical vessels. The transit time of the dye over a certain distance in a single vessel was determined with automated image analyses, and average flow velocity was mapped in each vessel. The average flow velocity measured in the rat pial artery and vein was 4.4 ± 1.2 and 2.4 ± 0.5 mm/sec, respectively. A similar range of flow velocity to those of the rats was observed in the mice; 4.9 ± 1.4 and 2.0 ± 0.9 mm/sec, respectively, although the vessel diameter in the mice was about half of that in the rats. Flow velocity in the cerebral microcirculation can be mapped based on fluorescent dye transit time measurements with conventional CLSFM in experimental animals. © 2016 John Wiley & Sons Ltd.

Amazon rainforest exchange of carbon and subcanopy air flow: Manaus LBA site--a complex terrain condition.

PubMed

Tóta, Julio; Fitzjarrald, David Roy; da Silva Dias, Maria A F

2012-01-01

On the moderately complex terrain covered by dense tropical Amazon Rainforest (Reserva Biologica do Cuieiras--ZF2--02°36'17.1'' S, 60°12'24.4'' W), subcanopy horizontal and vertical gradients of the air temperature, CO(2) concentration and wind field were measured for the dry and wet periods in 2006. We tested the hypothesis that horizontal drainage flow over this study area is significant and can affect the interpretation of the high carbon uptake rates reported by previous works at this site. A similar experimental design as the one by Tóta et al. (2008) was used with a network of wind, air temperature, and CO(2) sensors above and below the forest canopy. A persistent and systematic subcanopy nighttime upslope (positive buoyancy) and daytime downslope (negative buoyancy) flow pattern on a moderately inclined slope (12%) was observed. The microcirculations observed above the canopy (38 m) over the sloping area during nighttime presents a downward motion indicating vertical convergence and correspondent horizontal divergence toward the valley area. During the daytime an inverse pattern was observed. The micro-circulations above the canopy were driven mainly by buoyancy balancing the pressure gradient forces. In the subcanopy space the microcirculations were also driven by the same physical mechanisms but probably with the stress forcing contribution. The results also indicated that the horizontal and vertical scalar gradients (e.g., CO(2)) were modulated by these micro-circulations above and below the canopy, suggesting that estimates of advection using previous experimental approaches are not appropriate due to the tridimensional nature of the vertical and horizontal transport locally. This work also indicates that carbon budget from tower-based measurement is not enough to close the system, and one needs to include horizontal and vertical advection transport of CO(2) into those estimates.

In vivo imaging of mammalian cochlear blood flow using fluorescence microendoscopy.

PubMed

Monfared, Ashkan; Blevins, Nikolas H; Cheung, Eunice L M; Jung, Juergen C; Popelka, Gerald; Schnitzer, Mark J

2006-02-01

We sought to develop techniques for visualizing cochlear blood flow in live mammalian subjects using fluorescence microendoscopy. Inner ear microcirculation appears to be intimately involved in cochlear function. Blood velocity measurements suggest that intense sounds can alter cochlear blood flow. Disruption of cochlear blood flow may be a significant cause of hearing impairment, including sudden sensorineural hearing loss. However, inability to image cochlear blood flow in a nondestructive manner has limited investigation of the role of inner ear microcirculation in hearing function. Present techniques for imaging cochlear microcirculation using intravital light microscopy involve extensive perturbations to cochlear structure, precluding application in human patients. The few previous endoscopy studies of the cochlea have suffered from optical resolution insufficient for visualizing cochlear microvasculature. Fluorescence microendoscopy is an emerging minimally invasive imaging modality that provides micron-scale resolution in tissues inaccessible to light microscopy. In this article, we describe the use of fluorescence microendoscopy in live guinea pigs to image capillary blood flow and movements of individual red blood cells within the basal turn of the cochlea. We anesthetized eight adult guinea pigs and accessed the inner ear through the mastoid bulla. After intravenous injection of fluorescein dye, we made a limited cochleostomy and introduced a compound doublet gradient refractive index endoscope probe 1 mm in diameter into the inner ear. We then imaged cochlear blood flow within individual vessels in an epifluorescence configuration using one-photon fluorescence microendoscopy. We observed single red blood cells passing through individual capillaries in several cochlear structures, including the round window membrane, spiral ligament, osseous spiral lamina, and basilar membrane. Blood flow velocities within inner ear capillaries varied widely, with observed speeds reaching up to approximately 500 microm/s. Fluorescence microendoscopy permits visualization of cochlear microcirculation with micron-scale optical resolution and determination of blood flow velocities through analysis of video sequences.

Temporal and spatiotemporal variability in comprehensive forearm skin microcirculation assessment during occlusion protocols.

PubMed

Strömberg, Tomas; Sjöberg, Folke; Bergstrand, Sara

2017-09-01

Forearm skin hyperemia during release after brachial occlusion has been proposed for evaluating peripheral arterial disease and endothelial dysfunction. We used a novel fiberoptic system integrating Laser Doppler Flowmetry and Diffuse Reflectance Spectroscopy for a comprehensive pointwise model based microcirculation characterization. The aim was to evaluate and compare the temporal and the spatiotemporal variabilities in forearm skin microcirculation parameters (speed resolved perfusion; low speed <1mm/s, Perf SR, <1 ; mid-speed 1-10mm/s, high speed >10mm/s, and total perfusion (Perf SR, tot ); the concentration and oxygenation of red blood cells, C RBC and S O2 ). Ten healthy subjects underwent arterial and venous forearm occlusions (AO, VO), repeated within one week. The repeatability was calculated as the coefficient of variation (CV) and the agreement as the intra-class correlation coefficient (ICC). The temporal CVs for conventional perfusion, Perf conv , Perf SR, tot , C RBC and S O2 were 14%, 12%, 9% and 9%, respectively, while the ICC were >0.75 (excellent). The perfusion measures generally had a higher spatiotemporal than temporal variability, which was not the case for S O2 and C RBC . The corresponding spatiotemporal CVs were 33%, 32%, 18% and 15%, respectively. During VO, C RBC had a CV<35% and ICC>0.40 (fair-good), and after release this was the case for C RBC (AO and VO), S O2 (VO) and Perf SR, <1 (VO). In conclusion, the skin microcirculation parameters showed excellent temporal repeatability, while the spatiotemporal repeatability especially for perfusion was poorer. The parameters with acceptable repeatability and fair-good agreement were: C RBC during and after release of VO, the Perf SR, <1 after release of VO, the S O2 and the C RBC after release of AO. However, the value of these parameters in discriminating endothelial function remains to be studied. Copyright © 2017 Elsevier Inc. All rights reserved.

Amazon Rainforest Exchange of Carbon and Subcanopy Air Flow: Manaus LBA Site—A Complex Terrain Condition

PubMed Central

Tóta, Julio; Roy Fitzjarrald, David; da Silva Dias, Maria A. F.

2012-01-01

On the moderately complex terrain covered by dense tropical Amazon Rainforest (Reserva Biologica do Cuieiras—ZF2—02°36′17.1′′ S, 60°12′24.4′′ W), subcanopy horizontal and vertical gradients of the air temperature, CO2 concentration and wind field were measured for the dry and wet periods in 2006. We tested the hypothesis that horizontal drainage flow over this study area is significant and can affect the interpretation of the high carbon uptake rates reported by previous works at this site. A similar experimental design as the one by Tóta et al. (2008) was used with a network of wind, air temperature, and CO2 sensors above and below the forest canopy. A persistent and systematic subcanopy nighttime upslope (positive buoyancy) and daytime downslope (negative buoyancy) flow pattern on a moderately inclined slope (12%) was observed. The microcirculations observed above the canopy (38 m) over the sloping area during nighttime presents a downward motion indicating vertical convergence and correspondent horizontal divergence toward the valley area. During the daytime an inverse pattern was observed. The micro-circulations above the canopy were driven mainly by buoyancy balancing the pressure gradient forces. In the subcanopy space the microcirculations were also driven by the same physical mechanisms but probably with the stress forcing contribution. The results also indicated that the horizontal and vertical scalar gradients (e.g., CO2) were modulated by these micro-circulations above and below the canopy, suggesting that estimates of advection using previous experimental approaches are not appropriate due to the tridimensional nature of the vertical and horizontal transport locally. This work also indicates that carbon budget from tower-based measurement is not enough to close the system, and one needs to include horizontal and vertical advection transport of CO2 into those estimates. PMID:22619608

Microcirculation and structural reorganization of the bladder mucosa in chronic cystitis under conditions of ozone therapy.

PubMed

Neimark, A I; Nepomnyashchikh, L M; Lushnikova, E L; Bakarev, M A; Abdullaev, N A; Sizov, K A

2014-01-01

Structural reorganization of the bladder mucosa in chronic cystitis and its correction by ozone therapy were studied. A relationship between the epithelial layer restructuring of different kinds (dystrophy, metaplasia, and degeneration), level of cell proliferation, and ultrastructural organization of urotheliocytes was detected. This complex of structural reactions was combined with dysregulation of tissue bloodflow in the bladder mucosa, shown by laser Doppler flowmetry. Positive structural changes were most marked in intravesical and less so in parenteral ozone therapy added to the therapeutic complex and manifested in reduction of inflammation and alteration in parallel with more intense reparative reactions. A special feature of parenteral ozone therapy was a significant improvement of microcirculation in the bladder mucosa.

Ultrasound microscope: the new field in ultrasound diagnostics

NASA Astrophysics Data System (ADS)

Novyc'kyy, Victor V.; Lushchyk, Ulyana B.

2001-06-01

A device which is a new stage in the development of medical equipment has been developed. The device works as an ultrasound microscope in vivo and provides 4 up to 32 colored histological image. It gives possibility to estimate tissue acoustic density with the help of 4 up to 32 gradation coloring different tissues and enables tissue microcirculation visualization. With the help of the device a doctor can objectify fatty hepatitis and cirrhosis, edema of different organs and tissues as well as microcirculation in organs and tissues (e.g. muscles, myocard and bone system). New promising applications of ultrasound systems in diagnostics and for choosing individual treatment tactics, with pathogenesis being taken into account, may be developed with the help of the device.

An endoscopic laser Doppler flowmetry of a gastroduodenal mucosa at bleeding ulcer

NASA Astrophysics Data System (ADS)

Shapkin, U. G.; Kapralov, C. V.; Gogolev, A. A.; Lychagov, V. V.; Tuchin, V. V.

2006-08-01

One of the important problems of a bleeding gastroduodenal ulcer surgery is a prognosis of the recurrent hemorrhage and appraisal of endoscopic hemostasis quality. Endoscopic Laser Doppler Flowmetry of a mucous coat of stomach and a duodenum was made on 34 patients for the purpose of investigation of features of microcirculation. Analogous researches are made on 30 patients with a peptic ulcer and on 28 practically healthy people. Analysis of LDF-grams has shown certain differences in regional microcirculations in stomach and duodenal at normal and at a pathology. Increase of regional perfusion in periulcerose zone with its pathology disbalance can serve as a criterion for activities of an alteration processes in gastroduodenal ulcer defining the risk of possible hemorrhage.

Longitudinal studies on the microcirculation around the TheraCyte immunoisolation device, using the laser Doppler technique.

PubMed

Rafael, E; Gazelius, B; Wu, G S; Tibell, A

2000-01-01

Encapsulation of cellular grafts in an immunoisolation membrane device may make it possible to perform transplantation without having to give immunosuppressive drugs. A common problem is the development of an avascular fibrotic zone around the implants, leading to impaired graft survival. The TheraCyte macroencapsulation device has therefore been designed to facilitate neovascularization of the device's surface. In this study, we evaluated the microcirculation around empty TheraCyte devices implanted SC in rats at various times after implantation, using a laser Doppler probe introduced via the device port. Studies were performed on day 1 or at 1, 2, and 4 weeks or at 2, 3, and 12 months after implantation. The mean flow was 158+/-42, 148+/-50, 133+/-28, 72+/-17, 138+/-41, 165+/-43, and 160+/-29 perfusion units (PU), respectively. Thus, the microcirculation around the device was significantly reduced at 4 weeks after implantation (p < 0.01) while, from 2 months onwards the circulation had improved and did not differ significantly from that on day 1. The present study shows time-related changes in the microcirculatory flow around TheraCyte macroencapsulation devices that agree with our previous microdialysis studies on in vivo exchange of insulin and glucose between the device and the circulation. Laser Doppler flowmetry seems to provide a reliable technique for screening blood perfusion around macroencapsulation devices.

Endothelin-a receptor antagonist treatment improves the periosteal microcirculation after hindlimb ischemia and reperfusion in the rat.

PubMed

Wolfárd, Antal; Császár, József; Gera, László; Petri, András; Simonka, János Aurél; Balogh, Adáa; Boros, Mihály

2002-12-01

To examine the microcirculatory changes in the rat tibial periosteum after hindlimb ischemia and reperfusion and to evaluate the effects of endothelin-A (ET-A) receptor antagonist therapy in this condition. The healing and functioning of vascularized bone autografts depend mainly on the patency of the microcirculation, and the activation of ET-A receptors may be an important component of the tissue response that occurs during ischemia-reoxygenation injuries. Wistar rats were subjected to 1 hour of hindlimb ischemia and 3 hours of reperfusion. The periosteal microcirculation was visualized by intravital fluorescence microscopy. The leukocyte rolling and adherence in the postcapillary venules and the functional capillary density of the periosteum were determined. Two separate groups were treated with the selective ET-A receptor antagonist BQ 610 or the novel ET-A receptor antagonist ETR-p1/fl peptide at the onset of reperfusion. Reperfusion was accompanied by a significant decrease in functional capillary density and by an increase in the primary and secondary leukocyte-endothelial cell interactions. ET-A receptor inhibition reduced the leukocyte rolling and firm adherence and attenuated the decrease in functional capillary density in both treated groups. ET-1 plays a major role in microvascular dysfunction in the periosteum during reperfusion. The ET-1-ET-A receptor system might be an important target for tissue salvage therapy in transplantation surgery.

Cerebral microcirculation shear stress levels determine Neisseria meningitidis attachment sites along the blood–brain barrier

PubMed Central

Mairey, Emilie; Genovesio, Auguste; Donnadieu, Emmanuel; Bernard, Christine; Jaubert, Francis; Pinard, Elisabeth; Seylaz, Jacques; Olivo-Marin, Jean-Christophe; Nassif, Xavier; Duménil, Guillaume

2006-01-01

Neisseria meningitidis is a commensal bacterium of the human nasopharynx. Occasionally, this bacterium reaches the bloodstream and causes meningitis after crossing the blood–brain barrier by an unknown mechanism. An immunohistological study of a meningococcal sepsis case revealed that neisserial adhesion was restricted to capillaries located in low blood flow regions in the infected organs. This study led to the hypothesis that drag forces encountered by the meningococcus in the bloodstream determine its attachment site in vessels. We therefore investigated the ability of N. meningitidis to bind to endothelial cells in the presence of liquid flow mimicking the bloodstream with a laminar flow chamber. Strikingly, average blood flows reported for various organs strongly inhibited initial adhesion. As cerebral microcirculation is known to be highly heterogeneous, cerebral blood velocity was investigated at the level of individual vessels using intravital imaging of rat brain. In agreement with the histological study, shear stress levels compatible with meningococcal adhesion were only observed in capillaries, which exhibited transient reductions in flow. The flow chamber assay revealed that, after initial attachment, bacteria resisted high blood velocities and even multiplied, forming microcolonies resembling those observed in the septicemia case. These results argue that the combined mechanical properties of neisserial adhesion and blood microcirculation target meningococci to transiently underperfused cerebral capillaries and thus determine disease development. PMID:16864659

Quantitative estimation of antioxidant therapy efficiency in diabetes mellitus patients

NASA Astrophysics Data System (ADS)

Gurfinkel, Youri I.; Ishunina, Angela M.; Ovsyannickov, Konstantin V.; Strokov, Igor A.

2000-11-01

The aim of this work was to find out to which degree Tanakan affects the microcirculation parameters and the malonic dialdehyde level as a parameter of intense lipid peroxidation in insulin-independent diabetes patients with different disease durations. We used computerized capillaroscope GY-0.04 designed by the Centre for Analysis of Substances, Russia for the non-invasive measurement of capillary blood velocity as well as the size of the perivascular zone and density of blood aggregates and lipid inclusions. The microcirculation parameters were studied in two groups of insulin-independent diabetes patients. The basic group included 58 patients (61+/-9,0 years, disease duration 14,7+/-7,8 years). The patients had late diabetic complications as retinopathy and nephrophathy, neuropathy, confirmed by clinical and tool investigation. In this group we also studied the level of serum malonic dialdehyde, as a parameter of intense lipid peroxidation. The reference group included 31 patients (57+/-1,3 years, disease duration 3,6+/-0,6 years) with minimum diabetic complication. We show that Tanakan in daily dosage 120 mg for 2 months reduces the malonic dialdehyde level in the blood serum and the erythrocyte membranes of type II diabetes patients and improves the microcirculation parameters. There are correspondences between the density of lipid inclusions as determined with computerized capillaroscopy and the lipid exchange parameters as determined using a routing blood test. Thus, noninvasive blood lipid quantification is feasible and reliable.

Pilot Study of Laser Doppler Measurement of Flow Variability in the Microcirculation of the Palatal Mucosa

PubMed Central

Le Bars, Pierre; Niagha, Gaston; Kouadio, Ayepa Alain; Demoersman, Julien; Roy, Elisabeth; Armengol, Valérie; Soueidan, Assem

2016-01-01

Background. Histopathological alterations can arise when the denture-supporting mucosa experiences microbial and mechanical stress through the denture base and diagnosis of these diseases usually follows microvascular changes. Microcirculation measurement could allow for detection of such dysfunction and aid in the early diagnosis of palatal mucosa pathologies. Materials and Methods. We tested the sensitivity of laser Doppler for measuring the microcirculation of the palatal mucosa, assessing the median raphe (MR), Schroeder area (SA), and retroincisive papilla (RP). A Doppler PeriFlux 5000 System, containing a laser diode, was used. 54 healthy participants were recruited. We compare the measurements of PU (perfusion unit) using ANOVA test. Results. The numerical values for palatal mucosa blood flow differed significantly among the anatomical areas (p = 0.0167). The mean value of Schroeder area was 92.6 (SD: 38.4) and was significantly higher than the retroincisive papilla (51.9) (SD: 20.2) (p < 0.05), which in turn was higher than that of median raphe (31.9) (SD: 24.2) (p < 0.0001). Conclusion. Schroeder area appeared to have the greatest sensitivity, and vascular flow variability among individuals was also greatest in this region. We suggest that analysis of blood stream modification with laser Doppler of the palatal mucosa can help to detect onset signs of pathological alterations. PMID:27340663

Modeling malaria infected cells in microcirculation

NASA Astrophysics Data System (ADS)

Raffiee, Amir Hossein; Dabiri, Sadegh; Motavalizadeh Ardekani, Arezoo

2016-11-01

Plasmodim (P.) falciparum is one of the deadliest types of malaria species that invades healthy red blood cells (RBC) in human blood flow. This parasite develops through 48-hour intra-RBC process leading to significant morphological and mechanical (e.g., stiffening) changes in RBC membrane. These changes have remarkable effects on blood circulation such as increase in flow resistance and obstruction in microcirculation. In this work a computational framework is developed to model RBC suspension in blood flow using front-tracking technique. The present study focuses on blood flow behavior under normal and infected circumstances and predicts changes in blood rheology for different levels of parasitemia and hematocrit. This model allows better understanding of blood flow circulation up to a single cell level and provides us with realistic and deep insight into hematologic diseases such as malaria.

Label-free and highly sensitive optical imaging of detailed microcirculation within meninges and cortex in mice with the cranium left intact

NASA Astrophysics Data System (ADS)

Jia, Yali; An, Lin; Wang, Ruikang K.

2010-05-01

We demonstrate for the first time that the detailed blood flow distribution within intracranial dura mater and cortex can be visualized by an ultrahigh sensitive optical microangiography (UHS-OMAG). The study uses an UHS-OMAG system operating at 1310 nm with an imaging speed at 150 frames per second that requires ~10 s to complete one 3-D scan of ~2.5×2.5 mm2. The system is sensitive to blood flow with a velocity ranging from ~4 μm/s to ~23 mm/s. We show superior performance of UHS-OMAG in providing functional images of capillary level microcirculation within meninges in mice with the cranium left intact, the results of which correlate well with the standard dural histopathology.

Microcirculation and the physiome projects.

PubMed

Bassingthwaighte, James B

2008-11-01

The Physiome projects comprise a loosely knit worldwide effort to define the Physiome through databases and theoretical models, with the goal of better understanding the integrative functions of cells, organs, and organisms. The projects involve developing and archiving models, providing centralized databases, and linking experimental information and models from many laboratories into self-consistent frameworks. Increasingly accurate and complete models that embody quantitative biological hypotheses, adhere to high standards, and are publicly available and reproducible, together with refined and curated data, will enable biological scientists to advance integrative, analytical, and predictive approaches to the study of medicine and physiology. This review discusses the rationale and history of the Physiome projects, the role of theoretical models in the development of the Physiome, and the current status of efforts in this area addressing the microcirculation.

Increased NO bioavailability in aging male rats by genistein and exercise training: using 4, 5-diaminofluorescein diacetate.

PubMed

Eksakulkla, Sukanya; Suksom, Daroonwan; Siriviriyakul, Prasong; Patumraj, Suthiluk

2009-09-07

Several kinds of anti-oxidants have drawn a lot of intention for their benefits on vascular protection. In addition, it has been demonstrated that exercise training could improve endothelial function by up-regulating endothelial nitric oxide synthase (eNOS) protein. Therefore, the present study aims to investigate the effects of genistein, a potent phyto-antioxidant, and exercise training on age-induced endothelial dysfunction in relation to NO bioavailability using in situ NO-sensitive fluorescent dye detection. Male Wistar rats (20-22-month old) were divided into four groups: aged rats treated with corn oil, (Aged+Veh, n = 5), aged rats treated with genistein (Aged+Gen, n = 5, (0.25 mg/kg BW/day, s.c.)), aged rats with and without exercise training (Aged+Ex, n = 5, swimming 40 min/day, 5 days/week for 8 weeks) (Aged+Without-Ex, n = 5). Cremaster arterioles (15-35 micrometer) were visualized by fluorescein isothiocyanate labeled dextran (5 microgram/ml). The vascular response to acetylcholine (Ach; 10(-5)M, 5 ml/5 min) was accessed after 1-min norepinephrine preconstriction (10 micro molar). To determine NO bioavailability, the Krebs-Ringer buffer with 4, 5-diaminofluorescein-diacetate (3 micro molar DAF-2DA), and 10 micro- molar Ach saturated with 95%N2 and 5%CO2 were used. Changes of DAF-2T-intensities along the cremaster arterioles were analyzed by the Image Pro-Plus Software (Media Cybernatics, Inc, USA). Liver malondialdehyde (MDA) level was measured by thiobarbituric acid reaction and used as an indicator for oxidative stress. The results showed that means arterial blood pressure for both Aged+Gen and Aged+Ex groups were significantly reduced when compared to the Aged groups, Aged+Veh and Aged+Without-Ex (P < 0.05). Among the treated groups, Ach-induced vasodilatation were significantly increased (P < 0.05) and was associated with increased NO-associated fluorescent intensities (P < 0.05). On the other hand, MDA levels were significantly reduced (P < 0.05) when Aged+Veh was compared to Aged+Without-Ex. These findings showed that genistein and exercise training could improve age-induced endothelial dysfunction and is related to the increased NO bioavailability.

Implications Enzymatic Degradation of the Endothelial Glycocalyx on the Microvascular Hemodynamics and the Arteriolar Red Cell Free Layer of the Rat Cremaster Muscle.

PubMed

Yalcin, Ozlem; Jani, Vivek P; Johnson, Paul C; Cabrales, Pedro

2018-01-01

The endothelial glycocalyx is a complex network of glycoproteins, proteoglycans, and glycosaminoglycans; it lines the vascular endothelial cells facing the lumen of blood vessels forming the endothelial glycocalyx layer (EGL). This study aims to investigate the microvascular hemodynamics implications of the EGL by quantifying changes in blood flow hydrodynamics post-enzymatic degradation of the glycocalyx layer. High-speed intravital microscopy videos of small arteries (around 35 μm) of the rat cremaster muscle were recorded at various time points after enzymatic degradation of the EGL. The thickness of the cell free layer (CFL), blood flow velocity profiles, and volumetric flow rates were quantified. Hydrodynamic effects of the presence of the EGL were observed in the differences between the thickness of CFL in microvessels with an intact EGL and glass tubes of similar diameters. Maximal changes in the thickness of CFL were observed 40 min post-enzymatic degradation of the EGL. Analysis of the frequency distribution of the thickness of CFL allows for estimation of the thickness of the endothelial surface layer (ESL), the plasma layer, and the glycocalyx. Peak flow, maximum velocity, and mean velocity were found to statistically increase by 24, 27, and 25%, respectively, after enzymatic degradation of the glycocalyx. The change in peak-to-peak maximum velocity and mean velocity were found to statistically increase by 39 and 32%, respectively, after 40 min post-enzymatic degradation of the EGL. The bluntness of blood flow velocity profiles was found to be reduced post-degradation of the EGL, as the exclusion volume occupied by the EGL increased the effective volume impermeable to RBCs in microvessels. This study presents the effects of the EGL on microvascular hemodynamics. Enzymatic degradation of the EGL resulted in a decrease in the thickness of CFL, an increase in blood velocity, blood flow, and decrease of the bluntness of the blood flow velocity profile in small arterioles. In summary, the EGL functions as a molecular sieve to solute transport and as a lubrication layer to protect the endothelium from red blood cell (RBC) motion near the vessel wall, determining wall shear stress.

Intravoxel incoherent motion (IVIM) imaging in human achilles tendon.

PubMed

Wengler, Kenneth; Fukuda, Takeshi; Tank, Dharmesh; Huang, Mingqian; Gould, Elaine S; Schweitzer, Mark E; He, Xiang

2018-05-09

Limited microcirculation has been implicated in Achilles tendinopathy and may affect healing and disease progression. Existing invasive and noninvasive approaches to evaluate tendon microcirculation lack sensitivity and spatial coverage. To develop a novel Achilles tendon intravoxel incoherent motion (IVIM) MRI protocol to overcome the limitations from low tendon T 2 /T 2 * value and low intratendinous blood volume and blood velocity to evaluate tendon microcirculation. Prospective. Sixteen healthy male participants (age 31.0 ± 2.1) were recruited. A stimulated echo readout-segmented echo planar imaging (ste-RS-EPI) IVIM sequence at 3.0T. The feasibility of the proposed ste-RS-EPI IVIM protocol combined with Achilles tendon magic angle effect was evaluated. The sensitivity of the protocol was assessed by an exercise-induced intratendinous hemodynamic response in healthy participants. The vascular origin of the observed IVIM signal was validated by varying the diffusion mixing time and echo time. Two-tailed t-tests were used to evaluate differences (P < 0.05 was considered significant). Consistent with known tendon hypovascularity, the midportion Achilles tendon at baseline showed significantly lower IVIM-derived perfusion fraction (f p ) (3.1 ± 0.9%) compared to the proximal and distal Achilles tendon (6.0 ± 1.8% and 6.1 ± 2.0%, respectively; P < 0.01). Similarly, the midportion Achilles tendon exhibited significantly lower baseline blood flow index (D*×f p ) (40.9 ± 19.2, 18.3 ± 5.3, and 32.0 ± 9.4 in proximal, midportion, and distal Achilles tendon, respectively; P < 0.01). Eccentric heel-raise exercise led to ∼2 times increase of Achilles tendon blood flow in healthy participants. Consistent with its vascular origin, the estimated f p demonstrated a high dependency to IVIM protocol parameters, while the T 1 /T 2 -corrected absolute intratendinous microvascular blood volume fraction (V b ) did not vary. Achilles tendon ste-RS-EPI IVIM noninvasively assessed baseline values and exercise-induced changes to tendon microcirculation in healthy tendon. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Midportion achilles tendon microcirculation after intermittent combined cryotherapy and compression compared with cryotherapy alone: a randomized trial.

PubMed

Knobloch, Karsten; Grasemann, Ruth; Spies, Marcus; Vogt, Peter M

2008-11-01

The effect of combined cryotherapy/compression versus cryotherapy alone on the Achilles tendon is undetermined. Standardized combined cryotherapy/compression changes in midportion Achilles tendon microcirculation are superior to those with cryotherapy during intermittent application. Controlled laboratory study. Sixty volunteers were randomized for either combined cryotherapy/compression (Cryo/Cuff, DJO Inc, Vista, California: n = 30; 32 +/- 11 years) or cryotherapy alone (KoldBlue, TLP Industries, Kent, United Kingdom: n = 30; 33 +/- 12 years) with intermittent 3 x 10-minute application. Midportion Achilles tendon microcirculation was determined (O2C, LEA Medizintechnik, Giessen, Germany). Both Cryo/Cuff and KoldBlue significantly reduced superficial and deep capillary tendon blood flow within the first minute of application (43 +/- 46 arbitrary units [AU] vs 10 +/- 19 AU and 42 +/- 46 AU vs 12 +/- 10 AU; P = .0001) without a significant difference throughout all 3 applications. However, during recovery, superficial and deep capillary blood flow was reestablished significantly faster using Cryo/Cuff (P = .023). Tendon oxygen saturation was reduced in both groups significantly (3 minutes Cryo/Cuff: 36% +/- 20% vs 16% +/- 15%; KoldBlue: 42% +/- 19% vs 28% +/- 20%; P < .05) with significantly stronger effects using Cryo/Cuff (P = .014). Cryo/Cuff led to significantly higher tendon oxygenation (Cryo/Cuff: 62% +/- 28% vs baseline 36% +/- 20%; P = .0001) in superficial and deep tissue (Cryo/Cuff: 73% +/- 14% vs baseline 65% +/- 17%; P = .0001) compared with KoldBlue during all recoveries. Postcapillary venous filling pressures were significantly reduced in both groups during application; however, Cryo/Cuff led to significantly, but marginally, lower pressures (Cryo/Cuff: 41 +/- 7 AU vs baseline 51 +/- 13 AU; P = .0001 and KoldBlue: 46 +/- 7 AU vs baseline 56 +/- 11 AU; P = .026 for Cryo/Cuff vs KoldBlue). Increased tendon oxygenation is achieved as tendon preconditioning by combined cryotherapy and compression with significantly increased tendon oxygen saturation during recovery in contrast to cryotherapy alone. Both regimens lead to a significant amelioration of tendinous venous outflow. Combined cryotherapy and compression is superior to cryotherapy alone regarding the Achilles tendon microcirculation. Further studies in tendinopathy and tendon rehabilitation are warranted to elucidate its value regarding functional issues.

Model based inference from microvascular measurements: Combining experimental measurements and model predictions using a Bayesian probabilistic approach

PubMed Central

Rasmussen, Peter M.; Smith, Amy F.; Sakadžić, Sava; Boas, David A.; Pries, Axel R.; Secomb, Timothy W.; Østergaard, Leif

2017-01-01

Objective In vivo imaging of the microcirculation and network-oriented modeling have emerged as powerful means of studying microvascular function and understanding its physiological significance. Network-oriented modeling may provide the means of summarizing vast amounts of data produced by high-throughput imaging techniques in terms of key, physiological indices. To estimate such indices with sufficient certainty, however, network-oriented analysis must be robust to the inevitable presence of uncertainty due to measurement errors as well as model errors. Methods We propose the Bayesian probabilistic data analysis framework as a means of integrating experimental measurements and network model simulations into a combined and statistically coherent analysis. The framework naturally handles noisy measurements and provides posterior distributions of model parameters as well as physiological indices associated with uncertainty. Results We applied the analysis framework to experimental data from three rat mesentery networks and one mouse brain cortex network. We inferred distributions for more than five hundred unknown pressure and hematocrit boundary conditions. Model predictions were consistent with previous analyses, and remained robust when measurements were omitted from model calibration. Conclusion Our Bayesian probabilistic approach may be suitable for optimizing data acquisition and for analyzing and reporting large datasets acquired as part of microvascular imaging studies. PMID:27987383

[transcutaneous oximetry--between theory and practice].

PubMed

Zulec, Mirna

2014-10-01

Transcutaneous oximetry is a procedure used to measure the pressure of oxygen in tissue and to determine oxygenation level. It is essential to determine the state of microcirculation and is used to assess the necessity and level of amputation and the effect of revascularization procedures, as a predictor of wound healing and hyperbaric oxygen therapy (HBOT) effectiveness tool. The measurement is done by the application electrode measuring point and the result is measured in mm Hg. Tissue with adequate oxygen level has a value greater than 50 mm Hg. Values between 20 and 40 mm Hg are considered hypoxic, while those below 20 mm Hg indicate extreme hypoxia. In Croatia, TcPO2 is commonly used for HBOT assessment but there is the need of broader application to objectify and facilitate procedures in the care of persons with impaired microcirculation.

[Physiological features of skin ageing in human].

PubMed

Tikhonova, I V; Tankanag, A V; Chemeris, N K

2013-01-01

The issue deals with the actual problem of gerontology, notably physiological features of human skin ageing. In the present review the authors have considered the kinds of ageing, central factors, affected on the ageing process (ultraviolet radiation and oxidation stress), as well as the research guidelines of the ageing changes in the skin structure and fuctions: study of mechanical properties, microcirculation, pH and skin thickness. The special attention has been payed to the methods of assessment of skin blood flow, and to results of investigations of age features of peripheral microhemodynamics. The laser Doppler flowmetry technique - one of the modern, noninvasive and extensively used methods for the assessmant of skin blood flow microcirculation system has been expanded in the review. The main results of the study of the ageing changes of skin blood perfusion using this method has been also presented.

Video-rate imaging of microcirculation with single-exposure oblique back-illumination microscopy

NASA Astrophysics Data System (ADS)

Ford, Tim N.; Mertz, Jerome

2013-06-01

Oblique back-illumination microscopy (OBM) is a new technique for simultaneous, independent measurements of phase gradients and absorption in thick scattering tissues based on widefield imaging. To date, OBM has been used with sequential camera exposures, which reduces temporal resolution, and can produce motion artifacts in dynamic samples. Here, a variation of OBM that allows single-exposure operation with wavelength multiplexing and image splitting with a Wollaston prism is introduced. Asymmetric anamorphic distortion induced by the prism is characterized and corrected in real time using a graphics-processing unit. To demonstrate the capacity of single-exposure OBM to perform artifact-free imaging of blood flow, video-rate movies of microcirculation in ovo in the chorioallantoic membrane of the developing chick are presented. Imaging is performed with a high-resolution rigid Hopkins lens suitable for endoscopy.

Haemodynamic coherence - The relevance of fluid therapy.

PubMed

Arnemann, Philip; Seidel, Laura; Ertmer, Christian

2016-12-01

The ultimate goal of fluid therapy is to improve the oxygenation of cells by improving the cardiac output, thus improving microcirculation by optimizing macrocirculation. This haemodynamic coherence is often altered in patients with haemorrhagic shock and sepsis. The loss of haemodynamic coherence is associated with adverse outcomes. It may be influenced by the mechanisms of the underlying disease and properties of different fluids used for resuscitation in these critically ill patients. Monitoring microcirculation and haemodynamic coherence may be an additional tool to predict the response to fluid administration. In addition, microcirculatory analysis may support the clinician in his decision to not administer fluids when microcirculatory blood flow is preserved. In future, the indication, guidance and termination of fluid therapy may be assessed by bedside microvascular analysis in combination with standard haemodynamic monitoring. Copyright © 2016 Elsevier Ltd. All rights reserved.

Video-rate imaging of microcirculation with single-exposure oblique back-illumination microscopy.

PubMed

Ford, Tim N; Mertz, Jerome

2013-06-01

Oblique back-illumination microscopy (OBM) is a new technique for simultaneous, independent measurements of phase gradients and absorption in thick scattering tissues based on widefield imaging. To date, OBM has been used with sequential camera exposures, which reduces temporal resolution, and can produce motion artifacts in dynamic samples. Here, a variation of OBM that allows single-exposure operation with wavelength multiplexing and image splitting with a Wollaston prism is introduced. Asymmetric anamorphic distortion induced by the prism is characterized and corrected in real time using a graphics-processing unit. To demonstrate the capacity of single-exposure OBM to perform artifact-free imaging of blood flow, video-rate movies of microcirculation in ovo in the chorioallantoic membrane of the developing chick are presented. Imaging is performed with a high-resolution rigid Hopkins lens suitable for endoscopy.

Label-free and highly sensitive optical imaging of detailed microcirculation within meninges and cortex in mice with the cranium left intact.

PubMed

Jia, Yali; An, Lin; Wang, Ruikang K

2010-01-01

We demonstrate for the first time that the detailed blood flow distribution within intracranial dura mater and cortex can be visualized by an ultrahigh sensitive optical microangiography (UHS-OMAG). The study uses an UHS-OMAG system operating at 1310 nm with an imaging speed at 150 frames per second that requires approximately 10 s to complete one 3-D scan of approximately 2.5 x 2.5 mm(2). The system is sensitive to blood flow with a velocity ranging from approximately 4 microms to approximately 23 mms. We show superior performance of UHS-OMAG in providing functional images of capillary level microcirculation within meninges in mice with the cranium left intact, the results of which correlate well with the standard dural histopathology.

Label-free and highly sensitive optical imaging of detailed microcirculation within meninges and cortex in mice with the cranium left intact

PubMed Central

Jia, Yali; An, Lin; Wang, Ruikang K.

2010-01-01

We demonstrate for the first time that the detailed blood flow distribution within intracranial dura mater and cortex can be visualized by an ultrahigh sensitive optical microangiography (UHS-OMAG). The study uses an UHS-OMAG system operating at 1310 nm with an imaging speed at 150 frames per second that requires ∼10 s to complete one 3-D scan of ∼2.5×2.5 mm2. The system is sensitive to blood flow with a velocity ranging from ∼4 μm∕s to ∼23 mm∕s. We show superior performance of UHS-OMAG in providing functional images of capillary level microcirculation within meninges in mice with the cranium left intact, the results of which correlate well with the standard dural histopathology. PMID:20614993

Nailfold Capillaroscopy in Rheumatic Diseases: Which Parameters Should Be Evaluated?

PubMed Central

Etehad Tavakol, Mahnaz; Erlandsson, Björn-Erik

2015-01-01

Video nailfold capillaroscopy (NFC), considered as an extension of the widefield technique, allows a more accurate measuring and storing of capillary data and a better defining, analyzing, and quantifying of capillary abnormalities. Capillaroscopic study is often performed on the patients suspected of having microcirculation problems such as Raynaud's phenomenon as the main indication for nailfold capillaroscopy. Capillaroscopic findings based on microcirculation studies can provide useful information in the fields of pathophysiology, differential diagnosis, and monitoring therapy. Nailfold capillaroscopy provides a vital assessment in clinical practices and research; for example, its reputation in the early diagnosis of systemic sclerosis is well established and it is also used as a classification criterion in this regard. This review focuses on the manner of performing video nailfold capillaroscopy and on a common approach for measuring capillary dimensions in fingers and toes. PMID:26421308

Nailfold Capillaroscopy in Rheumatic Diseases: Which Parameters Should Be Evaluated?

PubMed

Etehad Tavakol, Mahnaz; Fatemi, Alimohammad; Karbalaie, Abdolamir; Emrani, Zahra; Erlandsson, Björn-Erik

2015-01-01

Video nailfold capillaroscopy (NFC), considered as an extension of the widefield technique, allows a more accurate measuring and storing of capillary data and a better defining, analyzing, and quantifying of capillary abnormalities. Capillaroscopic study is often performed on the patients suspected of having microcirculation problems such as Raynaud's phenomenon as the main indication for nailfold capillaroscopy. Capillaroscopic findings based on microcirculation studies can provide useful information in the fields of pathophysiology, differential diagnosis, and monitoring therapy. Nailfold capillaroscopy provides a vital assessment in clinical practices and research; for example, its reputation in the early diagnosis of systemic sclerosis is well established and it is also used as a classification criterion in this regard. This review focuses on the manner of performing video nailfold capillaroscopy and on a common approach for measuring capillary dimensions in fingers and toes.

[Transcranial magnetotherapy for the correction of initial manifestations of diabetic retinopathy in children].

PubMed

Nikolaeva, N V; Bolotova, N V; Kamenskikh, T G; Raĭgorodskiĭ, Iu M; Kolbenev, I O; Luk'ianov, V F

2009-01-01

This study included 45 children at the age from 5 to 17 years with type I diabetes mellitus complicated by diabetic retinopathy. All the patients showed retinal thickening at the macula and reduced amplitude of local electroretinogram suggesting compromised capillary circulation. The capillary blood flow was corrected by transcranial magnetotherapy with the use of an AMO-ATOS Ogolovie unit. The results of the treatment were evaluated from characteristics of laser Doppler flometry. A course of transcranial magnetotherapy comprising 10 daily seances resulted in a significant increase of microcirculation index, respiratory rhythm, and myogenic tone (by 1.64, 1.35, and 1.16 times respectively). In addition, morphometric and electrophysiological properties of the retina underwent positive changes. Transcranial exposure to the traveling magnetic field is recommended for the correction of intraocular microcirculation and prevention of diabetic macular oedema.

A new contrast-assisted method in microcirculation volumetric flow assessment

NASA Astrophysics Data System (ADS)

Lu, Sheng-Yi; Chen, Yung-Sheng; Yeh, Chih-Kuang

2007-03-01

Microcirculation volumetric flow rate is a significant index in diseases diagnosis and treatment such as diabetes and cancer. In this study, we propose an integrated algorithm to assess microcirculation volumetric flow rate including estimation of blood perfused area and corresponding flow velocity maps based on high frequency destruction/contrast replenishment imaging technique. The perfused area indicates the blood flow regions including capillaries, arterioles and venules. Due to the echo variance changes between ultrasonic contrast agents (UCAs) pre- and post-destruction two images, the perfused area can be estimated by the correlation-based approach. The flow velocity distribution within the perfused area can be estimated by refilling time-intensity curves (TICs) after UCAs destruction. Most studies introduced the rising exponential model proposed by Wei (1998) to fit the TICs. Nevertheless, we found the TICs profile has a great resemblance to sigmoid function in simulations and in vitro experiments results. Good fitting correlation reveals that sigmoid model was more close to actual fact in describing destruction/contrast replenishment phenomenon. We derived that the saddle point of sigmoid model is proportional to blood flow velocity. A strong linear relationship (R = 0.97) between the actual flow velocities (0.4-2.1 mm/s) and the estimated saddle constants was found in M-mode and B-mode flow phantom experiments. Potential applications of this technique include high-resolution volumetric flow rate assessment in small animal tumor and the evaluation of superficial vasculature in clinical studies.

Sublingual microcirculatory alterations in cirrhotic patients.

PubMed

Gonzalez Ballerga, Esteban; Pozo, Mario O; Rubatto Birri, Paolo N; Kanoore Edul, Vanina Siham; Sorda, Juan A; Daruich, Jorge; Dubin, Arnaldo

2018-05-01

To assess sublingual microcirculation in cirrhotic patients and its relationship to spider angiomas, complications, and outcome. Thirty-one cirrhotic patients were prospectively compared to 31 matched controls. Sublingual microcirculation was evaluated by videomicroscopy. We specifically looked for capillaries with increased RBCV, which was defined as a velocity higher than the percentile 100th of controls. Compared to controls, cirrhotic patients showed decreased total and PVD (14.4 ± 2.2 vs 16.0 ± 1.3 and 14.1 ± 2.3 vs 15.9 ± 1.6 mm/mm 2 , respectively, P < .001 for both) and increased HFI (0.64 ± 0.39 vs 0.36 ± 0.21, P = .001). They also exhibited high RBCV in 2% of the microvessels (P < .0001). Patients with MELD score ≥10 had higher RBCV than patients with score <10 (1414 ± 290 vs 1206 ± 239 μm/s, P < .05). Patients with spider angiomas showed lower vascular densities. Microcirculation did not differ between survivors and nonsurvivors. Cirrhosis is associated with microcirculatory alterations that can be easily monitored in the sublingual mucosa. Alterations included decreased density and PPV and hyperdynamic microvessels. The most striking finding, however, was the microvascular heterogeneity. Patients with spider angiomas had more severe alterations. Larger studies should clarify the relationship between microcirculatory abnormalities and outcome. © 2018 John Wiley & Sons Ltd.

Pre-augmentation soft tissue expansion improves scaffold-based vertical bone regeneration - a randomized study in dogs.

PubMed

Kaner, Doğan; Zhao, Han; Arnold, Wolfgang; Terheyden, Hendrik; Friedmann, Anton

2017-06-01

Soft tissue (ST) dehiscence with graft exposure is a frequent complication of vertical augmentation. Flap dehiscence is caused by failure to achieve tension-free primary wound closure and by the impairment of flap microcirculation due to surgical trauma. Soft tissue expansion (STE) increases ST quality and quantity prior to reconstructive surgery. We hypothesized that flap preconditioning using STE would reduce the incidence of ST complications after bone augmentation and that optimized ST healing would improve the outcome of bone regeneration. Self-filling tissue expanders were implanted in mandibular bone defects in ten beagle dogs. After expansion, alloplastic scaffolds were placed for vertical bone augmentation in STE sites and in control sites without STE pre-treatment. ST flap microcirculation was analysed using laser Doppler flowmetry. The incidence of graft exposures was evaluated after 2 weeks. Bone formation was assessed after 2 months, using histomorphometry and immunohistochemistry. Test sites showed significantly less impairment of perfusion and faster recovery of microcirculation after bone augmentation. Furthermore, no flap dehiscences occurred in STE sites. Bone regeneration was found in both groups; however, significantly greater formation of new bone was detected in test sites with preceding STE. Preconditioning using STE improved ST healing and bone formation after vertical augmentation. The combination of STE and the subsequent placement of alloplastic scaffolds may facilitate the reconstruction of severe bone defects. © 2016 The Authors. Clinical Oral Implants Research Published by John Wiley & Sons Ltd.

Evaluation of angiogenesis, epithelialisation and microcirculation after application of polyhexanide, chitosan and sodium chloride in rodents.

PubMed

Goertz, Ole; Lauer, Henrik; Hirsch, Tobias; Daigeler, Adrien; Harati, Kamran; Stricker, Ingo; Lehnhardt, Marcus; von der Lohe, Leon

2016-12-01

The purpose of this study was to investigate the effect of polyhexanide and a new developed chitin-based wound dressing on skin microcirculation, epithelialisation and angiogenesis. A full-thickness dermal layer extending to the underlying cartilage was excised on the dorsal side of hairless mice (n = 27; 2·3 ± 0·3 mm 2 ). A polyhexanide ointment, a chitosan solution and a sodium chloride group as control were analysed using intravital fluorescence microscopy. Angiogenesis, epithelialisation and microcirculatory standard parameters were measured over a time period of 20 days. The non-perfused area is regarded as a parameter for angiogenesis and showed the following results: on days 12, 16 and 20, the sodium chloride group was significantly superior to chitosan solution (P < 0·05) and, on days 8, 12, 16 and 20, the polyhexanide group was superior to chitosan solution (P < 0·05). The epithelialisation was measured significantly faster in the polyhexanide and control group on day 8 versus chitosan solution. Whereas polyhexanide and sodium chloride were nearly completely epithelialised, treatment with chitosan solution showed still an open wound of 11% of the initial wound size. Altogether, we could demonstrate the advantageous effects of a polyhexanide ointment on microcirculation, angiogenesis and epithelialisation. Chitosan solution appears to inhibit angiogenesis and delays epithelialisation. Further studies in different models would be worthwhile to confirm these results. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Using a laser-Doppler flowmetry to measure pulsatile microcirculation on the kidney in rats

NASA Astrophysics Data System (ADS)

Jan, Ming-Yie; Chao, Pin-Tsun; Hsu, Tse-Lin; Wang, Yuh-Yin L.; Wang, Wei-Kung

2001-10-01

Although Laser Doppler flowmetery (LDF) been extensively used in measurement of microvascular blood flow of different tissues. However, due to some physiological vibrations, fast oscillations of the renal cortical flux (RCF) are hard to be measured. In the study, a commercial 3mW 780nm Laser Doppler flowmetery, with a single fiber and a de-vibration holder, was used to measure the pulsatile RCF in rats. Considering the fast response due to the heart rate of rats, the time constant (TC) was set to 0.05 second and thus the frequency response is up to 20Hz. Furthermore, a calibration standard and a static blood sample were also measured as the references without the pulsatile driving force. In order not to perturb the RCF with tiny momentum, the applying force that the fiber exerted on the renal surface was controlled below 100 dyne. To enhance the signal to noise ratio (SNR), an averaged periodogram was used to estimate the frequency components of the pulsatile microcirculation. It is found that the dominating fast oscillation of RCF is pulsatile and its harmonic components are directly correlated with those of the heartbeat (correlation coefficient =0.999, P<0.001, n=17). The result shows that, in the kidney, the pulsatile RCF is the dominating component of microcirculation oscillation and driven by the fast propagating blood pressure. This technique could be further utilized to analyze the pharmacological effect and hemodynamic parameters on renal function.

Modeling the measurements of cochlear microcirculation and hearing function after loud noise.

PubMed

Arpornchayanon, Warangkana; Canis, Martin; Suckfuell, Markus; Ihler, Fritz; Olzowy, Bernhard; Strieth, Sebastian

2011-09-01

Recent findings support the crucial role of microcirculatory disturbance and ischemia for hearing impairment especially after noise-induced hearing loss (NIHL). The aim of this study was to establish an animal model for in vivo analysis of cochlear microcirculation and hearing function after a loud noise to allow precise measurements of both parameters in vivo. Randomized controlled trial. Setting. Animal study. Subjects and Methods. After assessment of normacusis (0 minutes) using evoked auditory brainstem responses (ABRs), noise (106-dB sound pressure level [SPL]) was applied to both ears in 6 guinea pigs for 30 minutes while unexposed animals served as controls. In vivo fluorescence microscopy of the stria vascularis capillaries was performed after surgical exposure of 1 cochlea. ABR measurements were derived from the contralateral ear. After noise exposure, red blood cell velocity was reduced significantly by 24.3% (120 minutes) and further decreased to 44.5% at the end of the observation (210 minutes) in contrast to stable control measurements. Vessel diameters were not affected in both groups. A gradual decrease of segmental blood flow became significant (38.1%) after 150 minutes compared with controls. Hearing thresholds shifted significantly from 20.0 ± 5.5 dB SPL (0 minutes) to 32.5 ± 4.2 dB SPL (60 minutes) only in animals exposed to loud noise. With regard to novel treatments targeting the stria vascularis in NIHL, this standardized model allows us to analyze in detail cochlear microcirculation and hearing function in vivo.

Aescin-based topical formulation to prevent foot wounds and ulcerations in diabetic microangiopathy.

PubMed

Hu, S; Belcaro, G; Dugall, M; Hosoi, M; Togni, S; Maramaldi, G; Giacomelli, L

2016-10-01

Impairment of the peripheral microcirculation in diabetic patients often leads to severe complications in the lower extremities, such as foot infections and ulcerations. In this study, a novel aescin-based formulation has been evaluated as a potential approach to prevent skin breaks and ulcerations by improving the peripheral microcirculation and skin hydration. In this registry study, 63 patients with moderate diabetic microangiopathy were recruited. Informed participants freely decided to follow either a standard management (SM) to prevent diabetic foot diseases (n = 31) or SM associated with topical application of the aescin-based cream (n = 32). Peripheral microcirculatory parameters such as resting skin flux, venoarteriolar response and transcutaneous gas tension were evaluated at inclusion and after 8 weeks. In addition, several skin parameters of the foot area, such as integrity (as number of skin breaks/patients), hydration and content of dead cells were assessed at the defined observational study periods. Improvements in cutaneous peripheral microcirculation parameters were observed at 8 weeks in both groups; however, a remarkable and significant beneficial effect resulted to be exerted by the aescin-based cream treatment. In fact, the microcirculatory parameters evaluated significantly improved in the standard management + aescin-based cream group, compared with baseline and with the standard management group. Similar findings were reported for skin parameters of the foot area. The topical formulation containing aescin could represent a valid approach to manage skin wounds and prevent skin ulcerations in patients affected by moderate diabetic microangiopathy.

Cyanotic congenital heart disease the coronary arterial circulation.

PubMed

Perloff, Joseph K

2012-02-01

The coronary circulation in cyanotic congenital heart disease (CCHD) includes the extramural coronary arteries, basal coronary blood flow, flow reserve, the coronary microcirculation, and coronary atherogenesis. Coronary arteriograms were analyzed in 59 adults with CCHD. Dilated extramural coronaries were examined histologically in six patients. Basal coronary blood flow was determined with N-13 positron emission tomography in 14 patients and in 10 controls. Hyperemic flow was induced by intravenous dipyridamole pharmacologic stress. Immunostaining against SM alpha-actin permitted microcirculatory morphometric analysis. Non-fasting total cholesterols were retrieved in 279 patients divided into four groups: Group A---143 cyanotic unoperated, Group B---47 rendered acyanotic by reparative surgery, Group C---41 acyanotic unoperated, Group D---48 acyanotic before and after operation. Extramural coronary arteries were mildly or moderately dilated to ectatic in 49/59 angiograms. Histologic examination disclosed loss of medial smooth muscle, increased medial collagen, and duplication of internal elastic lamina. Basal coronary flow was appreciably increased. Hyperemic flow was comparable to controls. Remodeling of the microcirculation was based upon coronary arteriolar length, volume and surface densities. Coronary atherosclerosis was absent in both the arteriograms and the necropsy specimens. Extramural coronary arteries in CCHD dilate in response to endothelial vasodilator substances supplemented by mural attenuation caused by medial abnormalities. Basal coronary flow was appreciably increased, but hyperemic flow was normal. Remodeling of the microcirculation was responsible for preservation of flow reserve. The coronaries were atheroma-free because of the salutory effects of hypocholesterolemia, hypoxemia, upregulated nitric oxide, low platelet counts, and hyperbilirubinrmia.

[Influences of high-voltage electrical burns on microcirculation perfusion on serosal surface of small intestine of rats and the interventional effects of pentoxifylline].

PubMed

Zhang, Q F; Xu, S J; Liang, L M; Feng, J K; Xu, Y F; Tu, L L

2017-03-20

Objective: To investigate influences of high-voltage electrical burns on microcirculation perfusion on serosal surface of small intestine of rats and the interventional effects of pentoxifylline (PTX). Methods: Totally 180 SD rats were divided into sham injury group, simple electrical burn group, and treatment group according to the random number table, with 60 rats in each group. The electrical current was applied to the outside proximal part of left forelimb of rats and exited from the outside proximal part of right hind limb of rats. Rats in simple electrical burn group and treatment group were inflicted with high-voltage electrical burn wounds of 1cm×1cm at current entrances and exits, with the voltage regulator and experimental transformer. Rats in sham injury group were sham injured through connecting the same equipments without electricity. At 2 min post injury, rats in sham injury group and simple electrical burn group were intraperitoneally injected with 2 mL normal saline, and rats in treatment group were injected with 2 mL PTX injection (50 mg/mL). At 15 min before injury and 5 min, 1 h, 2 h, 4 h, and 8 h post injury, 10 rats in each group were selected to collect blood of heart respectively. Serum were separated from the blood to determine the level of soluble vascular cell adhesion molecule-1(sVCAM-1) with enzyme-linked immunosorbent assay method. The number of adhesional leukocyte in mesenteric venule of rats was determined with Bradford variable projection microscope system. The microcirculation perfusion on serosal surface of small intestine of rats was detected with laser Doppler perfusion imager. Data were processed with analysis of variance of factorial design and LSD test. Results: (1) At 5 min, 1 h, 2 h, 4 h, 8 h post injury, the serum content of sVCAM-1 in rats of simple electrical burn group were (8 502±1 158), (11 793±3 310), (9 960±2 146), (9 708±1 429), (7 292±1 386) ng/mL respectively, higher than that in sham injury group and treatment group [ (1 897±946), (1 882±940), (1 882±938), (1 888±946), (1 884±942) ng/mL, and (6 840±1 558), (6 742±2 465), (5 625±2 593), (2 373±1 463), (5 187±2 797) ng/mL, respectively, with P values below 0.001]. The serum content of sVCAM-1 in rats of sham injury group and treatment group at all time points post injury, except 4 h post injury of treatment group, was higher than that of the same group at 15 min before injury (with P values below 0.001). (2) At all time points post injury, the number of adhesional leukocyte in mesenteric venule of rats in simple electrical burn group was higher than that in sham injury group and treatment group (with P values below 0.001). The number of adhesional leukocyte in mesenteric venule of rats in simple electrical burn group and treatment group at all time points post injury was higher than that of the same group at 15 min before injury (with P values below 0.001). (3) At all time points post injury, the microcirculation perfusion on serosal surface of small intestine of rats in simple electrical burn group was lower than that in sham injury group and treatment group (with P values below 0.001). The microcirculation perfusion on serosal surface of small intestine of rats in simple electrical burn group and treatment group at all time points post injury was lower than that of the same group at 15 min before injury (with P values below 0.001). Conclusions: High-voltage electrical burns can increase the serum content of sVCAM-1, the number of adhesional leukocyte in mesenteric venule, and reduce microcirculation perfusion on serosal surface of small intestine of rats. PTX can inhibit secretion of serum sVCAM-1, reduce the number of adhensional leukocyte in mesenteric venule to alleviate microcirculation disturbance caused by high-voltage electrical burns.

A Standardized Composition Comprised of Extracts from Rosmarinus officinalis, Annona squamosa and Zanthoxylum clava-herculis for Cellulite

PubMed Central

Yimam, Mesfin; Lee, Young-Chul; Jiao, Ping; Hong, Mei; Brownell, Lidia; Jia, Qi

2017-01-01

Background: Cellulite, characterized by changes in the skin morphology presented as dimpled or puckered skin appearance, is highly prevalent among postadolescent women. Cellulite management ranges from topical cream applications to invasive procedures. While some interventions showed improvements in physical appearances of affected areas, so far, none have reversed the condition to a full recovery. These unsuccessful measures signify the intricate nature of cellulite etiology highlighting its complexity leading to the possibility for a combination treatment approach to target multiple mechanisms. Materials and Methods: We screened our plant library for extracts that reduce cellular lipid accumulation, improve microcirculation, possess high total antioxidant capacity, significant anti-platelet aggregation, and anti-inflammatory activities using lipid accumulation assay in 3T3-L1 cells, Croton oil-induced hemorrhoid test in rats as a model for microcirculation, anti-platelet aggregation assay, nitric oxide (NO) inhibition assay, and 1,1-diphenyl-2-picrylhydrazyl assay. Results: Three known botanicals such as Rosemary officinalis, Annona squamosa and Zanthoxylum clava-herculis were identified as lead extracts in these tests. Treatment of 3T3 cell with A. squamosa at 1 μg/ml resulted in 68.8% reduction in lipid accumulation. In croton oil-induced hemorrhoid study, Z. clava-herculis reduced the recto-anus coefficient by 79.6% at 6 mg/kg indicating improvement in microcirculations. Similarly, R. officinalis caused inhibition of 82%, 71.8%, and 91.8% in platelet aggregation, NO production and free radical generation at 31.25 μg/ml, 6.2 μg/ml, and 40 μg/ml concentrations suggesting its anti-oxidant, and anti-inflammatory activities. Conclusions: Data depicted here suggest that formulation of these well-known botanicals at a specific ratio perhaps may yield a composition with a much wider spectrum of mechanisms of actions to impact the multiple pathways involved in cellulite onset, continuation, or exacerbations. SUMMARY Cellulite represents one of the main esthetic concerns of women with a likely cause of psychological insecurities. Its pathophysiology involves multiple pathways that include vascular, adipose tissues, inflammation, structural and physiological.Treatment strategies for cellulite comprises increasing microcirculation flow, reducing lipogenesis, promoting lipolysis, free radicals scavenging or formation reduction, anti-inflammation and other invasive procedures.We screened our plant library for extracts that reduces cellular lipid accumulation, improves microcirculation, possesses high total antioxidant capacity, inhibits platelet aggregation, and moderates inflammation.Botanical extracts from Rosmarinus officinalis, Annona squamosa and Zanthoxylum clava-herculis were identified as leads and formulated to yield a standardized composition designated as UP1307 and suggested its usage for cellulite. Abbreviations Used: GMP: Good Manufacturing Practice; CA: Carnosic acid; NF-kB: nuclear factor-kB; HPLC: high-performance liquid chromatography; EtOH: Ethanol; DMEM: Dulbecco's modified Eagle's medium; FBS: fetal bovine serum; SD: Sprague Dawley; RAC: recto-anus coefficient; LPS: Lipopolysaccharide; DPPH: 1,1-diphenyl-2-picryl-hydrazyl; TNF-α: tumor necrosis factor; NO: Nitric oxide PMID:29263624

Multimodal OCT for complex assessment of tumors response to therapy

NASA Astrophysics Data System (ADS)

Sirotkina, Marina A.; Kiseleva, Elena B.; Gubarkova, Ekaterina V.; Matveev, Lev A.; Zaitsev, Vladimir Yu.; Matveyev, Alexander L.; Shirmanova, Marina V.; Sovetsky, Alexander A.; Moiseev, Alexander A.; Zagaynova, Elena V.; Vitkin, Alex; Gladkova, Natalia D.

2017-07-01

Multimodal OCT is a promising tool for monitoring of individual tumor response to antitumor therapies. The changes of tumor cells, connective tissue, microcirculation and stiffness can be estimated simultaneously in real time with high resolution.

Wavelet analysis of skin perfusion to assess the effects of FREMS therapy before and after occlusive reactive hyperemia.

PubMed

Popa, Stefan Octavian; Ferrari, Myriam; Andreozzi, Giuseppe Maria; Martini, Romeo; Bagno, Andrea

2015-11-01

Laser Doppler Fluxmetry is used to evaluate the hemodynamics of skin microcirculation. Laser Doppler signals contain oscillations due to fluctuations of microvascular perfusion. By performing spectral analysis, six frequency intervals from 0.005 to 2 Hz have been identified and assigned to distinct cardiovascular structures: heart, respiration, vascular myocites, sympathetic terminations and endothelial cells (dependent and independent on nitric oxide). Transcutaneous electrical pulses are currently applied to treat several diseases, i.e. neuropathies and chronic painful leg ulcers. Recently, FREMS (Frequency Rhythmic Electrical Modulation System) has been applied to vasculopathic patients, too. In this study Laser Doppler signals of skin microcirculation were measured in five patients with intermittent claudication, before and after the FREMS therapy. Changes in vascular activities were assessed by wavelet transform analysis. Preliminary results demonstrate that FREMS induces alterations in vascular activities. Copyright © 2015 IPEM. Published by Elsevier Ltd. All rights reserved.

Microcirculation of the pancreas. A quantitative study of physiology and changes in pancreatitis.

PubMed

Klar, E; Endrich, B; Messmer, K

1990-02-01

A rabbit model was designed to study the microcirculation of the pancreas with special reference to changes occurring during acute pancreatitis. Intravital microscopy was used in conjunction with video techniques allowing for continuous observation and off-line evaluation of microvessel diameters and blood cell velocities. Based on the microvessel geometry a functional microvascular unit could be defined at the level of the pancreatic lobule consisting of intralobular arteries and veins and an arcade-like preferential pathway framing the capillary network. Experimental acute pancreatitis resulted in immediate leakage of the macromolecular plasma marker (FITC-Dextran 70) from the microvasculature suggesting increased permeability. In contrast to control conditions, pancreatic capillaries were excluded from the circulation during acute pancreatitis starting 30 min after induction with only single capillaries remaining perfused after 3 hours. At the same time, there was constant blood flow through the preferential pathways representing shunt perfusion.

Evaluation of blood microcirculation parameters by combined use of laser Doppler flowmetry and videocapillaroscopy methods

NASA Astrophysics Data System (ADS)

Volkov, M. V.; Kostrova, D. A.; Margaryants, N. B.; Gurov, I. P.; Erofeev, N. P.; Dremin, V. V.; Zharkikh, E. V.; Zherebtsov, E. A.; Kozlov, I. O.; Dunaev, A. V.

2017-03-01

Laser Doppler flowmetry (LDF) is widely used for diagnosing blood microcirculation diseases. It is well known that the Doppler shift of laser radiation scattered by moving red blood cells (RBC) can be assessed through analyzing photocurrent produced by a photodetector. LDF signal contains information about regulating blood flow rhythms: myogenic, cardiac, nervous and endothelial. The method of videocapillaroscopy (VCS) allows local capillary blood flow velocity evaluation and, using video data processing algorithms, is able to assess RBC velocity changes into capillary. We present the results of simultaneous investigations of changes in tissue perfusion of the distal phalanx of human finger by the LDF as well as changes in capillary blood flow velocity in the nail bed evaluated by the VCS method during arterial occlusion test. The experimental results confirmed the correspondence between blood perfusion and blood flow velocity.

Two dimensional microcirculation mapping with real time spatial frequency domain imaging

NASA Astrophysics Data System (ADS)

Zheng, Yang; Chen, Xinlin; Lin, Weihao; Cao, Zili; Zhu, Xiuwei; Zeng, Bixin; Xu, M.

2018-02-01

We present a spatial frequency domain imaging (SFDI) study of local hemodynamics in the human finger cuticle of healthy volunteers performing paced breathing and the forearm of healthy young adults performing normal breathing with our recently developed Real Time Single Snapshot Multiple Frequency Demodulation - Spatial Frequency Domain Imaging (SSMD-SFDI) system. A two-layer model was used to map the concentrations of deoxy-, oxy-hemoglobin, melanin, epidermal thickness and scattering properties at the subsurface of the forearm and the finger cuticle. The oscillations of the concentrations of deoxy- and oxy-hemoglobin at the subsurface of the finger cuticle and forearm induced by paced breathing and normal breathing, respectively, were found to be close to out-of-phase, attributed to the dominance of the blood flow modulation by paced breathing or heartbeat. Our results suggest that the real time SFDI platform may serve as one effective imaging modality for microcirculation monitoring.

The vascular neural network—a new paradigm in stroke pathophysiology

PubMed Central

Zhang, John H.; Badaut, Jerome; Tang, Jiping; Obenaus, Andre; Hartman, Richard; Pearce, William J.

2013-01-01

The concept of the neurovascular unit as the key brain component affected by stroke is controversial, because current definitions of this entity neglect mechanisms that control perfusion and reperfusion of arteries and arterioles upstream of the cerebral microcirculation. Indeed, although definitions vary, many researchers consider the neurovascular unit to be restricted to endothelial cells, neurons and glia within millimetres of the cerebral capillary microcirculation. This Perspectives article highlights the roles of vascular smooth muscle, endothelial cells and perivascular innervation of cerebral arteries in the initiation and progression of, and recovery from, ischaemic stroke. The concept of the vascular neural network—which includes cerebral arteries, arterioles, and downstream neuronal and glial cell types and structures—is introduced as the fundamental component affected by stroke pathophysiology. The authors also propose that the vascular neural network should be considered the main target for future therapeutic intervention after cerebrovascular insult. PMID:23070610

Label-free in vivo optical micro-angiography imaging of cerebral capillary blood flow within meninges and cortex in mice with the skull left intact

NASA Astrophysics Data System (ADS)

Jia, Yali; Wang, Ruikang K.

2011-03-01

Abnormal microcirculation within meninges is common in many neurological diseases. There is a need for an imaging method that is capable of visualizing functional meningeal microcirculations alone, preferably decoupled from the cortical blood flow. Optical microangiography (OMAG) is a recently developed label-free imaging method capable of producing 3D images of dynamic blood perfusion within micro-circulatory tissue beds at an imaging depth up to ~2 mm, with an unprecedented imaging sensitivity to the blood flow at ~4 μm/s. In this study, we demonstrate the utility of ultra-high sensitive OMAG in imaging the detailed blood flow distributions, at a capillary level resolution, within meninges and cortex in mice with the cranium left intact. The results indicate that OMAG can be a valuable tool for the study of meningeal circulations.

State of the art on nailfold capillaroscopy: a reliable diagnostic tool and putative biomarker in rheumatology?

PubMed

Cutolo, Maurizio; Smith, Vanessa

2013-11-01

Capillaroscopy is a non-invasive and safe tool to morphologically study the microcirculation. In rheumatology it has a dual use. First, it has a role in differential diagnosis of patients with RP. Second, it may have a role in the prediction of clinical complications in CTDs. In SSc, pilot studies have shown predictive associations with peripheral vascular and lung involvement hinting at a role of capillaroscopy as putative biomarker. Also and logically, in SSc, microangiopathy, as assessed by capillaroscopy, has been associated with markers of the disease such as angiogenic/static factors and SSc-specific antibodies. Moreover, morphological assessments of the microcirculation (capillaroscopy) seem to correlate with functional assessments (such as laser Doppler). Because of its clinical and research role, eyes are geared in Europe to expand the knowledge of this tool. Both the European League Against Rheumatism (EULAR) and the ACR are stepping forward to this need.

Application of optical non-invasive methods to diagnose the state of the lower limb tissues in patients with diabetes mellitus

NASA Astrophysics Data System (ADS)

Zharkikh, E. V.; Dremin, V. V.; Filina, M. A.; Makovik, I. N.; Potapova, E. V.; Zherebtsov, E. A.; Zherebtsova, A. I.; Dunaev, A. V.

2017-11-01

The paper shows the possibility of assessing the functional state of microcirculatory-tissue systems of patients with diabetes mellitus by laser Doppler flowmetry (LDF), diffuse reflectance spectroscopy (DRS) and fluorescence spectroscopy (FS) methods. A review of the existing non-invasive optical technologies used to assess the state of microcirculation and oxygen metabolism in tissues of patients with diabetes is conducted. A series of experimental studies involving 76 patients with diabetes and 46 healthy volunteers was carried out. A wavelet analysis of LDF-grams was used to evaluate the adaptive changes of microcirculation during the temperature tests. The obtained data revealed that the proposed methodology in the form of combined use of several diagnostic technologies (LDF, FS and DRS) allows us to detect the presence or absence of trophic disorders and to evaluate adaptation processes during thermal tests.

Cyanotic Congenital Heart Disease The Coronary Arterial Circulation

PubMed Central

Perloff, Joseph K

2012-01-01

Background: The coronary circulation in cyanotic congenital heart disease (CCHD) includes the extramural coronary arteries, basal coronary blood flow, flow reserve, the coronary microcirculation, and coronary atherogenesis. Methods: Coronary arteriograms were analyzed in 59 adults with CCHD. Dilated extramural coronaries were examined histologically in six patients. Basal coronary blood flow was determined with N-13 positron emission tomography in 14 patients and in 10 controls. Hyperemic flow was induced by intravenous dipyridamole pharmacologic stress. Immunostaining against SM alpha-actin permitted microcirculatory morphometric analysis. Non-fasting total cholesterols were retrieved in 279 patients divided into four groups: Group A---143 cyanotic unoperated, Group B---47 rendered acyanotic by reparative surgery, Group C---41 acyanotic unoperated, Group D---48 acyanotic before and after operation. Results: Extramural coronary arteries were mildly or moderately dilated to ectatic in 49/59 angiograms. Histologic examination disclosed loss of medial smooth muscle, increased medial collagen, and duplication of internal elastic lamina. Basal coronary flow was appreciably increased. Hyperemic flow was comparable to controls. Remodeling of the microcirculation was based upon coronary arteriolar length, volume and surface densities. Coronary atherosclerosis was absent in both the arteriograms and the necropsy specimens. Conclusions: Extramural coronary arteries in CCHD dilate in response to endothelial vasodilator substances supplemented by mural attenuation caused by medial abnormalities. Basal coronary flow was appreciably increased, but hyperemic flow was normal. Remodeling of the microcirculation was responsible for preservation of flow reserve. The coronaries were atheroma-free because of the salutory effects of hypocholesterolemia, hypoxemia, upregulated nitric oxide, low platelet counts, and hyperbilirubinrmia. PMID:22845810

Analysis of serial coronary artery flow patterns early after primary angioplasty: new insights into the dynamics of the microcirculation.

PubMed

Sharif, Dawod; Rofe, Guy; Sharif-Rasslan, Amal; Goldhammer, Ehud; Makhoul, Nabeel; Shefer, Arie; Hassan, Amin; Rauchfleisch, Shmuel; Rosenschein, Uri

2008-06-01

The temporal behavior of the coronary microcirculation in acute myocardial infarction may affect outcome. Diastolic deceleration time and early systolic flow reversal derived from coronary artery blood flow velocity patterns reflect microcirculatory function. To assess left anterior descending coronary artery flow velocity patterns using Doppler transthoracic echocardiography after primary percutaneous coronary intervention, in patients with anterior AMI. Patterns of flow velocity patterns of the LAD were obtained using transthoracic echocardiography-Doppler in 31 consecutive patients who presented with anterior AMI. Measurements were done at 6 hours, 36-48 hours, and 5 days after successful PPCI. Measurements of DDT and pressure half times (Pt%), as well as observation for ESFR were performed. In the first 2 days following PPCI, the average DDT (600 +/- 340 msec) was shorter than on day 5 (807 +/- 332 msec) (P < 0.012), FVP in the first 2 days were dynamic and bidirectional: from short DDT (< 600 msec) to long DDT (> 600 msec) and vice versa. On day 5 most DDTs became longer. Pt1/2 at 6 hours was not different than at day 2 (174 +/- 96 vs. 193 +/- 99 msec, P = NS) and became longer on day 5 (235 +/- 98 msec, P = 0.012). Bidirectional patterns were also observed in the ESFR in 6 patients (19%) at baseline, in 4 (13%) at 36 hours, and in 2 (6.5%) on day 5 after PPCI. Flow velocity patterns of the LAD after PPCI in AMI are dynamic and reflect unpredictable changes in microcirculation.

Acute effects of local cold therapy in superficial burns on pain, in vivo microcirculation, edema formation and histomorphology.

PubMed

Altintas, B; Altintas, A A; Kraemer, R; Sorg, H; Vogt, P M; Altintas, M A

2014-08-01

Local cold therapy for burns is generally recommended to relief pain and limit tissue damage, however, there is limited data of its physiological benefit. This study aimed to evaluate pathophysiological effects of cold therapy in superficial burn on microcirculation, edema formation, and histomorphology. In 12 volunteers (8f, 4m; aged 30.4±14.1 years) circumscribed superficial burn was induced on both hand back and either left untreated as control (control-group) or treated by local-cold-application (cold-treatment-group). Prior to burn (t0), immediately (t1), 15 min (t2), and 30 min (t3) following cold therapy, following parameter was evaluated using intravital-microscopy; epidermal-thickness (ET), granular-cell-size (GCS), individual-blood-cell-flow (IBCF), and functional-capillary-density (FCD). Both ET and GCS increased significantly more in control-group and slightly in cold-treatment-group in t1, while turns to insignificant t2 onwards. IBCF and FCD raised up in control-group compared to dramatically decrease in cold-treatment-group in t1. In t2 both parameter remains in control-group and increased in cold-treatment-group. Comparison of both groups for IBCF and FCD indicates significant difference in t1 and t2, however, insignificant in t0 and t3. Microcirculation, edema formation, and histomorphology of superficial burn has been significantly influenced through immediate cold therapy, however, this alterations are transient and turns to ineffective after 30 min. Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.

Second consensus on the assessment of sublingual microcirculation in critically ill patients: results from a task force of the European Society of Intensive Care Medicine.

PubMed

Ince, Can; Boerma, E Christiaan; Cecconi, Maurizio; De Backer, Daniel; Shapiro, Nathan I; Duranteau, Jacques; Pinsky, Michael R; Artigas, Antonio; Teboul, Jean-Louis; Reiss, Irwin K M; Aldecoa, Cesar; Hutchings, Sam D; Donati, Abele; Maggiorini, Marco; Taccone, Fabio S; Hernandez, Glenn; Payen, Didier; Tibboel, Dick; Martin, Daniel S; Zarbock, Alexander; Monnet, Xavier; Dubin, Arnaldo; Bakker, Jan; Vincent, Jean-Louis; Scheeren, Thomas W L

2018-03-01

Hand-held vital microscopes (HVMs) were introduced to observe sublingual microcirculatory alterations at the bedside in different shock states in critically ill patients. This consensus aims to provide clinicians with guidelines for practical use and interpretation of the sublingual microcirculation. Furthermore, it aims to promote the integration of routine application of HVM microcirculatory monitoring in conventional hemodynamic monitoring of systemic hemodynamic variables. In accordance with the Delphi method we organized three international expert meetings to discuss the various aspects of the technology, physiology, measurements, and clinical utility of HVM sublingual microcirculatory monitoring to formulate this consensus document. A task force from the Cardiovascular Dynamics Section of the European Society of Intensive Care Medicine (with endorsement of its Executive Committee) created this consensus as an update of a previous consensus in 2007. We classified consensus statements as definitions, requirements, and/or recommendations, with a minimum requirement of 80% agreement of all participants. In this consensus the nature of microcirculatory alterations is described. The nature of variables, which can be extracted from analysis of microcirculatory images, is presented and the needed dataset of variables to identify microcirculatory alterations is defined. Practical aspects of sublingual HVM measurements and the nature of artifacts are described. Eleven statements were formulated that pertained to image acquisitions and quality statements. Fourteen statements addressed the analysis of the images, and 13 statements are related to future developments. This consensus describes 25 statements regarding the acquisition and interpretation of microcirculatory images needed to guide the assessment of the microcirculation in critically ill patients.

A new model for studying the revascularization of skin grafts in vivo: the role of angiogenesis.

PubMed

Lindenblatt, Nicole; Calcagni, Maurizio; Contaldo, Claudio; Menger, Michael D; Giovanoli, Pietro; Vollmar, Brigitte

2008-12-01

Models of skin graft revascularization are based mostly on histologic evaluations but lack the possibility of analyzing the vascular biology in vivo. The aim of the present study was therefore to develop an animal model that allows continuous monitoring of the microcirculation during skin graft healing. Skin and subcutaneous tissue were removed from the back of dorsal skinfold chamber preparations in mice, leaving one layer of striated muscle and subcutaneous tissue as a wound bed (n = 5). A corresponding full-thickness skin graft was harvested from the groin and sutured into the defect in the back of the chamber. To study graft healing, repetitive intravital microscopy was performed during the first 10 days after engraftment. Capillary widening in the wound bed appeared at day 1 after grafting and increased until day 4. Capillary buds and sprouts first appeared at day 2. Blood filling of autochthonous graft capillaries occurred at day 3, resulting in almost complete restoration of the original skin microcirculation on day 5. This was achieved by interconnections between the microvasculature of the wound bed and the skin graft through a temporary angiogenic response. In principle, angiogenic blood vessel growth originated in the wound bed and was directed toward the graft. This new model allows for repetitive analysis of the microcirculation during skin graft healing. It provides ideal in vivo conditions to further delineate the exact mechanisms of blood vessel interconnection during the complex process of angiogenesis, and may also allow study of the vascularization of tissue-engineered skin substitutes.

[Obesity as pathology of adipocytes: number of cells, volume of arterial bloodstream,local pools of circulation in vivo, natriuretic peptides and arterial hypertension].

PubMed

Titov, V N; Dmitriev, V A

2015-03-01

The non-specific systemic biological reaction of arterial pressure from the level of organism. vasomotor center and proximal section of arterial bloodstream is appealed to compensate disorders of metabolism and microcirculation in distal section of arteries. This phenomenon occurs in several cases. The primarily local disorders of metabolism at autocrine level, physiological (aphysiological) death of cells, "littering" of intercellular medium become the cause of disorder of microcirculation in paracrin cenosises and deteriorate realization of biological functions of homeostasis, trophology, endoecology and adaptation. The local compensation of affected perfusion in paracrin cenosises at the expense of function of peripheral peristaltic pumps, redistribution of local bloodflow in biological reaction of endothelium-depended vaso-dilation has no possibility to eliminate disorders in realization of biological functions. The systemic increase of arterial pressure under absence of specific symptoms of symptomatic arterial hypertension is a test to detect disorder of biological functions of homeostasis, trophology, biological function of endoecology and adaptation. Allforms of arterial hypertension develop by common algorithm independently from causes of disorders of blood flow, microcirculation in distal section of arteries. The non-specific systemic compensation ofdisorders of metabolism from level of organism, in proximal section of arterial bloodstream always is the same one and results in aphysiological alterations in organs-targets. To comprehend etiological characteristics of common pathogenesis of arterial hypertension is possible in case of application of such technically complicated and still unclear in differential diagnostic of deranged functions modes of metabolomics.

SEM corrosion-casts study of the microcirculation of the flat bones in the rat.

PubMed

Pannarale, L; Morini, S; D'Ubaldo, E; Gaudio, E; Marinozzi, G

1997-04-01

Little is known about the organization of microcirculation in flat bones in comparison with long bones. This study, therefore, helps us to determine the design of this vascular system in flat bones in relation to their structure and function. The organization of microvasculature in parietal, scapula, and ileum bones of 15 young sexually mature rats, aged 6-7 weeks, was studied by light and scanning electron microscopy (SEM) from vascular corrosion cast (vcc), a resin-cast obtained material. Our observations show that the pattern of the microcirculation in flat bones is different in the thick and thin parts of such bones. Where the bone is thinner than 0.4 mm, only periosteal and dural network exist. Larger vessels which do not form a real network connect the two tables of the bones in these regions. In thicker areas, the organization of the microvasculature is similar to that in long bones, with distinct periosteal, cortical and bone marrow networks. Moreover, in different bones, outer networks show slightly different characteristics according to the different adjacent structures (dura mater, muscles etc.). Different types of vessels were recognized by comparing their different diameter, course and endothelial imprints. The microvascular patterns of the flat bones are strongly influenced by the bone thickness. The different microvascular systems can interact both with the bone modelling and remodeling and with the variable metabolic needs, modifying the microvascular pattern and the blood flow. This is even more important in view of the reciprocal influence of the different networks within the same bone.

The asymmetric facial skin perfusion distribution of Bell's palsy discovered by laser speckle imaging technology.

PubMed

Cui, Han; Chen, Yi; Zhong, Weizheng; Yu, Haibo; Li, Zhifeng; He, Yuhai; Yu, Wenlong; Jin, Lei

2016-01-01

Bell's palsy is a kind of peripheral neural disease that cause abrupt onset of unilateral facial weakness. In the pathologic study, it was evidenced that ischemia of facial nerve at the affected side of face existed in Bell's palsy patients. Since the direction of facial nerve blood flow is primarily proximal to distal, facial skin microcirculation would also be affected after the onset of Bell's palsy. Therefore, monitoring the full area of facial skin microcirculation would help to identify the condition of Bell's palsy patients. In this study, a non-invasive, real time and full field imaging technology - laser speckle imaging (LSI) technology was applied for measuring facial skin blood perfusion distribution of Bell's palsy patients. 85 participants with different stage of Bell's palsy were included. Results showed that Bell's palsy patients' facial skin perfusion of affected side was lower than that of the normal side at the region of eyelid, and that the asymmetric distribution of the facial skin perfusion between two sides of eyelid is positively related to the stage of the disease (P <  0.001). During the recovery, the perfusion of affected side of eyelid was increasing to nearly the same with the normal side. This study was a novel application of LSI in evaluating the facial skin perfusion of Bell's palsy patients, and we discovered that the facial skin blood perfusion could reflect the stage of Bell's palsy, which suggested that microcirculation should be investigated in patients with this neurological deficit. It was also suggested LSI as potential diagnostic tool for Bell's palsy.

Complications and risk factors of castration with primary wound closure: Retrospective study in 159 horses.

PubMed

Robert, Mickaël P; Chapuis, Ronan J J; de Fourmestraux, Claire; Geffroy, Olivier J

2017-05-01

Castration with primary wound closure reportedly has lower complication rates and shorter recovery periods compared to castration with second intention healing. However, little is known about risk factors associated with complications using primary wound closure. Medical records of 159 horses castrated and having primary wound closure were reviewed. Main short-term complications were: scrotal hematoma in 12 horses (7.6%), signs of colic in 6 horses (3.8%), fever in 4 horses (2.5%), and peri-incisional edema in 3 horses (1.9%). As for long-term complications, 24 out of 105 (23%) horses sustained some form of edema. One horse was euthanized because of a suspected inguinal abscess. Among tested parameters, horses aged 3 to 6 years old and French trotters appeared to be more at risk of developing complications. Intraoperative ligation of the cremaster muscle and use of electrocautery prevented complications. Overall, client satisfaction was excellent (98%).

Increased pulmonary arteriolar tone associated with lung oxidative stress and nitric oxide in a mouse model of Alzheimer's disease.

PubMed

Roberts, Andrew M; Jagadapillai, Rekha; Vaishnav, Radhika A; Friedland, Robert P; Drinovac, Robert; Lin, Xingyu; Gozal, Evelyne

2016-09-01

Vascular dysfunction and decreased cerebral blood flow are linked to Alzheimer's disease (AD). Loss of endothelial nitric oxide (NO) and oxidative stress in human cerebrovascular endothelium increase expression of amyloid precursor protein (APP) and enhance production of the Aβ peptide, suggesting that loss of endothelial NO contributes to AD pathology. We hypothesize that decreased systemic NO bioavailability in AD may also impact lung microcirculation and induce pulmonary endothelial dysfunction. The acute effect of NO synthase (NOS) inhibition on pulmonary arteriolar tone was assessed in a transgenic mouse model (TgAD) of AD (C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax) and age-matched wild-type controls (C57BL/6J). Arteriolar diameters were measured before and after the administration of the NOS inhibitor, L-NAME Lung superoxide formation (DHE) and formation of nitrotyrosine (3-NT) were assessed as indicators of oxidative stress, inducible NOS (iNOS) and tumor necrosis factor alpha (TNF-α) expression as indicators of inflammation. Administration of L-NAME caused either significant pulmonary arteriolar constriction or no change from baseline tone in wild-type (WT) mice, and significant arteriolar dilation in TgAD mice. DHE, 3-NT, TNF-α, and iNOS expression were higher in TgAD lung tissue, compared to WT mice. These data suggest L-NAME could induce increased pulmonary arteriolar tone in WT mice from loss of bioavailable NO In contrast, NOS inhibition with L-NAME had a vasodilator effect in TgAD mice, potentially caused by decreased reactive nitrogen species formation, while significant oxidative stress and inflammation were present. We conclude that AD may increase pulmonary microvascular tone as a result of loss of bioavailable NO and increased oxidative stress. Our findings suggest that AD may have systemic microvascular implications beyond central neural control mechanisms. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

[Treatment of small and sublingual salivary glands cysts by laser].

PubMed

Bogatov, V V; Vybornov, V V; Malinovskiĭ, I Iu

2011-01-01

The differents variants of treatment of retention cysts of mucous membrane of oral cavity and sublingual salivary gland cysts were presented and analysed. Results of doppler examination as a method of research blood microcirculation in postoperation time were presented.

[AETIOLOGY AND PATHOGENESIS GASTRO-DUODENALES ULCERATIVE LESIONS IN ELDERLY].

PubMed

Chernekhovskaya, N E; Povalayev, A V; Layshenko, G A

2015-01-01

In review today conceptions of view to aetiology and pathogenesis gastro-duodenales ulcerative lesions in elderly. Atherosclerosis, ischemic disease of the heart and hypertension are reasons of acute ulcers and erosions in elderly. The breaking of microcirculation are very importance.

In vivo reflectance-mode confocal microscopy assessments: impact of overweight on human skin microcirculation and histomorphology

NASA Astrophysics Data System (ADS)

Altintas, Ahmet A.; Aust, Matthias C.; Krämer, Robert; Vogt, Peter M.; Altintas, Mehmet A.

2016-03-01

Reflectance-mode confocal microscopy (RCM) enables in vivo assessment of the human skin. Impact of overweight on both human skin microcirculation and histomorphology has not been investigated in vivo. The purpose of this study is to evaluate both microcirculation and histomorphology in vivo in overweight. In 10 normotensive overweight nondiabetic individuals (OW-group, BMI 29.1±2.7 kg/m2) and 10 age- and sex-matched healthy lean controls (CO-group, BMI 20.4±1.9 kg/m2) the following parameters were evaluated using RCM: dermal blood cell flow (DBCF), density of dermal capillaries (DDC), epidermal thickness (ET), and epidermal cell size (ECS). DBCF was counted at 63.11±4.14 cells/min in OW-group and at 51.06±3.84 cells/min in CO-group (P<0.05). DDC was reduced in OW-group (4.91±0.39 capillaries/mm2) compared to the controls (6.02±0.64 capillaries/mm2, P<0.05). Histometric evaluation of ET reveals thickening in OW-group compared to the CO-group (54.79±4.25 μm versus 44.03±3.11 μm, P<0.05). ECS differed significantly (P<0.05) in OW-group (821.3±42.02 μm2) compared to the controls (772.6±34.79 μm2). Inverse correlation of dermal capillary density and overweight point to reduced total tissue perfusion while positive related blood cell flow reveals vasodilatation. Increase of both ET and cell size indicates remodeling of cutaneous histomorphology, maybe as an early stage of adiposity-related skin condition.

The effects of intra-aortic balloon pump support on macrocirculation and tissue microcirculation in patients with cardiogenic shock.

PubMed

den Uil, Corstiaan A; Lagrand, Wim K; van der Ent, Martin; Jewbali, Lucia S D; Brugts, Jasper J; Spronk, Peter E; Simoons, Maarten L

2009-01-01

It was the aim of this study to evaluate the effects of intra-aortic balloon pump (IABP) counterpulsation on sublingual microcirculation as a model for tissue perfusion. In 13 patients with cardiogenic shock treated with IABP, the IABP assist ratio was reduced from 1:1 to 1:8 for 15 min. Using sidestream dark field imaging, 117 movie files of the sublingual microcirculation were obtained and quantified at different IABP assist ratios at 3 time points: 1:1 (T0), 1:8 (T1) and 1:1 (T2), respectively. Data are presented as the median and interquartile range. The median age of the patients was 59 years (range 56-73), and 62% were males. Discontinuation of IABP decreased the mean arterial pressure [75 mm Hg (71-84) at T0 vs. 69 mm Hg (64-79) at T1; p < 0.001], cardiac index [2.9 l/min/m2 (1.6-3.3) at T0 vs. 2.4 l/min/m2 (1.5-2.8) at T1; p = 0.005] and cardiac power index [0.46 W/m2 (0.29-0.59) at T0 vs. 0.36 W/m2 (0.24-0.50) at T1; p = 0.006]. However, these modest changes in macrohemodynamics did not significantly influence sublingual perfused capillary density and capillary red blood cell velocity (p = 0.28 and 0.73, respectively). A temporary, modest decrease in microcirculatory driving force, induced by lowering the IABP assist ratio, does not impair sublingual microcirculatory perfusion as measured by a novel 2-dimensional imaging technique. Copyright 2009 S. Karger AG, Basel.

High-resolution label-free vascular imaging using a commercial, clinically approved dermatological OCT scanner

NASA Astrophysics Data System (ADS)

Byers, R. A.; Tozer, G.; Brown, N. J.; Matcher, S. J.

2016-02-01

Background and Aim: Recently developed decorrelative techniques such as speckle-variance optical coherence tomography (svOCT) have demonstrated non-invasive depth-resolved imaging of the microcirculation in-vivo. However, bulk tissue motion (BTM) originating from the subject's breathing or heartbeat remains problematic at low imaging speeds, often resulting in full frame decorrelation and a loss of vascular contrast. The aim of this study was to build upon existing svOCT techniques through utilisation of a commercially available, probe-based VivoSight OCT system running at 20 kHz Axial-scan rate. Methods and results: Custom four-dimensional scanning strategies were developed and utilised in order to maximise the interframe correlation during image acquisition. Volumes of structural OCT data were collected from various anatomical regions and processed using the aforementioned svOCT algorithm to reveal angiographic information. Following data collection, three dimensional image registration and novel filtering algorithms were applied to each volume in order to ensure that BTM artefacts were sufficiently suppressed. This enabled accurate visualisation of the microcirculation within the papillary dermis, to a depth of approximately 2mm. Applications of this technique, including quantitative capillary loop density measurement and visualisation of wound healing are demonstrated and enhanced through widefield mosaicing of the svOCT data. Conclusions: Non-invasive microcirculation imaging using an FDA 510(k) approved OCT scanner such as the VivoSight allows direct clinical utilisation of these techniques, in particular for the pathological analysis of skin diseases. This research was supported by BBSRC Doctoral Training Grant: BB/F016840/1. The authors also gratefully acknowledge the use of equipment funded by MRC grant: MR/L012669/1.

Collagen-induced arthritis increases inducible nitric oxide synthase not only in aorta but also in the cardiac and renal microcirculation of mice.

PubMed

Palma Zochio Tozzato, G; Taipeiro, E F; Spadella, M A; Marabini Filho, P; de Assis, M R; Carlos, C P; Girol, A P; Chies, A B

2016-03-01

Rheumatoid arthritis (RA) may promote endothelial dysfunction. This phenomenon requires further investigation, especially in collagen-induced arthritis (CIA), as it is considered the experimental model most similar to RA. The objectives of this study were to identify CIA-induced changes in noradrenaline (NE) and acetylcholine (ACh) responses in mice aortas that may suggest endothelial dysfunction in these animals. Moreover, we characterize CIA-induced modifications in inducible nitric oxide synthase (iNOS) expression in the aortas and cardiac and renal tissues taken from these mice that may be related to possible endothelial dysfunction. Male DBA/1J mice were immunized with 100 μg of emulsified bovine collagen type II (CII) plus complete Freund's adjuvant. Twenty-one days later, these animals received a boost of an additional 100 μg plus incomplete Freund's adjuvant. Fifteen days after the onset of the disease, aortic rings from CIA and control mice were challenged with NE and ACh in an organ bath. In these animals, iNOS was detected through immunohistochemical analysis of aorta, heart and kidneys. Plasma nitrite concentration was determined using the Griess reaction. CIA did not change NE or ACh responses in mice aorta but apparently increased the iNOS expression not only in aorta, but also in cardiac and renal microcirculation. In parallel, CIA reduced nitrite plasma concentration. In mice, CIA appears to increase the presence of iNOS in aorta, as well as in heart and in kidney microcirculation. This iNOS increase occurs apparently in parallel to a reduction of the bioavailability of NO. This phenomenon does not appear to change NE or ACh responses in aorta. © 2015 British Society for Immunology, Clinical and Experimental Immunology.

Quantitative analysis of nailfold capillary morphology in patients with fibromyalgia

PubMed Central

Choi, Dug-Hyun

2015-01-01

Background/Aims Nailfold capillaroscopy (NFC) has been used to examine morphological and functional microcirculation changes in connective tissue diseases. It has been demonstrated that NFC patterns reflect abnormal microvascular dynamics, which may play a role in fibromyalgia (FM) syndrome. The aim of this study was to determine NFC patterns in FM, and their association with clinical features of FM. Methods A total of 67 patients with FM, and 30 age- and sex-matched healthy controls, were included. Nailfold capillary patterns were quantitatively analyzed using computerized NFC. The parameters of interest were as follows: number of capillaries within the central 3 mm, deletion score, apical limb width, capillary width, and capillary dimension. Capillary dimension was determined by calculating the number of capillaries using the Adobe Photoshop version 7.0. Results FM patients had a lower number of capillaries and higher deletion scores on NFC compared to healthy controls (17.3 ± 1.7 vs. 21.8 ± 2.9, p < 0.05; 2.2 ± 0.9 vs. 0.7 ± 0.6, p < 0.05, respectively). Both apical limb width (µm) and capillary width (µm) were significantly decreased in FM patients (1.1 ± 0.2 vs. 3.7 ± 0.6; 5.4 ± 0.5 vs. 7.5 ± 1.4, respectively), indicating that FM patients have abnormally decreased digital capillary diameter and density. Interestingly, there was no difference in capillary dimension between the two groups, suggesting that the length or tortuosity of capillaries in FM patients is increased to compensate for diminished microcirculation. Conclusions FM patients had altered capillary density and diameter in the digits. Diminished microcirculation on NFC may alter capillary density and increase tortuosity. PMID:26161020

Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis.

PubMed

Zhou, Hao; Zhang, Ying; Hu, Shunying; Shi, Chen; Zhu, Pingjun; Ma, Qiang; Jin, Qinhua; Cao, Feng; Tian, Feng; Chen, Yundai

2017-08-01

The cardiac microvascular system, which is primarily composed of monolayer endothelial cells, is the site of blood supply and nutrient exchange to cardiomyocytes. However, microvascular ischemia/reperfusion injury (IRI) following percutaneous coronary intervention is a woefully neglected topic, and few strategies are available to reverse such pathologies. Here, we studied the effects of melatonin on microcirculation IRI and elucidated the underlying mechanism. Melatonin markedly reduced infarcted area, improved cardiac function, restored blood flow, and lower microcirculation perfusion defects. Histological analysis showed that cardiac microcirculation endothelial cells (CMEC) in melatonin-treated mice had an unbroken endothelial barrier, increased endothelial nitric oxide synthase expression, unobstructed lumen, reduced inflammatory cell infiltration, and less endothelial damage. In contrast, AMP-activated protein kinase α (AMPKα) deficiency abolished the beneficial effects of melatonin on microvasculature. In vitro, IRI activated dynamin-related protein 1 (Drp1)-dependent mitochondrial fission, which subsequently induced voltage-dependent anion channel 1 (VDAC1) oligomerization, hexokinase 2 (HK2) liberation, mitochondrial permeability transition pore (mPTP) opening, PINK1/Parkin upregulation, and ultimately mitophagy-mediated CMEC death. However, melatonin strengthened CMEC survival via activation of AMPKα, followed by p-Drp1 S616 downregulation and p-Drp1 S37 upregulation, which blunted Drp1-dependent mitochondrial fission. Suppression of mitochondrial fission by melatonin recovered VDAC1-HK2 interaction that prevented mPTP opening and PINK1/Parkin activation, eventually blocking mitophagy-mediated cellular death. In summary, this study confirmed that melatonin protects cardiac microvasculature against IRI. The underlying mechanism may be attributed to the inhibitory effects of melatonin on mitochondrial fission-VDAC1-HK2-mPTP-mitophagy axis via activation of AMPKα. © 2017 The Authors. Journal of Pineal Research Published by John Wiley & Sons Ltd.

The Effect of Polyhexanide, Octenidine Dihydrochloride, and Tea Tree Oil as Topical Antiseptic Agents on In Vivo Microcirculation of the Human Skin: A Noninvasive Quantitative Analysis.

PubMed

Rothenberger, Jens; Krauss, Sabrina; Tschumi, Christian; Rahmanian-Schwarz, Afshin; Schaller, Hans-Eberhard; Held, Manuel

2016-10-01

Antiseptics are indispensable for wound management and should focus not only on the efficacy in reducing the bacterial burden but also on how much they interfere in wound healing. In this study, the authors analyzed the direct effect of topical antiseptic agents on the microcirculation of intact human skin. The perfusion dynamics were assessed before, and 10 minutes after, the volunteers' fingers of the right hand (n = 20) were immersed in the following solutions - octenidine dihydrochloride, polyhexanide, tea tree oil, and saline solution. The authors used the Oxygen to See (LEA Medizintechnik GmbH, Giessen, Germany) diagnostic device for noninvasive determination of oxygen supply in microcirculation of blood perfused tissues, which combines a laser light to determine blood flow, as well as white light to determine hemoglobin oxygenation and the relative amount of hemoglobin. Tea tree oil (÷19.0%) (B. Braun Melsungen AG, Melsungen, Germany) and polyhexanide (÷12.4%) (Lavanid, Serag Wiessner GmbH, Naila, Germany) caused a significant increase in blood flow compared to the negative control (-25.6%). Octenidine (Octenisept, Schülke & Mayr GmbH, Norderstedt, Germany) showed a nonsignificant trend towards an increase in blood flow (÷7.2%). There were alterations in the values of hemoglobin oxygenation and the relative amount of hemoglobin, but these were not significant. Perfusion is an important factor for wound healing. Therefore, it might be advantageous if antiseptic agents would increase blood flow. Tea tree oil and polyhexanide have a positive effect on skin blood flow and can therefore be used especially in critically perfused wounds, provided the adverse reactions and the antimicrobial efficacy are comparable.

Pretreatment with endothelium-derived nitric oxide synthesis modulators on gastrointestinal microcirculation during NOTES: an experimental study.

PubMed

Taurà, Pilar; Ibarzabal, Aitnitze; Vendrell, Marina; Adelsdorfer, Cedric; Delitala, Alberto; de Lacy, Borja; Deulofeu, Ramon; Delgado, Salvadora; Lacy, Antonio M

2016-12-01

On-demand endoscopic insufflation during natural orifice transluminal endoscopic surgery (NOTES) adversely affects microcirculatory blood flow (MBF), even with low mean intra-abdominal pressure, suggesting that shear stress caused by time-varying flow fluctuations has a great impact on microcirculation. As shear stress is inversely related to vascular diameter, nitric oxide (NO) production acts as a brake to vasoconstriction. To assess whether pretreatment by NO synthesis modulators protects gastrointestinal MBF during transgastric peritoneoscopy. Fourteen pigs submitted to cholecystectomy by endoscope CO 2 insufflation for 60 min were randomized into 2 groups: (1) 150 mg/kg of N-acetyl cysteine (NAC, n = 7) and (2) 4 ml/kg of hypertonic saline 7.5 % (HS, n = 7), and compared to a non-treated NOTES group (n = 7). Five animals made up a sham group. Colored microspheres were used to assess changes in MBF. The average level of intra-abdominal pressure was similar in all groups (9 mmHg). In NOTES group microcirculation decrease compared with baseline was greater in renal cortex, mesocolon, and mesentery (41, 42, 44 %, respectively, p < 0.01) than in renal medulla, colon, and small bowel (29, 32, 34, respectively, p < 0.05). NAC avoided the peritoneoscopy effect on renal medulla and cortex (4 and 14 % decrease, respectively) and reduced the impact on colon and small bowel (20 % decrease). HS eliminated MBF changes in colon and small bowel (14 % decrease) and modulated MBF in renal medulla and cortex (19 % decrease). Neither treatment influenced mesentery MBF decrease. Both pretreatments can effectively attenuate peritoneoscopy-induced deleterious effects on gastrointestinal MBF.

Protection of cerebral microcirculation, mitochondrial function, and electrocortical activity by small-volume resuscitation with terlipressin in a rat model of haemorrhagic shock.

PubMed

Ida, K K; Chisholm, K I; Malbouisson, L M S; Papkovsky, D B; Dyson, A; Singer, M; Duchen, M R; Smith, K J

2018-06-01

During early treatment of haemorrhagic shock, cerebral perfusion pressure can be restored by small-volume resuscitation with vasopressors. Whether this therapy is improved with additional fluid remains unknown. We assessed the value of terlipressin and lactated Ringer's solution (LR) on early recovery of microcirculation, tissue oxygenation, and mitochondrial and electrophysiological function in the rat cerebral cortex. Animals treated with LR replacing three times (3LR) the volume bled (n=26), terlipressin (n=27), terlipressin plus 1LR (n=26), 2LR (n=16), or 3LR (n=15) were compared with untreated (n=36) and sham-operated rats (n=17). In vivo confocal microscopy was used to assess cortical capillary perfusion, changes in tissue oxygen concentration, and mitochondrial membrane potential and redox state. Electrophysiological function was assessed by cortical somatosensory evoked potentials, spinal cord dorsum potential, and peripheral electromyography. Compared with sham treatment, haemorrhagic shock reduced the mean (SD) area of perfused vessels [82% (sd 10%) vs 38% (12%); P<0.001] and impaired oxygen concentration, mitochondrial redox state [99% (4%) vs 59% (15%) of baseline; P<0.001], and somatosensory evoked potentials [97% (13%) vs 27% (19%) of baseline]. Administration of terlipressin plus 1LR or 2LR was able to recover these measures, but terlipressin plus 3LR or 3LR alone were not as effective. Spinal cord dorsum potential was preserved in all groups, but no therapy protected electromyographic function. Resuscitation from haemorrhagic shock using terlipressin with small-volume LR was superior to high-volume LR, with regard to cerebral microcirculation, and mitochondrial and electrophysiological functions. Copyright © 2018 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

Use of intravoxel incoherent motion diffusion-weighted imaging in identifying the vascular and avascular zones of human meniscus.

PubMed

Guo, Tan; Chen, Juan; Wu, Bing; Zheng, Dandan; Jiao, Sheng; Song, Yan; Chen, Min

2017-04-01

To investigate the hypothesis that the intravoxel incoherent motion (IVIM) diffusion-weighted imaging may depict microcirculation of meniscus and the perfusion changes in meniscal disorder. Fifty patients received diffusion-weighted MRI with multiple b-values ranging from 0 to 400 s/mm 2 . The four horns of the menisci were divided into normal, degenerated, and torn groups. IVIM parameters including perfusion fraction (f), pseudo-diffusion coefficient (D*), true diffusion coefficient (D), and the product of f and D* (f D*) of normal meniscal red zone and white zone were derived and compared for microcirculation changes of normal, degenerated, and torn posterior horn of the medial meniscus (PMM). The parameters between red and white zones among the groups were compared. Significant differences were considered when P < 0.05. Mean f and fD* were significantly higher in the red zone than those in the white zone for the normal four meniscal horns (P < 0.05), whereas D* (P = 0.882, 0.011, 0.593, and 0.33) and D (P = 0.186, 0.099, 0.767, and 0.041) did not significantly differ between the two zones. Among the normal, degenerated, and torn PMM, f was observed to be lower in the red zone of torn horns as compared to the normal horns (P = 0.013). D*, fD*, and D did not exhibit statistically significant difference among different groups (P = 0.353, 0.661, and 0.327, respectively). This hypothesis driven work shows that IVIM imaging is able to depict microcirculation of meniscus and the perfusion changes in meniscal disorder. 3 J. Magn. Reson. Imaging 2017;45:1090-1096. © 2016 International Society for Magnetic Resonance in Medicine.

Healing process of venous ulcers: the role of microcirculation.

PubMed

Ambrózy, Ewald; Waczulíková, Iveta; Willfort, Andrea; Böhler, Kornelia; Cauza, Karla; Ehringer, Herbert; Heinz, Gottfried; Koppensteiner, Renate; Marić, Snezana; Gschwandtner, Michael E

2013-02-01

In order to describe adequately the process of healing in the intermediate degrees, we investigated microcirculatory changes in the venous ulcers at well-defined stages of wound repair. We investigated dynamic changes in microcirculation during the healing process of venous ulcers. Ten venous ulcers were investigated in three consecutive clinical stages of wound healing: non granulation tissue (NGTA), GTA and scar. Subpapillary microcirculation was measured by laser Doppler perfusion (LDP) imaging and expressed using LDP values in arbitrary units. Nutritive perfusion by capillary microscopy and expressed as capillary density (CD) - the number of capillaries per square millimetre. Before the development of GTA the LDP was low (median 1·35; lower-upper quartiles 0·71-1·83) accompanied with zero CD in all but one patient who had a density of 1. With the first appearance of GTA in the same area, the LDP was improved (2·22; 1·12-2·33; P = 0·0024) when compared with NGTA, in combination with a significant increase in CD (1·75; 0-3; P = 0·0054). In scar, the LDP was similar to that in the NGTA (1·03; 0·77-1·83; P = 0·278), combined with the highest CD (5·75; 4·5-8) in comparison with the previous stages of the area (for both pairs, P < 0·0001). Venous ulcers are caused by poor nutritive and subpapillary perfusion. Subpapillary perfusion plays a major role in the formation of GTA. In a scar, the increased nutritive perfusion is sufficient to cover the blood supply and keep skin viable while subpapillary perfusion is low. © 2012 The Authors. International Wound Journal © 2012 Blackwell Publishing Ltd and Medicalhelplines.com Inc.

Propionyl-L-carnitine improves endothelial function, microcirculation and pain management in critical limb ischemia.

PubMed

De Marchi, S; Zecchetto, S; Rigoni, A; Prior, M; Fondrieschi, L; Scuro, A; Rulfo, F; Arosio, E

2012-10-01

Chronic critical limb ischemia (CLI) is a severe condition of hypo-perfusion of lower limbs, which is associated with inflammation and a pro-coagulative state. It is a disease at high risk of amputation and cardiovascular death. Propionyl-L-carnitine (PLC) is efficacious in improving pain free walking distance in peripheral arterial disease with claudication; it also exerts favorable effects on the arterial wall and on endothelial function. The purpose of this study was to evaluate the effects of PLC on microcirculation, endothelial function and pain relief in patients affected by CLI not suitable for surgical intervention. We enrolled 48 patients with CLI. Patients were randomized into two groups: the first group was treated with PLC, the second was treated with saline solution. All of them underwent the following tests: laser Doppler flowmetry at the forefoot at rest and after ischemia, trans cutaneous oxygen partial pressure and carbon dioxide partial pressure at the forefoot at rest and after ischemia, endothelium dependent dilation of the brachial artery. All tests were repeated after treatments. Pain was assessed by visual analog pain scale. Endothelium dependent dilation increased after PLC (9.5 ± 3.2 vs 4.9 ± 1.4 %; p < 0.05). Post-ischemic peak flow with laser-Doppler flow increased after PLC. TcPO2 increased, while TcPCO2 decreased after PLC; CO2 production decreased after PLC. VAS showed a significant reduction in pain perception after active treatment. In CLI patients, PLC can improve microcirculation (post ischemic hyperemia, TcPO2 and TcPCO2 production). PLC also enhances endothelium dependent dilation and reduces analgesic consumption and pain perception.

How to evaluate the microcirculation: report of a round table conference

PubMed Central

De Backer, Daniel; Hollenberg, Steven; Boerma, Christiaan; Goedhart, Peter; Büchele, Gustavo; Ospina-Tascon, Gustavo; Dobbe, Iwan; Ince, Can

2007-01-01

Introduction Microvascular alterations may play an important role in the development of organ failure in critically ill patients and especially in sepsis. Recent advances in technology have allowed visualization of the microcirculation, but several scoring systems have been used so it is sometimes difficult to compare studies. This paper reports the results of a round table conference that was organized in Amsterdam in November 2006 in order to achieve consensus on image acquisition and analysis. Methods The participants convened to discuss the various aspects of image acquisition and the different scores, and a consensus statement was drafted using the Delphi methodology. Results The participants identified the following five key points for optimal image acquisition: five sites per organ, avoidance of pressure artifacts, elimination of secretions, adequate focus and contrast adjustment, and recording quality. The scores that can be used to describe numerically the microcirculatory images consist of the following: a measure of vessel density (total and perfused vessel density; two indices of perfusion of the vessels (proportion of perfused vessels and microcirculatory flow index); and a heterogeneity index. In addition, this information should be provided for all vessels and for small vessels (mostly capillaries) identified as smaller than 20 μm. Venular perfusion should be reported as a quality control index, because venules should always be perfused in the absence of pressure artifact. It is anticipated that although this information is currently obtained manually, it is likely that image analysis software will ease analysis in the future. Conclusion We proposed that scoring of the microcirculation should include an index of vascular density, assessment of capillary perfusion and a heterogeneity index. PMID:17845716

Functional and morphological evaluation of hand microcirculation with nailfold capillaroscopy and laser Doppler imaging in Raynaud's and Sjögren's syndrome and poly/dermatomyositis.

PubMed

Szabo, N; Csiki, Z; Szanto, A; Danko, K; Szodoray, P; Zeher, M

2008-01-01

Nailfold capillaroscopy is widely used in autoimmune patients to determine capillary morphology. Laser Doppler imaging (LDI) is a relatively new method for measuring the microcirculation of cutaneous perfusion. The aim of this study was to investigate the capillary morphology and microcirculation among patients with Sjögren's syndrome (SS) and poly/dermatomyositis (PM/DM) with these two non-invasive methods and to detect secondary Raynaud's syndrome (SRS) in these autoimmune diseases. Thirty patients with primary SS, 30 patients with PM/DM, 30 patients with primary Raynaud's syndrome (PRS), and 30 healthy volunteers were included in the study. Nailfold capillaroscopy and LDI were performed on each patient. A comprehensive analysis was performed among the patients and healthy individuals. Among SS patients avascularity and among PM/DM patients avascularity and capillary morphology changes were most often detected by capillaroscopy. With LDI the mean steady-state cutaneous perfusion was 1.25 perfusion units (PU) in region of interest 1 (ROI1), 1.22 in ROI2, and 1.49 at the fingertips in PRS patients; the corresponding values were 1.2, 1.03, and 1.48 PU in SS, 0.91, 0.76, and 1.19 PU in PM/DM, and 1.79, 1.62, and 2.2 PU in the controls. The differences were significant between each autoimmune group compared to the control group (p<0.02, p<0.001, and p<0.001, respectively). By using nailfold capillaroscopy, abnormalities in capillary morphology can be detected, and by using LDI, the reduced blood flow in the capillaries can be detected. These investigations can be useful in the detection of SRS, or in distinguishing whether the reduced blood flow is due to primary/systemic autoimmune diseases.

The Nervous System and Gastrointestinal Function

ERIC Educational Resources Information Center

Altaf, Muhammad A.; Sood, Manu R.

2008-01-01

The enteric nervous system is an integrative brain with collection of neurons in the gastrointestinal tract which is capable of functioning independently of the central nervous system (CNS). The enteric nervous system modulates motility, secretions, microcirculation, immune and inflammatory responses of the gastrointestinal tract. Dysphagia,…

77 FR 2303 - Center for Scientific Review; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-17

...: Diabetes and Obesity. Date: January 26, 2012. Time: 9:30 a.m. to 4 p.m. Agenda: To review and evaluate..., Hypertension and Microcirculation A. Date: February 7, 2012. Time: 1 p.m. to 1:45 p.m. Agenda: To review and...

Enhanced in vivo visualization of the microcirculation by topical application of fructose solution confirmed with correlation mapping optical coherence tomography

NASA Astrophysics Data System (ADS)

Enfield, Joey; McGrath, James; Daly, Susan M.; Leahy, Martin

2016-08-01

Changes within the microcirculation can provide an early indication of the onset of a plethora of ailments. Various techniques have thus been developed that enable the study of microcirculatory irregularities. Correlation mapping optical coherence tomography (cmOCT) is a recently proposed technique, which enables mapping of vasculature networks at the capillary level in a noninvasive and noncontact manner. This technique is an extension of conventional optical coherence tomography (OCT) and is therefore likewise limited in the penetration depth of ballistic photons in biological media. Optical clearing has previously been demonstrated to enhance the penetration depth and the imaging capabilities of OCT. In order to enhance the achievable maximum imaging depth, we propose the use of optical clearing in conjunction with the cmOCT technique. We demonstrate in vivo a 13% increase in OCT penetration depth by topical application of a high-concentration fructose solution, thereby enabling the visualization of vessel features at deeper depths within the tissue.

Intravital imaging of a pulmonary endothelial surface layer in a murine sepsis model.

PubMed

Park, Inwon; Choe, Kibaek; Seo, Howon; Hwang, Yoonha; Song, Eunjoo; Ahn, Jinhyo; Hwan Jo, You; Kim, Pilhan

2018-05-01

Direct intravital imaging of an endothelial surface layer (ESL) in pulmonary microcirculation could be a valuable approach to investigate the role of a vascular endothelial barrier in various pathological conditions. Despite its importance as a marker of endothelial cell damage and impairment of the vascular system, in vivo visualization of ESL has remained a challenging technical issue. In this work, we implemented a pulmonary microcirculation imaging system integrated to a custom-design video-rate laser scanning confocal microscopy platform. Using the system, a real-time cellular-level microscopic imaging of the lung was successfully performed, which facilitated a clear identification of individual flowing erythrocytes in pulmonary capillaries. Subcellular level pulmonary ESL was identified in vivo by fluorescence angiography using a dextran conjugated fluorophore to label blood plasma and the red blood cell (RBC) exclusion imaging analysis. Degradation of ESL width was directly evaluated in a murine sepsis model in vivo , suggesting an impairment of pulmonary vascular endothelium and endothelial barrier dysfunction.

Intravital imaging of a pulmonary endothelial surface layer in a murine sepsis model

PubMed Central

Park, Inwon; Choe, Kibaek; Seo, Howon; Hwang, Yoonha; Song, Eunjoo; Ahn, Jinhyo; Hwan Jo, You; Kim, Pilhan

2018-01-01

Direct intravital imaging of an endothelial surface layer (ESL) in pulmonary microcirculation could be a valuable approach to investigate the role of a vascular endothelial barrier in various pathological conditions. Despite its importance as a marker of endothelial cell damage and impairment of the vascular system, in vivo visualization of ESL has remained a challenging technical issue. In this work, we implemented a pulmonary microcirculation imaging system integrated to a custom-design video-rate laser scanning confocal microscopy platform. Using the system, a real-time cellular-level microscopic imaging of the lung was successfully performed, which facilitated a clear identification of individual flowing erythrocytes in pulmonary capillaries. Subcellular level pulmonary ESL was identified in vivo by fluorescence angiography using a dextran conjugated fluorophore to label blood plasma and the red blood cell (RBC) exclusion imaging analysis. Degradation of ESL width was directly evaluated in a murine sepsis model in vivo, suggesting an impairment of pulmonary vascular endothelium and endothelial barrier dysfunction. PMID:29760995

Fluid therapy and the hypovolemic microcirculation.

PubMed

Gruartmoner, G; Mesquida, J; Ince, Can

2015-08-01

In shock states, optimizing intravascular volume is crucial to promote an adequate oxygen delivery to the tissues. Our current practice in fluid management pivots on the Frank-Starling law of the heart, and the effects of fluids are measured according to the induced changes on stroke volume. The purpose of this review is to evaluate the boundaries of current macrohemodynamic approach to fluid administration, and to introduce the microcirculatory integration as a fundamental part of tissue perfusion monitoring. Macrocirculatory changes induced by volume expansion are not always coupled to proportional changes in microcirculatory perfusion. Loss of hemodynamic coherence limits the value of guiding fluid therapy according to macrohemodynamics, and highlights the importance of evaluating the ultimate target of volume administration, the microcirculation. Current approach to intravascular volume optimization is made from a macrohemodynamic perspective. However, several situations wherein macrocirculatory and microcirculatory coherence is lost have been described. Future clinical trials should explore the usefulness of integrating the microcirculatory evaluation in fluid optimization.

Improvement of hepatic microhemodynamics by N-acetylcysteine after warm ischemia.

PubMed

Koeppel, T A; Thies, J C; Lehmann, T; Gebhard, M M; Herfarth, C; Otto, G; Post, S

1996-01-01

In this study we investigated the influence of N-acetylcysteine (NAC) on the hepatic microcirculation after warm ischemia by intravital fluorescence microscopy. Clamping of the left liver lobe was performed in 20 male Wistar rats for 70 min. The treatment group (n = 10) received 400 mg NAC/kg body weight 20 min prior to clamping. After reperfusion, acinar and sinusoidal perfusions were observed as well as the leukocyte-endothelium interaction. Phagocytic activity was assessed after application of latex beads. NAC reduced the number of nonperfused sinusoids in all acinar zones. A reduction in zone 1 (portal) was achieved from 15.5 to 7.1% (p < 0.0001), in zone 2 (midzonal) from 14.6 to 6.1% (p < 0.0001) and in zone 3 (central) from 11.9 to 2.9% (p < 0.0001). There were no significant differences in leukocyte adherence as well as in phagocytic activity detectable. We conclude that NAC improves hepatic microcirculation after warm ischemia by increasing sinusoidal blood flow.

Real time diffuse reflectance polarisation spectroscopy imaging to evaluate skin microcirculation

NASA Astrophysics Data System (ADS)

O'Doherty, Jim; Henricson, Joakim; Nilsson, Gert E.; Anderson, Chris; Leahy, Martin J.

2007-07-01

This article describes the theoretical development and design of a real-time microcirculation imaging system, an extension from a previously technology developed by our group. The technology utilises polarisation spectroscopy, a technique used in order to selectively gate photons returning from various compartments of human skin tissue, namely from the superficial layers of the epidermis, and the deeper backscattered light from the dermal matrix. A consumer-end digital camcorder captures colour data with three individual CCDs, and a custom designed light source consisting of a 24 LED ring light provides broadband illumination over the 400 nm - 700 nm wavelength region. Theory developed leads to an image processing algorithm, the output of which scales linearly with increasing red blood cell (RBC) concentration. Processed images are displayed online in real-time at a rate of 25 frames s -1, at a frame size of 256 x 256 pixels, and is limited only by computer RAM memory and processing speed. General demonstrations of the technique in vivo display several advantages over similar technology.

In vivo correlation mapping microscopy

NASA Astrophysics Data System (ADS)

McGrath, James; Alexandrov, Sergey; Owens, Peter; Subhash, Hrebesh; Leahy, Martin

2016-04-01

To facilitate regular assessment of the microcirculation in vivo, noninvasive imaging techniques such as nailfold capillaroscopy are required in clinics. Recently, a correlation mapping technique has been applied to optical coherence tomography (OCT), which extends the capabilities of OCT to microcirculation morphology imaging. This technique, known as correlation mapping optical coherence tomography, has been shown to extract parameters, such as capillary density and vessel diameter, and key clinical markers associated with early changes in microvascular diseases. However, OCT has limited spatial resolution in both the transverse and depth directions. Here, we extend this correlation mapping technique to other microscopy modalities, including confocal microscopy, and take advantage of the higher spatial resolution offered by these modalities. The technique is achieved as a processing step on microscopy images and does not require any modification to the microscope hardware. Results are presented which show that this correlation mapping microscopy technique can extend the capabilities of conventional microscopy to enable mapping of vascular networks in vivo with high spatial resolution in both the transverse and depth directions.

[Measurement of pancreatic microcirculation using hydrogen gas generated by electrolysis in dogs].

PubMed

Nishiwaki, H; Satake, K; Ko, I; Tanaka, H; Kanazawa, G; Nagai, Y; Umeyama, K

1986-11-01

Measurements of pancreatic microflow were investigated using hydrogen gas generated by electrolysis in dog. After laparatomy under general anesthesia, uncinate process of the pancreas was punctured by a needle electrode for electrolysis and determination of hydrogen gas. The consecutive measurements of pancreatic microflow revealed the good reproducibility at the same point of the pancreas. The simultaneous measurements of pancreatic microflow by electrolysis and pancreatic tissue blood flow by H2 inhalation method were carried out at the same point of the pancreas. Correlation analysis of both measurements revealed coefficient of 0.751 and a significant relationship was observed (p less than 0.05). However, the value was a little higher in pancreatic microflow as compared with pancreatic tissue blood flow. Pancreatic microflow and pancreatic exocrine secretion increased after intravenous administration of Dopamine and Secretin (10 micrograms/kg/min). It is concluded that the measurement of pancreatic microflow by hydrogen gas generated by electrolysis is a useful method on understanding the microcirculation of the pancreas.

Effects of heme oxygenase-1-modified bone marrow mesenchymal stem cells on microcirculation and energy metabolism following liver transplantation

PubMed Central

Yang, Liu; Shen, Zhong-Yang; Wang, Rao-Rao; Yin, Ming-Li; Zheng, Wei-Ping; Wu, Bin; Liu, Tao; Song, Hong-Li

2017-01-01

AIM To investigate the effects of heme oxygenase-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) on the microcirculation and energy metabolism of hepatic sinusoids following reduced-size liver transplantation (RLT) in a rat model. METHODS BMMSCs were isolated and cultured in vitro using an adherent method, and then transduced with HO-1-bearing recombinant adenovirus to construct HO-1/BMMSCs. A rat acute rejection model following 50% RLT was established using a two-cuff technique. Recipients were divided into three groups based on the treatment received: normal saline (NS), BMMSCs and HO-1/BMMSCs. Liver function was examined at six time points. The levels of endothelin-1 (ET-1), endothelial nitric-oxide synthase (eNOS), inducible nitric-oxide synthase (iNOS), nitric oxide (NO), and hyaluronic acid (HA) were detected using an enzyme-linked immunosorbent assay. The portal vein pressure (PVP) was detected by Power Lab ML880. The expressions of ET-1, iNOS, eNOS, and von Willebrand factor (vWF) protein in the transplanted liver were detected using immunohistochemistry and Western blotting. ATPase in the transplanted liver was detected by chemical colorimetry, and the ultrastructural changes were observed under a transmission electron microscope. RESULTS HO-1/BMMSCs could alleviate the pathological changes and rejection activity index of the transplanted liver, and improve the liver function of rats following 50% RLT, with statistically significant differences compared with those of the NS group and BMMSCs group (P < 0.05). In term of the microcirculation of hepatic sinusoids: The PVP on POD7 decreased significantly in the HO-1/BMMSCs and BMMSCs groups compared with that of the NS group (P < 0.01); HO-1/BMMSCs could inhibit the expressions of ET-1 and iNOS, increase the expressions of eNOS and inhibit amounts of NO production, and maintain the equilibrium of ET-1/NO (P < 0.05); and HO-1/BMMSCs increased the expression of vWF in hepatic sinusoidal endothelial cells (SECs), and promoted the degradation of HA, compared with those of the NS group and BMMSCs group (P < 0.05). In term of the energy metabolism of the transplanted liver, HO-1/BMMSCs repaired the damaged mitochondria, and improved the activity of mitochondrial aspartate aminotransferase (ASTm) and ATPase, compared with the other two groups (P <0.05). CONCLUSION HO-1/BMMSCs can improve the microcirculation of hepatic sinusoids significantly, and recover the energy metabolism of damaged hepatocytes in rats following RLT, thus protecting the transplanted liver. PMID:28596681

Functional evaluation of sublingual microcirculation indicates successful weaning from VA-ECMO in cardiogenic shock.

PubMed

Akin, Sakir; Dos Reis Miranda, Dinis; Caliskan, Kadir; Soliman, Osama I; Guven, Goksel; Struijs, Ard; van Thiel, Robert J; Jewbali, Lucia S; Lima, Alexandre; Gommers, Diederik; Zijlstra, Felix; Ince, Can

2017-10-26

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly adopted for the treatment of cardiogenic shock (CS). However, a marker of successful weaning remains largely unknown. Our hypothesis was that successful weaning is associated with sustained microcirculatory function during ECMO flow reduction. Therefore, we sought to test the usefulness of microcirculatory imaging in the same sublingual spot, using incident dark field (IDF) imaging in assessing successful weaning from VA-ECMO and compare IDF imaging with echocardiographic parameters. Weaning was performed by decreasing the VA-ECMO flow to 50% (F 50 ) from the baseline. The endpoint of the study was successful VA-ECMO explantation within 48 hours after weaning. The response of sublingual microcirculation to a weaning attempt (WA) was evaluated. Microcirculation was measured in one sublingual area (single spot (ss)) using CytoCam IDF imaging during WA. Total vessel density (TVDss) and perfused vessel density (PVDss) of the sublingual area were evaluated before and during 50% flow reduction (TVDss F50 , PVDss F50 ) after a WA and compared to conventional echocardiographic parameters as indicators of the success or failure of the WA. Patients (n = 13) aged 49 ± 18 years, who received VA-ECMO for the treatment of refractory CS due to pulmonary embolism (n = 5), post cardiotomy (n = 3), acute coronary syndrome (n = 2), myocarditis (n = 2) and drug intoxication (n = 1), were included. TVDss F50 (21.9 vs 12.9 mm/mm 2 , p = 0.001), PVDss F50 (19.7 vs 12.4 mm/mm 2 , p = 0.01) and aortic velocity-time integral (VTI) at 50% flow reduction (VTI F50 ) were higher in patients successfully weaned vs not successfully weaned. The area under the curve (AUC) was 0.99 vs 0.93 vs 0.85 for TVDss F50 (small vessels) >12.2 mm/mm 2 , left ventricular ejection fraction (LVEF) >15% and aortic VTI >11 cm. Likewise, the AUC was 0.91 vs 0.93 vs 0.85 for the PVDss F50 (all vessels) >14.8 mm/mm 2 , LVEF >15% and aortic VTI >11 cm. This study identified sublingual microcirculation as a novel potential marker for identifying successful weaning from VA-ECMO. Sustained values of TVDss F50 and PVDss F50 were found to be specific and sensitive indicators of successful weaning from VA-ECMO as compared to echocardiographic parameters.

[Thermoregulation in hypertensive elderly patients during physiotherapy].

PubMed

Abramovich, S G

2002-01-01

Effects of therapeutic physical factors on thermoregulation and thermoreactivity of skin were studied in 222 elderly patients with hypertension. It is shown that sodium chloride half-baths, "dry" carbon dioxide baths and general magnetotherapy correct thermal asymmetry and normalize skin thermoreactivity, i.e. produce a positive effect on microcirculation.

Endothelium-dependent Hyperpolarization-mediated Vasodilatation Compensates Nitric Oxide-mediated Endothelial Dysfunction during Ischemia in Diabetes-induced Canine Coronary Collateral Microcirculation in Vivo.

PubMed

Yada, Toyotaka; Shimokawa, Hiroaki; Tachibana, Hiroyuki

2018-04-17

It has been previously demonstrated that endothelial caveolin-1 plays crucial roles to produce an endothelium-derived hyperpolarizing factor in mouse mesenteric arteries. We examined whether this mechanism is involved in the endothelium-derived hyperpolarizing-mediated responses to compensate reduced NO-mediated responses in diabetes mellitus during coronary occlusion in dogs in vivo. Canine subepicardial collateral coronary small arteries (≥100 μm) and arterioles (<100 μm) were observed by an intravital microscope. Experiments were performed during occlusion of the left anterior descending coronary artery (90 min) under the following conditions (n=6 each); (i) control, (ii) diabetes mellitus, and (iii) diabetes mellitus+L-NMMA+K C a channel blockade. Vascular and myocardial levels of caveolin-1, eNOS and caspase-3 were measured by ELISA. Caveolin-1 levels in the ischemic area were greater in coronary microvessels than in conduit arteries in the control group. NO-mediated coronary vasodilatations of small arteries to bradykinin did not increase in diabetes mellitus associated with decreased eNOS phosphorylation at Ser1177 compared with baseline of controls, and were restored by compensation of endothelium-derived hyperpolarizing, and were suppressed by K C a channel blockade. NO-mediated vasodilatations of small coronary arteries during coronary occlusion are impaired in diabetes mellitus and are compensated by endothelium-derived hyperpolarizing of arterioles in dogs in vivo. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The association of socio-economic factors with physical fitness and activity behaviours, spinal posture and retinal vessel parameters in first graders in urban Switzerland.

PubMed

Imhof, Katharina; Faude, Oliver; Donath, Lars; Bean-Eisenhut, Salome; Hanssen, Henner; Zahner, Lukas

2016-01-01

Socio-economic status during childhood has been shown to be a strong predictor of adult health outcome. Therefore, we examined associations of parental educational level, household income and migrant background with physical fitness, spinal flexibility, spinal posture as well as retinal vessel diameters in children of an urban Swiss region. A total of 358 first graders of the Swiss canton Basel-Stadt (age: 7.3, SD: 0.4) were examined. Physical fitness (20 m shuttle run test, 20 m sprint, jumping sidewards and balancing backwards), spinal flexibility and spinal posture (MediMouse®, Idiag, Fehraltdorf, Switzerland) and retinal microcirculation (Static Retinal Vessel Analyzer, Imedos Systems UG, Jena, Germany) were assessed. Parental education, household income, migrant background and activity behaviour were evaluated with a questionnaire. Parental education was associated with child aerobic fitness (P = 0.03) and screen time (P < 0.001). Household income was associated with jumping sidewards (P = 0.009), balancing backwards (P = 0.03) and sports club participation (P = 0.02). Migrant background was associated with BMI (P = 0.001), body fat (P = 0.03), aerobic fitness (P = 0.007), time spent playing outdoors (P < 0.001) and screen time (P < 0.001). For spinal flexibility and retinal vessel diameter, no associations were found (0.06 < P < 0.8). Low parental education, low household income and a migrant background are associated with poor physical fitness, higher BMI and body fat percentage and low-activity behaviour.

Inhibition of caspase activity prevents CD95-mediated hepatic microvascular perfusion failure and restores Kupffer cell clearance capacity.

PubMed

Wanner, G A; Mica, L; Wanner-Schmid, E; Kolb, S A; Hentze, H; Trentz, O; Ertel, W

1999-07-01

Using a murine model, we studied the effect of agonistic anti-CD95 antibodies (aCD95) on sinusoidal lining cells and a potential protection by caspase inhibition. C3H/HeN mice were intravenously administered aCD95 (10 microgram/mouse) or unspecific IgG (control) in the presence or absence of the caspase inhibitor z-VAD-fmk. Analysis of hepatic microcirculation using intravital fluorescence microscopy revealed severe (P<0.01) sinusoidal perfusion failure and reduced (P<0.05) phagocytic activity of Kupffer cells (KC) within 2 h. Transmission electron micrographs demonstrated loss of integrity of sinusoidal endothelial cells as early as 1 h after aCD95 application, whereas histological manifestation of hepatocellular apoptosis and hemorrhagic necrosis was most pronounced at 6 h. Blocking of caspase activity attenuated (P<0.01) both hepatic microvascular perfusion failure and KC dysfunction. Accordingly, full protection of the liver from apoptotic damage and intact microarchitecture was observed in histological sections after z-VAD-fmk treatment. Mortality rate was 40% 6 h after aCD95 administration, whereas all animals survived in the z-VAD-fmk group (P<0.05). The activation of caspases through CD95 may primarily lead to damage of sinusoidal endothelial cells and hepatic microvascular perfusion failure. Moreover, reduced phagocytic capacity of KC may contribute to accumulation of toxic metabolites released by dying cells at the local site of inflammation, further aggravating liver injury.

Development and Application of a Tendon Prosthesis for Early Functional Restoration of the Hand.

DTIC Science & Technology

1975-09-01

number of studies to fully elucidate this problem. A. Human Foetus Circulation This study dealt with the intrinsic microcirculation in the human... foetus . The work was done by Dr. Howard Caplan. This study resulted in an entirely new understanding of tendon vasculature. A copy of his paper is

[Capillaroscopy in patients with chronic alcoholic pancreatitis].

PubMed

Teixeira, G P; de Alencar, R; Fonseca, M de O; Bernardini, E M

1996-01-01

The aim of this study was verify frequency and morphological presentations of microangiopathy in patients with alcoholic chronic pancreatitis, using nailfold capillaroscopy. All patients showed morphological and functional capillary abnormalities. None of them had a normal capillaroscopy. Our findings may suggest an important role of microcirculation in Alcoholic Chronic Pancreatitis pathogenesis and/or its course.

78 FR 64961 - Center for Scientific Review; Amended Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Center for Scientific Review; Amended Notice of Meeting Notice is hereby given of a change in the meeting of the Hypertension and Microcirculation Study Section, October 10, 2013, 08:00 a.m. to October 10, 2013, 07:30 p.m., Washington Hilton...

Accessing the biocompatibility of layered double hydroxide by intramuscular implantation: histological and microcirculation evaluation

PubMed Central

Cunha, Vanessa Roberta Rodrigues; de Souza, Rodrigo Barbosa; da Fonseca Martins, Ana Maria Cristina Rebello Pinto; Koh, Ivan Hong Jun; Constantino, Vera Regina Leopoldo

2016-01-01

Biocompatibility of layered double hydroxides (LDHs), also known as hydrotalcite-like materials or double metal hydroxides, was investigated by in vivo assays via intramuscular tablets implantation in rat abdominal wall. The tablets were composed by chloride ions intercalated into LDH of magnesium/aluminum (Mg2Al-Cl) and zinc/aluminum (Zn2Al-Cl). The antigenicity and tissue integration capacity of LDHs were assessed histologically after 7 and 28 days post-implantation. No fibrous capsule nearby the LDH was noticed for both materials as well any sign of inflammatory reactions. Sidestream Dark Field imaging, used to monitor in real time the microcirculation in tissues, revealed overall integrity of the microcirculatory network neighboring the tablets, with no blood flow obstruction, bleeding and/or increasing of leukocyte endothelial adhesion. After 28 days Mg2Al-Cl promoted multiple collagen invaginations (mostly collagen type-I) among its fragments while Zn2Al-Cl induced predominantly collagen type–III. This work supports previous results in the literature about LDHs compatibility with living matter, endorsing them as functional materials for biomedical applications. PMID:27480483

The Role of Aquaporins in Ocular Lens Homeostasis

PubMed Central

Schey, Kevin L.; Petrova, Rosica S.; Gletten, Romell B.; Donaldson, Paul J.

2017-01-01

Aquaporins (AQPs), by playing essential roles in the maintenance of ocular lens homeostasis, contribute to the establishment and maintenance of the overall optical properties of the lens over many decades of life. Three aquaporins, AQP0, AQP1 and AQP5, each with distinctly different functional properties, are abundantly and differentially expressed in the different regions of the ocular lens. Furthermore, the diversity of AQP functionality is increased in the absence of protein turnover by age-related modifications to lens AQPs that are proposed to alter AQP function in the different regions of the lens. These regional differences in AQP functionality are proposed to contribute to the generation and directionality of the lens internal microcirculation; a system of circulating ionic and fluid fluxes that delivers nutrients to and removes wastes from the lens faster than could be achieved by passive diffusion alone. In this review, we present how regional differences in lens AQP isoforms potentially contribute to this microcirculation system by highlighting current areas of investigation and emphasizing areas where future work is required. PMID:29231874

Blood Perfusion in Microfluidic Models of Pulmonary Capillary Networks: Role of Geometry and Hematocrit

NASA Astrophysics Data System (ADS)

Stauber, Hagit; Waisman, Dan; Sznitman, Josue; Technion-IIT Team; Department of Neonatology Carmel Medical Center; Faculty of Medicine-Technion IIT Collaboration

2015-11-01

Microfluidic platforms are increasingly used to study blood microflows at true physiological scale due to their ability to overcome manufacturing obstacle of complex anatomical morphologies, such as the organ-specific architectures of the microcirculation. In the present work, we utilize microfluidic platforms to devise in vitro models of the underlying pulmonary capillary networks (PCN), where capillary lengths and diameters are similar to the size of RBCs (~ 5-10 μm). To better understand flow characteristics and dispersion of red blood cells (RBCs) in PCNs, we have designed microfluidic models of alveolar capillary beds inspired by the seminal ``sheet flow'' model of Fung and Sobin (1969). Our microfluidic PCNs feature confined arrays of staggered pillars with diameters of ~ 5,7 and 10 μm, mimicking the dense structure of pulmonary capillary meshes. The devices are perfused with suspensions of RBCs at varying hematocrit levels under different flow rates. Whole-field velocity patterns using micro-PIV and single-cell tracking using PTV are obtained with fluorescently-labelled RBCs and discussed. Our experiments deliver a real-scale quantitative description of RBC perfusion characteristics across the pulmonary capillary microcirculation.

Microfluidic approach of Sickled Cell Anemia

NASA Astrophysics Data System (ADS)

Abkarian, Manouk; Loiseau, Etienne; Massiera, Gladys

2012-11-01

Sickle Cell Anemia is a disorder of the microcirculation caused by a genetic point mutation that produces an altered hemoglobin protein called HbS. HbS self-assembles reversibly into long rope like fibers inside the red blood cells. The resulting distorded sickled red blood cells are believed to block the smallest capillaries of the tissues producing anemia. Despite the large amount of work that provided a thorough understanding of HbS polymerization in bulk as well as in intact red blood cells at rest, no consequent cellular scale approaches of the study of polymerization and its link to the capillary obstruction have been proposed in microflow, although the problem of obstruction is in essence a circulatory problem. Here, we use microfluidic channels, designed to mimic physiological conditions (flow velocity, oxygen concentration, hematocrit...) of the microcirculation to carry out a biomimetic study at the cellular scale of sickled cell vaso-occlusion. We show that flow geometry, oxygen concentration, white blood cells and free hemoglobin S are essential in the formation of original cell aggregates which could play a role in the vaso-occlusion events.

Bifurcations: Focal Points of Particle Adhesion in Microvascular Networks

PubMed Central

Prabhakarpandian, Balabhaskar; Wang, Yi; Rea-Ramsey, Angela; Sundaram, Shivshankar; Kiani, Mohammad F.; Pant, Kapil

2011-01-01

Objective Particle adhesion in vivo is dependent on microcirculation environment which features unique anatomical (bifurcations, tortuosity, cross-sectional changes) and physiological (complex hemodynamics) characteristics. The mechanisms behind these complex phenomena are not well understood. In this study, we used a recently developed in vitro model of microvascular networks, called Synthetic Microvascular Network, for characterizing particle adhesion patterns in the microcirculation. Methods Synthetic microvascular networks were fabricated using soft lithography processes followed by particle adhesion studies using avidin and biotin-conjugated microspheres. Particle adhesion patterns were subsequently analyzed using CFD based modeling. Results Experimental and modeling studies highlighted the complex and heterogeneous fluid flow patterns encountered by particles in microvascular networks resulting in significantly higher propensity of adhesion (>1.5X) near bifurcations compared to the branches of the microvascular networks. Conclusion Bifurcations are the focal points of particle adhesion in microvascular networks. Changing flow patterns and morphology near bifurcations are the primary factors controlling the preferential adhesion of functionalized particles in microvascular networks. Synthetic microvascular networks provide an in vitro framework for understanding particle adhesion. PMID:21418388

Accessing the biocompatibility of layered double hydroxide by intramuscular implantation: histological and microcirculation evaluation.

PubMed

Cunha, Vanessa Roberta Rodrigues; de Souza, Rodrigo Barbosa; da Fonseca Martins, Ana Maria Cristina Rebello Pinto; Koh, Ivan Hong Jun; Constantino, Vera Regina Leopoldo

2016-08-02

Biocompatibility of layered double hydroxides (LDHs), also known as hydrotalcite-like materials or double metal hydroxides, was investigated by in vivo assays via intramuscular tablets implantation in rat abdominal wall. The tablets were composed by chloride ions intercalated into LDH of magnesium/aluminum (Mg2Al-Cl) and zinc/aluminum (Zn2Al-Cl). The antigenicity and tissue integration capacity of LDHs were assessed histologically after 7 and 28 days post-implantation. No fibrous capsule nearby the LDH was noticed for both materials as well any sign of inflammatory reactions. Sidestream Dark Field imaging, used to monitor in real time the microcirculation in tissues, revealed overall integrity of the microcirculatory network neighboring the tablets, with no blood flow obstruction, bleeding and/or increasing of leukocyte endothelial adhesion. After 28 days Mg2Al-Cl promoted multiple collagen invaginations (mostly collagen type-I) among its fragments while Zn2Al-Cl induced predominantly collagen type-III. This work supports previous results in the literature about LDHs compatibility with living matter, endorsing them as functional materials for biomedical applications.

Enhanced visualization of the retinal vasculature using depth information in OCT.

PubMed

de Moura, Joaquim; Novo, Jorge; Charlón, Pablo; Barreira, Noelia; Ortega, Marcos

2017-12-01

Retinal vessel tree extraction is a crucial step for analyzing the microcirculation, a frequently needed process in the study of relevant diseases. To date, this has normally been done by using 2D image capture paradigms, offering a restricted visualization of the real layout of the retinal vasculature. In this work, we propose a new approach that automatically segments and reconstructs the 3D retinal vessel tree by combining near-infrared reflectance retinography information with Optical Coherence Tomography (OCT) sections. Our proposal identifies the vessels, estimates their calibers, and obtains the depth at all the positions of the entire vessel tree, thereby enabling the reconstruction of the 3D layout of the complete arteriovenous tree for subsequent analysis. The method was tested using 991 OCT images combined with their corresponding near-infrared reflectance retinography. The different stages of the methodology were validated using the opinion of an expert as a reference. The tests offered accurate results, showing coherent reconstructions of the 3D vasculature that can be analyzed in the diagnosis of relevant diseases affecting the retinal microcirculation, such as hypertension or diabetes, among others.

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

Renal Vascular Structure and Rarefaction

PubMed Central

Chade, Alejandro R.

2014-01-01

An intact microcirculation is vital for diffusion of oxygen and nutrients and for removal of toxins of every organ and system in the human body. The functional and/or anatomical loss of microvessels is known as rarefaction, which can compromise the normal organ function and have been suggested as a possible starting point of several diseases. The purpose of this overview is to discuss the potential underlying mechanisms leading to renal microvascular rarefaction, and the potential consequences on renal function and on the progression of renal damage. Although the kidney is a special organ that receives much more blood than its metabolic needs, experimental and clinical evidence indicates that renal microvascular rarefaction is associated to prevalent cardiovascular diseases such as diabetes, hypertension, and atherosclerosis, either as cause or consequence. On the other hand, emerging experimental evidence using progenitor cells or angiogenic cytokines supports the feasibility of therapeutic interventions capable of modifying the progressive nature of microvascular rarefaction in the kidney. This overview will also attempt to discuss the potential renoprotective mechanisms of the therapeutic targeting of the renal microcirculation. PMID:23720331

Subtle exchange model of flow depended on the blood cell shape to enhance the micro-circulation in capillary

NASA Astrophysics Data System (ADS)

Chan, Iatneng

2012-02-01

In general the exchange of gases or other material in capillary system is conceptualized by the diffusion effect. But in this model, we investigate a micro-flow pattern by simulation and computation on a micro-exchange model in which the blood cell is a considered factor, especially on its shape. It shows that the cell benefits the circulation while it is moving in the capillary. In the study, the flow detail near the cell surface is mathematically analyzed, such that the Navier-Stokes equations are applied and the viscous factor is also briefly considered. For having a driven force to the motion of micro-circulation, a breathing mode is suggested to approximately compute on the flow rate in the blood capillary during the transfer of cell. The rate is also used to estimate the enhancement to the circulation in additional to the outcome of diffusion. Moreover in the research, the shape change of capillary wall under pressure influence is another element in the beginning calculation for the effect in the assistance to cell motion.

Retinal microvascular network alterations: potential biomarkers of cerebrovascular and neural diseases.

PubMed

Cabrera DeBuc, Delia; Somfai, Gabor Mark; Koller, Akos

2017-02-01

Increasing evidence suggests that the conditions of retinal microvessels are indicators to a variety of cerebrovascular, neurodegenerative, psychiatric, and developmental diseases. Thus noninvasive visualization of the human retinal microcirculation offers an exceptional opportunity for the investigation of not only the retinal but also cerebral microvasculature. In this review, we show how the conditions of the retinal microvessels could be used to assess the conditions of brain microvessels because the microvascular network of the retina and brain share, in many aspects, standard features in development, morphology, function, and pathophysiology. Recent techniques and imaging modalities, such as optical coherence tomography (OCT), allow more precise visualization of various layers of the retina and its microcirculation, providing a "microscope" to brain microvessels. We also review the potential role of retinal microvessels in the risk identification of cerebrovascular and neurodegenerative diseases. The association between vision problems and cerebrovascular and neurodegenerative diseases, as well as the possible role of retinal microvascular imaging biomarkers in cerebrovascular and neurodegenerative screening, their potentials, and limitations, are also discussed. Copyright © 2017 the American Physiological Society.

Tissue viability imaging for quantification of skin erythema and blanching

NASA Astrophysics Data System (ADS)

Nilsson, Gert E.; Leahy, Martin J.

2010-02-01

Naked eye observation has up to recently been the main method of determining skin erythema (vasodilatation) and blanching (vasoconstriction) in skin testing. Since naked eye observation is a highly subjective and investigatordependent method, it is difficult to attain reproducibility and to compare results reported by different researchers performing their studies at different laboratories. Consequently there is a need for more objective, quantitative and versatile methods in the assessment of alterations in skin erythema and blanching caused by internal and external factors such as the intake of vasoactive drugs, application of agents on the skin surface and by constituents in the environment. Since skin microcirculation is sensitive to applied pressure and heat, such methods should preferably be noninvasive and designed for remote use without touching the skin. As skin microcirculation further possesses substantial spatial variability, imaging techniques are to be preferred before single point measurements. An emerging technology based on polarization digital camera spectroscopy - Tissue Viability Imaging (TiVi) - fulfills these requirements. The principles of TiVi (1) and some of its early applications (2-5) are addressed in this paper.

Puerarin Attenuates Cerebral Damage by Improving Cerebral Microcirculation in Spontaneously Hypertensive Rats

PubMed Central

Wu, Xu-Dong; Wang, Chen; Zhang, Zhen-Ying; Fu, Yan; Liu, Feng-Ying; Liu, Xiu-Hua

2014-01-01

Puerariae Lobatae Radix (Gegen in Chinese) is the dried root of Pueraria lobata, a semiwoody, perennial, and leguminous vine native to China. Puerarin is one of the effective components of isoflavones isolated from the root of Pueraria lobata. Previous studies showed that extracts derived from the root of Pueraria lobata possessed antihypertensive effect. Our study is to investigate whether puerarin contributes to prevention of stroke by improving cerebral microcirculation in rats. Materials and Methods. Video microscopy and laser Doppler perfusion imaging on the pia mater were used to measure the diameter of microvessel and blood perfusion in 12-week old spontaneously hypertensive rats (SHRs) and age-matched normotensive WKY rats. Histological alterations were observed by hematoxylin and eosin staining, and microvessel density in cerebral tissue was measured by immunohistochemical analysis with anti-Factor VIII antibody. Cell proliferation was detected by [3H]-TdR incorporation, and activities of p42/44 mitogen activated protein kinases (p42/44 MAPKs) were detected by western blot analysis in cultured cerebral microvascular endothelial cells (MECs). Results. Intravenous injection of puerarin relaxed arterioles and increased the blood flow perfusion in the pia mater in SHRs. Puerarin treatment for 14 days reduced the blood pressure to a normal level in SHRs (P < 0.05) and increased the arteriole diameter in the pia mater significantly as compared with vehicle treatment. Arteriole remodeling, edema, and ischemia in cerebral tissue were attenuated in puerarin-treated SHRs. Microvessel density in cerebral tissue was greater with puerarin than with vehicle treatment. Puerarin-treated MECs showed greater proliferation and p42/44 MAPKs activities than vehicle treatment. Conclusions. Puerarin possesses effects of antihypertension and stroke prevention by improved microcirculation in SHRs, which results from the increase in cerebral blood perfusion both by arteriole relaxation and p42/44 MAPKs-mediated angiogenesis. PMID:24715930

Peripheral microcirculation during pregnancy and in women with pregnancy induced hypertension.

PubMed

Ohlmann, P; Jung, F; Mrowietz, C; Alt, T; Alt, S; Schmidt, W

2001-01-01

During pregnancy the cardiovascular system undergoes several changes so as to adapt the maternal organism to the strains of pregnancy. These adaptations can assume a pathological development in persons with a previous history of cardiovascular problems. On the other hand the absence of these adaptations may lead to a pathological course of pregnancy. Pregnancy induced hypertension (PIH) may be such a pathological development due to maladaptation. The causes are for the most part unknown. For some time it has been assumed that it is due to microcirculatory disorders. Using periungual capillary microscopy the present study prospectively investigated the changes in peripheral microcirculation during pregnancy focussing on pregnancy induced hypertension. Sixty-seven women with a normal course of pregnancy and 28 women with pregnancy induced hypertension were evaluated. Throughout the prospective study 3 examinations were performed during pregnancy and one during childbed. The women who developed a PIH were registered during the third trimester. Erythrocyte velocity at rest and vascular reagibility of capillaries following a 3 minute ischaemia were evaluated. In the course of pregnancy a significant increase of approximately 30% in erythrocyte velocity could be observed. Interpolation to obtain the best strait line result demonstrates that it is a continuous increase. Erythrocyte velocity returns to normal in the course of 14 weeks post partum. Due to a physiological vasodilatation during pregnancy, vascular reaction to ischaemic stress significantly decreases. During childbed these changes return to normal. Examinations on women with pregnancy induced hypertension not only showed a significant reduction of microcirculation under resting conditions but also a different pattern of reaction to ischaemic stress. Erythrocyte velocity under resting conditions lies 36% below normal values. Furthermore the distinctly shortened hyperaemic period indicates a hightened sensitivity to vasoconstrictive substances in women with PIH. While taking into account the clinical data a positive correlation with the severity of the illness was able to be established.

Eccentric exercises for the management of tendinopathy of the main body of the Achilles tendon with or without the AirHeel Brace. A randomized controlled trial. A: effects on pain and microcirculation.

PubMed

Knobloch, Karsten; Schreibmueller, Louisa; Longo, Umile Giuseppe; Vogt, Peter M

2008-01-01

To compare eccentric training and the combination of eccentric training with the AirHeel Brace for the management of tendinopathy of the main body of the Achilles tendon. We recruited 116 subjects with unilateral tendinopathy of the main body of the Achilles tendon, who were randomized in two groups. Group A performed a regimen of daily eccentric training associated with the AirHeel Brace (Donjoy Orthopedics, Vista, CA, USA). Group B performed the same eccentric training without the AirHeel Brace. Tendon microcirculatory mapping was performed using combined Laser-Doppler and spectrophotometry. Pre- and post-operative FAOS score and VAS score were used to evaluate the patients. The FAOS score and the VAS score showed significant improvements from pre-operative to post-operative values in both groups (A 5.1 +/- 2 vs. 2.9 +/- 2.4, 43% reduction and B: 5.4 +/- 2.1 vs. 3.6 +/- 2.4, 33% reduction, both p = 0.0001). There were no statistically significant differences in FAOS score and VAS score when comparing the two groups after the end of the intervention. In Group A, tendon oxygen saturation in the main body of the Achilles tendon showed significant increase from pre- to post-management values (68 +/- 12 vs.74 +/- 8%, p = 0.003). Post-capillary venous filling pressures showed significant reduction from pre- to post-intervention values. Eccentric training, associated or not with the AirHeel Brace, produces the same effect in patients with tendinopathy of the main body of the Achilles tendon. The combination of eccentric training with the AirHeel Brace can optimize tendon microcirculation, but these micro-circulator advantages do not translate into superior clinical performance when compared with eccentric training alone.

Progressive thermopreconditioning attenuates rat cardiac ischemia/reperfusion injury by mitochondria-mediated antioxidant and antiapoptotic mechanisms.

PubMed

Chien, Chen-Yen; Chien, Chiang-Ting; Wang, Shoei-Shen

2014-08-01

Progressive thermal preconditioning (PTP) provides vascular protection with less hemodynamic fluctuations, endoplasmic reticulum (ER), and oxidative stress compared with whole body hyperthermia. We suggest PTP might efficiently diminish cardiac ischemia/reperfusion-induced apoptosis and autophagy injury. A total of 67 male Wistar rats were divided into a non-PTP control group, 24 or 72 hours after a single cycle or 3 consecutive cycles of PTP in a 42°C water bath (1-24, 1-72, 3-24, and 3-72 groups). We measured the cardiac O2(-) amount in vivo in response to left anterior descending coronary artery ligation for 2 hours and reperfusion for 3 hours. Cardiac function and injury were determined by microcirculation, electrocardiography, and infarct size. The PTP-induced protective effects on nicotinamide adenine dinucleotide phosphate oxidase gp91-mediated oxidative stress, ER stress, and apoptosis- and autophagy-related mechanisms were examined using Western blot and immunohistochemistry. Coronary arterial ischemia/reperfusion depressed cardiac microcirculation, induced ST-segment elevation and increased infarct size in non-PTP and PTP rats. Ischemia/reperfusion enhanced the cardiac O2(-) levels by enhanced nicotinamide adenine dinucleotide phosphate oxidase gp91 expression, cytosolic cytochrome C release, and decreased mitochondrial Bcl-2 expression. Cardiac injury activated ER stress-78-kDa glucose-regulated protein expression, increased the Bax/Bcl-2 ratio, cleaved caspase 3 expression and poly-(ADP-ribose)-polymerase fragments, leading to apoptosis formation, and promoted LC3-II expression, resulting in autophagy formation. PTP treatment elevated heat shock protein 70, heat shock protein 32, Bcl-2, Bcl-xL, and manganese superoxide dismutase in the rat heart, especially in the 3-72 group. PTP treatment significantly restored cardiac microcirculation, decreased oxidative stress, ER stress, apoptosis, autophagy, and infarct size. PTP significantly reduced cardiac ischemia/reperfusion injury by upregulating antioxidant, antiapoptotic, and antiautophagic mechanisms. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Can intravoxel incoherent motion diffusion-weighted imaging characterize the cellular injury and microcirculation alteration in hepatic ischemia-reperfusion injury? An animal study.

PubMed

Ye, Weitao; Li, Jinglei; Guo, Chengwei; Chen, Shuting; Liu, Yu-Bao; Liu, Zaiyi; Wu, Haijun; Wang, Guangyi; Liang, Changhong

2016-06-01

To investigate whether intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) can be used to quantitatively analyze the cellular injury and microcirculation alterations in hepatic ischemia-reperfusion injury (HIRI). Thirty-two New Zealand white rabbits were randomly and equally assigned to the sham group, 1-hour, 4-hour, and 12-hour groups according to the reperfusion time after 1 hour of ischemia using a 70% liver ischemia-reperfusion injury model. All the animals underwent IVIM-DWI with 12 b values at 1.5T. The imaging parameters (IVIM parameters and apparent diffusion coefficient [ADC]) among different groups were compared. The correlations between imaging parameters and histological scores, and the ratio of serum aspartate aminotransferase to serum alanine aminotransferase (serum AST/ALT) were analyzed. During the first hour of HIRI, true diffusion coefficient (D) and ADC significantly decreased (P < 0.05), while there was no significant decrease in perfusion fraction (f) (P = 0.708). There was fair to good correlation between histological scores and f (rs  = -0.493 with the sham cases excluded, and -0.682 with all cases, both P < 0.05) and ADC (rs  = -0.479 with the sham cases excluded, and -0.766 with all cases, both P < 0.05). There was no correlation between imaging parameters and serum AST/ALT with the sham cases excluded (P = 0.673 for f, 0.568 for D, 0.403 for ADC), and good correlation between D, ADC, and serum AST/ALT (r = 0.747 and 0.748, both P < 0.001) with all cases. IVIM-DWI can quantitatively characterize an animal model of HIRI, with D and ADC sensitive in early detection of cellular injury, as well as fair to good correlation between f, ADC, and microcirculation alteration. J. Magn. Reson. Imaging 2016;43:1327-1336. © 2015 Wiley Periodicals, Inc.

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/dysfunction, such as mechanotransduction, leukocyte-endothelial interactions and the development of atherosclerosis, indicate that alterations in the endothelial glycocalyx may also be playing a role in the dysfunction of other organs observed in these disease states. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

[Effect of extracts from Dendrobii ifficinalis flos on hyperthyroidism Yin deficiency mice].

PubMed

Lei, Shan-shan; Lv, Gui-yuan; Jin, Ze-wu; Li, Bo; Yang, Zheng-biao; Chen, Su-hong

2015-05-01

Some unhealthy life habits, such as long-term smoking, heavy drinking, sexual overstrain and frequent stay-up could induce the Yin deficiency symptoms of zygomatic red and dysphoria. Stems of Dendrobii officinalis flos (DOF) showed the efficacy of nourishing Yin. In this study, the hyperthyroidism Yin deficiency model was set up to study the yin nourishing effect and action mechanism of DOF, in order to provide the pharmacological basis for developing DOF resources and decreasing resource wastes. ICR mice were divided into five groups: the normal control group, the model control group, the positive control group and DOF extract groups (6.4 g · kg(-1)). Except for the normal group, the other groups were administrated with thyroxine for 30 d to set up the hyperthyroidism yin deficiency model. At the same time, the other groups were administrated with the corresponding drugs for 30 d. After administration for 4 weeks, the signs (facial temperature, pain domain, heart rate and autonomic activity) in mice were measured, and the facial and ear micro-circulation blood flow were detected by laser Doppler technology. After the last administration, all mice were fasted for 12 hours, blood were collected from their orbits, and serum were separated to detect AST, ALT, TG and TP by the automatic biochemistry analyzer and test T3, T4 and TSH levels by ELISA. (1) Compared with the normal control group, the model control group showed significant increases in facial and ear micro-circulation blood flow, facial temperature and heart rate (P < 0.05, P < 0.01), serum AST, ALT (P < 0.01), T3 level (P < 0.05), TSH level (P < 0.05) and notable deceases in pain domain (P < 0.01), TG level (P < 0.01). (2) Compared with the model control group, extracts from DOF (6 g · kg(-1)) could notably reduce facial and ear micro-circulation blood flow, facial temperature and heart rate (P < 0.05, P < 0.01) and AST (P < 0.05) and enhance pain domain (P < 0.01) and TG (P < 0.01). Extracts from DOF (4 g · kg(-1)) could remarkably reduce AST and ALT levels (P < 0.01, 0.05). Extracts from DOF (6 g · kg(-1) 4 g · kg(-1)) could significantly reduce T3 and increase serum TSH level (P < 0.05). DOF could improve Yin deficiency symptoms of zygomatic red and dysphoria in mice as well as liver function injury caused by overactive thyroid axis. According to its action mechanism, DOF may show yin nourishing and hepatic protective effects by impacting thyroxin substance metabolism, improving micro-circulation and reducing heart rate.

Hemorheological changes, the state of microcirculation, and blood acid-base balance in rats under conditions of a 30-day limiting of the motor activity

NASA Technical Reports Server (NTRS)

Shtykhno, Y. M.; Udovichenko, V. I.

1980-01-01

Changes were expressed in reduction in number of true capillaries, the appearance of nonfunctioning empty vessels and in the opening of the arteriolo-venular shunts. Changes in the acid-base balance in the direction of reduction of buffer blood content were also noted.

[Mesenteric circulation evaluation during myocardial revascularization with different temperature modes of extracorporeal circulation].

PubMed

Iavorovskiĭ, A G; Novikova, O V; Aksel'rod, B A; Guleshov, V A; Amelina, M A; Bulganina, N A; Morozov, Iu A

2013-01-01

The Mesenteric blood circulation during myocardium revasculization was investigated 40 patients were divided in 2 groups: 1st group - normothermia CPB, 2nd group hypothermia CPB. It was found that reduced mesenteric perfusion occurred in both groups, but it was more pronounced in hypothermia CPB group and was caused by a significant deterioration of the microcirculation.

Systemic and Microvascular Effects of Resuscitation with Blood Products After Severe Hemorrhage in Rats

DTIC Science & Technology

2014-01-01

thickness, blood flow, and microvascular permeability were studied using intravital microscopy. Hemodynamics and coagulation tests (rotational...Microcirculation; packed red blood cells; intravital microscopy; ROTEM; plasma proteins; rats. Current US military guidance for the resuscitation of warfighters...was used for coagulation assays (rotational thromboelast- ometry [ROTEM], TEM Innovations GmbH, Germany). Intravital Microscopy and Animal Preparation

Study of toxic properties of prototypes of photo inactivated vaccines against tularemia and brucellosis by speckle microscopy

NASA Astrophysics Data System (ADS)

Ulianova, Onega V.; Ulyanov, Sergey

2010-10-01

Testing of prototypes of vaccines against extremely dangerous diseases, such as tularemia and brucellosis has been performed using speckle-microscopy. Changes of microcirculation caused by effect of toxins at applications of suspension of photoinactivated bacteria have been studied. Toxic properties of prototypes of vaccines against tularemia and brucellosis have been analyzed.

Study of toxic properties of prototypes of photo inactivated vaccines against tularemia and brucellosis by speckle microscopy

NASA Astrophysics Data System (ADS)

Ulianova, Onega V.; Ulyanov, Sergey

2011-03-01

Testing of prototypes of vaccines against extremely dangerous diseases, such as tularemia and brucellosis has been performed using speckle-microscopy. Changes of microcirculation caused by effect of toxins at applications of suspension of photoinactivated bacteria have been studied. Toxic properties of prototypes of vaccines against tularemia and brucellosis have been analyzed.

Optimization of camera exposure durations for multi-exposure speckle imaging of the microcirculation

PubMed Central

Kazmi, S. M. Shams; Balial, Satyajit; Dunn, Andrew K.

2014-01-01

Improved Laser Speckle Contrast Imaging (LSCI) blood flow analyses that incorporate inverse models of the underlying laser-tissue interaction have been used to develop more quantitative implementations of speckle flowmetry such as Multi-Exposure Speckle Imaging (MESI). In this paper, we determine the optimal camera exposure durations required for obtaining flow information with comparable accuracy with the prevailing MESI implementation utilized in recent in vivo rodent studies. A looping leave-one-out (LOO) algorithm was used to identify exposure subsets which were analyzed for accuracy against flows obtained from analysis with the original full exposure set over 9 animals comprising n = 314 regional flow measurements. From the 15 original exposures, 6 exposures were found using the LOO process to provide comparable accuracy, defined as being no more than 10% deviant, with the original flow measurements. The optimal subset of exposures provides a basis set of camera durations for speckle flowmetry studies of the microcirculation and confers a two-fold faster acquisition rate and a 28% reduction in processing time without sacrificing accuracy. Additionally, the optimization process can be used to identify further reductions in the exposure subsets for tailoring imaging over less expansive flow distributions to enable even faster imaging. PMID:25071956

N-Acetylcysteine's Role in Sepsis and Potential Benefit in Patients With Microcirculatory Derangements.

PubMed

Chertoff, Jason

2018-02-01

To review the data surrounding the utility of N-acetylcysteine (NAC) in sepsis and identify areas needed for additional research. A review of articles describing the mechanisms of action and clinical use of NAC in sepsis. Despite many advances in critical care medicine, still as many as 50% of patients with septic shock die. Treatments thus far have focused on resuscitation and restoration of macrocirculatory targets in the early phases of sepsis, with less focus on microcirculatory dysfunction. N-acetylcysteine, due to its anti-inflammatory and antioxidative properties, has been readily investigated in sepsis and has yielded largely incongruous and disappointing results. In addition to its known anti-inflammatory and antioxidative roles, one underappreciated property of NAC is its ability to vasodilate the microcirculation and improve locoregional blood flow. Some investigators have sought to capitalize on this mechanism with promising results, as evidenced by microcirculatory vasodilation, improvements in regional blood flow and oxygen delivery, and reductions in lactic acidosis, organ failure, and mortality. In addition to its antioxidant and anti-inflammatory properties, N-acetylcysteine possesses vasodilatory properties that could benefit the microcirculation in sepsis. It is imperative that we investigate these properties to uncover NAC's full potential for benefit in sepsis.

Rheological effects of drag-reducing polymers improve cerebral blood flow and oxygenation after traumatic brain injury in rats.

PubMed

Bragin, Denis E; Kameneva, Marina V; Bragina, Olga A; Thomson, Susan; Statom, Gloria L; Lara, Devon A; Yang, Yirong; Nemoto, Edwin M

2017-03-01

Cerebral ischemia has been clearly demonstrated after traumatic brain injury (TBI); however, neuroprotective therapies have not focused on improvement of the cerebral microcirculation. Blood soluble drag-reducing polymers (DRP), prepared from high molecular weight polyethylene oxide, target impaired microvascular perfusion by altering the rheological properties of blood and, until our recent reports, has not been applied to the brain. We hypothesized that DRP improve cerebral microcirculation and oxygenation after TBI. DRP were studied in healthy and traumatized rat brains and compared to saline controls. Using in-vivo two-photon laser scanning microscopy over the parietal cortex, we showed that after TBI, nanomolar concentrations of intravascular DRP significantly enhanced microvascular perfusion and tissue oxygenation in peri-contusional areas, preserved blood-brain barrier integrity and protected neurons. The mechanisms of DRP effects were attributable to reduction of the near-vessel wall cell-free layer which increased near-wall blood flow velocity, microcirculatory volume flow, and number of erythrocytes entering capillaries, thereby reducing capillary stasis and tissue hypoxia as reflected by a reduction in NADH. Our results indicate that early reduction in CBF after TBI is mainly due to ischemia; however, metabolic depression of contused tissue could be also involved.

Skeletal muscle fiber, nerve, and blood vessel breakdown in space-flown rats

NASA Technical Reports Server (NTRS)

Riley, D. A.; Ilyina-Kakueva, E. I.; Ellis, S.; Bain, J. L.; Slocum, G. R.; Sedlak, F. R.

1990-01-01

Histochemical and ultrastructural analyses were performed postflight on hind limb skeletal muscles of rats orbited for 12.5 days aboard the unmanned Cosmos 1887 biosatellite and returned to Earth 2 days before sacrifice. The antigravity adductor longus (AL), soleus, and plantaris muscles atrophied more than the non-weight-bearing extensor digitorum longus, and slow muscle fibers were more atrophic than fast fibers. Muscle fiber segmental necrosis occurred selectively in the AL and soleus muscles; primarily, macrophages and neutrophils infiltrated and phagocytosed cellular debris. Granule-rich mast cells were diminished in flight AL muscles compared with controls, indicating the mast cell secretion contributed to interstitial tissue edema. Increased ubiquitination of disrupted myofibrils implicated ubiquitin in myofilament degradation. Mitochondrial content and succinic dehydrogenase activity were normal, except for subsarcolemmal decreases. Myofibrillar ATPase activity of flight AL muscle fibers shifted toward the fast type. Absence of capillaries and extravasation of red blood cells indicated failed microcirculation. Muscle fiber regeneration from activated satellite cells was detected. About 17% of the flight AL end plates exhibited total or partial denervation. Thus, skeletal muscle weakness associated with spaceflight can result from muscle fiber atrophy and segmental necrosis, partial motor denervation, and disruption of the microcirculation.

Assessment of muscle tissue oxygen saturation after out-of-hospital cardiac arrest.

PubMed

Orban, Jean-Christophe; Scarlatti, Audrey; Danin, Pierre-Eric; Dellamonica, Jean; Bernardin, Gilles; Ichai, Carole

2015-12-01

Pathophysiology of cardiac arrest corresponds to an ischemia-reperfusion syndrome with deep impairment of microcirculation. Muscular tissue oxygen saturation (StO2) is a noninvasive method of evaluation of microcirculation. Our study was aimed at assessing the prognosis value of muscular StO2 in patients admitted for out-of-hospital cardiac arrest (OHCA) and treated with hypothermia. We conducted a prospective bicentric observational study including OHCA patients treated with therapeutic hypothermia. Baseline StO2, derived variables (desaturation and resaturation slopes), and lactate levels were compared at different times between patients with good and poor outcomes. Prognosis was assessed by the Cerebral Performance Category (CPC) score at 6 months after admission (CPC 1-2, good outcome; CPC 3-5, poor outcome). Forty-four patients were included, 17 good and 27 poor outcomes at 6 months. At admission, StO2 and lactate levels were lower in good outcome patients. Desaturation and resaturation slopes did not differ between groups. After an OHCA treated with therapeutic hypothermia, StO2 was correlated with outcome. Further research is needed to better understand the pathophysiological process underlying our results. Copyright © 2015 Elsevier Inc. All rights reserved.

Cardiac microvascular rarefaction in hyperthyroidism-induced left ventricle dysfunction.

PubMed

Freitas, Felipe; Estato, Vanessa; Carvalho, Vinícius Frias; Torres, Rafael Carvalho; Lessa, Marcos Adriano; Tibiriçá, Eduardo

2013-10-01

The pathophysiology underlying hyperthyroidism-induced left ventricle (LV) dysfunction and hypertrophy directly involves the heart and indirectly involves the neuroendocrine systems. The effects of hyperthyroidism on the microcirculation are still controversial in experimental models. We investigated the effects of hyperthyroidism on the cardiac function and microcirculation of an experimental rat model. Male Wistar rats (170-250 g) were divided into two groups: the euthyroid group (n = 10), which was treated with 0.9% saline solution, and the hyperthyroid group (n = 10), which was treated with l-thyroxine (600 μg/kg/day, i.p.) during 14 days. An echocardiographic study was performed to evaluate the alterations in cardiac function, structure and geometry. The structural capillary density and the expression of angiotensin II AT1 receptor in the LV were analyzed using histochemistry and immunohistochemistry, respectively. Hyperthyroidism was found to induce profound cardiovascular alterations, such as systolic hypertension, tachycardia, LV dysfunction, cardiac hypertrophy, and myocardial fibrosis. This study demonstrates the existence of structural capillary rarefaction and the down-regulation of the cardiac angiotensin II AT1 receptor in the myocardium of hyperthyroid rats in comparison with euthyroid rats. Microvascular rarefaction may be involved in the pathophysiology of hyperthyroidism-induced cardiovascular alterations. © 2013 John Wiley & Sons Ltd.

[Investigation of postconditioning in intestinal ischemia-reperfusion experimental models].

PubMed

Rosero, Olivér; Onody, Péter; Stangl, Rita; Hegedus, Viktor; Lotz, Gábor; Blázovics, Anna; Kupcsulik, Péter; Szijártó, Attila

2011-02-01

The ischemic-reperfusion injury of the intestine, which occurs as a consequence of circulatory redistribution or occlusion of the superior mesenteric artery, is associated with high mortality rates. Postconditioning may reduce ischemic-reperfusion damage in such cases. Effects of this new surgical method were investigated in rats. Male Wistar rats underwent 60 minutes of superior mesenteric artery occlusion in four groups: sham-operated, control and two postconditioned groups with different algorithms. Postconditioning was performed immediately at the beginning of reperfusion, by repetitive cycles of reperfusion and reocclusion. 3 cycles of 1 minute and 6 cycles of 10 seconds were applied according to groups. Intestinal microcirculation was followed by laser Doppler flowmetry. Blood and tissue samples were taken after 60 minutes of reperfusion. Histological analayses of the small intestine, measurement of serum necroenzyme levels and IL-6, mesenterial venous blood gas analyses were preformed and antioxidant state of the mucosa was investigated. The microcirculation during the reperfusion showed significant improvement in both postconditioned groups. Histological damage, necroenzyme and IL-6 levels were significantly reduced, while antioxidant state was improved in the postconditioned groups. Postconditioning was capable of increasing the guts chance to survive ischemic-reperfusion injury caused by superior mesenteric artery occlusion.

The rationale for microcirculatory guided fluid therapy.

PubMed

Ince, Can

2014-06-01

The ultimate purpose of fluid administration in states of hypovolemia is to correct cardiac output to improve microcirculatory perfusion and tissue oxygenation. Observation of the microcirculation using handheld microscopes gives insight into the nature of convective and diffusive defect in hypovolemia. The purpose of this article is to introduce a new platform for hemodynamic-targeted fluid therapy based on the correction of tissue and microcirculatory perfusion assumed to be at risk during hypovolemia. Targeting systemic hemodynamic targets and/or clinical surrogates of hypovolemia gives inadequate guarantee for the correction of tissue perfusion by fluid therapy especially in conditions of distributive shock as occur in inflammation and sepsis. Findings are presented, which support the idea that only clinical signs of hypovolemia associated with low microcirculatory flow can be expected to benefit from fluid therapy and that fluid overload causes a defect in the diffusion of oxygen transport. We hypothesized that the optimal amount of fluid needed for correction of hypovolemia is defined by a physiologically based functional microcirculatory hemodynamic platform where convection and diffusion need to be optimized. Future clinical trials using handheld microscopes able to automatically evaluate the microcirculation at the bedside will show whether such a platform will indeed optimize fluid therapy.

[Contrast-enhanced ultrasound in animal models].

PubMed

Paprottka, P M; Zengel, P; Ingrisch, M; Cyran, C C; Eichhorn, M; Reiser, M F; Nikolaou, K; Clevert, D-A

2011-06-01

In the past the detection of tumor perfusion was achieved solely via invasive procedures, such as intravital microscopy or with the help of costly modalities, such as multidetector computed tomography (MDCT), magnetic resonance tomography (MRT) or the combined use of positron emission tomography and computed tomography (PET/CT). Ultrasound offers the non-invasive display of organs without usage of ionizing radiation and it is widely available. However, colour-coded ultrasound and power Doppler do not allow the detection of tumor microcirculation. The introduction of contrast-enhanced ultrasound (CEUS) as well as new high-frequency ultrasound probes made it possible to detect and quantify tumor microcirculation with high resolution. CEUS has been used clinically on human beings for more than 10 years. During the last years different tumor models in experimental animals were used for the establishment of this new technique, e.g. in rats, hamsters and mice. CEUS allows the detection of functional parameters, such as the angiogenetic metabolic status of tissue pretreatment and posttreatment. Further research is required to solve the problems of absolute quantification of these perfusion parameters to allow the comparison of CEUS with other modalities (e.g. MRT and CT).

Betahistine metabolites, aminoethylpyridine, and hydroxyethylpyridine increase cochlear blood flow in guinea pigs in vivo.

PubMed

Bertlich, Mattis; Ihler, Fritz; Sharaf, Kariem; Weiss, Bernhard G; Strupp, Michael; Canis, Martin

2014-10-01

Betahistine is a histamine-like drug that is used in the treatment of Ménière's disease. It is commonly believed that betahistine increases cochlear blood flow and thus decreases the endolymphatic hydrops that is the cause of Ménière's. Despite common clinical use, there is little understanding of the kinetics or effects of its metabolites. This study investigated the effect of the betahistine metabolites aminoethylpyridine, hydroxyethylpyridine, and pyridylacetic acid on cochlear microcirculation. Guinea pigs were randomly assigned to one of the groups: placebo, betahistine, or equimolar amounts of aminoethylpyridine, hydroxyethylpyridine, or pyridylacetic acid. Cochlear blood flow and mean arterial pressure were recorded for three minutes before and 15 minutes after treatment. Thirty Dunkin-Hartley guinea pigs assigned to one of five groups with six guinea pigs per group. Betahistine, aminoethylpyridine, and hydroxyethylpyridine caused a significant increase in cochlear blood flow in comparison to placebo. The effect seen under aminoethylpyridin was greatest. The group treated with pyridylacetic acid showed no significant effect on cochlear blood flow. Aminoethylpyridine and hydroxyethylpyridine are, like betahistine, able to increase cochlear blood flow significantly. The effect of aminoethylpyridine was greatest. Pyridylacetic acid had no effect on cochlear microcirculation.

Acute hyperfibrinogenemia impairs cochlear blood flow and hearing function in guinea pigs in vivo.

PubMed

Ihler, Fritz; Strieth, Sebastian; Pieri, Nicos; Göhring, Peter; Canis, Martin

2012-03-01

Impairment of microcirculation is a possible cause of sudden sensorineural hearing loss (SSNHL). Fibrinogen is known as a risk factor for both microvascular dysfunction and SSNHL. Therefore, the aim of this study was to investigate the effect of elevated serum levels of fibrinogen on cochlear blood flow and hearing function in vivo. One group of guinea pigs received two consecutive injections of 100 mg fibrinogen while a control group received equimolar doses of albumin. Measurements of cochlear microcirculation by intravital microscopy and of hearing thresholds by auditory brainstem response (ABR) recordings were carried out before, after first and after second injection. Ten healthy guinea pigs were randomly assigned to a treatment group or a control group of five animals each. Serum fibrinogen levels were elevated after the first and second injections of fibrinogen compared to basal values and control group respectively. Increasing levels of fibrinogen were paralleled by decreasing cochlear blood flow as well as increasing hearing thresholds. Hearing threshold correlated negatively with cochlear blood flow. The effect of microcirculatory impairment on hearing function could be explained by a malfunction of the cochlear amplifier. Further investigation is needed to quantify cochlear potentials under elevated serum fibrinogen levels.

EASApprox® skin-stretching system: A secure and effective method to achieve wound closure.

PubMed

Song, Mingzhi; Zhang, Zhen; Liu, Tao; Liu, Song; Li, Gang; Liu, Zhaochang; Huang, Jingyang; Chen, Song; Li, Linan; Guo, Li; Qiu, Yang; Wan, Jiajia; Liu, Yuejian; Wu, Tao; Wang, Xiaoyong; Lu, Ming; Wang, Shouyu

2017-07-01

Large skin defects are commonly observed in the clinic and have attracted much attention recently. Therefore, finding an effective solution for large skin defects is a global problem. The objective of the present study was to assess the effectiveness of the EASApprox ® skin-stretching system for closing large skin defects. Skin defects (5×5 cm) were created on the forearms of 9 Bama miniature pigs, which were randomly divided into the following three groups: Direct suture, the new EASApprox ® skin-stretching device and Kirschner wires. Microcirculation was assessed before surgery and after wound closure. Following the different treatments, the defects were sutured, and wound healing was assessed based on a clinical score. Furthermore, microscopic and ultramicroscopic structures were evaluated, including collagen, elastic fibers and the microvessel density. Significant differences in the clinical score and microvessel density were observed among the groups. Additionally, the mean length obtained for elastic fibers was larger than that obtained for the other two groups. Finally, the new EASApprox ® skin-stretching device resulted in successful wound management and with only minor side effects on skin histology and microcirculation. Therefore, this method has the potential to be used for healing large skin defects.

In vivo functional photoacoustic microscopy of cutaneous microvasculature in human skin.

PubMed

Favazza, Christopher P; Cornelius, Lynn A; Wang, Lihong V

2011-02-01

Microcirculation is an important component of the cardiovascular system and can be used to assess systemic cardiovascular health. Numerous studies have investigated cutaneous microcirculation as an indicator of cardiovascular related diseases. Such research has shown promising results; however, there are many limitations regarding the employed measurement techniques, such as poor depth and spatial resolution and measurement versatility. Here we show the results of functional cutaneous microvascular experiments measured with photoacoustic microscopy, which provides high spatial resolution and multiparameter measurements. In a set of experiments, microvascular networks located in the palms of volunteers were perturbed by periodic ischemic events, and the subsequent hemodynamic response to the stimulus was recorded. Results indicate that during periods of arterial occlusion, the relative oxygen saturation of the capillary vessels decreased below resting levels, and temporarily increased above resting levels immediately following the occlusion. Furthermore, a hyperemic reaction to the occlusions was measured, and the observation agreed well with similar measurements using more conventional imaging techniques. Due to its exceptional capability to functionally image vascular networks with high spatial resolution, photoacoustic microscopy could be a beneficial biomedical tool to assess microvascular functioning and applied to patients with diseases that affect cardiovascular health. © 2011 Society of Photo-Optical Instrumentation Engineers.

Mechanisms of tumor necrosis in photodynamic therapy with a chlorine photosensitizer: experimental studies

NASA Astrophysics Data System (ADS)

Privalov, Valeriy A.; Lappa, Alexander V.; Bigbov, Elmir N.

2011-02-01

A photodynamic therapy experiment on 118 inbred white mice with transplanted Ehrlich's tumor (mouse mammary gland adenocarcinoma) is performed to reveal mechanisms of necrosis formation. In 7-10 days the tumor of 1-1.5 cm diameter is formed under skin at the injection point, and PDT procedure is applied. There were used a chlorine type photosensitizer RadachlorineTM and 662 nm wavelength diode laser. The drug is injected by intravenously at the dose of 40 mg/kg; the irradiation is executed in 2-2.5 hours at the surface dose of about 200 J/cm2. Each of the mice had a photochemical reaction in form of destructive changes at the irradiation region with subsequent development of dry coagulation necrosis. After rejection of the necrosis there occurred epithelization of defect tissues in a tumor place. Histological investigations were conducted in different follow-up periods, in 5 and 30 min, 1, 3, 6, and 12 hours, 1, 3, 7 and 28 days after irradiation. They included optical microscopy, immune marker analysis, morphometry with measurements of volume density of epithelium, tumor stroma and necroses, vascular bed. The investigations showed that an important role in damaging mechanisms of photodynamic action belongs to hypoxic injuries of tumor mediated by micro vascular disorders and blood circulatory disturbances. The injuries are formed in a few stages: microcirculation angiospasm causing vessel paresis, irreversible stases in capillaries, diapedetic hemorrhages, thromboses, and thrombovasculitis. It is marked mucoid swelling and fibrinoid necrosis of vascular tissue. Progressive vasculitises result in total vessel obliteration and tumor necrosis.

The endothelin B receptor plays a crucial role in the adhesion of neutrophils to the endothelium in sickle cell disease

PubMed Central

Koehl, Bérengère; Nivoit, Pierre; El Nemer, Wassim; Lenoir, Olivia; Hermand, Patricia; Pereira, Catia; Brousse, Valentine; Guyonnet, Léa; Ghinatti, Giulia; Benkerrou, Malika; Colin, Yves; Le Van Kim, Caroline; Tharaux, Pierre-Louis

2017-01-01

Although the primary origin of sickle cell disease is a hemoglobin disorder, many types of cells contribute considerably to the pathophysiology of the disease. The adhesion of neutrophils to activated endothelium is critical in the pathophysiology of sickle cell disease and targeting neutrophils and their interactions with endothelium represents an important opportunity for the development of new therapeutics. We focused on endothelin-1, a mediator involved in neutrophil activation and recruitment in tissues, and investigated the involvement of the endothelin receptors in the interaction of neutrophils with endothelial cells. We used fluorescence intravital microscopy analyses of the microcirculation in sickle mice and quantitative microfluidic fluorescence microscopy of human blood. Both experiments on the mouse model and patients indicate that blocking endothelin receptors, particularly ETB receptor, strongly influences neutrophil recruitment under inflammatory conditions in sickle cell disease. We show that human neutrophils have functional ETB receptors with calcium signaling capability, leading to increased adhesion to the endothelium through effects on both endothelial cells and neutrophils. Intact ETB function was found to be required for tumor necrosis factor α-dependent upregulation of CD11b on neutrophils. Furthermore, we confirmed that human neutrophils synthesize endothelin-1, which may be involved in autocrine and paracrine pathophysiological actions. Thus, the endothelin-ETB axis should be considered as a cytokine-like potent pro-inflammatory pathway in sickle cell disease. Blockade of endothelin receptors, including ETB, may provide major benefits for preventing or treating vaso-occlusive crises in sickle cell patients. PMID:28385784

Exercise restores coronary vascular function independent of myogenic tone or hyperglycemic status in db/db mice.

PubMed

Moien-Afshari, Farzad; Ghosh, Sanjoy; Elmi, Shahrzad; Khazaei, Majid; Rahman, Mohammad M; Sallam, Nada; Laher, Ismail

2008-10-01

Regulation of coronary function in diabetic hearts is an important component in preventing ischemic cardiac events but remains poorly studied. Exercise is recommended in the management of diabetes, but its effects on diabetic coronary function are relatively unknown. We investigated coronary artery myogenic tone and endothelial function, essential elements in maintaining vascular fluid dynamics in the myocardium. We hypothesized that exercise reduces pressure-induced myogenic constriction of coronary arteries while improving endothelial function in db/db mice, a model of type 2 diabetes. We used pressurized mouse coronary arteries isolated from hearts of control and db/db mice that were sedentary or exercised for 1 h/day on a motorized exercise-wheel system (set at 5.2 m/day, 5 days/wk). Exercise caused a approximately 10% weight loss in db/db mice and decreased whole body oxidative stress, as measured by plasma 8-isoprostane levels, but failed to improve hyperglycemia or plasma insulin levels. Exercise did not alter myogenic regulation of arterial diameter stimulated by increased transmural pressure, nor did it alter smooth muscle responses to U-46619 (a thromboxane agonist) or sodium nitroprusside (an endothelium-independent dilator). Moderate levels of exercise restored ACh-simulated, endothelium-dependent coronary artery vasodilation in db/db mice and increased expression of Mn SOD and decreased nitrotyrosine levels in hearts of db/db mice. We conclude that the vascular benefits of moderate levels of exercise were independent of changes in myogenic tone or hyperglycemic status and primarily involved increased nitric oxide bioavailability in the coronary microcirculation.

Nano-Computed Tomography: Technique and Applications.

PubMed

Kampschulte, M; Langheinirch, A C; Sender, J; Litzlbauer, H D; Althöhn, U; Schwab, J D; Alejandre-Lafont, E; Martels, G; Krombach, G A

2016-02-01

Nano-computed tomography (nano-CT) is an emerging, high-resolution cross-sectional imaging technique and represents a technical advancement of the established micro-CT technology. Based on the application of a transmission target X-ray tube, the focal spot size can be decreased down to diameters less than 400 nanometers (nm). Together with specific detectors and examination protocols, a superior spatial resolution up to 400 nm (10 % MTF) can be achieved, thereby exceeding the resolution capacity of typical micro-CT systems. The technical concept of nano-CT imaging as well as the basics of specimen preparation are demonstrated exemplarily. Characteristics of atherosclerotic plaques (intraplaque hemorrhage and calcifications) in a murine model of atherosclerosis (ApoE (-/-)/LDLR(-/-) double knockout mouse) are demonstrated in the context of superior spatial resolution in comparison to micro-CT. Furthermore, this article presents the application of nano-CT for imaging cerebral microcirculation (murine), lung structures (porcine), and trabecular microstructure (ovine) in contrast to micro-CT imaging. This review shows the potential of nano-CT as a radiological method in biomedical basic research and discusses the application of experimental, high resolution CT techniques in consideration of other high resolution cross-sectional imaging techniques. Nano-computed tomography is a high resolution CT-technology for 3D imaging at sub-micrometer resolution. The technical concept bases on a further development of the established ex-vivo-micro-CT technology. By improvement of the spatial resolution, structures at a cellular level become visible (e.g. osteocyte lacunae). © Georg Thieme Verlag KG Stuttgart · New York.

Pathophysiology of spontaneous venous gas embolism

NASA Technical Reports Server (NTRS)

Lambertsen, C. J.; Albertine, K. H.; Pisarello, J. B.; Flores, N. D.

1991-01-01

The use of controllable degrees and durations of continuous isobaric counterdiffusion venous gas embolism to investigate effects of venous gas embolism upon blood, cardiovascular, and respiratory gas exchange function, as well as pathological effects upon the lung and its microcirculation is discussed. Use of N2O/He counterdiffusion permitted performance of the pathophysiologic and pulmonary microstructural effects at one ATA without hyperbaric or hypobaric exposures.

Local fluid shifts and edema in humans during simulated microgravity

NASA Technical Reports Server (NTRS)

Hargens, Alan R.

1991-01-01

Local fluid shifts and edema in humans during simulated microgravity is studied. Recent results and significance and future plans on the following research topics are discussed: mechanisms of headward edema formation during head-down tilt; postural responses of head and foot microcirculations and their sensitivity to bed rest; and transcapillary fluid transport associated with lower body negative pressure (LBNP) with and without saline ingestion.

Laser Doppler assessment of dermal circulatory changes in people with coronary artery disease.

PubMed

Agarwal, Sharad C; Allen, John; Murray, Alan; Purcell, Ian F

2012-07-01

Dermal microcirculation provides an easily accessible vasculature bed which can be used to assess endothelial mediated vasodilatation. We studied and compared microcirculatory changes in response to acetylcholine iontophoresis (ACh), local heating of the skin and reactive hyperaemia in patients with coronary artery disease (CAD). Forty eight patients with CAD were studied and compared with 25 age and sex matched control subjects. Vasodilatory changes in the dermal microcirculation were assessed in response to ACh iontophoresis, local heating of the skin and reactive hyperaemia using a laser Doppler flowmeter (LDF). Body mass index (BMI) and systolic BP were higher in people with CAD, (p=0.001, 0.043). The perfusion change (measured as absolute in agreement with our previous publish results) in response to ACh iontophoresis, local heating of the skin and reactive hyperaemia, in healthy controls was 234 (190-286), 90 (69-118), 139(106-172) arbitrary perfusion units (APU) compared to 161 (121-214), 50 (39-63), 116(77-143) APU in patients with CAD; p<0.03. The time to peak perfusion in response to reactive hyperaemia was significantly higher in patients with CAD, 14.1±4.0 vs 10.9±1.7s; p=0.001. There was a small but significant positive correlation between the perfusion change in response to ACh iontophoresis and local heating (r=0.31, p=0.035). On ROC curve analysis, perfusion changes with heating had higher sensitivity and specificity in discriminating patients with CAD from the healthy controls with an area under the curve (AUC) of 0.86, with a specificity of 92% and sensitivity of 77% compared to a perfusion changes by reactive hyperaemia, AUC of 0.68 (41% sensitivity and 91% specificity) and ACh iontophoresis, AUC of 0.76 (88% sensitivity and 60% specificity). Vasodilatation in the dermal microcirculation measured by the three techniques is attenuated in patients with coronary artery disease. Local heating of the skin is a better discriminator of patients with CAD than ACh iontophoresis and reactive hyperaemia. Copyright © 2012 Elsevier Inc. All rights reserved.

Transmission of arterial oxygen partial pressure oscillations to the cerebral microcirculation in a porcine model of acute lung injury caused by cyclic recruitment and derecruitment.

PubMed

Klein, K U; Boehme, S; Hartmann, E K; Szczyrba, M; Heylen, L; Liu, T; David, M; Werner, C; Markstaller, K; Engelhard, K

2013-02-01

Cyclic recruitment and derecruitment (R/D) play a key role in the pathomechanism of acute lung injury (ALI) leading to respiration-dependent oscillations of arterial partial pressure of oxygen (Pa(O(2))). These Pa(O(2)) oscillations could also be forwarded to the cerebral microcirculation. In 12 pigs, partial pressure of oxygen was measured in the thoracic aorta (Pa(O(2))) and subcortical cerebral tissue (Pbr(O(2))). Cerebral cortical haemoglobin oxygen saturation (Sbr(O(2))), cerebral blood flow (CBF), and peripheral haemoglobin saturation (Sp(O(2))) were assessed by spectroscopy and laser Doppler flowmetry. Measurements at different fractions of inspired oxygen (F(I(O(2)))) were performed at baseline and during cyclic R/D. frequency domain analysis, the Mann-Whitney test, linear models to test the influence of Pa(O(2)) and systolic arterial pressure (SAP) oscillations on cerebral measurements. Parameters [mean (SD)] remained stable during baseline. Pa(O(2)) oscillations [10.6 (8) kPa, phase(reference)], systemic arterial pressure (SAP) oscillations [20 (9) mm Hg, phase(Pa(O(2))-SAP) -33 (72)°], and Sp(O(2))oscillations [1.9 (1.7)%, phase(Pa(O(2))-Sp(O(2))) 264 (72)°] were detected during lung R/D at 1.0. Pa(O(2)) oscillations decreased [2.7 (3.5) kPa, P=0.0008] and Sp(O(2)) oscillations increased [6.8 (3.9)%, P=0.0014] at F(I(O(2))) 0.3. In the brain, synchronized Pbr(O(2)) oscillations [0.6 (0.4) kPa, phase(Pa(O(2))-Pbr(O(2))) 90 (39)°], Sbr(O(2)) oscillations [4.1 (1.5)%, phase(Pa(O(2))-Sbr(O(2))) 182 (54)°], and CBF oscillations [198 (176) AU, phase(Pa(O(2))-CBF) 201 (63)°] occurred that were dependent on Pa(O(2)) and SAP oscillations. Pa(O(2)) oscillations caused by cyclic R/D are transmitted to the cerebral microcirculation in a porcine model of ALI. These cyclic oxygen alterations could play a role in the crosstalk of acute lung and brain injury.

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 of indices of microvascular perfusion (density, filling) and extravasated plasma constituents in damaged and intact brain areas. In this model, the presence of extravasated plasma constituents the size of proteins did not immediately influence indices of cortical microcirculation. However, microvascular perfusion may be perturbed surrounding such an area of advancing vasogenic edema formation.

Study of the functional state of peripheral vessels in fingers of rheumatological patients by means of laser Doppler flowmetry and cutaneous thermometry measurements

NASA Astrophysics Data System (ADS)

Zherebtsova, Angelina I.; Zherebtsov, Evgeny A.; Dunaev, Andrey V.; Podmasteryev, Konstantin V.; Pilipenko, Olga V.; Krupatkin, Alexander I.; Khakhicheva, Lyudmila S.; Muradyan, Vadim F.

2016-04-01

Vasospastic disorders are a common class of rheumatic disease. These include syndromes such as vegetative dystonia, Raynaud's syndrome, vibration disease and rheumatoid arthritis among others. The aim of this work is to develop an original method of diagnosing the functional state of peripheral vessels of the fingers, based on the simultaneous recording of LDF- and thermograms during the occlusion test, for determining vascular disorders of rheumatological patients. A diagnostic method was developed for assessing the functional state of the peripheral vessels of fingers, based on carrying out occlusion test in a thermally stabilized environment, with simultaneous recording of signals of laser Doppler flowmetry and skin thermometry. To verify the diagnostic value of the proposed method, a series of experiments were carried out on 41 rheumatological patients: 5 male and 36 females (average age 56.0+/-12.2 years). The most common diagnoses in the patient group were rheumatoid arthritis, arthrosis, gout and systemic lupus erythematosus. The laser analyser of blood microcirculation "LAKK-02" (SPE "LAZMA" Ltd, Russia) and a custom developed multi-channel thermometry device for low inertia thermometry were used for experimental measurements. The measurements of cutaneous temperature and the index of microcirculation were performed on the distal phalanx of the third finger of the right hand. Occlusion tests were performed with water baths at 25 and 42 °C and a tonometer cuff with a pressure of 200-220 mmHg for 3 min on the upper arm. The results of experimental studies are presented and interpreted. These data indicate a violation of the blood supply regulation in the form of a pronounced tendency towards microvascular vasoconstriction in the fingers. Thus, the response displaying a tendency toward angiospasm among patients in the rheumatological diseases profile group was observed mainly in the most severe cases (49 % of this group). The prospects of the developed diagnostic method of microcirculatory disorders in rheumatic diseases are evaluated. Thus, cutaneous blood microcirculation and temperature measurements performed together can help in diagnosis of the functional state of peripheral vessels both in a healthy state and when expressing pathology.

Tissue Oxygenation Monitoring using Resonance Raman Spectroscopy during Hemorrhage

DTIC Science & Technology

2013-12-27

saturation measurements using resonance Raman intravital micros- copy. Am J Physiol Heart Circ Physiol. 2005;289:H488 H495. 14. Ward KR, Ivatury RR, Barbee...Nighswander-Rempel SP, Kupriyanov VV, Shaw RA. Relative contribu- tions of hemoglobin and myoglobin to near-infrared spectroscopic images of cardiac tissue...DC, Shapiro NI. The microcirculation image quality score: development and preliminary evaluation of a proposed approach to grading quality of image

Laser diagnostics in orthodontics

NASA Astrophysics Data System (ADS)

Ryzhkova, Anastasia V.; Lebedeva, Nina G.; Sedykh, Alexey V.; Ulyanov, Sergey S.; Lepilin, Alexander V.; Kharish, Natalia A.

2003-10-01

The results of statistical analysis of Doppler spectra of intensity fluctuations of light, scattered from mucose membrane of oral cavity of healthy volunteers and patients, abused by the orthodontic diseases, are presented. Analysis of Doppler spectra, obtained from tooth pulp of patients, is carried out. New approach to monitoring of blood microcirculation in orthodontics is suggested. Influence of own noise of measuring system on formation of the speckle-interferometric signal is studied.

Laser Doppler diagnostics for orthodontia

NASA Astrophysics Data System (ADS)

Ryzhkova, Anastasia V.; Lebedeva, Nina G.; Sedykh, Alexey V.; Ulyanov, Sergey S.; Lepilin, Alexander V.; Kharish, Natalia A.

2004-06-01

The results of statistical analysis of Doppler spectra of intensity fluctuations of light, scattered from mucous membrane of oral cavity of healthy volunteers and patients, abused by the orthodontic diseases, are presented. Analysis of Doppler spectra, obtained from tooth pulp of patients, is carried out. New approach to monitoring of blood microcirculation in orthodontics is suggested. Influence of own noise of Doppler measuring system on formation of the output signal is studied.

[Effect of complex sanatorium treatment including magnetotherapy on hemodynamics in patients with arterial hypertension].

PubMed

Efremushkin, G G; Duruda, N V

2003-01-01

Forty nine patients with arterial hypertension of stage I-II received combined sanatorium treatment. Of them, 21 had adjuvant total magnetotherapy. All the patients were examined for parameters of central, cerebral hemodynamics and microcirculation. The adjuvant magnetotherapy produced a beneficial effect on hypertension: clinical symptoms attenuated, arterial pressure became more stable, hemodynamics improved, duration of hospitalization reduced, requirement in hypotensive drugs diminished.

Assessing the evidence: Exploring the effects of exercise on diabetic microcirculation.

PubMed

Lenasi, Helena; Klonizakis, Markos

2016-01-01

Diabetes mellitus (DM) is associated with cardiovascular complications. Impairment of glycemic control induces noxious glycations, an increase in oxydative stress and dearangement of various metabolic pathways. DM leads to dysfunction of micro- and macrovessels, connected to metabolic, endothelial and autonomic nervous system. Thus, assessing vascular reactivity might be one of the clinical tools to evaluate the impact of harmful effects of DM and potential benefit of treatment; skin and skeletal muscle microcirculation have usually been tested. Physical exercise improves vascular dysfunction through various mechanisms, and is regarded as an additional effective treatment strategy of DM as it positively impacts glycemic control, improves insulin sensitivity and glucose uptake in the target tissues, thus affecting glucose and lipid metabolism, and increases the endothelium dependent vasodilation. Yet, not all patients respond in the same way so titrating the exercise type individualy would be desirable. Resistance training has, apart from aerobic one, been shown to positively correlate to glycemic control, and improve vascular reactivity. It has been prescribed in various forms or in combination with aerobic training. This review would assess the impact of different modes of exercise, the mechanisms involved, and its potential positive and negative effects on treating patients with Type I and Type II DM, focusing on the recent literature.

Eye lens membrane junctional microdomains: a comparison between healthy and pathological cases

NASA Astrophysics Data System (ADS)

Buzhynskyy, Nikolay; Sens, Pierre; Behar-Cohen, Francine; Scheuring, Simon

2011-08-01

The eye lens is a transparent tissue constituted of tightly packed fiber cells. To maintain homeostasis and transparency of the lens, the circulation of water, ions and metabolites is required. Junctional microdomains connect the lens cells and ensure both tight cell-to-cell adhesion and intercellular flow of fluids through a microcirculation system. Here, we overview membrane morphology and tissue functional requirements of the mammalian lens. Atomic force microscopy (AFM) has opened up the possibility of visualizing the junctional microdomains at unprecedented submolecular resolution, revealing the supramolecular assembly of lens-specific aquaporin-0 (AQP0) and connexins (Cx). We compare the membrane protein assembly in healthy lenses with senile and diabetes-II cataract cases and novel data of the lens membranes from a congenital cataract. In the healthy case, AQP0s form characteristic square arrays confined by connexons. In the cases of senile and diabetes-II cataract patients, connexons were degraded, leading to malformation of AQP0 arrays and breakdown of the microcirculation system. In the congenital cataract, connexons are present, indicating probable non-membranous grounds for lens opacification. Further, we discuss the energetic aspects of the membrane organization in junctional microdomains. The AFM hence becomes a biomedical nano-imaging tool for the analysis of single-membrane protein supramolecular association in healthy and pathological membranes.

Rheological effects of drag-reducing polymers improve cerebral blood flow and oxygenation after traumatic brain injury in rats

PubMed Central

Kameneva, Marina V; Bragina, Olga A; Thomson, Susan; Statom, Gloria L; Lara, Devon A; Yang, Yirong; Nemoto, Edwin M

2016-01-01

Cerebral ischemia has been clearly demonstrated after traumatic brain injury (TBI); however, neuroprotective therapies have not focused on improvement of the cerebral microcirculation. Blood soluble drag-reducing polymers (DRP), prepared from high molecular weight polyethylene oxide, target impaired microvascular perfusion by altering the rheological properties of blood and, until our recent reports, has not been applied to the brain. We hypothesized that DRP improve cerebral microcirculation and oxygenation after TBI. DRP were studied in healthy and traumatized rat brains and compared to saline controls. Using in-vivo two-photon laser scanning microscopy over the parietal cortex, we showed that after TBI, nanomolar concentrations of intravascular DRP significantly enhanced microvascular perfusion and tissue oxygenation in peri-contusional areas, preserved blood–brain barrier integrity and protected neurons. The mechanisms of DRP effects were attributable to reduction of the near-vessel wall cell-free layer which increased near-wall blood flow velocity, microcirculatory volume flow, and number of erythrocytes entering capillaries, thereby reducing capillary stasis and tissue hypoxia as reflected by a reduction in NADH. Our results indicate that early reduction in CBF after TBI is mainly due to ischemia; however, metabolic depression of contused tissue could be also involved. PMID:28155574

Effect of Topical Iloprost and Nitroglycerin on Gastric Microcirculation and Barrier Function during Hemorrhagic Shock in Dogs.

PubMed

Truse, Richard; Hinterberg, Jonas; Schulz, Jan; Herminghaus, Anna; Weber, Andreas; Mettler-Altmann, Tabea; Bauer, Inge; Picker, Olaf; Vollmer, Christian

2017-01-01

Topical drug application is used to avoid systemic side effects. The aim of this study was to analyze whether locally applied iloprost or nitroglycerin influence gastric mucosal perfusion, oxygenation, and barrier function during physiological and hemorrhagic conditions. In repeated experiments, 5 anesthetized dogs received iloprost, nitroglycerin, or normal saline during physiological and hemorrhagic (-20% blood volume) conditions. Macro- and microcirculatory variables were recorded continuously. Gastric barrier function was assessed via translocation of sucrose into the blood. During hemorrhage, gastric mucosal oxygenation decreased from 77 ± 4 to 37 ± 7%. This effect was attenuated by nitroglycerin (78 ± 6 to 47 ± 13%) and iloprost (82 ± 4 to 54 ± 9%). Sucrose plasma levels increased during hemorrhage from 7 ± 4 to 55 ± 15 relative amounts. This was alleviated by nitroglycerin (5 ± 8 to 29 ± 38 relative amounts). These effects were independent of systemic hemodynamic variables. During hemorrhage, topical nitroglycerin and iloprost improve regional gastric oxygenation without affecting perfusion. Nitroglycerin attenuated the shock-induced impairment of the mucosal barrier integrity. Thus, local drug application improves gastric microcirculation without compromising systemic hemodynamic variables, and it may also protect mucosal barrier function. © 2017 S. Karger AG, Basel.

Age-related Changes in the Hepatic Microcirculation in Mice

PubMed Central

Ito, Yoshiya; Sørensen, Karen K.; Bethea, Nancy W.; Svistounov, Dmitri; McCuskey, Margaret K.; Smedsrød, Bård H.; McCuskey, Robert S.

2007-01-01

Aging of the liver is associated with impaired metabolism of drugs, adverse drug interactions, and susceptibility to toxins. Since reduced hepatic blood flow is suspected to contribute this impairment, we examined age-related alterations in hepatic microcirculation.. Livers of C57Bl/6 mice were examined at 0.8 (pre-pubertal), 3 (young adult), 14 (middle-aged) and 27 (senescent) months of age using in vivo and electron microscopic methods. The results demonstrated a 14% reduction in the numbers of perfused sinusoids between 0.8 and 27 month mice associated with 35% reduction in sinusoidal blood flow. This was accompanied by an inflammatory response evidenced by a 5-fold increase in leukocyte adhesion in 27 month mice, up-regulated expression of ICAM-1, and increases in intrahepatic macrophages. Sinusoidal diameter decreased 6-10%. Liver sinusoidal endothelial cell (LSEC) dysfunction was seen as early as 14 months when there was a 3-fold increase in the numbers of swollen LSEC. The endocytotic capacity of LSEC also was found to be reduced in older animals. The sinusoidal endothelium in 27 month old mice exhibited pseudocapillarization. In conclusion, the results suggest that leukocyte accumulation in the sinusoids and narrowing of sinusoidal lumens due to pseudocapillarization and dysfunction of LSEC reduce sinusoidal blood flow in aged livers. PMID:17582718

Milrinone attenuates arteriolar vasoconstriction and capillary perfusion deficits on endotoxemic hamsters.

PubMed

de Miranda, Marcos Lopes; Pereira, Sandra J; Santos, Ana O M T; Villela, Nivaldo R; Kraemer-Aguiar, Luiz Guilherme; Bouskela, Eliete

2015-01-01

Apart from its inotropic property, milrinone has vasodilator, anti-inflammatory and antithrombotic effects that could assist in the reversal of septic microcirculatory changes. This paper investigates the effects of milrinone on endotoxemia-related microcirculatory changes and compares them to those observed with the use of norepinephrine. After skinfold chamber implantation procedures and endotoxemia induction by intravenous Escherichia coli lipopolysaccharide administration (2 mg.kg-1), male golden Syrian hamsters were treated with two regimens of intravenous milrinone (0.25 or 0.5 μg.kg-1.min-1). Intravital microscopy of skinfold chamber preparations allowed quantitative analysis of microvascular variables. Macro-hemodynamic, biochemical, and hematological parameters and survival rate were also analyzed. Endotoxemic non-treated animals, endotoxemic animals treated with norepinephrine (0.2 μg.kg-1.min-1), and non-endotoxemic hamsters served as controls. Milrinone (0.5 μg.kg-1.min-1) was effective in reducing lipopolysaccharide-induced arteriolar vasoconstriction, capillary perfusion deficits, and inflammatory response, and in increasing survival. Norepinephrine treated animals showed the best mean arterial pressure levels but the worst functional capillary density values among all endotoxemic groups. Our data suggests that milrinone yielded protective effects on endotoxemic animals' microcirculation, showed anti-inflammatory properties, and improved survival. Norepinephrine did not recruit the microcirculation nor demonstrated anti-inflammatory effects.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reekers, Jim A., E-mail: j.a.reekers@amc.uva.nl; Koelemay, Mark J. W., E-mail: m.j.koelemaij@amc.uva.nl; Marquering, Henk A., E-mail: h.a.marquering@amc.uva.nl

PurposeTo report on the first clinical experience with perfusion angiography (PA) of the foot in patients with chronic critical limb ischemia.Materials and MethodsPA is a post-processing software algorithm and no extra digital subtraction angiography (DSA) has to be performed for this analysis. The data used to test the feasibility of PA were obtained from a consecutive group of 89 patients with CLI who were treated with standard below the knee angioplasty and 12 separate patients who were not suitable for endovascular revascularization.ResultsMotion artifacts in the dataset of the DSA made post-procedural analysis impossible in 10 % intervention. In the majority ofmore » patients (59/68) PA showed an increase in volume flow in the foot after successful angioplasty of the crural vessels. However, in 9/68 patients no increase was seen after successful angioplasty. With the use of a local administered competitive α-adrenergic receptor antagonist, it is also possible to test and quantify the capillary resistance index which is a parameter for the remaining functionality of the microcirculation in CLI patients.ConclusionPA might be used as a new endpoint for lower limb revascularization and can also be used to test the functionality the microcirculation to identify sub-types of patients with CLI. Clinical evaluation and standardization of PA is mandatory before introduction in daily practice.« less

Thermostatic tissue platform for intravital microscopy: 'the hanging drop' model.

PubMed

Pavlovic, Dragan; Frieling, Helge; Lauer, Kai-Stephan; Bac, Vo Hoai; Richter, Joern; Wendt, Michael; Lehmann, Christian; Usichenko, Taras; Meissner, Konrad; Gruendling, Matthias

2006-11-01

Intravital microscopy imposes the particular problem of the combined control of the body temperature of the animal and the local temperature of the observed organ or tissues. We constructed and tested, in the rat ileum microcirculation preparation, a new organ-support platform. The platform consisted of an organ bath filled with physiological solution, and contained a suction tube, a superfusion tube, an intestine-support hand that was attached to a micromanipulator and a thermometer probe. To cover the intestine we used a cover glass plate with a plastic ring glued on its upper surface. After a routine procedure (anaesthesia, monitoring and surgery), the intestine segment (2-3 cm long) was gently exteriorized and placed on the 'hand' of the organ support. A small part of the intestine formed a small 'island' in the bath that was filled with physiological salt solution. The cover glass was secured in place. The physiological salt solution from the superfusion tube, which was pointed to the lower surface of the cover glass, formed a 'hanging drop'. The objective of the microscope was then immersed into distilled water that was formed by the cover glass plastic ring. The 'hanging drop' technique prevented any tissue quenching, ensured undisturbed microcirculation, provided for stable temperature and humidity, and permitted a clear visual field.

Using synchrotron radiation angiography with a highly sensitive detector to identify impaired peripheral perfusion in rat pulmonary emphysema

PubMed Central

Ito, Hiromichi; Matsushita, Shonosuke; Hyodo, Kazuyuki; Sato, Yukio; Sakakibara, Yuzuru

2013-01-01

Owing to limitations in spatial resolution and sensitivity, it is difficult for conventional angiography to detect minute changes of perfusion in diffuse lung diseases, including pulmonary emphysema (PE). However, a high-gain avalanche rushing amorphous photoconductor (HARP) detector can give high sensitivity to synchrotron radiation (SR) angiography. SR angiography with a HARP detector provides high spatial resolution and sensitivity in addition to time resolution owing to its angiographic nature. The purpose of this study was to investigate whether this SR angiography with a HARP detector could evaluate altered microcirculation in PE. Two groups of rats were used: group PE and group C (control). Transvenous SR angiography with a HARP detector was performed and histopathological findings were compared. Peak density of contrast material in peripheral lung was lower in group PE than group C (p < 0.01). The slope of the linear regression line in scattering diagrams was also lower in group PE than C (p < 0.05). The correlation between the slope and extent of PE in histopathology showed significant negative correlation (p < 0.05, r = 0.61). SR angiography with a HARP detector made it possible to identify impaired microcirculation in PE by means of its high spatial resolution and sensitivity. PMID:23412496

[Comparative pathology of the microcirculatory bed].

PubMed

Strukov, A I; Vorob'eva, A A

1976-11-01

This paper presents an analysis of publications, mostly by Soviet authores, on clinical studies and morphological examinations of the microcirculatory bed in different pathology. It is concluded that the microcirculatory bed should be regarded as an integral system responding to the pathological effects by a local and general reaction of its structural components and by changing the rheological properties of blood. Two types of changes develop in the microcirculatory system -- sterotyped ones, typical for extreme states (various kinds of shock, hypertensive crisis, stress situations), and those specific for certain diseases (diabetes melitus, essential hypertension, athersclerosis, collagenoses, etc.). In all the above diseases the pathological process affects the functional structures of microcirculation that undergo a rearrangement in accordance with the requirements of the body. In the initial period of the disease this re-arrangement is of a compensatory nature and passes ahead of the clinical manifestations. A comparison of the pictutrs obtained by biomicroscopy of the bulbconjunctiva of the eye and of other mucosae with film preparations of the serosae demonstrates their complete similarity. Therefore, the method of biomicroscopy of the eyeball and of the mucosae as a method reflecting the state of microcirculation in the body as a whole should become an integral part of the clinical examination of patients.

Switchable skin window induced by optical clearing method for dermal blood flow imaging

NASA Astrophysics Data System (ADS)

Wang, Jing; Shi, Rui; Zhu, Dan

2013-06-01

Optical imaging techniques have shown tremendous potential for assessing cutaneous microcirculation, but the imaging depth and contrast is limited by the strong scattering of skin. Current skin windows have to be fulfilled by surgical operation and suffer from some side effects. In this study, a switchable skin window was developed by topical application of an optical clearing agent (OCA) and saline on rat skin in vivo. The validity of the skin window was evaluated by the laser speckle contrast imaging technique, and the safety of OCA to the body was tested through histologic examinations. The results indicated that administration of OCA or saline on rat skin in vivo can open or close the window of skin repeatedly for three days. With the repair effect of hyaluronic acid and Vaseline, it is able to repeatedly visualize the dermal blood vessels and flow distribution. Long-term observation shows that there is no abnormal reflection in micro-structure, body weight, organ coefficients, histopathologic lesions, or toxic reactions compared with a control group. This switchable window will provide an effective tool not only for cutaneous microcirculation with laser speckle contrast imaging, but also for diagnosis and treatment of peripheral vascular diseases, including tumor research with various optical imaging techniques.

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

Retention of Plasmodium falciparum ring-infected erythrocytes in the slow, open microcirculation of the human spleen.

PubMed

Safeukui, Innocent; Correas, Jean-Michel; Brousse, Valentine; Hirt, Déborah; Deplaine, Guillaume; Mulé, Sébastien; Lesurtel, Mickael; Goasguen, Nicolas; Sauvanet, Alain; Couvelard, Anne; Kerneis, Sophie; Khun, Huot; Vigan-Womas, Inès; Ottone, Catherine; Molina, Thierry Jo; Tréluyer, Jean-Marc; Mercereau-Puijalon, Odile; Milon, Geneviève; David, Peter H; Buffet, Pierre A

2008-09-15

The current paradigm in Plasmodium falciparum malaria pathogenesis states that young, ring-infected erythrocytes (rings) circulate in peripheral blood and that mature stages are sequestered in the vasculature, avoiding clearance by the spleen. Through ex vivo perfusion of human spleens, we examined the interaction of this unique blood-filtering organ with P falciparum-infected erythrocytes. As predicted, mature stages were retained. However, more than 50% of rings were also retained and accumulated upstream from endothelial sinus wall slits of the open, slow red pulp microcirculation. Ten percent of rings were retained at each spleen passage, a rate matching the proportion of blood flowing through the slow circulatory compartment established in parallel using spleen contrast-enhanced ultrasonography in healthy volunteers. Rings displayed a mildly but significantly reduced elongation index, consistent with a retention process, due to their altered mechanical properties. This raises the new paradigm of a heterogeneous ring population, the less deformable subset being retained in the spleen, thereby reducing the parasite biomass that will sequester in vital organs, influencing the risk of severe complications, such as cerebral malaria or severe anemia. Cryptic ring retention uncovers a new role for the spleen in the control of parasite density, opening novel intervention opportunities.

In vivo functional photoacoustic microscopy of cutaneous microvasculature in human skin

PubMed Central

Favazza, Christopher P.; Cornelius, Lynn A.; Wang, Lihong V.

2011-01-01

Microcirculation is an important component of the cardiovascular system and can be used to assess systemic cardiovascular health. Numerous studies have investigated cutaneous microcirculation as an indicator of cardiovascular related diseases. Such research has shown promising results; however, there are many limitations regarding the employed measurement techniques, such as poor depth and spatial resolution and measurement versatility. Here we show the results of functional cutaneous microvascular experiments measured with photoacoustic microscopy, which provides high spatial resolution and multiparameter measurements. In a set of experiments, microvascular networks located in the palms of volunteers were perturbed by periodic ischemic events, and the subsequent hemodynamic response to the stimulus was recorded. Results indicate that during periods of arterial occlusion, the relative oxygen saturation of the capillary vessels decreased below resting levels, and temporarily increased above resting levels immediately following the occlusion. Furthermore, a hyperemic reaction to the occlusions was measured, and the observation agreed well with similar measurements using more conventional imaging techniques. Due to its exceptional capability to functionally image vascular networks with high spatial resolution, photoacoustic microscopy could be a beneficial biomedical tool to assess microvascular functioning and applied to patients with diseases that affect cardiovascular health. © 2011 Society of Photo-Optical Instrumentation Engineers. PMID:21361688

The venous-arterial difference in CO2 should be interpreted with caution in case of respiratory alkalosis in healthy volunteers.

PubMed

Morel, Jerome; Gergelé, Laurent; Dominé, Alexandre; Molliex, Serge; Perrot, Jean-Luc; Labeille, Bruno; Costes, Frederic

2017-08-01

The venous-arterial difference in CO 2 (ΔCO 2 ) has been proposed as an index of the adequacy of tissue perfusion in shock states. We hypothesized that the variation in PaCO 2 (hyper- or hypocapnia) could impact ΔCO 2 , partly through microcirculation adaptations. Fifteen healthy males volunteered to participate. For hypocapnia condition (hCO 2 ), the subjects were asked to hyperventilate, while they were asked to breathe a gas mixture containing 8 % CO 2 for hypercapnia condition (HCO 2 ). The 2 conditions were randomly assigned. Blood gases were measured at baseline before each condition, and after 5-7 min of either hCO 2 or HCO 2 condition. Microcirculation was assessed by the muscle reoxygenation slope measured with near infrared spectroscopy following a vascular occlusion test and by skin circulation with in vivo reflectance confocal microscopy. ΔCO 2 was significantly increased with hCO 2 while it tended to decrease with HCO 2 (non-significant). HCO 2 induced a moderate increase of the resaturation slope of NIRS oxygenation. Skin microcirculatory blood flow significantly dropped with hCO 2 , while it remained unchanged with hypercapnia. Our results warrant cautious interpretation of ΔCO 2 as an indicator of tissue perfusion during respiratory alkalosis.

Intracoronary and Retrograde Coronary Venous Myocardial Delivery of Adipose-Derived Stem Cells in Swine Infarction Lead to Transient Myocardial Trapping with Predominant Pulmonary Redistribution

PubMed Central

Hong, Soon Jun; Hou, Dongming; Brinton, Todd J.; Johnstone, Brian; Feng, Dongni; Rogers, Pamela; Fearon, William F.; Yock, Paul; March, Keith L.

2012-01-01

Objectives To examine the comparative fate of adipose-derived stem cells (ASCs) as well as their impact on coronary microcirculation following either retrograde coronary venous or arterial delivery. Background Local delivery of ASCs to the heart has been proposed as a practical approach to limiting the extent of myocardial infarction. Mouse models of mesenchymal stem cell effects on the heart have also demonstrated significant benefits from systemic (intravenous) delivery, prompting a question about the advantage of local delivery. There has been no study addressing the extent of myocardial vs. systemic disposition of ASCs in large animal models following local delivery to the myocardium. Methods In an initial experiment, dose-dependent effects of ASC delivery on coronary circulation in normal swine were evaluated to establish a tolerable ASC dosing range for intracoronary delivery. In a set of subsequent experiments, an anterior acute myocardial infarction (AMI) was created by balloon occlusion of the proximal left anterior descending (LAD) artery, followed by either intracoronary (IC) or retrograde coronary venous (RCV) infusion of 107 111Indium-labeled autologous ASCs 6 days following AMI. Indices of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured before sacrifices to collect tissues for analysis at 1 or 24 hours after cell delivery. Results IC delivery of porcine ASCs to normal myocardium was well-tolerated up to a cumulative dose of 14×106 cells (approximately 0.5×106 cells/kg). There was evidence suggesting microcirculatory trapping of ASC: at unit doses of 50×106 ASCs, IMR and CFR were found to be persistently altered in the target LAD distribution at 7 days following delivery, while at 10×106 ASCs, only CFR was altered. In the context of recent MI, a significantly higher percentage of ASCs was retained at 1 hour with IC delivery compared to RCV delivery (57.2 ± 12.7% vs. 17.9 ± 1.6%, p=0.037) but this initial difference was not apparent at 24 hours (22.6 ± 5.5% vs. 18.7 ± 8.6%; p= 0.722). In both approaches, most ASC redistributed to the pulmonary circulation by 24 hours post-delivery. There were no significant differences in CFR or IMR following ASC delivery to infarcted tissue by either route. Conclusions Selective intravascular delivery of ASC by coronary arterial and venous routes leads to similarly limited myocardial cell retention with predominant redistribution of cells to the lungs. Intracoronary arterial delivery of ASC leads to only transiently greater myocardial retention, which is accompanied by obstruction of normal regions of coronary microcirculation at higher doses. The predominant intrapulmonary localization of cells following local delivery via both methods prompts the notion that systemic delivery of ASC might provide similarly beneficial outcomes while avoiding risks of inadvertent microcirculatory compromise. PMID:22972685

Intracoronary and retrograde coronary venous myocardial delivery of adipose-derived stem cells in swine infarction lead to transient myocardial trapping with predominant pulmonary redistribution.

PubMed

Hong, Soon Jun; Hou, Dongming; Brinton, Todd J; Johnstone, Brian; Feng, Dongni; Rogers, Pamela; Fearon, William F; Yock, Paul; March, Keith L

2014-01-01

To examine the comparative fate of adipose-derived stem cells (ASCs) as well as their impact on coronary microcirculation following either retrograde coronary venous (RCV) or arterial delivery. Local delivery of ASCs to the heart has been proposed as a practical approach to limiting the extent of myocardial infarction. Mouse models of mesenchymal stem cell effects on the heart have also demonstrated significant benefits from systemic (intravenous) delivery, prompting a question about the advantage of local delivery. There has been no study addressing the extent of myocardial vs. systemic disposition of ASCs in large animal models following local delivery to the myocardium. In an initial experiment, dose-dependent effects of ASC delivery on coronary circulation in normal swine were evaluated to establish a tolerable ASC dosing range for intracoronary (IC) delivery. In a set of subsequent experiments, an anterior acute myocardial infarction (AMI) was created by balloon occlusion of the proximal left anterior descending (LAD) artery, followed by either IC or RCV infusion of 10(7) (111)Indium-labeled autologous ASCs 6 days following AMI. Indices of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured before sacrifices to collect tissues for analysis at 1 or 24 hr after cell delivery. IC delivery of porcine ASCs to normal myocardium was well tolerated up to a cumulative dose of 14 × 10(6) cells (approximately 0.5 × 10(6) cells/kg). There was evidence suggesting microcirculatory trapping of ASC: at unit doses of 50 × 10(6) ASCs, IMR and CFR were found to be persistently altered in the target LAD distribution at 7 days following delivery, whereas at 10 × 10(6) ASCs, only CFR was altered. In the context of recent MI, a significantly higher percentage of ASCs was retained at 1 hr with IC delivery compared with RCV delivery (57.2 ± 12.7% vs. 17.9 ± 1.6%, P = 0.037) but this initial difference was not apparent at 24 hr (22.6 ± 5.5% vs. 18.7 ± 8.6%; P = 0.722). In both approaches, most ASC redistributed to the pulmonary circulation by 24 hr postdelivery. There were no significant differences in CFR or IMR following ASC delivery to infarcted tissue by either route. Selective intravascular delivery of ASC by coronary arterial and venous routes leads to similarly limited myocardial cell retention with predominant redistribution of cells to the lungs. IC arterial delivery of ASC leads to only transiently greater myocardial retention, which is accompanied by obstruction of normal regions of coronary microcirculation at higher doses. The predominant intrapulmonary localization of cells following local delivery via both methods prompts the notion that systemic delivery of ASC might provide similarly beneficial outcomes while avoiding risks of inadvertent microcirculatory compromise. Copyright © 2012 Wiley Periodicals, Inc.

[Influence of high-voltage electric burn on the microcirculation of heart in rabbit].

PubMed

Zhang, Qing-fu; Zhou, Hui-min; Wang, Che-jiang; Shao, Hong-bo

2012-06-01

To study the influence of high-voltage electric burn on the microcirculation of heart in rabbit. One-hundred and twenty New Zealand rabbits of clean grade were divided into control group (C) and electric burn group (EB) according to the random number table, with 60 rabbits in each group. Rabbits in EB group were subjected to high-voltage electric burn (the electrical current flow into the left foreleg at the lateral side of proximal end and out from the corresponding site of the right hind leg) with voltage regulator and experimental transformer. Rabbits in C group were sham injured with the same devices without electrification. At 15 minutes before injury, and 5 minutes, 1, 2, 4, 8 hour (s) post injury (PIM or PIH), ten rabbits in each group were chosen to examine the cardiac apex microcirculation hemoperfusion (CAMH) with laser Doppler hemoperfusion image instrument. The morphologic changes of microvessels of left ventricular wall tissues of 2 rabbits from each of the 10 rabbits collected at above-mentioned time points were observed with light microscope and transmission electron microscope. Auricular vein blood of rabbit was harvested at above-mentioned time points for the determination of aspartate amino transferase (AST), lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), creatine kinase (CK), and creatine kinase isozyme MB (CK-MB) by full-automatic biochemical analyzer. Data were processed with two-factor analysis of variance and LSD test. (1) The differences between C group and EB group in detection results were statistically significant, with F values from 425.991 to 3046.834, P values all below 0.01. Only the data within EB group were comparable. (2) At PIM 5, the CAMH value of rabbits in EB group was (1.96 ± 0.09) V, which was lower than that at 15 minutes before injury [(4.34 ± 0.35) V, P < 0.01]. The CAMH value of rabbits in EB group was increased at PIH 1 [(3.43 ± 0.30) V], and then it showed a tendency of decrease. (3) Bleeding and microthrombus formation were observed in venule and capillary vessel of rabbits in EB group at PIH 8. Breakage of basement membrane of capillary endothelial cells, mitochondrial swelling, and severe degranulation from damaged endoplasmic reticulum were observed in rabbits of EB group at PIH 8. (4) Levels of AST, LDH, HBDH, CK, and CK-MB in rabbits of EB group were significantly higher at PIH 1, 2, 4, 8 than at 15 minutes before injury (with P values all below 0.01). The AST level peaked at PIH 2 [(164 ± 39) U/L]. Levels of LDH and HBDH peaked at PIH 4, which were respectively (1016 ± 246) U/L and (487 ± 54) U/L. The CK level peaked at PIH 8 [(7799 ± 738) U/L]. The CK-MB level peaked at PIH 2 [(1848 ± 65) U/L]. High-voltage electric burn can bring damage to the microvessels of heart in rabbits and change blood flow of microcirculation, which should be given adequate attention during the treatment.

Monitoring of the microhemodynamic in an aggressive clinical behavior of cerebral hemorrhage using dynamic light scattering techniques

NASA Astrophysics Data System (ADS)

Vilensky, M. A.; Semyachkina-Glushkovskaya, O. V.; Timoshina, P. A.; Berdnikova, V. A.; Kuznetsova, Y. V.; Semyachkin-Glushkovsky, I. A.; Agafonov, D. N.; Tuchin, V. V.

2012-06-01

This paper presents the results of experimental study of full field laser speckle imaging due to cortex microcirculation state monitoring for laboratory rats under conditions of stroke and the introduction of agents. Three groups of experimental animals from five animals in each group were studied. The behavior of blood flow, studied by speckle imaging technique, matched the expected physiological response to an impact.

He-Ne ILLLI used for brain trauma: a clinical observation of 46 cases

NASA Astrophysics Data System (ADS)

Yang, Da-Ke; Ru, Zheng-Guo; Ge, Sheng-Li; Shuo, Wei-Lan

1998-11-01

With the background that ILLLI can lower the viscosity of blood, improve the microcirculation, we investigated and compared the therapeutic effect of conventional drug therapy and ILLLI combined drug therapy for brain trauma. We found that ILLLI combined drug therapy could effectively alleviate some symptoms such as headache, vertigo, nausea, vomiting, blurred vision, anorexia caused by brain trauma. the therapeutic effect of treated group was prior to control group.

Laser methods of caries prophylaxis

NASA Astrophysics Data System (ADS)

Kunin, Anatoly A.; Dergunova, Elvira I.; Kazmina, Svetlana G.

1996-01-01

Low intensive laser irradiation is widely used for the treatment of many stomatological diseases. The caries static activity of HNL light and infrared lasers, its influence on the activation of microcirculation of the pulp enzyme system and on the increase of enamel permeability became clear. These data allow us to suppose that the low intensive laser irradiation may potent the activity of the initial caries by the increase of teeth stability to the factors provoking the caries.

A role for long chain myosin light chain kinase (MLCK-210) in microvascular hyperpermeability during severe burns.

PubMed

Reynoso, Rashell; Perrin, Rachel M; Breslin, Jerome W; Daines, Dayle A; Watson, Katherine D; Watterson, D Martin; Wu, Mack H; Yuan, Sarah

2007-11-01

Microvascular leakage has been implicated in the pathogenesis of multiple organ dysfunction during trauma. Previous studies suggest the involvement of myosin light chain (MLC) phosphorylation-triggered endothelial contraction in the development of microvascular hyperpermeability. Myosin light chain kinase (MLCK) plays a key role in the control of MLC-phosphorylation status; thus, it is thought to modulate barrier function through its regulation of intracellular contractile machinery. The aim of this study was to further investigate the endothelial mechanism of MLC-dependent barrier injury in burns, focusing on the long isoform of MLCK (MLCK-210) that has recently been identified as the predominant isoform expressed in vascular endothelial cells. An MLCK-210 knockout mouse model was subjected to third-degree scald burn covering 25% total body surface area. The mesenteric microcirculation was observed using intravital microscopy, and the microvascular permeability was assessed by measuring the transvenular flux of fluorescein isothiocyanate-albumin. In a separate experiment, in vivo mesenteric hydraulic conductivity (Lp) was measured using the modified Landis technique. The injury caused a profound microvascular leakage, as indicated by a 2-fold increase in albumin flux and 4-fold increase in Lp at the early stages, which was associated with a high mortality within the 24-h period. Compared with wild-type control, the MLCK-210-deficient mice displayed a significantly improved survival with a greatly attenuated microvascular hyperpermeability response to albumin and fluid. These results provide direct evidence for a role of MLCK-210 in mediating burn-induced microvascular barrier injury and validate MLCK-210 as a potential therapeutic target in the treatment of burn edema.

The inhibitor of 20-HETE synthesis, TS-011, improves cerebral microcirculatory autoregulation impaired by middle cerebral artery occlusion in mice.

PubMed

Marumo, Toshiyuki; Eto, Kei; Wake, Hiroaki; Omura, Tomohiro; Nabekura, Junichi

2010-11-01

20-Hydroxyeicosatetraenoic acid is a potent vasoconstrictor that contributes to cerebral ischaemia. An inhibitor of 20-Hydroxyeicosatetraenoic acid synthesis, TS-011, reduces infarct volume and improves neurological deficits in animal stroke models. However, little is known about how TS-011 affects the microvessels in ischaemic brain. Here, we investigated the effect of TS-011 on microvessels after cerebral ischaemia. TS-011 (0.3 mg·kg(-1) ) or a vehicle was infused intravenously for 1 h every 6 h in a mouse model of stroke, induced by transient occlusion of the middle cerebral artery occlusion following photothrombosis. The cerebral blood flow velocity and the vascular perfusion area of the peri-infarct microvessels were measured using in vivo two-photon imaging. The cerebral blood flow velocities in the peri-infarct microvessels decreased at 1 and 7 h after reperfusion, followed by an increase at 24 h after reperfusion in the vehicle-treated mice. We found that TS-011 significantly inhibited both the decrease and the increase in the blood flow velocities in the peri-infarct microvessels seen in the vehicle-treated mice after reperfusion. In addition, TS-011 significantly inhibited the reduction in the microvascular perfusion area after reperfusion, compared with the vehicle-treated group. Moreover, TS-011 significantly reduced the infarct volume by 40% at 72 h after middle cerebral artery occlusion. These findings demonstrated that infusion of TS-011 improved defects in the autoregulation of peri-infarct microcirculation and reduced the infarct volume. Our results could be relevant to the treatment of cerebral ischaemia. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.

Sex-dependent expression of TRPV1 in bladder arterioles

PubMed Central

Phan, Thieu X.; Ton, Hoai T.; Chen, Yue; Basha, Maureen E.

2016-01-01

Transient receptor potential vanilloid type 1 (TRPV1) is a major nociceptive ion channel implicated in bladder physiology and/or pathophysiology. However, the precise expression of TRPV1 in neuronal vs. nonneuronal bladder cells is uncertain. Here we used reporter mouse lines (TRPV1-Cre:tdTomato and TRPV1PLAP-nlacZ) to map expression of TRPV1 in postnatal bladder. TRPV1 was not detected in the urothelium, however, we found marked expression of TRPV1 lineage in sensory nerves, and surprisingly, in arterial/arteriolar smooth muscle (ASM) cells. Tomato fluorescence was prominent in the vesical arteries and in small-diameter (15–40 μm) arterioles located in the suburothelial layer with a near equal distribution in bladder dome and base. Notably, arteriolar TRPV1 expression was greater in females than in males and increased in both sexes after 90 days of age, suggesting sex hormone and age dependency. Analysis of whole bladder and vesical artery TRPV1 mRNA revealed a similar sex and developmental dependence. Pharmacological experiments confirmed functional TRPV1 protein expression; capsaicin increased intracellular Ca2+ in ∼15% of ASM cells from wild-type female bladders, but we observed no responses to capsaicin in bladder arterioles isolated from TRPV1-null mice. Furthermore, capsaicin triggered arteriole constriction that was rapidly reversed by the TRPV1 antagonist, BCTC. These data show that predominantly in postpubertal female mice, bladder ASM cells express functional TRPV1 channels that may act to constrict arterioles. TRPV1 may therefore play an important role in regulating the microcirculation of the female bladder, and this effect may be of significance during inflammatory conditions. PMID:27654891

The Natural History of Kidney Graft Cortical Microcirculation Determined by Real-Time Contrast-Enhanced Sonography (RT-CES).

PubMed

Jiménez, Carlos; López, María Ovidia; Ros, Amaia; Aguilar, Ana; Menendez, David; Rivas, Begoña; Santana, María José; Vaca, Marco Antonio; Escuin, Fernando; Madero, Rosario; Selgas, Rafael

2016-01-01

Kidney transplantation is the therapy of choice for end-stage kidney disease. Graft's life span is shorter than expected due in part to the delayed diagnosis of various complications, specifically those related to silent progression. It is recognized that serum creatinine levels and proteinuria are poor markers of mild kidney lesions, which results in delayed clinical information. There are many investigation looking for early markers of graft damage. Decreasing kidney graft cortical microcirculation has been related to poor prognosis in kidney transplantation. Cortical capillary blood flow (CCBF) can be measured by real-time contrast-enhanced sonography (RT-CES). Our aim was to describe the natural history of CCBF over time under diverse conditions of kidney transplantation, to explore the influence of donor conditions and recipient events, and to determine the capacity of CCBF for predicting renal function in medium term. RT-CES was performed in 79 consecutive kidney transplant recipients during the first year under regular clinical practice. Cortical capillary blood flow was measured. Clinical variables were analyzed. The influence of CCBF has been determined by univariate and multivariate analysis using mixed regression models based on sequential measurements for each patient over time. We used a first-order autoregression model as the structure of the covariation between measures. The post-hoc comparisons were considered using the Bonferroni correction. The CCBF values varied significantly over the study periods and were significantly lower at 48 h and day 7. Brain-death donor age and CCBF levels showed an inverse relationship (r: -0.62, p<0.001). Living donors showed higher mean CCBF levels than brain-death donors at each point in the study. These significant differences persisted at month 12 (54.5 ± 28.2 vs 33.7 ± 30 dB/sec, living vs brain-death donor, respectively, p = 0.004) despite similar serum creatinine levels (1.5 ± 0.3 and 1.5 ± 0.5 mg/dL). A sole rejection episode was associated with lower overall CCBF values over the first year. CCBF defined better than level of serum creatinine the graft function status at medium-term. RT-CES is a non-invasive tool that can quantify and iteratively estimate cortical microcirculation. We have described the natural history of cortical capillary blood flow under regular clinical conditions.

Telomerase reverse transcriptase protects against angiotensin II-induced microvascular endothelial dysfunction.

PubMed

Ait-Aissa, Karima; Kadlec, Andrew O; Hockenberry, Joseph; Gutterman, David D; Beyer, Andreas M

2018-05-01

A rise in reactive oxygen species (ROS) may contribute to cardiovascular disease by reducing nitric oxide (NO) levels, leading to loss of NO's vasodilator and anti-inflammatory effects. Although primarily studied in larger conduit arteries, excess ROS release and a corresponding loss of NO also occur in smaller resistance arteries of the microcirculation, but the underlying mechanisms and therapeutic targets have not been fully characterized. We examined whether either of the two subunits of telomerase, telomerase reverse transcriptase (TERT) or telomerase RNA component (TERC), affect microvascular ROS production and peak vasodilation at baseline and in response to in vivo administration to angiotensin II (ANG II). We report that genetic loss of TERT [maximal dilation: 52.0 ± 6.1% with vehicle, 60.4 ± 12.9% with N ω -nitro-l-arginine methyl ester (l-NAME), and 32.2 ± 12.2% with polyethylene glycol-catalase (PEG-Cat) ( P < 0.05), means ± SD, n = 9-19] but not TERC [maximal dilation: 79 ± 5% with vehicle, 10.7 ± 9.8% with l-NAME ( P < 0.05), and 86.4 ± 8.4% with PEG-Cat, n = 4-7] promotes flow-induced ROS formation. Moreover, TERT knockout exacerbates the microvascular dysfunction resulting from in vivo ANG II treatment, whereas TERT overexpression is protective [maximal dilation: 88.22 ± 4.6% with vehicle vs. 74.0 ± 7.3% with ANG II (1,000 ng·kg -1 ·min -1 ) ( P = not significant), n = 4]. Therefore, loss of TERT but not TERC may be a key contributor to the elevated microvascular ROS levels and reduced peak dilation observed in several cardiovascular disease pathologies. NEW & NOTEWORTHY This study identifies telomerase reverse transcriptase (TERT) but not telomerase RNA component as a key factor regulating endothelium-dependent dilation in the microcirculation. Loss of TERT activity leads to microvascular dysfunction but not conduit vessel dysfunction in first-generation mice. In contrast, TERT is protective in the microcirculation in the presence of prolonged vascular stress. Understanding the mechanism of how TERT protects against vascular stress represents a novel target for the treatment of vascular disorders.

Thalidomide Improves the Intestinal Mucosal Injury and Suppresses Mesenteric Angiogenesis and Vasodilatation by Down-Regulating Inflammasomes-Related Cascades in Cirrhotic Rats

PubMed Central

Li, Tzu-Hao; Huang, Chia-Chang; Yang, Ying-Ying; Lee, Kuei-Chuan; Hsieh, Shie-Liang; Hsieh, Yun-Cheng; Alan, Lin; Lin, Han-Chieh; Lee, Shou-Dong; Tsai, Chang-Youh

2016-01-01

Background and Aims By blocking TNFα-related effects, thalidomide not only inhibits hepatic fibrogenesis but improves peripheral vasodilatation and portal hypertension in cirrhotic rats. Nonetheless, the investigation of thalidomide's effects on splanchnic and collateral microcirculation has been limited. Our study explored the roles of intestinal and mesenteric TNFα along with inflammasome-related pathway in relation to cirrhosis and the splanchnic/collateral microcirculation. Methods Using in vivo and in vitro approaches, mechanisms of the effects of thalidomide on intestinal and mesenteric inflammatory, vasodilatory and angiogenic cascades-related abnormalities were explored in cirrhotic rats that had received 1-month thalidomide (C-T) treatment. Results In cirrhotic rats, high tumor necrosis factor (TNF)α, vascular endothelial growth factor (VEGF) and nitric oxide (NO)x levels were associated with the NOD-like receptors protein 3 (NLRP3), IL-1β and caspase-1 inflammasome over-expression in splenorenal shunt and mesenteric tissues. The thalidomide-related inhibition of mesenteric and splenorenal shunt inflammasome expression was accompanied by a significantly decreased intestinal mucosal injury and inflammasome immunohistochemical staining expression. Suppression of various angiogenic cascades, namely VEGF-NOS-NO, was paralleled by a decrease in mesenteric angiogenesis as detected by CD31 immunofluorescence staining and by reduced portosystemic shunting (PSS) in C-T rats. The down-regulation of the mesenteric and collateral vasodilatory VEGF-NOS-NO cascades resulted in a correction of vasoconstrictive hypo-responsiveness and in an attenuation of vasodilatory hyper-responsiveness when analyzed by in situ perfusion of the superior mesenteric arterial (SMA) and portosystemic collaterals. There was also a decrease in SMA blood flow and an increase in SMA resistance in the C-T rats. Additionally, acute incubation with thalidomide abolished TNFα-augmented VEGF-mediated migration of and tube formation of human umbilical vein endothelial cells, which was accompanied by corresponding changes in inflammatory and angiogenic substances release. Conclusions The suppression of inflammasome over-expression by chronic thalidomide treatment ameliorates inflammatory, angiogenic and vasodilatory cascades-related pathogenic changes in the splanchnic and collateral microcirculation of cirrhotic rats. Thalidomide seems to be a promising agent that might bring about beneficial changes to the disarrangements of peripheral, hepatic, splanchnic and collateral systems in cirrhosis. PMID:26820153

Immediate Dose-Response Effect of High-Energy Versus Low-Energy Extracorporeal Shock Wave Therapy on Cutaneous Microcirculation.

PubMed

Kraemer, Robert; Sorg, Heiko; Forstmeier, Vinzent; Knobloch, Karsten; Liodaki, Eirini; Stang, Felix Hagen; Mailaender, Peter; Kisch, Tobias

2016-12-01

Elucidation of the precise mechanisms and therapeutic options of extracorporeal shock wave therapy (ESWT) is only at the beginning. Although immediate real-time effects of ESWT on cutaneous hemodynamics have recently been described, the dose response to different ESWT energies in cutaneous microcirculation has never been examined. Thirty-nine Sprague-Dawley rats were randomly assigned to three groups that received either focused high-energy shock waves (group A: total of 1000 impulses, 10 J) to the lower leg of the hind limb, focused low-energy shock waves (group B: total of 300 impulses, 1 J) or placebo shock wave treatment (group C: 0 impulses, 0 J) using a multimodality shock wave delivery system (Duolith SD-1 T-Top, Storz Medical, Tägerwilen, Switzerland). Immediate microcirculatory effects were assessed with the O2C (oxygen to see) system (LEA Medizintechnik, Giessen, Germany) before and for 20 min after application of ESWT. Cutaneous tissue oxygen saturation increased significantly higher after high-energy ESWT than after low-energy and placebo ESWT (A: 29.4% vs. B: 17.3% vs. C: 3.3%; p = 0.003). Capillary blood velocity was significantly higher after high-energy ESWT and lower after low-energy ESWT versus placebo ESWT (group A: 17.8% vs. group B: -22.1% vs. group C: -5.0%, p = 0.045). Post-capillary venous filling pressure was significantly enhanced in the high-energy ESWT group in contrast to the low-energy ESWT and placebo groups (group A: 25% vs. group B: 2% vs. group C: -4%, p = 0.001). Both high-energy and low-energy ESWT affect cutaneous hemodynamics in a standard rat model. High-energy ESWT significantly increases parameters of cutaneous microcirculation immediately after application, resulting in higher tissue oxygen saturation, venous filling pressure and blood velocity, which suggests higher tissue perfusion with enhanced oxygen saturation, in contrast to low-energy as well as placebo ESWT. Low-energy ESWT also increased tissue oxygen saturation, albeit to a lower extent, and decreases both blood velocity and venous filling pressure. Low-energy ESWT reduced tissue perfusion, but improved oxygen saturation immediately after the application. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Is the EDRF in the cerebral circulation NO? Its release by shear and the dangers in interpreting the effects of NOS inhibitors.

PubMed

Rosenblum, W I

1998-09-01

Evidence from investigations of brain microcirculation (pial arterioles) reveals at least 3 different endothelium (EC) dependent mechanisms for dilation. Only one of the three can be triggered by acetylcholine (ACh) and in this vascular bed it is only this path that is dependent upon endothelial nitric oxide synthase (NOS) which produces nitric oxide (NO) from arginine. In this vascular bed the ACh sensitive path cannot be triggered by bradykinin (BK). This state of affairs appears to differ from that found in other beds or in endothelium cultured from conductance vessels. In the cerebral microcirculation there is considerable pharmacological evidence that the endothelium derived relaxing factor (EDRF) for ACh is not NO itself but may contain NO. In many experimental vascular settings the release of the NOS dependent EDRF is shear dependent. In the cerebral microcirculation there are several studies suggesting, in vivo, that this is correct. Among these are the following: (1) vessels narrow when shear is reduced after carotid ligation, and remain so along with unresponsiveness to ACh for at least ten minutes following resumption of flow. This may be important in developing stroke. The collapse is not passive due to low pressure. We know this because the narrowed vessels with their low intraluminal shear and pressure are still capable of large dilation by the NO donor, sodium nitropruside; (2) the antiplatelet effects of EC which are mediated, in part, by the EDRF for ACh are enhanced for 10 to 20 minutes following the transient increase and return of shear within these vessels. If the reverse is also true, reductions of shear may have important harmful proaggregant effects on platelets (and leukocytes) in the microvascular bed of developing infarcts. However most of the cited work depends upon pharmacological inhibitors of NOS to "prove" that NOS and an EDRF/NO are involved. In the last three years evidence in cats and rats shows that many of the NOS inhibitors also block K channels in cerebrovascular smooth muscle and that arginine, the "antidote" to the NOS inhibitors keeps the channels open. This latter work must force a reexamination of the conclusions reached in many studies.

The association between diabetes and dermal microvascular dysfunction non-invasively assessed by laser Doppler with local thermal hyperemia: a systematic review with meta-analysis.

PubMed

Fuchs, Dagmar; Dupon, Pepijn P; Schaap, Laura A; Draijer, Richard

2017-01-19

Diabetes and cardiovascular disease develop in concert with metabolic abnormalities mirroring and causing changes in the vasculature, particularly the microcirculation. The microcirculation can be affected in different parts of the body of which the skin is the most easily accessible tissue. The association between diabetes and dermal microvascular dysfunction has been investigated in observational studies. However, the strength of the association is unknown. Therefore we conducted a systematic review with meta-analysis on the association between diabetes and dermal microvascular dysfunction as assessed by laser Doppler/laser speckle contrast imaging with local thermal hyperaemia as non-invasive indicator of microvascular functionality. PubMed and Ovid were  systematically searched for eligible studies through March 2015. During the first selection, studies were included if they were performed in humans and were related to diabetes or glucose metabolism disorders and to dermal microcirculation. During the second step we selected studies based on the measurement technique, measurement location (arm or leg) and the inclusion of a healthy control group. A random effects model was used with the standardised mean difference as outcome measure. Calculations and imputation of data were done according to the Cochrane Handbook. Of the 1445 studies found in the first search, thirteen cross-sectional studies were included in the meta-analysis, comprising a total of 857 subjects. Resting blood flow was similar between healthy control subjects and diabetes patients. In contrast, the microvascular response to local skin heating was reduced in diabetic patients compared to healthy control subjects [pooled effect of -0.78 standardised mean difference (95% CI -1.06, -0.51)]. This effect is considered large according to Cohen's effect size definition. The variability in effect size was high (heterogeneity 69%, p < 0.0001). However, subgroup analysis revealed no difference between the type and duration of diabetes and other health related factors, indicating that diabetes per se causes the microvascular dysfunction. Our meta-analysis shows that diabetes is associated with a large reduction of dermal microvascular function in diabetic patients. The local thermal hyperaemia methodology may become a valuable non-invasive tool for diagnosis and assessing progress of diabetes-related microvascular complications, but standardisation of the technique and quality of study conduct is urgently required.

Combined Laser-Doppler Flowmetry and Spectrophotometry: Feasibility Study of a Novel Device for Monitoring Local Cortical Microcirculation during Aneurysm Surgery.

PubMed

Sommer, Björn; Kreuzer, Maximilian; Bischoff, Barbara; Wolf, Dennis; Schmitt, Hubert; Eyupoglu, Ilker Y; Rössler, Karl; Buchfelder, Michael; Ganslandt, Oliver; Wiendieck, Kurt

2017-01-01

Background  Monitoring of cortical cerebral perfusion is essential, especially in neurovascular surgery. Study Aims  To test a novel noninvasive laser-Doppler flowmetry and spectrophotometry device for feasibility during elective cerebral aneurysm surgery. Material and Methods  In this prospective single-institution nonrandomized trial, we studied local cerebral microcirculation using the noninvasive laser-Doppler spectrophotometer "Oxygen-to-see" (O2C) in 20 consecutive patients (15 female, 5 male; median age: 60.5 ± 11.7 years) who were operated on for incidental cerebral aneurysms. Capillary-venous oxygenation (oxygen saturation ["SO 2 "]), postcapillary venous filling pressures (relative hemoglobin content ["rHb"]), blood cell velocity ("velo"), and blood flow ("flow") were measured in 7-mm tissue depth using a subdural fiberoptic probe. Results  Representative recordings were acquired immediately after dural opening over a median time span of 88 ± 21.8 seconds (range: 60-128 seconds) before surgical manipulation. Baseline values (median ± 2 standard deviations) of brain perfusion as measured with the O2C device were SO 2 , 39 ± 16.6%; rHb, 53 ± 18.6 arbitrary units (AU); velo, 60 ± 20.4 AU; and flow, 311 ± 72.8 AU. Placement of the self-retaining retractor led to a decrease in SO 2 of 17% ± 29% ( p  < .05) and flow of 10% ± 11% ( p  < .01); rHb increased by 18% ± 20% ( p  < .01), and velo remained unchanged. Retractor removal caused the opposite with an increased flow of 10% ± 7% ( p  < 0.001) and velo (3% ± 6%, p  = 0.11), but a decrease in SO 2 of 24% ± 33% ( p  = 0.09) and rHb of 12% ± 20% ( p =0.18). No neurologic or surgical complications occurred. Conclusion  Using this novel noninvasive system, we were able to measure local cerebral microcirculation during aneurysm surgery. Our data indicate that this device is able to detect changes during routine neurosurgical maneuvers. Thus it may be useful for early detection of cerebral microcirculatory disturbances. Georg Thieme Verlag KG Stuttgart · New York.

Study on the antiulcer effects of Veronicastrum axillare on gastric ulcer in rats induced by ethanol based on tumor necrosis factor-α (TNF-α) and endothelin-1 (ET-1).

PubMed

Du, Yong; Zhao, Weichun; Lu, Leilei; Zheng, Jiayan; Hu, Xishi; Yu, Zhehan; Zhu, Lixin

2013-12-01

To assess whether Veronicastrum axillare (V. axillare) can ameliorate ethanol-induced gastric mucosal lesions in rats, reduce the production of pro-inflammatory cytokines, suppress apoptosis and improve local microcirculation disturbances. Totally 48 male Sprague-Dawley rats were randomly divided into six groups, eight rats in each group. Rats in the normal group and the model group were administered with 0.9% normal saline respectively. Rats in the positive group and ranitidine group were administered with 0.18% ranitidine suspension by intragastric administration respectively. Those in the high dose V. axillare group, the medium dose V. axillare group and the low dose V. axillare group were administrated with V. axillare at the daily dose of 2.8 g/kg, 1.4 g/kg and 0.7 g/kg by intragastric administration. Gastric mucosal lesions were produced by intragastric administration of absolute ethanol. Water extract of V. axillare was successively injected for 14 d and last day was injected 1 h before ethanol administration. Gastric mucosal ulcer index and ulcer inhibitory rate were counted by improved Guth methods. The tissue sections were made for pathological histology analysis. Also, we measured the concentrations of tumor necrosis factor-α (TNF-α) and endothelin-1 (ET-1) in gastric mucosal, as an index of the pro-inflammatory cytokines, apoptosis and local microcirculation. Besides, the mRNA contents of TNF-α and ET-1 were measured to verify effects on gene expression by real-time fluorescent quantitative PCR. Water extract of V. axillare significantly ameliorated the gastric mucosal lesions induced by ethanol administration (P<0.01). Pro-inflammatory cytokines, TNF-α and ET-1 were increased after ethanol administration and significantly reduced by water extract of V. axillare. The expressions of TNF-α and ET-1 mRNA were also be inhibited by water extract of V. axillare. Current evidences show water extract of V. axillare is effective for defending against ethanol-induced gastric mucosal lesions, significantly inhibiting the production of pro-inflammatory cytokines and the expressions of TNF-α and ET-1 mRNA, which may be useful for inhibiting apoptosis and improving local microcirculation. Copyright © 2013 Asian Pacific Tropical Biomedical Magazine. Published by Elsevier B.V. All rights reserved.

Regeneration of the Adult Rat Spinal Cord in Response to Ensheathing Cells and Methylprednisolone

DTIC Science & Technology

2002-01-01

me in academics and research, and also as my friend. I thank Dr. Linda L. Porter, for her continuous efforts on my behalf as the Chairperson of...and Spinal Cord Injury Program. We are grateful to Drs. Barbara S. Bregman and Linda L. Porter for their wonderful suggestions and guidance; to Anna...ES, Pietronigro DD, Seligman ML (1980) The free radical pathology and the microcirculation in the major central nervous system disorders. Acta

Doppler and speckle methods for diagnostics in dentistry

NASA Astrophysics Data System (ADS)

Ulyanov, Sergey S.; Lepilin, Alexander V.; Lebedeva, Nina G.; Sedykh, Alexey V.; Kharish, Natalia A.; Osipova, Yulia; Karpovich, Alexander

2002-02-01

The results of statistical analysis of Doppler spectra of scattered intensity, obtained from tissues of oral cavity membrane of healthy volunteers, are presented. The dependence of the spectral moments of Doppler signal on cutoff frequency is investigated. Some results of statistical analysis of Doppler spectra, obtained from tooth pulp of patients, are presented. New approach for monitoring of blood microcirculation in orthodontics is suggested. Influence of own noise of measuring system on formation of speckle-interferometric signal is studied.

The heart, macrocirculation and microcirculation in hypertension: a unifying hypothesis.

PubMed

Struijker Boudier, Harry A J; Cohuet, Géraldine M S; Baumann, Marcus; Safar, Michel E

2003-06-01

Epidemiological studies in the past decade have stressed the importance of both pulse pressure and mean arterial pressure (MAP) as important risk factors in hypertension-related cardiovascular disease. Pulse pressure and MAP are determined by different segments of the cardiovascular system. Pulse pressure is the pulsatile component of the blood pressure curve. It is determined by left ventricular ejection, the cushioning capacity (compliance) of the large arteries, and the timing and intensity of wave reflections from the microcirculation. MAP is the steady component; it is determined by cardiac output and peripheral (micro)vascular resistance. To a large degree, the structural design of the heart and vascular tree determine the pulse pressure and MAP, in addition to the propagation of the pressure wave through the vasculature. Pressure and flow, in contrast, influence the composition and geometry of the heart and vasculature. Hypertensive disease is associated with important structural alterations of the heart, such as hypertrophy and fibrosis, and of the vasculature, such as large artery stiffening, small artery remodelling and microvascular rarefaction. Recent basic research has revealed some of the molecular pathways involved in the remodelling of the cardiovascular system under the influence of physical forces. For correct understanding of the pathophysiology of hypertensive disease, its risks for target-organ damage and its effective treatment, both the pulsatile and steady components of the blood pressure curve must be considered.

A computational model of microbubble transport through a blood-filled vessel bifurcation

NASA Astrophysics Data System (ADS)

Calderon, Andres

2005-11-01

We are developing a novel gas embolotherapy technique to occlude blood vessels and starve tumors using gas bubbles that are produced by the acoustic vaporization of liquid perfluorocarbon droplets. The droplets are small enough to pass through the microcirculation, but the subsequent bubbles are large enough to lodge in vessels. The uniformity of tumor infarction depends on the transport the blood-borne bubbles before they stick. We examine the transport of a semi-infinite bubble through a single bifurcation in a liquid-filled two-dimensional channel. The flow is governed by the conservation of fluid mass and momentum equations. Reynolds numbers in the microcirculation are small, and we solve the governing equations using the boundary element method. The effect of gravity on bubble splitting is investigated and results are compared with our previous bench top experiments and to a quasi-steady one-dimensional analysis. The effects of daughter tube outlet pressures and bifurcation geometry are also considered. The findings suggest that slow moving bubbles will favor the upper branch of the bifurcation, but that increasing the bubble speed leads to more even splitting. It is also found that some bifurcation geometries and flow conditions result in severe thinning of the liquid film separating the bubble from the wall, suggesting the possibility bubble-wall contact. This work is supported by NSF grant BES-0301278 and NIH grant EB003541.

Efficiency of use endobronchial laser doppler-flowmetry in patients with chronic leukemia

NASA Astrophysics Data System (ADS)

Vanina, E. A.; Voitsekhovskiy, V. V.; Landyshev, Y. S.; Tkacheva, S. I.

2016-11-01

In this work indicatorsendobronchial microcirculation were investigated in patients with chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), polycythemia vera (PV), idiopathic myelofibrosis (IMF). A diagnostic bronchoscopy was performed using fibreoptic «Olympus» (Japan).Endobronchial laser Doppler flowmetry was carried out on the laser analyzer capillary blood LAK-02 (Russia). Laser Doppler flowmetry indicators such as parameter of microcirculation, the oscillation amplitude in the endothelial, neurogenic, myogenic, cardiac and respiratory ranges were calculated by continuous the Wavelet transforms. Reduced cardiac and respiratory amplitudes in CML and CLL are primarily due to the development leukostasis. If PV is the case, this is due to sludge syndrome. And when MM occurs, it is caused by protein stasis in the vessels of the bronchial tubes. Increased endothelial oscillation amplitudes in the range in CML, PV, IMF and their reduction in MM indicate the presence of endothelial dysfunction in these patients. Increasing the amplitude of oscillations in the range of neurogenic indicates the development of arteriolar vasodilation as a compensatory response to the violation of blood flow. Increasing the amplitude of oscillations of myogenic tone indicating decrease precapillaries as a compensatory reaction to improve blood flow. It is concluded that endobronchial laser Doppler flowmetry is an important method allowing diagnosing the pathology of the microvasculature of the bronchi in chronic leukemia.

Practical importance and modern methods of the evaluation of skin microcirculation during chronic lower limb ischemia in patients with peripheral arterial occlusive disease and/or diabetes.

PubMed

Kluz, J; Małecki, R; Adamiec, R

2013-02-01

Skin ischemia is one of the crucial phenomena during chronic lower limb ischemia in patients with peripheral arterial occlusive disease and/or diabetes. However, risk stratification for development of ischemic ulceration and/or skin necrosis in those patients is not easy, mostly due to the complex structure of the dermal vascular bed and limited possibilities for studying the skin capillaries in everyday practice. All definitions of critical limb ischemia thus far have considered mostly the clinical symptoms and the degree of macrocirculatory impairment. Despite the fact that the reduction of absolute dermal perfusion and improper distribution of perfusion in ischemic feet, primarily diminished perfusion or even a complete loss of blood flow in nutritional capillaries, rather than arterial occlusion per se, is the eventual reason for critical limb ischemia symptoms, the vessels of the microcirculation are not routinely assessed in clinical practice. Monitoring of microcirculatory parameters, as a part of integrated diagnostic approach, may have a considerable value in the evaluation of risk, progression of the disease and the effectiveness of therapeutic intervention in individual patients. Relative simplicity and availability of different non-invasive methods, including video capillaroscopy and laser Doppler fluxmetry, should constitute a premise to their wider application in clinical management of chronic limb ischemia.

Milrinone Attenuates Arteriolar Vasoconstriction and Capillary Perfusion Deficits on Endotoxemic Hamsters

PubMed Central

de Miranda, Marcos Lopes; Pereira, Sandra J.; Santos, Ana O. M. T.; Villela, Nivaldo R.; Kraemer-Aguiar, Luiz Guilherme; Bouskela, Eliete

2015-01-01

Background and Objective Apart from its inotropic property, milrinone has vasodilator, anti-inflammatory and antithrombotic effects that could assist in the reversal of septic microcirculatory changes. This paper investigates the effects of milrinone on endotoxemia-related microcirculatory changes and compares them to those observed with the use of norepinephrine. Materials and Methods After skinfold chamber implantation procedures and endotoxemia induction by intravenous Escherichia coli lipopolysaccharide administration (2 mg.kg-1), male golden Syrian hamsters were treated with two regimens of intravenous milrinone (0.25 or 0.5 μg.kg-1.min-1). Intravital microscopy of skinfold chamber preparations allowed quantitative analysis of microvascular variables. Macro-hemodynamic, biochemical, and hematological parameters and survival rate were also analyzed. Endotoxemic non-treated animals, endotoxemic animals treated with norepinephrine (0.2 μg.kg-1.min-1), and non-endotoxemic hamsters served as controls. Results Milrinone (0.5 μg.kg-1.min-1) was effective in reducing lipopolysaccharide-induced arteriolar vasoconstriction, capillary perfusion deficits, and inflammatory response, and in increasing survival. Norepinephrine treated animals showed the best mean arterial pressure levels but the worst functional capillary density values among all endotoxemic groups. Conclusion Our data suggests that milrinone yielded protective effects on endotoxemic animals’ microcirculation, showed anti-inflammatory properties, and improved survival. Norepinephrine did not recruit the microcirculation nor demonstrated anti-inflammatory effects. PMID:25646813

In vivo microvascular imaging of human oral and nasal cavities using swept-source optical coherence tomography with a single forward/side viewing probe

NASA Astrophysics Data System (ADS)

Choi, Woo June; Wang, Ruikang K.

2015-03-01

We report three-dimensional (3D) imaging of microcirculation within human cavity tissues in vivo using a high-speed swept-source optical coherence tomography (SS-OCT) at 1.3 μm with a modified probe interface. Volumetric structural OCT images of the inner tissues of oral and nasal cavities are acquired with a field of view of 2 mm x 2 mm. Two types of disposable and detachable probe attachments are devised and applied to the port of the imaging probe of OCT system, enabling forward and side imaging scans for selective and easy access to specific cavity tissue sites. Blood perfusion is mapped with OCT-based microangiography from 3D structural OCT images, in which a novel vessel extraction algorithm is used to decouple dynamic light scattering signals, due to moving blood cells, from the background scattering signals due to static tissue elements. Characteristic tissue anatomy and microvessel architectures of various cavity tissue regions of a healthy human volunteer are identified with the 3D OCT images and the corresponding 3D vascular perfusion maps at a level approaching capillary resolution. The initial finding suggests that the proposed method may be engineered into a promising tool for evaluating and monitoring tissue microcirculation and its alteration within a wide-range of cavity tissues in the patients with various pathological conditions.

Pericytes as a supplementary source of osteoblasts in periosteal osteogenesis.

PubMed

Diaz-Flores, L; Gutierrez, R; Lopez-Alonso, A; Gonzalez, R; Varela, H

1992-02-01

In the adult rat femur, lifting a periosteum strip with microscopic bone flakes on its deep surface, if performed without damaging the surrounding microcirculation, rapidly leads to new bone formation and angiogenesis. Using vascular labeling, the pericytes and endothelial cells (ECs) were labeled with monastral blue (MB) in the preformed, preexisting postcapillary venules of the periosteal microcirculation. MB was detectable by light and electron microscopy and it persisted in some of the daughter cells. Between one and 21 hours, the MB labeling was restricted to the pericytes and ECs of postcapillary venules. Immediately afterward, both pericytes and ECs of these vessels were activated and continued to show MB. The phenomenon of pericyte activation includes enlargement, disruption of their basal lamina, separation from the walls of the preformed vessels, and the presence of mitotic figures. At this stage, activated pericytes with MB in their cytoplasm, fibroblast-like cells, and transitional cell forms between them were seen in interstitial areas. After 27 hours, vascular buds appeared and MB was detected in some ECs and pericytes. Between three and six days, when bone-tissue development was observed, some osteoblasts were MB labeled. Previous findings support the hypothesis that when the periosteum is activated, the process of bone formation from cells already present in the periosteum is augmented by proliferation and differentiation of pericytes, which contribute a supplementary population of osteoprogenitor cells.

Quantifying the correlation between photoplethysmography and laser Doppler flowmetry microvascular low-frequency oscillations

NASA Astrophysics Data System (ADS)

Mizeva, Irina; Di Maria, Costanzo; Frick, Peter; Podtaev, Sergey; Allen, John

2015-03-01

Photoplethysmography (PPG) and laser Doppler flowmetry (LDF) are two recognized optical techniques that can track low-frequency perfusion changes in microcirculation. The aim of this study was to determine, in healthy subjects, the correlation between the techniques for specific low-frequency bands previously defined for microcirculation. Twelve healthy male subjects (age range 18 to 50 years) were studied, with PPG and LDF signals recorded for 20 min from their right and left index (PPG) and middle (LDF) fingers. Wavelet analysis comprised dividing the low-frequency integral wavelet spectrum (IWS) into five established physiological bands relating to cardiac, respiratory, myogenic, neurogenic, and endothelial activities. The correlation between PPG and LDF was quantified using wavelet correlation analysis and Spearman correlation analysis of the median IWS amplitude. The median wavelet correlation between signals (right-left side average) was 0.45 (cardiac), 0.49 (respiratory), 0.86 (myogenic), 0.91 (neurogenic), and 0.91 (endothelial). The correlation of IWS amplitude values (right-left side average) was statistically significant for the cardiac (ρ=0.64, p<0.05) and endothelial (ρ=0.62, p<0.05) bands. This pilot study has shown good correlation between PPG and LDF for specific physiological frequency bands. In particular, the results suggest that PPG has the potential to be a low-cost replacement for LDF for endothelial activity assessments.

Effect of N-acetylcysteine on microcirculation of mucosa in rat ileum in a model of intestinal inflammation.

PubMed

Ruh, Joachim; Schmidt, Eduard; Vogel, Frank

2003-05-01

Oxygen radicals are formed by the endothelium and blood cells and have specific functions in various organs systems. On the level of the microcirculation, oxygen radicals take part in the regulation of the leukocyte-endothelial interaction. The involvement of oxygen radicals has previously been found in conditions such as sepsis, ischemia-reperfusion, and inflammation. Indomethacin is a clinically applied nonsteroidal antiphlogistic, and in previous studies in the rat, it has been found to induce an inflammatory reaction in the small intestine characterized by edema and reddening of the intestinal epithelium, ulceration, and dysregulation in the intestinal-epithelial barrier function. In the present study, we investigated the effect of N-acetylcysteine on erythrocyte velocity and the arteriolar diameter of the main arteriole in single villi, thus providing insight in the perfusion of the mucosa in indomethacin-induced intestinal inflammation. N-Acetylcysteine is known to inactivate superoxide and its precursors. Therefore, we used N-acetylcysteine to investigate whether superoxide and its precursors participate in the regulation of blood supply to single villi in this animal model. We found that indomethacin induced an increase in villous perfusion that was significantly reduced by N-acetylcysteine, indicating that superoxide and its precursors may participate in the regulation of blood supply to the mucosa in this animal model of intestinal inflammation.

Etanercept prevents decrease of cochlear blood flow dose-dependently caused by tumor necrosis factor alpha.

PubMed

Ihler, Friedrich; Sharaf, Kariem; Bertlich, Mattis; Strieth, Sebastian; Reichel, Christoph A; Berghaus, Alexander; Canis, Martin

2013-07-01

Tumor necrosis factor alpha (TNF-alpha) is a mediator of inflammation and microcirculation in the cochlea. This study aimed to quantify the effect of a local increase of TNF-alpha and study the effect of its interaction with etanercept on cochlear microcirculation. Cochlear lateral wall vessels were exposed surgically and assessed by intravital microscopy in guinea pigs in vivo. First, 24 animals were randomly distributed into 4 groups of 6 each. Exposed vessels were superfused repeatedly either with 1 of 3 different concentrations of TNF-alpha (5.0, 0.5, and 0.05 ng/mL) or with placebo (0.9% saline solution). Second, 12 animals were randomly distributed into 2 groups of 6 each. Vessels were pretreated with etanercept (1.0 microg/ mL) or placebo (0.9% saline solution), and then treated by repeated superfusion with TNF-alpha (5.0 ng/mL). TNF-alpha was shown to be effective in decreasing cochlear blood flow at a dose of 5.0 ng/mL (p < 0.01, analysis of variance on ranks). Lower concentrations or placebo treatment did not lead to significant changes. After pretreatment with etanercept, TNF-alpha at a dose of 5.0 ng/mL no longer led to a change in cochlear blood flow. The decreasing effect that TNF-alpha has on cochlear blood flow is dose-dependent. Etanercept abrogates this effect.

Characterizing the microcirculation of atopic dermatitis using angiographic optical coherence tomography

NASA Astrophysics Data System (ADS)

Byers, R. A.; Maiti, R.; Danby, S. G.; Pang, E. J.; Mitchell, B.; Carré, M. J.; Lewis, R.; Cork, M. J.; Matcher, S. J.

2017-02-01

Background and Aim: With inflammatory skin conditions such as atopic dermatitis (AD), epidermal thickness is mediated by both pathological hyperplasia and atrophy such as that resulting from corticosteroid treatment. Such changes are likely to influence the depth and shape of the underlying microcirculation. Optical coherence tomography (OCT) provides a non-invasive view into the tissue, however structural measures of epidermal thickness are made challenging due to the lack of a delineated dermal-epidermal junction in AD patients. Instead, angiographic extensions to OCT may allow for direct measurement of vascular depth, potentially presenting a more robust method of estimating the degree of epidermal thickening. Methods and results: To investigate microcirculatory changes within AD patients, volumes of angiographic OCT data were collected from 5 healthy volunteers and compared to that of 5 AD patients. Test sites included the cubital and popliteal fossa, which are commonly affected by AD. Measurements of the capillary loop and superficial arteriolar plexus (SAP) depth were acquired and used to estimate the lower and upper bounds of the undulating basement membrane of the dermal-epidermal junction. Furthermore, quantitative parameters such as vessel density and diameter were derived from each dataset and compared between groups. Capillary loop depth increased slightly for AD patients at the poplitial fossa and SAP was found to be measurably deeper in AD patients at both sites, likely due to localized epidermal hyperplasia.

Fibroblast Growth Factor 9 Imparts Hierarchy and Vasoreactivity to the Microcirculation of Renal Tumors and Suppresses Metastases*

PubMed Central

Yin, Hao; Frontini, Matthew J.; Arpino, John-Michael; Nong, Zengxuan; O'Neil, Caroline; Xu, Yiwen; Balint, Brittany; Ward, Aaron D.; Chakrabarti, Subrata; Ellis, Christopher G.; Gros, Robert; Pickering, J. Geoffrey

2015-01-01

Tumor vessel normalization has been proposed as a therapeutic paradigm. However, normal microvessels are hierarchical and vasoreactive with single file transit of red blood cells through capillaries. Such a network has not been identified in malignant tumors. We tested whether the chaotic tumor microcirculation could be reconfigured by the mesenchyme-selective growth factor, FGF9. Delivery of FGF9 to renal tumors in mice yielded microvessels that were covered by pericytes, smooth muscle cells, and a collagen-fortified basement membrane. This was associated with reduced pulmonary metastases. Intravital microvascular imaging revealed a haphazard web of channels in control tumors but a network of arterioles, bona fide capillaries, and venules in FGF9-expressing tumors. Moreover, whereas vasoreactivity was absent in control tumors, arterioles in FGF9-expressing tumors could constrict and dilate in response to adrenergic and nitric oxide releasing agents, respectively. These changes were accompanied by reduced hypoxia in the tumor core and reduced expression of the angiogenic factor VEGF-A. FGF9 was found to selectively amplify a population of PDGFRβ-positive stromal cells in the tumor and blocking PDGFRβ prevented microvascular differentiation by FGF9 and also worsened metastases. We conclude that harnessing local mesenchymal stromal cells with FGF9 can differentiate the tumor microvasculature to an extent not observed previously. PMID:26183774

[Outlook for clinical hemorheology].

PubMed

Stoltz, J F

1996-01-01

Harvey may be considered to be the precursor of modern hemorheology, but it was not until the pioneering work of Loewenhoeck, Poiseuille, Fahraeus and Copley that the essential role of the hemorheological properties of blood and its cellular components was recognized. Before the advent of modern hemorheology in the 70s, studies were mainly focussed on microcirculation and validation of global hemorheological equations applied to blood circulation. Parallel studies on the microrheological properties (erythrocyte deformability and aggregation) explained analytically the non-Newtonian behavior of blood, and the essential contribution of these parameters to the understanding hyperviscosity syndromes. The development of clinical hemorheology in fact started at the international conferences held in Reykjavik (1966) and Heidelberg (1969), and with the initiation of the periodical European Microcirculation (since Nancy in 1960) and Clinical Hemorheology (since Nancy in 1979) Conferences. The current main avenues of research involve flow modelling, studies of cell-cell interaction mechanisms (aggregation and adhesion), in relation to the associated pathophysiological phenomena, such as cellular activation (platelets and leukocytes in particular), gene expression linked to blood flow (e.g. endothelial cells)... Clinically and therapeutically, it is crucial that pathophysiological studies be undertaken on the relationship existing between rheological parameters and objective clinical data (local flow rates, ischemic markers, hemostatic parameters, tissue oxygen, clinical symptoms,...). The main clinical application fields are cardiovascular diseases, thrombosis, diabetes, hypercholesterolemia... Also, studies on new therapeutics or on biomaterials should also be given priority.

Impact of mean arterial pressure on sublingual microcirculation during cardiopulmonary bypass - secondary outcome from a randomised clinical trial.

PubMed

Holmgaard, Frederik; Vedel, Anne G; Ravn, Hanne Berg; Nilsson, Jens C; Rasmussen, Lars S

2018-05-13

In this substudy of a randomised, clinical trial, we explored the sublingual microcirculation during cardiac surgery at two different levels of blood pressure. We hypothesised that a higher mean arterial pressure during cardiopulmonary bypass would cause higher Microvascular Flow Index. Thirty-six cardiac surgery patients undergoing coronary artery bypass grafting were included and randomised to either low (40-50 mmHg) or high (70-80 mmHg) mean arterial pressure during cardiopulmonary bypass. Sidestream Dark Field video images were recorded from the sublingual mucosa. Recordings were analysed in a blinded fashion to quantify microcirculatory variables. Mean arterial pressure during cardiopulmonary bypass in the low target group was 45.0 mmHg (SD 5.3) vs. 67.2 mmHg (SD 8.9) in the high target group. We found no significant difference between the two groups in Microvascular Flow Index during cardiopulmonary bypass evaluated for all vessels: 2.91 vs. 2.90 (p = 0.82). For small vessels (< 20 micrometers), the corresponding values were 2.87 and 2.85 in the low and high target groups, respectively (p = 0.82). We found no significant difference in sublingual microcirculatory flow expressed as Microvascular Flow Index according to two different levels of mean arterial pressure during cardiopulmonary bypass. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Estimation of reactogenicity of preparations produced on the basis of photoinactivated live vaccines against brucellosis and tularaemia on the organismic level.1. Using the LASCA method

NASA Astrophysics Data System (ADS)

Ulianova, O. V.; Uianov, S. S.; Li, Pengcheng; Luo, Qingming

2011-04-01

A new method of photoinactivation of bacteria aimed at producing prototypes of vaccine preparations against extremely dangerous infections is described. The reactogenicity of the new prophylactic preparations was studied using the laser speckle contrast analysis (LASCA). The performed experimental studies show that bacterial suspensions, irradiated using different regimes of photoinactivation, do not cause detrimental effect on the blood microcirculation in laboratory animals.

[The use of sodium chloride baths in the treatment of diabetic patients with micro- and macroangiopathies].

PubMed

Davydova, O B; Turova, E A; Grishina, E V

1998-01-01

Patients suffering from insulin-dependent or non-insulin-dependent diabetes mellitus with micro- and macroangiopathy took sodium chloride baths of diverse concentration (30 and 50 g/l). A control group consisted of patients who had taken "neutral" baths. The response to sodium chloride baths was registered in carbohydrate and lipid metabolism, microcirculation, hemorheology, lower limbs circulation, exercise tolerance. Baths with sodium chloride concentrations 50 g/l have advantages, especially in patients with insulin-dependent diabetes mellitus.

Estimation of reactogenicity of preparations produced on the basis of photoinactivated live vaccines against brucellosis and tularaemia on the organismic level. 1. Using the LASCA method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ulianova, O V; Uianov, S S; Li Pengcheng

2011-04-30

A new method of photoinactivation of bacteria aimed at producing prototypes of vaccine preparations against extremely dangerous infections is described. The reactogenicity of the new prophylactic preparations was studied using the laser speckle contrast analysis (LASCA). The performed experimental studies show that bacterial suspensions, irradiated using different regimes of photoinactivation, do not cause detrimental effect on the blood microcirculation in laboratory animals. (optical technologies in biophysics and medicine)

Photoacoustic Doppler effect from flowing small light-absorbing particles.

PubMed

Fang, Hui; Maslov, Konstantin; Wang, Lihong V

2007-11-02

From the flow of a suspension of micrometer-scale carbon particles, the photoacoustic Doppler shift is observed. As predicted theoretically, the observed Doppler shift equals half of that in Doppler ultrasound and does not depend on the direction of laser illumination. This new physical phenomenon provides a basis for developing photoacoustic Doppler flowmetry, which can potentially be used for detecting fluid flow in optically scattering media and especially low-speed blood flow of relatively deep microcirculation in biological tissue.

Efficiency evaluation of mud applications of laser doppler of skin

NASA Astrophysics Data System (ADS)

Kasimova, S. K.; Kondratenko, E. I.; Alykova, O. M.; Lomtieva, N. A.; Alykova, A. F.

2017-01-01

The mechanism of the microcirculation’s change of the face skin of the women under the influence of the sulfur silt mud application of the lake Karantinnoe of Astrakhan region was studied. The age particularities of vasorelaxation’s peloid action on the microcirculation of the face skin was installed. Peloid promotes the influx of arterial blood, the improvement of the tissue’s feeding and the reduction of the stagnant events. The prolonged action of the sulfur silt mud application reveals at more mature age.

Determination of oxygen tension in the subcutaneous tissue of cosmonauts during the Salyut-6 mission

NASA Technical Reports Server (NTRS)

Baranski, S.; Bloszczynski, R.; Hermaszewski, M.; Kubiczkowa, J.; Piorko, A.; Saganiak, R.; Sarol, Z.; Skibniewsky, F.; Stendera, J.; Walichnowski, W.

1982-01-01

A polarographic technique was used to measure the oxygen tension in subcutaneous tissue of the forearm of a cosmonaut prior to, after, and on the fourth day of a space mission performed by Salut-6. A drop in the oxygen exchange rate in the peripheral tissues during weightlessness was observed. The mechanisms of this change are studied, taking into consideration the blood distribution in the organism and microcirculation disorders reflected by a decreased blood flow rate in arterial-venous junctions.

Nailfold Capillaroscopy and Clinical Applications in Systemic Sclerosis.

PubMed

Smith, Vanessa; Thevissen, Kristof; Trombetta, Amelia C; Pizzorni, Carmen; Ruaro, Barbara; Piette, Yves; Paolino, Sabrina; De Keyser, Filip; Sulli, Alberto; Melsens, Karin; Cutolo, Maurizio

2016-07-01

Capillary microscopy is a safe and non-invasive tool to evaluate the morphology of the microcirculation typically affected in SSc. Next to being paramount for the "(very) early" diagnosis of SSc eyes are also geared toward capillaroscopy with the aim to be able to use it as a biomarker, especially in the prediction of future occurrence of DU. The following review will explain what capillary microscopy is and will focus additionally on studies evaluating the association between capillaroscopy and DU. © 2016 John Wiley & Sons Ltd.

Acute microcirculatory response to nicotine in frog web.

PubMed

Horimoto, M; Koyama, T

1982-01-01

Acute effects of nicotine (NC) on the microcirculation of frog webs were studied by measuring the blood flow velocity in arterioles, and by determining the diameter of both arterioles and venules. Simultaneous recordings of the ventricular pressure and heart rate were obtained in order to compute the vascular resistance and to interpret the changes in microcirculation. The web of right hindlimb was immersed in a solution of NC (2.6 to 3.4 mg/ml) for 4 min. Blood flow velocity in web arterioles of left hindlimb was measured by means of a laser Doppler microscope. Internal diameters of web microvessels were determined using a micrometer on the ocular lens of the microscope. Mean flow velocity (MV) and pulsatile amplitude (PA) were calculated from the pulsatile flow-velocity contour for each vessel. Both MV and PA were increased after the immersion of the web in NC solution. Although the magnitude of the increment in MV was proportional to that in ventricular pressure, the vasodilation of both arterioles and venules and the flow rate in arterioles higher than the initial state continued even after the ventricular pressure had returned to the initial control value. Calculation of the relative change in vascular resistance in web arterioles following NC administration suggested a vasodilator response to NC. Furthermore, our results indicate that sufficient NC can be absorbed across the web epithelium to produce a systemic vascular response when the concentration of NC in the bathing solution is 2.6 mg/ml.

Numerical Simulation of Sickle Cell Blood Flow in the Microcirculation

NASA Astrophysics Data System (ADS)

Berger, Stanley A.; Carlson, Brian E.

2001-11-01

A numerical simulation of normal and sickle cell blood flow through the transverse arteriole-capillary microcirculation is carried out to model the dominant mechanisms involved in the onset of vascular stasis in sickle cell disease. The transverse arteriole-capillary network is described by Strahler's network branching method, and the oxygen and blood transport in the capillaries is modeled by a Krogh cylinder analysis utilizing Lighthill's lubrication theory, as developed by Berger and King. Poiseuille's law is used to represent blood flow in the arterioles. Applying this flow and transport model and utilizing volumetric flow continuity at each network bifurcation, a nonlinear system of equations is obtained, which is solved iteratively using a steepest descent algorithm coupled with a Newton solver. Ten different networks are generated and flow results are calculated for normal blood and sickle cell blood without and with precapillary oxygen loss. We find that total volumetric blood flow through the network is greater in the two sickle cell blood simulations than for normal blood owing to the anemia associated with sickle cell disease. The percentage of capillary blockage in the network increases dramatically with decreasing pressure drop across the network in the sickle cell cases while there is no blockage when normal blood flows through simulated networks. It is concluded that, in sickle cell disease, without any vasomotor dilation response to decreasing oxygen concentrations in the blood, capillary blockage will occur in the microvasculature even at average pressure drops across the transverse arteriole-capillary networks.

Perioperative fluid management: From physiology to improving clinical outcomes.

PubMed

Bennett, Victoria A; Cecconi, Maurizio

2017-08-01

Perioperative fluid management is a key component in the care of the surgical patient. It is an area that has seen significant changes and developments, however there remains a wide disparity in practice between clinicians. Historically, patients received large volumes of intravenous fluids perioperatively. The concept of goal directed therapy was then introduced, with the early studies showing significant improvements in morbidity and mortality. The current focus is on fluid therapy guided by an individual patient's physiology. A fluid challenge is commonly performed as part of an assessment of a patient's fluid responsiveness. There remains wide variation in how clinicians perform a fluid challenge and this review explores the evidence for how to administer an effective challenge that is both reliable and reproducible. The methods for monitoring cardiac output have evolved from the pulmonary artery catheter to a range of less invasive techniques. The different options that are available for perioperative use are considered. Fluid status can also be assessed by examining the microcirculation and the importance of recognising the possibility of a lack of coherence between the macro and microcirculation is discussed. Fluid therapy needs to be targeted to specific end points and individualised. Not all patients who respond to a fluid challenge will necessarily require additional fluid administration and care should be aimed at identifying those who do. This review aims to explain the underlying physiology and describe the evidence base and the changes that have been seen in the approach to perioperative fluid therapy.

Age-Related Alterations in the Retinal Microvasculature, Microcirculation, and Microstructure.

PubMed

Wei, Yantao; Jiang, Hong; Shi, Yingying; Qu, Dongyi; Gregori, Giovanni; Zheng, Fang; Rundek, Tatjana; Wang, Jianhua

2017-07-01

To characterize age-related alterations in the retinal microcirculation, microvascular network, and microstructure in healthy subjects. Seventy-four healthy subjects aged from 18 to 82 years were recruited and divided into four age groups (G1 with age <35 years, G2 with age 35 ∼ 49 years, G3 with age 50 ∼ 64 years, and G4 with age ≥65 years). Custom ultra-high resolution optical coherence tomography (UHR-OCT) was used to acquire six intraretinal layers of the macula. OCT angiography (OCTA) was used to image the retinal microvascular network. The retinal blood flow velocity (BFV) was measured using a Retinal Function Imager (RFI). Compared to G1, G2 had significant thinning of the retinal nerve fiber layer (RNFL) (P < 0.05), while G3 had thinning of the RNFL and ganglion cell and inner plexiform layer (GCIPL) (P < 0.05), in addition to thickening of the outer plexiform layer (OPL) and photoreceptor layer (PR) (P < 0.05). G4 had loss in retinal vessel density, thinning in RNFL and GCIPL, and decrease in venular BFV, in addition to thickening of the OPL and PR (P < 0.05). Age was negatively related to retinal vessel densities, the inner retinal layers, and venular BFV (P < 0.05). By contrast, age was positively related to OPL and PR (P < 0.05). During aging, decreases in retinal vessel density, inner retinal layer thickness, and venular BFV were evident and impacted each other as observed by simultaneous changes in multiple retinal components.

Remote effects of extracorporeal shock wave therapy on cutaneous microcirculation.

PubMed

Kisch, Tobias; Sorg, Heiko; Forstmeier, Vinzent; Knobloch, Karsten; Liodaki, Eirini; Stang, Felix; Mailänder, Peter; Krämer, Robert

2015-11-01

Extracorporeal shock wave treatment (ESWT) has proven its clinical benefits in different fields of medicine. Tissue regeneration and healing is improved after shock wave treatment. Even in the case of burn wounds angiogenesis and re-epithelialization is accelerated, but ESWT in extensive burn wounds is impracticable. High energy ESWT influences cutaneous microcirculation at body regions remote from application site. Eighteen Sprague Dawley rats were randomly assigned to two groups and received either high energy ESWT (Group A: total 1000 impulses, 10 J) or placebo shock wave treatment (Group B: 0 impulses, 0 J), applied to the dorsal lower leg of the hind limb. Ten minutes later microcirculatory effects were assessed at the contralateral lower leg of the hind limb (remote body region) by combined Laser-Doppler-Imaging and Photospectrometry. In Group A cutaneous capillary blood velocity was significantly increased by 152.8% vs. placebo ESWT at the remote body location (p = 0.01). Postcapillary venous filling pressure remained statistically unchanged (p > 0.05), while cutaneous tissue oxygen saturation increased by 12.7% in Group A (p = 0.220). High energy ESWT affects cutaneous hemodynamics in body regions remote from application site in a standard rat model. The results of this preliminary study indicate that ESWT might be beneficial even in disseminated and extensive burn wounds by remote shock wave effects and should therefore be subject to further scientific evaluation. Copyright © 2015 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

Vasculogenic Mimicry and Tumor Angiogenesis

PubMed Central

Folberg, Robert; Hendrix, Mary J. C.; Maniotis, Andrew J.

2000-01-01

Tumors require a blood supply for growth and hematogenous dissemination. Much attention has been focused on the role of angiogenesis—the recruitment of new vessels into a tumor from pre-existing vessels. However, angiogenesis may not be the only mechanism by which tumors acquire a microcirculation. Highly aggressive and metastatic melanoma cells are capable of forming highly patterned vascular channels in vitro that are composed of a basement membrane that stains positive with the periodic acid-Schiff (PAS) reagent in the absence of endothelial cells and fibroblasts. These channels formed in vitro are identical morphologically to PAS-positive channels in histological preparations from highly aggressive primary uveal melanomas, in the vertical growth phase of cutaneous melanomas, and in metastatic uveal and cutaneous melanoma. The generation of microvascular channels by genetically deregulated, aggressive tumor cells was termed “vasculogenic mimicry” to emphasize their de novo generation without participation by endothelial cells and independent of angiogenesis. Techniques designed to identify the tumor microcirculation by the staining of endothelial cells may not be applicable to tumors that express vasculogenic mimicry. Although it is not known if therapeutic strategies targeting endothelial cells will be effective in tumors whose blood supply is formed by tumor cells in the absence of angiogenesis, the biomechanical and molecular events that regulate vasculogenic mimicry provide opportunities for the development of novel forms of tumor-targeted treatments. The unique patterning characteristic of vasculogenic mimicry provides an opportunity to design noninvasive imaging techniques to detect highly aggressive neoplasms and their metastases. PMID:10666364

ROLE OF THE RENAL MICROCIRCULATION IN PROGRESSION OF CHRONIC KIDNEY INJURY IN OBESITY

PubMed Central

Chade, Alejandro R.; Hall, John E.

2016-01-01

Background Obesity is largely responsible for the growing incidence and prevalence of diabetes, cardiovascular, and renal disease. Current strategies to prevent and treat obesity and its consequences have been insufficient to reverse the ongoing trends. Lifestyle modification or pharmacological therapies often produce modest weight loss which is not sustained and recurrence of obesity is frequently observed, leading to progression of target organ damage in many obese subjects. Therefore, research efforts have focused not only on the factors that regulate energy balance, but also on understanding mechanisms of target organ injury in obesity. Summary and Key message Microvascular disease plays a pivotal role in progressive kidney injury from different etiologies such as hypertension, diabetes, and atherosclerosis, which are all important consequences of chronic obesity. The microvascular networks are anatomical units that are closely adapted to specific functions of nutrition and removal of waste in every organ. Damage of the small vessels in several tissues and organs has been reported in obesity and may increase cardio-renal risk. However, the mechanisms by which obesity and its attendant cardiovascular and metabolic consequences interact to cause renal microvascular injury and chronic kidney disease are still unclear, although substantial progress has been made in recent years. This review addresses potential mechanisms and consequences of obesity-induced renal microvascular injury as well as current treatments that may provide protection of the renal microcirculation and slow progressive kidney injury in obesity. PMID:27771702

Interleukin 2 Activates Brain Microvascular Endothelial Cells Resulting in Destabilization of Adherens Junctions.

PubMed

Wylezinski, Lukasz S; Hawiger, Jacek

2016-10-28

The pleiotropic cytokine interleukin 2 (IL2) disrupts the blood-brain barrier and alters brain microcirculation, underlying vascular leak syndrome that complicates cancer immunotherapy with IL2. The microvascular effects of IL2 also play a role in the development of multiple sclerosis and other chronic neurological disorders. The mechanism of IL2-induced disruption of brain microcirculation has not been determined previously. We found that both human and murine brain microvascular endothelial cells express constituents of the IL2 receptor complex. Then we established that signaling through this receptor complex leads to activation of the transcription factor, nuclear factor κB, resulting in expression of proinflammatory interleukin 6 and monocyte chemoattractant protein 1. We also discovered that IL2 induces disruption of adherens junctions, concomitant with cytoskeletal reorganization, ultimately leading to increased endothelial cell permeability. IL2-induced phosphorylation of vascular endothelial cadherin (VE-cadherin), a constituent of adherens junctions, leads to dissociation of its stabilizing adaptor partners, p120-catenin and β-catenin. Increased phosphorylation of VE-cadherin was also accompanied by a reduction of Src homology 2 domain-containing protein-tyrosine phosphatase 2, known to maintain vascular barrier function. These results unravel the mechanism of deleterious effects induced by IL2 on brain microvascular endothelial cells and may inform the development of new measures to improve IL2 cancer immunotherapy, as well as treatments for autoimmune diseases affecting the central nervous system. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Quantitative evaluation of capillaroscopic microvascular changes in patients with established coronary heart disease.

PubMed

Sanchez-Garcia, M Esther; Ramirez-Lara, Irene; Gomez-Delgado, Francisco; Yubero-Serrano, Elena M; Leon-Acuña, Ana; Marin, Carmen; Alcala-Diaz, Juan F; Camargo, Antonio; Lopez-Moreno, Javier; Perez-Martinez, Pablo; Tinahones, Francisco José; Ordovas, Jose M; Caballero, Javier; Blanco-Molina, Angeles; Lopez-Miranda, Jose; Delgado-Lista, Javier

2018-02-23

Microcirculation disturbances have been associated to most of the cardiovascular risk factors as well as to multiple inflammatory diseases. However, whether these abnormalities are specifically augmented in patients with coronary heart disease is still unknown. We aimed to evaluate if there is a relationship between the presence of coronary heart disease and the existence of functional and structural capillary abnormalities evaluated in the cutaneous microcirculation by videocapillaroscopy. Two matched samples of 30 participants with and without coronary heart disease but with similar clinical and anthropometric characteristics were evaluated by videocapillaroscopy at the dorsal skin of the third finger of the non-dominant hand. We calculated basal capillary density as well as capillary density after a period of arterial and venous occlusion in order to evaluate functionality and maximum capillary density. We also measured capillary recruitment. Microvascular capillary density at rest was significantly lower in patients suffering from coronary heart disease than in controls. This fact was also found after dynamic tests (arterial and venous occlusion), suggesting functional impairments. Capillary recruitment of the samples was not different in our sample. In our study, patients with coronary heart disease exhibit functional and structural microvascular disturbances. Although this is a very preliminary study, these findings open the door for further studying the microvascular functionality in coronary patients and how it relates to the response to treatment and/or the prognosis of the disease. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

Intraoperative Vascular Neuromonitoring in Patients with Subarachnoid Hemorrhage: A Pilot Study Using Combined Laser-Doppler Spectrophotometry.

PubMed

Schmitz, Emilija; Bischoff, Barbara; Wolf, Dennis; Schmitt, Hubert J; Eyupoglu, Ilker Y; Roessler, Karl; Buchfelder, Michael; Sommer, Björn

2017-11-01

Intraoperative monitoring of cerebral microcirculation in patients with subarachnoid hemorrhage (SAH) may predict the postoperative neurologic outcome. In this pilot study, we examined the value of a novel noninvasive real-time measurement technique for detecting changes in local microcirculation. We used the O2C (Oxygen to see) laser-Doppler spectrophotometry system in 14 patients with Hunt & Hess grade 2-5 SAH who underwent microsurgical cerebral aneurysm clipping. A subdural probe recorded capillary venous oxygenation (SO 2 ), relative hemoglobin concentration, blood cell velocity, and blood flow at a tissue depth of 7 mm. Data were recorded immediately before dural closure. We also recorded somatosensory evoked potentials (SEPs) with median and tibial nerve stimulation. Results were compared with neurologic performance, as measured on the modified Rankin Scale, at the day of discharge from the hospital and 12 months thereafter. Patient functional outcomes after discharge and 12 months were correlated with pathological decreased flow and increased SO 2 values. In 6 of 8 patients, microcirculatory monitoring parameters indicated ischemia during surgery, as shown by electrophysiological SEP changes and infarction detected on the postoperative computed tomography (CT) scan. Pathological SEP results correlated closely with infarct demarcation as seen on CT. Our results indicate the potential benefit of intraoperative combined laser-Doppler flowmetry and spectrophotometry for predicting postoperative clinical outcomes in this small patient sample. Larger-cohort testing is needed to verify our findings and show the possible merits of this novel method. Copyright © 2017 Elsevier Inc. All rights reserved.

Use of micro-lightguide spectrophotometry for evaluation of microcirculation in the small and large intestines of horses without gastrointestinal disease.

PubMed

Reichert, Christof; Kästner, Sabine B R; Hopster, Klaus; Rohn, Karl; Rötting, Anna K

2014-11-01

To evaluate the use of a micro-lightguide tissue spectrophotometer for measurement of tissue oxygenation and blood flow in the small and large intestines of horses under anesthesia. 13 adult horses without gastrointestinal disease. Horses were anesthetized and placed in dorsal recumbency. Ventral midline laparotomy was performed. Intestinal segments were exteriorized to obtain measurements. Spectrophotometric measurements of tissue oxygenation and regional blood flow of the jejunum and pelvic flexure were obtained under various conditions that were considered to have a potential effect on measurement accuracy. In addition, arterial oxygen saturation at the measuring sites was determined by use of pulse oximetry. 12,791 single measurements of oxygen saturation, relative amount of hemoglobin, and blood flow were obtained. Errors occurred in 381 of 12,791 (2.98%) measurements. Most measurement errors occurred when surgical lights were directed at the measuring site; covering the probe with the surgeon's hand did not eliminate this error source. No measurement errors were observed when the probe was positioned on the intestinal wall with room light, at the mesenteric side, or between the mesenteric and antimesenteric side. Values for blood flow had higher variability, and this was most likely caused by motion artifacts of the intestines. The micro-lightguide spectrophotometry system was easy to use on the small and large intestines of horses and provided rapid evaluation of the microcirculation. Results indicated that measurements should be performed with room light only and intestinal motion should be minimized.

Gastroprotective effects of flavonoids in plant extracts.

PubMed

Zayachkivska, O S; Konturek, S J; Drozdowicz, D; Konturek, P C; Brzozowski, T; Ghegotsky, M R

2005-03-01

The purpose of this paper is to overview the relations between plant-originated substances and their bioactivity measured in terms of antioxidant, cytoprotective and antiulcer activities. In addition, we assessed whether these compounds are capable of affecting the gastric mucosal lesions induced by absolute ethanol applied intragastrically (i.g.). The following plant-originated flavonoid substances were considered; Solon (Sophoradin extract), Amaranth seed extract, grapefruit-seed extract (GSE) and capsaicin (extract of chilly pepper). The area of gastric mucosa lesions and gastric blood flow were measured in rats with ethanol-induced lesions without (control) and with one of the tested substances without and with capsaicin denervation of afferent nerves or administration of L-nitro-arginine (L-NNA), an inhibitor of nitric oxide synthase (NOS). Male Wistar rats, weighing 180-220 g fasted for 24 h before the study where used 100% ethanol was applied i.g. to induce gastric lesions, whose area was determined by planimetry. Gastric blood flow was assessed using electrolytic regional blood flowmeter. All tested plant-originated substances afforded gastroprotection against ethanol-induced damage and this was accompanied by increase in gastric microcirculation, both changes being reversed by pretreatment with neurotoxic dose of capsaicin or by pretreatment with L-NNA. We conclude that plant-originated flavonoid substances are highly gastroprotective probably due to enhancement of the expression of constitutive NOS and release of NO and neuropeptides such as calcitonin gene related peptide (CGRP) released from sensory afferent nerves increasing gastric microcirculation.

Influence of plant-originated gastroproteciive and antiulcer substances on gastric mucosal repair.

PubMed

Zayachkivska, O S; Konturek, S J; Drozdowicz, D; Brzozowski, T; Gzhegotsky, M R

2004-01-01

Fundamental basis of cellular and molecular mechanisms involved in mucosal injury and repair in gastrointestinal tract helps to develop new therapeutic approaches to various gut mucosal injury- related diseases. The study was aimed to assess the relations between plant-originated substances and their bioactivity measured in terms of antioxidant, cytoprotective and antiulceric activities and to deteminate if these effects are capable of affecting the gastric mucosal lesions induced by absolute ethanol applied intragastrically. The following plant-originated substances were considered: Solon, capsaicin, grapefruit-seed extract and amaranth. The area of gastric mucosa lesions and gastric blood flow were measured in rats with ethanol-induced lesions without (control) and with one of the tested substances without and with capsaicin denervation of afferent nerves or administration of L-nitro-arginine (L-NNA), an inhibitor of nitric oxide synthase (NOS). male Wistar rats, weighing 180-220 g fasted for 24 h before the study, 100% ethanol was applied ig to induced gastric lesions, whose area was determined by planimetry. Gastric blood flow was assessed using electrolytic regional blood flowmeter. All tested plant-originated substances afforded gastroprotection against ethanol-induced damage and this was accompanied by an increase in gastric microcirculation, both changes being reversed by pretreatment with neurotoxic dose of capsaicin or by pretreatment-with L-NNA. Plant-originated substances are highly gastroprotective probably due to enhancement of the expression of NOS I, NO release and an increase in gastric microcirculation.

Peritoneal dialysis solution attenuates microvascular leukocyte adhesion induced by nitric oxide synthesis inhibition.

PubMed

White, R; Ram, S

1996-01-01

In the mesenteric microcirculation, inhibition of nitric oxide (NO) synthesis results in an inflammatory response through increased leukocyte adherence to the microvascular postcapillary venular endothelium. Recent studies have demonstrated that elevated concentrations of endogenous NO synthesis inhibitors are present in renal failure. How peritoneal dialysis solutions may affect leukocyte-endothelial interactions during inflammation induced by NO synthesis inhibition has been previously unknown. Using in vivo intravital microscopy of the rat mesenteric postcapillary venules, microvascular leukocyte adherence was quantitated during baseline conditions in which the mesentery was superfused with a buffer solution, followed by the superfusion of a NO synthesis inhibitor NG-nitro-L-ARGININE methyl ester (L-NAME) added to the buffer, followed by 4.25% Dianeal (4.25% D). When compared to baseline, L-NAME increased the mean number of adherent leukocytes by fivefold (2.2 +/- 0.9 vs 11.6 +/- 3.6 leukocytes/100 microns venule/10 min, p < 0.05), while 4.25% D quickly reversed the L-NAME-induced inflammatory response, returning the number of adherent leukocytes back to baseline values (11.6 +/- 3.6 vs 2.4 +/- 1.3 leukocytes/100 microns venule/ 10 min, p < 0.05). These results confirm that NO synthesis inhibition induces inflammation in mesenteric postcapillary venules. Superfusion of 4.25% D reverses leukocyte adhesion induced by NO synthesis inhibition. Thus, a standard peritoneal dialysis solution (4.25% D) reverses the leukocyte-adhesive effects of NO synthesis inhibition in the mesenteric microcirculation.

Consumption of flavanol-rich cocoa acutely increases microcirculation in human skin.

PubMed

Neukam, Karin; Stahl, Wilhelm; Tronnier, Hagen; Sies, Helmut; Heinrich, Ulrike

2007-02-01

Long term cocoa ingestion leads to an increased resistance against UV-induced erythema and a lowered transepidermal water loss. To investigate the acute effects of a single dose of cocoa rich in flavanols on dermal microcirculation. In a crossover design study, 10 healthy women ingested a cocoa drink (100 ml) with high (329 mg) or low (27 mg) content of flavanols. The major flavanol monomer in both drinks was epicatechin, 61 mg in the high flavanol, and 6.6 mg in the low flavanol product per 100 ml. Dermal blood flow and oxygen saturation of hemoglobin were examined by laser Doppler flowmetry and spectroscopically at 1 mm skin depth at t = 0, 1, 2, 4, and 6 h. At the same time points, plasma levels of total epicatechin (free compound plus conjugates) were measured by means of HPLC. Subsequent to the intake of high flavanol cocoa, dermal blood flow was significantly increased by 1.7-fold at t = 2 h and oxygen saturation was elevated 1.8-fold. No statistically significant changes were found upon intake of low flavanol cocoa. Maximum plasma levels of total epicatechin were observed 1 h after ingestion of the high flavanol cocoa drink, 11.6 +/- 7.4 nmol/l at baseline, and 62.9 +/- 35.8 nmol/l at 1 h. No change of total epicatechin was found in the low flavanol group. Flavanol-rich cocoa consumption acutely increases dermal blood flow and oxygen saturation.

MicroDAIMON study: Microcirculatory DAIly MONitoring in critically ill patients: a prospective observational study.

PubMed

Scorcella, Claudia; Damiani, Elisa; Domizi, Roberta; Pierantozzi, Silvia; Tondi, Stefania; Carsetti, Andrea; Ciucani, Silvia; Monaldi, Valentina; Rogani, Mara; Marini, Benedetto; Adrario, Erica; Romano, Rocco; Ince, Can; Boerma, E Christiaan; Donati, Abele

2018-05-15

Until now, the prognostic value of microcirculatory alterations in critically ill patients has been mainly evaluated in highly selected subgroups. Aim of this study is to monitor the microcirculation daily in mixed group of Intensive Care Unit (ICU)-patients and to establish the association between (the evolution of) microcirculatory alterations and outcome. This is a prospective longitudinal observational single-centre study in adult patients admitted to a 12-bed ICU in an Italian teaching hospital. Sublingual microcirculation was evaluated daily, from admission to discharge/death, using Sidestream Dark Field imaging. Videos were analysed offline to assess flow and density variables. Laboratory and clinical data were recorded simultaneously. A priori, a Microvascular Flow Index (MFI) < 2.6 was defined as abnormal. A binary logistic regression analysis was performed to evaluate the association between microcirculatory variables and outcomes; a Kaplan-Meier survival curve was built. Outcomes were ICU and 90-day mortality. A total of 97 patients were included. An abnormal MFI was present on day 1 in 20.6%, and in 55.7% of cases during ICU admission. Patients with a baseline MFI < 2.6 had higher ICU, in-hospital and 90-day mortality (45 vs. 15.6%, p = 0.012; 55 vs. 28.6%, p = 0.035; 55 vs. 26%, p = 0.017, respectively). An independent association between baseline MFI < 2.6 and outcome was confirmed in a binary logistic analysis (odds ratio 4.594 [1.340-15.754], p = 0.015). A heart rate (HR) ≥ 90 bpm was an adjunctive predictor of mortality. However, a model with stepwise inclusion of mean arterial pressure < 65 mmHg, HR ≥ 90 bpm, lactate > 2 mmol/L and MFI < 2.6 did not detect significant differences in ICU mortality. In case an abnormal MFI was present on day 1, ICU mortality was significantly higher in comparison with patients with an abnormal MFI after day 1 (38 vs. 6%, p = 0.001), indicating a time-dependent significant difference in prognostic value. In a general ICU population, an abnormal microcirculation at baseline is an independent predictor for mortality. In this setting, additional routine daily microcirculatory monitoring did not reveal extra prognostic information. Further research is needed to integrate microcirculatory monitoring in a set of commonly available hemodynamic variables. Trial registration NCT 02649088, www.clinicaltrials.gov . Date of registration: 23 December 2015, retrospectively registered.

Tyrosine kinase Btk regulates E-selectin-mediated integrin activation and neutrophil recruitment by controlling phospholipase C (PLC) gamma2 and PI3Kgamma pathways.

PubMed

Mueller, Helena; Stadtmann, Anika; Van Aken, Hugo; Hirsch, Emilio; Wang, Demin; Ley, Klaus; Zarbock, Alexander

2010-04-15

Selectins mediate leukocyte rolling, trigger beta(2)-integrin activation, and promote leukocyte recruitment into inflamed tissue. E-selectin binding to P-selectin glycoprotein ligand 1 (PSGL-1) leads to activation of an immunoreceptor tyrosine-based activation motif (ITAM)-dependent pathway, which in turn activates the spleen tyrosine kinase (Syk). However, the signaling pathway linking Syk to integrin activation after E-selectin engagement is unknown. To identify the pathway, we used different gene-deficient mice in autoperfused flow chamber, intravital microscopy, peritonitis, and biochemical studies. We report here that the signaling pathway downstream of Syk divides into a phospholipase C (PLC) gamma2- and phosphoinositide 3-kinase (PI3K) gamma-dependent pathway. The Tec family kinase Bruton tyrosine kinase (Btk) is required for activating both pathways, generating inositol-3,4,5-trisphosphate (IP(3)), and inducing E-selectin-mediated slow rolling. Inhibition of this signal-transduction pathway diminished Galpha(i)-independent leukocyte adhesion to and transmigration through endothelial cells in inflamed postcapillary venules of the cremaster. Galpha(i)-independent neutrophil recruitment into the inflamed peritoneal cavity was reduced in Btk(-/-) and Plcg2(-/-) mice. Our data demonstrate the functional importance of this newly identified signaling pathway mediated by E-selectin engagement.

Plasmin Inhibitors Prevent Leukocyte Accumulation and Remodeling Events in the Postischemic Microvasculature

PubMed Central

Reichel, Christoph A.; Lerchenberger, Max; Uhl, Bernd; Rehberg, Markus; Berberich, Nina; Zahler, Stefan; Wymann, Matthias P.; Krombach, Fritz

2011-01-01

Clinical trials revealed beneficial effects of the broad-spectrum serine protease inhibitor aprotinin on the prevention of ischemia-reperfusion (I/R) injury. The underlying mechanisms remained largely unclear. Using in vivo microscopy on the cremaster muscle of male C57BL/6 mice, aprotinin as well as inhibitors of the serine protease plasmin including tranexamic acid and ε-aminocaproic acid were found to significantly diminish I/R-elicited intravascular firm adherence and (subsequent) transmigration of neutrophils. Remodeling of collagen IV within the postischemic perivenular basement membrane was almost completely abrogated in animals treated with plasmin inhibitors or aprotinin. In separate experiments, incubation with plasmin did not directly activate neutrophils. Extravascular, but not intravascular administration of plasmin caused a dose-dependent increase in numbers of firmly adherent and transmigrated neutrophils. Blockade of mast cell activation as well as inhibition of leukotriene synthesis or antagonism of the platelet-activating-factor receptor significantly reduced plasmin-dependent neutrophil responses. In conclusion, our data suggest that extravasated plasmin(ogen) mediates neutrophil recruitment in vivo via activation of perivascular mast cells and secondary generation of lipid mediators. Aprotinin as well as the plasmin inhibitors tranexamic acid and ε-aminocaproic acid interfere with this inflammatory cascade and effectively prevent postischemic neutrophil responses as well as remodeling events within the vessel wall. PMID:21364954

Elastohydrodynamic Lift at a Soft Wall

NASA Astrophysics Data System (ADS)

Davies, Heather S.; Débarre, Delphine; El Amri, Nouha; Verdier, Claude; Richter, Ralf P.; Bureau, Lionel

2018-05-01

We study experimentally the motion of nondeformable microbeads in a linear shear flow close to a wall bearing a thin and soft polymer layer. Combining microfluidics and 3D optical tracking, we demonstrate that the steady-state bead-to-surface distance increases with the flow strength. Moreover, such lift is shown to result from flow-induced deformations of the layer, in quantitative agreement with theoretical predictions from elastohydrodynamics. This study thus provides the first experimental evidence of "soft lubrication" at play at small scale, in a system relevant, for example, to the physics of blood microcirculation.

Estimation of reactogenicity of preparations produced on the basis of photoinactivated live vaccines against brucellosis and tularaemia on the organismic level.2. Using the method of speckle-microscopy with high spatial resolution

NASA Astrophysics Data System (ADS)

Ulianova, O. V.; Uianov, S. S.; Li, Pengcheng; Luo, Qingming

2011-04-01

The method of speckle microscopy was adapted to estimate the reactogenicity of the prototypes of vaccine preparations against extremely dangerous infections. The theory is proposed to describe the mechanism of formation of the output signal from the super-high spatial resolution speckle microscope. The experimental studies show that bacterial suspensions, irradiated in different regimes of inactivation, do not exert negative influence on the blood microcirculations in laboratory animals.

Role of the Hemostatic System on SCD Pathophysiology and Potential Therapeutics

PubMed Central

Pakbaz, Zahra; Wun, Ted

2014-01-01

Synopsis Recent studies suggest that sickle cell disease is a hypercoagulable state contributing to the vaso-occlusive events in microcirculation resulting in acute and chronic sickle cell related organ damage. In this article, we will review the existing evidence for contribution of hemostatic system perturbation to sickle cell disease pathophysiology. We will also review the data showing increased risk of thromboembolic events, particularly newer information on the incidence of VTE. Finally, the potential role of platelet inhibitors and anticoagulants in SCD will be briefly reviewed. PMID:24589271

Rheological properties of RBC in the microcirculation of mammalian skeletal muscle. [red blood cells

NASA Technical Reports Server (NTRS)

Ehrenberg, M. H.

1974-01-01

In the investigation the established technique of direct microscopic viewing was combined with the use of a closed circuit television system and cinematography. The red cell flow patterns in all capillaries were found to be oscillatory with characteristic cycle frequencies and amplitudes for all concentrations of inspired oxygen greater than 8%. Generally, there was a transient decrease in mean flow rate with increasing severity of hypoxia, with a gradual return toward control values. Red cell flow patterns are discussed along with questions of red cell configuration.

Low ADAMTS-13 in plavix induced thrombotic thrombocytopenic purpura.

PubMed

Cao, Long Bao; Jones, Christopher; Movahed, Assad

2013-04-16

Thrombotic thrombocytopenia purpura (TTP) was first described in 1924 as a "pathologic alteration of the microvasculature, with detachment or swelling of the endothelium, amorphous material in the sub-endothelial space, and luminal platelet aggregation leading to compromise of the microcirculation". Ticlopidine induced TTP has been highly associated with autoimmune induced reduction in ADAMTS-13 activity. These findings, to a lesser extent, have also been found in clopidogrel induced TTP. We report a case of clopidogrel associated TTP in a patient that presented with acute stroke, renal failure, and non-ST elevation myocardial infarction.

Photochemical mechanisms of biological action of low-intensity laser irradiation

NASA Astrophysics Data System (ADS)

Klebanov, Gennady I.; Poltanov, Evgeny A.

2004-08-01

Low-intensity laser irradiation (LILI) is effectively used in clinical practice but the mechanisms of its stimulating action are still far from being understood completely and considered in the scientific literature only hypothetically. The main effects of LILI proved both in clinics and in experiments are bactericidal effect, vasodilatation, improved microcirculation, formation and growth of new microvessels, acceleration of wound healing, relieving of pain syndrome. We put forward a free radical conception underlying these effects. In this paper the experimental evidences of this conception is considered.

Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease.

PubMed

Pereira, Evelyn Nunes Goulart da Silva; Silvares, Raquel Rangel; Flores, Edgar Eduardo Ilaquita; Rodrigues, Karine Lino; Ramos, Isalira Peroba; da Silva, Igor José; Machado, Marcelo Pelajo; Miranda, Rosiane Aparecida; Pazos-Moura, Carmen Cabanelas; Gonçalves-de-Albuquerque, Cassiano F; Faria-Neto, Hugo Caire de Castro; Tibiriça, Eduardo; Daliry, Anissa

2017-01-01

This study aimed to investigate the pathophysiology of hepatic microcirculatory dysfunction in non-alcoholic fatty liver disease (NAFLD). In Wistar rats, NAFLD model was induced by 20 weeks of high-fat diet (HFD) feeding. Rolling and adhesion of leukocytes and tissue perfusion in hepatic microcirculation were examined using in vivo microscopic and laser speckle contrast imaging (LSCI), respectively. Oxidative stress and inflamatory parameters were analysed by TBARs, catalase enzyme activity, RT-PCR and ELISA. The participation of advanced glycation end-products (AGE) and its receptor RAGE was evaluated by the measurement of gene and protein expression of RAGE by RT-PCR and Western-blot, respectively and by liver and serum quantification of fluorescent AGEs. Wistar rats fed high-fat diet (HFD) showed increase in epididymal and abdominal fat content, systolic arterial blood pressure, fasting blood glucose levels, hepatic triglycerides and cholesterol, and impairment of glucose and insulin metabolisms. Liver histology confirmed the presence of steatosis and ultrasound analysis revealed increased liver size and parenchymal echogenicity in HFD-fed rats. HFD causes significant increases in leukocyte rolling and adhesion on hepatic microcirculation and decrease in liver microvascular blood flow. Liver tissue presented increase in oxidative stress and inflammtion. At 20 weeks, there was a significantly increase in AGE content in the liver and serum of HFD-fed rats and an increase in RAGE gene expression in the liver. The increase in liver AGE levels and microcirculatory disturbances could play a role in the pathogenesis of liver injury and are key components of NAFLD.

Age-Related Alterations in the Retinal Microvasculature, Microcirculation, and Microstructure

PubMed Central

Wei, Yantao; Jiang, Hong; Shi, Yingying; Qu, Dongyi; Gregori, Giovanni; Zheng, Fang; Rundek, Tatjana; Wang, Jianhua

2017-01-01

Purpose To characterize age-related alterations in the retinal microcirculation, microvascular network, and microstructure in healthy subjects. Methods Seventy-four healthy subjects aged from 18 to 82 years were recruited and divided into four age groups (G1 with age <35 years, G2 with age 35 ∼ 49 years, G3 with age 50 ∼ 64 years, and G4 with age ≥65 years). Custom ultra-high resolution optical coherence tomography (UHR-OCT) was used to acquire six intraretinal layers of the macula. OCT angiography (OCTA) was used to image the retinal microvascular network. The retinal blood flow velocity (BFV) was measured using a Retinal Function Imager (RFI). Results Compared to G1, G2 had significant thinning of the retinal nerve fiber layer (RNFL) (P < 0.05), while G3 had thinning of the RNFL and ganglion cell and inner plexiform layer (GCIPL) (P < 0.05), in addition to thickening of the outer plexiform layer (OPL) and photoreceptor layer (PR) (P < 0.05). G4 had loss in retinal vessel density, thinning in RNFL and GCIPL, and decrease in venular BFV, in addition to thickening of the OPL and PR (P < 0.05). Age was negatively related to retinal vessel densities, the inner retinal layers, and venular BFV (P < 0.05). By contrast, age was positively related to OPL and PR (P < 0.05). Conclusions During aging, decreases in retinal vessel density, inner retinal layer thickness, and venular BFV were evident and impacted each other as observed by simultaneous changes in multiple retinal components. PMID:28744554

Medical applications of VIS/NIR spectroscopy of human tissue surfaces by a novel portable instrumentation

NASA Astrophysics Data System (ADS)

Otto, Thomas; Stock, Volker; Schmidt, Wolf-Dieter; Liebold, Kristin; Fassler, Dieter; Wollina, Uwe; Fritzsch, Uwe; Gessner, Thomas

2001-11-01

In medical diagnostics, non invasive optical techniques will become common at a variety of applications because they contribute to objectivity and precision. The spectral properties of human tissue are an important field of interest. They offer opportunities of detection of skin diseases and of evaluation of chronic wounds. In the visible range, the hemoglobin absorption corresponds to blood microcirculation and the melanin absorption to the skin-type. Two types of diode-array equipment will be described: a combined VIS-NIR spectrometer system from J&M Aalen/Germany (400 nm to 1600 nm) and a stand-alone spectrometer from COLOUR CONTROL Farbmesstechnik Chemnitz/Germany (400 nm to 1000 nm). Non-contacting sensing is essential for investigating chronic wounds (no disturbances of blood microcirculation by contact pressure). The spectroscopic VIS-NIR readings of chronic wounds mainly depend on the absorption of hemoglobin and water. Multivariate analysis was applied for an objective spectral classification of eight different wound scores. Some results regarding spectral measurements of wounds and skin will be discussed. The spectrometer of COLOUR CONTROL was tested in dental surgery. To select dentures, its color has to be determined exactly to meet beauty culture demands. Color determination by dentist is not sufficient enough because of possible metameric effects of illumination. Results of spectral evaluation of denture material and human teeth will be given. Medical examination requires portable and ease equipment suitable for precise measurements. This is solved by a modular measurement system comprising microcomputer, display, light source, fiber probe, and diode-array spectrometer. It is efficient to process primary spectral data to appropriate medical interpretations.

Novel capsaicin-induced parameters of microcirculation in migraine patients revealed by imaging photoplethysmography.

PubMed

Kamshilin, Alexei A; Volynsky, Maxim A; Khayrutdinova, Olga; Nurkhametova, Dilyara; Babayan, Laura; Amelin, Alexander V; Mamontov, Oleg V; Giniatullin, Rashid

2018-06-18

The non-invasive biomarkers of migraine can help to develop the personalized medication of this disorder. In testing of the antimigraine drugs the capsaicin-induced skin redness with activated TRPV1 receptors in sensory neurons associated with the release of the migraine mediator CGRP has already been widely used. Fourteen migraine patients (mean age 34.6 ± 10.2 years) and 14 healthy volunteers (mean age 29.9 ± 9.7 years) participated in the experiment. A new arrangement of imaging photoplethysmography recently developed by us was used here to discover novel sensitive parameters of dermal blood flow during capsaicin applications in migraine patients. Blood pulsation amplitude (BPA) observed as optical-intensity waveform varying synchronously with heartbeat was used for detailed exploration of microcirculatory perfusion induced by capsicum patch application. The BPA signals, once having appeared after certain latent period, were progressively rising until being saturated. Capsaicin-induced high BPA areas were distributed unevenly under the patch, forming "hot spots." Interestingly the hot spots were much more variable in migraine patients than in the control group. In contrast to BPA, a slow component of waveforms related to the skin redness changed significantly less than BPA highlighting the latter parameter as the potential sensitive biomarker of capsaicin-induced activation of the blood flow. Thus, in migraine patients, there is a non-uniform (both in space and in time) reaction to capsaicin, resulting in highly variable openings of skin capillaries. BPA dynamics measured by imaging photoplethysmography could serve as a novel sensitive non-invasive biomarker of migraine-associated changes in microcirculation.

Levosimendan: a cardiovascular drug to prevent liver ischemia-reperfusion injury?

PubMed

Onody, Peter; Stangl, Rita; Fulop, Andras; Rosero, Oliver; Garbaisz, David; Turoczi, Zsolt; Lotz, Gabor; Rakonczay, Zoltan; Balla, Zsolt; Hegedus, Viktor; Harsanyi, Laszlo; Szijarto, Attila

2013-01-01

Temporary occlusion of the hepatoduodenal ligament leads to an ischemic-reperfusion (IR) injury in the liver. Levosimendan is a new positive inotropic drug, which induces preconditioning-like adaptive mechanisms due to opening of mitochondrial KATP channels. The aim of this study was to examine possible protective effects of levosimendan in a rat model of hepatic IR injury. Levosimendan was administered to male Wistar rats 1 hour (early pretreatment) or 24 hours (late pretreatment) before induction of 60-minute segmental liver ischemia. Microcirculation of the liver was monitored by laser Doppler flowmeter. After 24 hours of reperfusion, liver and blood samples were taken for histology, immuno- and enzyme-histochemistry (TUNEL; PARP; NADH-TR) as well as for laboratory tests. Furthermore, liver antioxidant status was assessed and HSP72 expression was measured. In both groups pretreated with levosimendan, significantly better hepatic microcirculation was observed compared to respective IR control groups. Similarly, histological damage was also reduced after levosimendan administration. This observation was supported by significantly lower activities of serum ALT (p early = 0.02; p late = 0.005), AST (p early = 0.02; p late = 0.004) and less DNA damage by TUNEL test (p early = 0.05; p late = 0.034) and PAR positivity (p early = 0.02; p late = 0.04). Levosimendan pretreatment resulted in significant improvement of liver redox homeostasis. Further, significantly better mitochondrial function was detected in animals receiving late pretreatment. Finally, HSP72 expression was increased by IR injury, but it was not affected by levosimendan pretreatment. Levosimendan pretreatment can be hepatoprotective and it could be useful before extensive liver resection.

Postconditioning of the small intestine: which is the most effective algorithm in a rat model?

PubMed

Rosero, Oliver; Onody, Peter; Stangl, Rita; Turoczi, Zsolt; Fulop, Andras; Garbaisz, David; Lotz, Gabor; Harsanyi, Laszlo; Szijarto, Attila

2014-04-01

Mesenteric ischemia is a serious clinical condition requiring immediate surgical intervention. The unavoidable ischemic-reperfusion (IR) injury may be ameliorated using the appropriate postconditioning protocol. The aim of the present study was to investigate the optimal postconditioning algorithm in a rat model of intestinal ischemic-reperfusion injury. Male Wistar rats were randomized into five groups (n = 10), one sham-operated, one IR, and three postconditioned groups, each with different protocols. The animals were subjected to 60 min of mesenteric ischemia, followed by 60 min of reperfusion. Postconditioning was applied at the onset of reperfusion using three different algorithms. Arterial pressure and mucosal microcirculation were monitored throughout the experiment. Mesenteric pH was determined at the early phase of reperfusion. Blood and tissue samples were taken at the end of reperfusion for histologic evaluation, serum lactate dehydrogenase, serum creatine kinase, serum tumor necrosis factor-α, serum interleukin-6, detailed mucosal antioxidant, and scavenger capacity assays. The shorter and intermediate length cycles of postconditioning enhanced mucosal microcirculation and redox state and significantly delayed the normalization of mesenteric pH. Furthermore, milder histopathologic lesions and lower concentrations of serum necroenzymes and proinflammatory cytokines were detected compared with the IR group. The protective effect of postconditioning using longer cycles could only be seen in a tendentious manner. In a rat model of intestinal ischemia-reperfusion, the shorter and intermediate length cycles of postconditioning proved to be more effective than the use of longer cycles. Copyright © 2014 Elsevier Inc. All rights reserved.

In-line filtration minimizes organ dysfunction: new aspects from a prospective, randomized, controlled trial.

PubMed

Boehne, Martin; Jack, Thomas; Köditz, Harald; Seidemann, Kathrin; Schmidt, Florian; Abura, Michaela; Bertram, Harald; Sasse, Michael

2013-02-06

Infused particles induce thrombogenesis, impair microcirculation and modulate immune response. We have previously shown in critically ill children, that particle-retentive in-line filtration reduced the overall complication rate of severe events, length of stay and duration of mechanical ventilation. We now evaluated the influence of in-line filtration on different organ function and thereby elucidated the potential underlying pathophysiological effects of particle infusion. In this single-centre, prospective, randomized controlled trial 807 critically ill children were assigned to either control (n = 406) or filter group (n = 401), the latter receiving in-line filtration for complete infusion therapy. Both groups were compared regarding the differences of incidence rates and its 95% confidence interval (CI) of different organ dysfunction as defined by the International Pediatric Sepsis Consensus Conference 2005. The incidence rates of respiratory (-5.06%; 95% CI, -9.52 to -0.59%), renal (-3.87%; 95% CI, -7.58 to -0.15%) and hematologic (-3.89%; 95% CI, -7.26 to -0.51%) dysfunction were decreased in the filter group. No difference was demonstrated for the occurrence rates of cardiovascular, hepatic, or neurologic dysfunction between both groups. In-line filtration has beneficial effects on the preservation of hematologic, renal and respiratory function in critically ill patients. The presented clinical data further support our hypothesis regarding potential harmful effects of particles. In critically ill patients infused particles may lead to further deterioration of the microcirculation, induce a systemic hypercoagulability and inflammation with consecutive negative effects on organ function. ClinicalTrials.gov number; NCT00209768.

Gravitational effects on global hemodynamics in different postures: A closed-loop multiscale mathematical analysis

NASA Astrophysics Data System (ADS)

Zhang, Xiancheng; Noda, Shigeho; Himeno, Ryutaro; Liu, Hao

2017-06-01

We present a novel methodology and strategy to predict pressures and flow rates in the global cardiovascular network in different postures varying from supine to upright. A closed-loop, multiscale mathematical model of the entire cardiovascular system (CVS) is developed through an integration of one-dimensional (1D) modeling of the large systemic arteries and veins, and zero-dimensional (0D) lumped-parameter modeling of the heart, the cardiac-pulmonary circulation, the cardiac and venous valves, as well as the microcirculation. A versatile junction model is proposed and incorporated into the 1D model to cope with splitting and/or merging flows across a multibranched junction, which is validated to be capable of estimating both subcritical and supercritical flows while ensuring the mass conservation and total pressure continuity. To model gravitational effects on global hemodynamics during postural change, a robust venous valve model is further established for the 1D venous flows and distributed throughout the entire venous network with consideration of its anatomically realistic numbers and locations. The present integrated model is proven to enable reasonable prediction of pressure and flow rate waveforms associated with cardiopulmonary circulation, systemic circulation in arteries and veins, as well as microcirculation within normal physiological ranges, particularly in mean venous pressures, which well match the in vivo measurements. Applications of the cardiovascular model at different postures demonstrate that gravity exerts remarkable influence on arterial and venous pressures, venous returns and cardiac outputs whereas venous pressures below the heart level show a specific correlation between central venous and hydrostatic pressures in right atrium and veins.

In-vivo assessment of microvascular functional dynamics by combination of cmOCT and wavelet transform

NASA Astrophysics Data System (ADS)

Smirni, Salvatore; MacDonald, Michael P.; Robertson, Catherine P.; McNamara, Paul M.; O'Gorman, Sean; Leahy, Martin J.; Khan, Faisel

2018-02-01

The cutaneous microcirculation represents an index of the health status of the cardiovascular system. Conventional methods to evaluate skin microvascular function are based on measuring blood flow by laser Doppler in combination with reactive tests such as post-occlusive reactive hyperaemia (PORH). Moreover, the spectral analysis of blood flow signals by continuous wavelet transform (CWT) reveals nonlinear oscillations reflecting the functionality of microvascular biological factors, e.g. endothelial cells (ECs). Correlation mapping optical coherence tomography (cmOCT) has been previously described as an efficient methodology for the morphological visualisation of cutaneous micro-vessels. Here, we show that cmOCT flow maps can also provide information on the functional components of the microcirculation. A spectral domain optical coherence tomography (SD-OCT) imaging system was used to acquire 90 sequential 3D OCT volumes from the forearm of a volunteer, while challenging the micro-vessels with a PORH test. The volumes were sampled in a temporal window of 25 minutes, and were processed by cmOCT to obtain flow maps at different tissue depths. The images clearly show changes of flow in response to the applied stimulus. Furthermore, a blood flow signal was reconstructed from cmOCT maps intensities to investigate the microvascular nonlinear dynamics by CWT. The analysis revealed oscillations changing in response to PORH, associated with the activity of ECs and the sympathetic innervation. The results demonstrate that cmOCT may be potentially used as diagnostic tool for the assessment of microvascular function, with the advantage of also providing spatial resolution and structural information compared to the traditional laser Doppler techniques.

Dynamic change in cerebral microcirculation and focal cerebral metabolism in experimental subarachnoid hemorrhage in rabbits.

PubMed

Song, Jin-Ning; Chen, Hu; Zhang, Ming; Zhao, Yong-Lin; Ma, Xu-Dong

2013-03-01

Regional cerebral blood flow (rCBF) in the cerebral metabolism and energy metabolism measurements can be used to assess blood flow of brain cells and to detect cell activity. Changes of rCBF in the cerebral microcirculation and energy metabolism were determined in an experimental model of subarachnoid hemorrhage (SAH) model in 56 large-eared Japanese rabbits about 12 to 16-month old. Laser Doppler flowmetry was used to detect the blood supply to brain cells. Internal carotid artery and vein blood samples were used for duplicate blood gas analysis to assess the energy metabolism of brain cells. Cerebral blood flow (CBF) was detected by single photon emission computed tomography (SPECT) perfusion imaging using Tc-99m ethyl cysteinate dimer (Tc-99m ECD) as an imaging reagent. The percentage of injected dose per gram of brain tissue was calculated and analyzed. There were positive correlations between the percentage of radionuclide injected per gram of brain tissue and rCBF supply and cerebral metabolic rate for oxygen (P < 0.05). However, there was a negative correlation between radioactivity counts per unit volume detected on the SPECT rheoencephalogram and lactic acid concentration in the homolateral internal carotid artery and vein. In summary, this study found abnormal CBF in metabolism and utilization of brain cells after SAH, and also found that deterioration of energy metabolism of brain cells played a significant role in the development of SAH. There are matched reductions in CBF and metabolism. Thus, SPECT imaging could be used as a noninvasive method to detect CBF.

Renoprotective effects of hepatocyte growth factor in the stenotic kidney

PubMed Central

Stewart, Nicholas

2013-01-01

Renal microvascular (MV) damage and loss contribute to the progression of renal injury in renal artery stenosis (RAS). Hepatocyte growth factor (HGF) is a powerful angiogenic and antifibrotic cytokine that we showed to be decreased in the stenotic kidney. We hypothesized that renal HGF therapy will improve renal function mainly by protecting the renal microcirculation. Unilateral RAS was induced in 15 pigs. Six weeks later, single-kidney RBF and GFR were quantified in vivo using multidetector computed tomography (CT). Then, intrarenal rh-HGF or vehicle was randomly administered into the stenotic kidney (RAS, n = 8; RAS+HGF, n = 7). Pigs were observed for 4 additional weeks before CT studies were repeated. Renal MV density was quantified by 3D micro-CT ex vivo and histology, and expression of angiogenic and inflammatory factors, apoptosis, and fibrosis was determined. HGF therapy improved RBF and GFR compared with vehicle-treated pigs. This was accompanied by improved renal expression of angiogenic cytokines (VEGF, p-Akt) and tissue-healing promoters (SDF-1, CXCR4, MMP-9), reduced MV remodeling, apoptosis, and fibrosis, and attenuated renal inflammation. However, HGF therapy did not improve renal MV density, which was similarly reduced in RAS and RAS+HGF compared with controls. Using a clinically relevant animal model of RAS, we showed novel therapeutic effects of a targeted renal intervention. Our results show distinct actions on the existing renal microcirculation and promising renoprotective effects of HGF therapy in RAS. Furthermore, these effects imply plasticity of the stenotic kidney to recuperate its function and underscore the importance of MV integrity in the progression of renal injury in RAS. PMID:23269649

The margination propensity of spherical particles for vascular targeting in the microcirculation

PubMed Central

Gentile, Francesco; Curcio, Antonio; Indolfi, Ciro; Ferrari, Mauro; Decuzzi, Paolo

2008-01-01

The propensity of circulating particles to drift laterally towards the vessel walls (margination) in the microcirculation has been experimentally studied using a parallel plate flow chamber. Fluorescent polystyrene particles, with a relative density to water of just 50 g/cm3comparable with that of liposomal or polymeric nanoparticles used in drug delivery and bio-imaging, have been used with a diameter spanning over three order of magnitudes from 50 nm up to 10 μm. The number n∼s of particles marginating per unit surface have been measured through confocal fluorescent microscopy for a horizontal chamber, and the corresponding total volume V∼s of particles has been calculated. Scaling laws have been derived as a function of the particle diameter d. In horizontal capillaries, margination is mainly due to the gravitational force for particles with d > 200 nm and V∼s increases with d4; whereas for smaller particles V∼s increases with d3. In vertical capillaries, since the particles are heavier than the fluid they would tend to marginate towards the walls in downward flows and towards the center in upward flows, with V∼s increasing with d9/2. However, the margination in vertical capillaries is predicted to be much smaller than in horizontal capillaries. These results suggest that, for particles circulating in an external field of volume forces (gravitation or magnetic), the strategy of using larger particles designed to marginate and adhere firmly to the vascular walls under flow could be more effective than that of using particles sufficiently small (d < 200 nm) to hopefully cross a discontinuous endothelium. PMID:18702833

The VO(2)-on kinetics in constant load exercise sub-anaerobic threshold reflects endothelial function and dysfunction in muscle microcirculation.

PubMed

Maione, D; Cicero, A Fg; Bacchelli, S; Cosentino, E R; Degli Esposti, D; Manners, D N; Rinaldi, E R; Rosticci, M; Senaldi, R; Ambrosioni, E; Borghi, C

2015-01-01

To propose a test to evaluate endothelial function, based on VO(2) on-transition kinetics in sub-anaerobic threshold (AT) constant load exercise, we tested healthy subjects and patients with ischemic-hypertensive cardiopathy by two cardiopulmonary tests on a cycle ergometer endowed with an electric motor to overcome initial inertia: a pre-test and, after at least 24 h, one 6 min constant load exercise at 90 % AT. We measured net phase 3 VO(2)-on kinetics and, by phase 2 time constant (tau), valued endothelial dysfunction. We found shorter tau in repeated tests, shorter time between first and second test, by persisting endothelium-dependent arteriolar vasodilatation and/or several other mechanisms. Reducing load to 80 % and 90 % AT did not produce significant changes in tau of healthy volunteers, while in heart patients an AT load of 70 %, compared to 80 % AT, shortened tau (delta=4.38+/-1.65 s, p=0.013). In heart patients, no correlation was found between NYHA class, ejection fraction (EF), and the two variables derived from incremental cycle cardio-pulmonary exercise, as well as between EF and tau; while NYHA class groups were well correlated with tau duration (r=0.92, p=0.0001). Doxazosin and tadalafil also significantly reduced tau. In conclusion, the O(2) consumption kinetics during the on-transition of constant load exercise below the anaerobic threshold are highly sensitive to endothelial function in muscular microcirculation, and constitute a marker for the evaluation of endothelial dysfunction.

An animal model for the analysis of cochlear blood flow [corrected] disturbance and hearing threshold in vivo.

PubMed

Canis, Martin; Arpornchayanon, Warangkana; Messmer, Catalina; Suckfuell, Markus; Olzowy, Bernhard; Strieth, Sebastian

2010-02-01

Impairment of cochlear blood flow (CBF) is considered to be important in inner ear pathology. However, direct measurement of CBF is difficult and has not been investigated in combination with hearing function. Six guinea pigs were used to show feasibility of an animal model for the analysis of cochlear microcirculation by intravital microscopy in combination with investigation of the hearing threshold by brainstem response audiometry (ABR). By the application of sodium nitroprusside (SNP), CBF was increased over 30 min. Reproducibility of measurements was shown by retest measurements. Mean baseline velocity of CBF was 109 +/- 19 mum/s. Vessel diameters had a mean value of 9.4 +/- 2.7 mum. Mean hearing threshold was 19 +/- 6 dB. In response to SNP, CBF velocity increased significantly to 161 +/- 26 mum/s. Mean arterial pressure decreased significantly to 36 +/- 11 mmHg. After the end of the application, CBF velocity recovered to a minimum of 123 +/- 17 microm/s. Within the retest, CBF velocity significantly increased to a maximum of 160 +/- 31 microm/s. Second recovery of CBF velocity was 125 +/- 14 mum/s. Within the second retest, CBF increased significantly to 157 +/- 25 microm/s. ABR thresholds did not change significantly. The increase in blood flow velocity occurred in spite of substantial hypotension as induced by a vasodilator. This may explain the fact that ABR threshold remained unchanged reflecting a maintained blood supply in this part of the brain. This technique can be used to evaluate effects of treatments aimed at cochlear microcirculation in inner ear pathologies.

The melanocortin MC1 receptor agonist BMS-470539 inhibits leucocyte trafficking in the inflamed vasculature

PubMed Central

Leoni, G; Voisin, M-B; Carlson, K; Getting, SJ; Nourshargh, S; Perretti, M

2010-01-01

Background and purpose: Over three decades of research evaluating the biology of melanocortin (MC) hormones and synthetic peptides, activation of the MC type 1 (MC1) receptor has been identified as a viable target for the development of novel anti-inflammatory therapeutic agents. Here, we have tested a recently described selective agonist of MC1 receptors, BMS-470539, on leucocyte/post-capillary venule interactions in murine microvascular beds. Experimental approach: Intravital microscopy of two murine microcirculations were utilized, applying two distinct modes of promoting inflammation. The specificity of the effects of BMS-470539 was assessed using mice bearing mutant inactive MC1 receptors (the recessive yellow e/e colony). Key results: BMS-470539, given before an ischaemia–reperfusion protocol, inhibited cell adhesion and emigration with no effect on cell rolling, as assessed 90 min into the reperfusion phase. These properties were paralleled by inhibition of tissue expression of both CXCL1 and CCL2. Confocal investigations of inflamed post-capillary venules revealed immunostaining for MC1 receptors on adherent and emigrated leucocytes. Congruently, the anti-inflammatory properties of BMS-470539 were lost in mesenteries of mice bearing the inactive mutant MC1 receptors. Therapeutic administration of BMS-470539 stopped cell emigration, but did not affect cell adhesion in the cremasteric microcirculation inflamed by superfusion with platelet-activating factor. Conclusions and implications: Activation of MC1 receptors inhibited leucocyte adhesion and emigration. Development of new chemical entities directed at MC1 receptors could be a viable approach in the development of novel anti-inflammatory therapeutic agents with potential application to post-ischaemic conditions. PMID:20331604

Ascorbic acid prevents vascular dysfunction induced by oral glucose load in healthy subjects.

PubMed

De Marchi, Sergio; Prior, Manlio; Rigoni, Anna; Zecchetto, Sara; Rulfo, Fanny; Arosio, Enrico

2012-01-01

To examine the effects of oral glucose load on forearm circulatory regulation before and after ascorbic acid administration in healthy subjects. Microcirculation study with laser Doppler was performed at the hand in basal conditions, after ischemia and after acetylcholine and nitroprusside; strain gauge plethysmography was performed at basal and after ischemia. The tests were repeated in the same sequence 2 hour after oral administration of glucose (75 g). The subjects were randomised for administration of ascorbic acid (1 g bid) or placebo (sodium bicarbonate 1 g bid) for 10 days. After that, the tests were repeated before and after a new oral glucose load. Blood pressure and heart rate were monitored. Macrocirculatory flux, pressure values and heart rate were unvaried throughout the study. The glucose load caused a reduction in the hyperemic peak flow with laser Doppler and plethysmography; it reduced flux recovery time and hyperemic curve area after ischemia; acetylcholine elicited a minor increase in flux with laser Doppler. The response to nitroprusside was unvaried after glucose load as compared to basal conditions. Treatment with ascorbic acid prevented the decrease in hyperemia after glucose, detected with laser Doppler and plethysmography. Ascorbic acid prevented the decreased response to acetylcholine after glucose, the response to nitroprusside was unaffected by ascorbic acid. Results after placebo were unvaried. Oral glucose load impairs endothelium dependent dilation and hyperaemia at microcirculation, probably via oxidative stress; ascorbic acid can prevent it. Copyright © 2011 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Alteration of microcirculation is a hallmark of very early systemic sclerosis patients: a laser speckle contrast analysis.

PubMed

Della Rossa, Alessandra; Cazzato, Massimiliano; d'Ascanio, Anna; Tavoni, Antonio; Bencivelli, Walter; Pepe, Pasquale; Mosca, Marta; Baldini, Chiara; Rossi, Marco; Bombardieri, Stefano

2013-01-01

To investigate blood flow and microvascular reactivity by laser speckle perfusion imager (Perimed, Jarfalla) in consecutive patients affected by Raynaud's phenomenon at baseline and following dynamic stimulations. Skin blood flow in the dorsum of the hand was measured at baseline and after cold test and post-occlusive hyperemia test in 56 consecutive subjects affected by Raynaud's phenomenon (RP), 20 primary (PRP) and 36 secondary to systemic sclerosis (SSc). Twenty healthy subjects (HS) were studied as controls. After cold test, SSc had a significant reduction of blood flow (-58%) as compared to HS (-19%) (p=0.01). Recovery time was significantly higher in SSc (58 minutes) as compared to HS (18 minutes) and PRP (19 minutes) (p=0.006 and 0.0016, respectively). Peak flow after ischaemic test was significantly reduced in SSc (+237%) as compared to PRP (+485%) (p=0.0068). Post-ischaemic hyperemic area under the curve (AUC) was blunted in SSc (79U/sec) compared to PRP (167 U/sec) (p=0.0126). Proximal distal gradient was noticed in 74% of HS, 45% of PRP and 36% of SSc (p=0.01). Homogeneous pattern of flux distribution was significantly different between HS (95%), PRP (80%), and SSc (16%) (p<0.0001). Among SSc patients, a significant difference in ischaemic challenge was shown between patients with early-SSc versus patients with definite-SSc. Our preliminary results indicate a clearcut alteration of the dynamic of microcirculation in SSc-RP as compared to PRP and HS. Among SSc patients, early-SSc is a separate entity as compared to established disease.

The effect of low-level laser in knee osteoarthritis: a double-blind, randomized, placebo-controlled trial.

PubMed

Hegedus, Béla; Viharos, László; Gervain, Mihály; Gálfi, Márta

2009-08-01

Low-level laser therapy (LLLT) is thought to have an analgesic effect as well as a biomodulatory effect on microcirculation. This study was designed to examine the pain-relieving effect of LLLT and possible microcirculatory changes measured by thermography in patients with knee osteoarthritis (KOA). Patients with mild or moderate KOA were randomized to receive either LLLT or placebo LLLT. Treatments were delivered twice a week over a period of 4 wk with a diode laser (wavelength 830 nm, continuous wave, power 50 mW) in skin contact at a dose of 6 J/point. The placebo control group was treated with an ineffective probe (power 0.5 mW) of the same appearance. Before examinations and immediately, 2 wk, and 2 mo after completing the therapy, thermography was performed (bilateral comparative thermograph by AGA infrared camera); joint flexion, circumference, and pressure sensitivity were measured; and the visual analogue scale was recorded. In the group treated with active LLLT, a significant improvement was found in pain (before treatment [BT]: 5.75; 2 mo after treatment : 1.18); circumference (BT: 40.45; AT: 39.86); pressure sensitivity (BT: 2.33; AT: 0.77); and flexion (BT: 105.83; AT: 122.94). In the placebo group, changes in joint flexion and pain were not significant. Thermographic measurements showed at least a 0.5 degrees C increase in temperature--and thus an improvement in circulation compared to the initial values. In the placebo group, these changes did not occur. Our results show that LLLT reduces pain in KOA and improves microcirculation in the irradiated area.

Correction of biochemical and functional disorders in brain ischaemia with laser therapy

NASA Astrophysics Data System (ADS)

Musienko, Julia I.; Nechipurenko, Natalia I.; Vasilevskaya, Ludmila A.

2005-08-01

Application of intravenous laser irradiation of blood (ILIB) is considered to be the most effective method of laser therapy and its application is expedient pathogenetically in the ischemic disturbances. The aim of this study is to investigate ILIB influence with red helium-neon laser (HNL) with 630 nm wavelength and different powers on blood oxygen transport (BOT), cerebral and dermal microhaemodynamics (MGD), hydro-ion balance in normal rabbits and after modeling of local ischemia of brain (LIB). Experimental cerebral ischemia is characterized by development of BOT disturbance, ionic disbalance and edema in the ischemic brain region. Microcirculation disturbances with worsening of the cerebral and dermal MHD were revealed. ILIB with HNL radiation of 2.5 and 4.5 mW powers provokes dehydratation of brain structure alone with the K+, Na+ concentration decreasing and hemoglobin-oxygen affinity increasing in intact group of animals. There was not revealed marked changes of cerebral MHD condition here. Using of ILIB in rabbits after LIB contributes for improving function of BOT, normalizing of water content in all cerebral structures compared to operated animals. Preventive ILIB provoked improvement of speckl-optical parameters and marked protective effect on microhaemodynamics processes in superficial brain structures. HNL radiation with 1.0 mW power results in worsening of oxygen transport, cerebral and skin MHD, hydro-ion homeostasis in animals with LIB modeling. Thus, laser haemotherapy contributes for improving of hydro-ion status, blood oxygen transport and cerebral microcirculation in brain ischemia, what allows considering that helium-neon radiation with the pointed regimen is substantiated pathogenetically in brain ischaemia.

Microvascular flow estimation by contrast-assisted ultrasound B-scan and statistical parametric images.

PubMed

Tsui, Po-Hsiang; Yeh, Chih-Kuang; Chang, Chien-Cheng

2009-05-01

The microbubbles destruction/replenishment technique has been previously applied to estimating blood flow in the microcirculation. The rate of increase of the time-intensity curve (TIC) due to microbubbles flowing into the region of interest (ROI), as measured from B-mode images, closely reflects the flow velocity. In previous studies, we proposed a new approach called the time-Nakagami-parameter curve (TNC) obtained from Nakagami images to monitor microbubble replenishment for quantifying the microvascular flow velocity. This study aimed to further explore some effects that may affect the TNC to estimate the microflow, including microbubble concentration, ultrasound transmitting energy, attenuation, intrinsic noise, and tissue clutter. In order to well control each effect production, we applied a typical simulation method to investigate the TIC and TNC. The rates of increase of the TIC and TNC were expressed by the rate constants beta(I) and beta(N), respectively, of a monoexponential model. The results show that beta(N) quantifies the microvascular flow velocity similarly to the conventional beta(I) . Moreover, the measures of beta(I) and beta(N) are not influenced by microbubble concentration, transducer excitation energy, and attenuation effect. Although the effect of intrinsic signals contributed by noise and blood would influence the TNC behavior, the TNC method has a better tolerance of tissue clutter than the TIC does, allowing the presence of some clutter components in the ROI. The results suggest that the TNC method can be used as a complementary tool for the conventional TIC to reduce the wall filter requirements for blood flow measurement in the microcirculation.

Non-invasive assessment of cerebral microcirculation with diffuse optics and coherent hemodynamics spectroscopy

NASA Astrophysics Data System (ADS)

Fantini, Sergio; Sassaroli, Angelo; Kainerstorfer, Jana M.; Tgavalekos, Kristen T.; Zang, Xuan

2016-03-01

We describe the general principles and initial results of coherent hemodynamics spectroscopy (CHS), which is a new technique for the quantitative assessment of cerebral hemodynamics on the basis of dynamic near-infrared spectroscopy (NIRS) measurements. The two components of CHS are (1) dynamic measurements of coherent cerebral hemodynamics in the form of oscillations at multiple frequencies (frequency domain) or temporal transients (time domain), and (2) their quantitative analysis with a dynamic mathematical model that relates the concentration and oxygen saturation of hemoglobin in tissue to cerebral blood volume (CBV), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen (CMRO2). In particular, CHS can provide absolute measurements and dynamic monitoring of CBF, and quantitative measures of cerebral autoregulation. We report initial results of CBF measurements in hemodialysis patients, where we found a lower CBF (54 +/- 16 ml/(100 g-min)) compared to a group of healthy controls (95 +/- 11 ml/(100 g-min)). We also report CHS measurements of cerebral autoregulation, where a quantitative index of autoregulation (its cutoff frequency) was found to be significantly greater in healthy subjects during hyperventilation (0.034 +/- 0.005 Hz) than during normal breathing (0.017 +/- 0.002 Hz). We also present our approach to depth resolved CHS, based on multi-distance, frequency-domain NIRS data and a two-layer diffusion model, to enhance sensitivity to cerebral tissue. CHS offers a potentially powerful approach to the quantitative assessment and continuous monitoring of local brain perfusion at the microcirculation level, with prospective brain mapping capabilities of research and clinical significance.

The Place of Nailfold Capillaroscopy Among Instrumental Methods for Assessment of Some Peripheral Ischaemic Syndromes in Rheumatology.

PubMed

Lambova, Sevdalina N

2016-01-01

Micro- and macrovascular pathology is a frequent finding in a number of common rheumatic diseases. Secondary Raynaud's phenomenon (RP) is among the most common symptoms in systemic sclerosis and several other systemic autoimmune diseases including a broad differential diagnosis. It should be also differential from other peripheral vascular syndromes such as embolism, thrombosis, etc., some of which lead to clinical manifestation of the blue toe syndrome. The current review discusses the instrumental methods for vascular assessments. Nailfold capillaroscopy is the only method among the imaging techniques that can be used for morphological assessment of the nutritive capillaries in the nailfold area. Laser-Doppler flowmetry and laser-Doppler imaging are methods for functional assessment of microcirculation, while thermography and plethysmography reflect both blood flow in peripheral arteries and microcirculation. Doppler ultrasound and angiography visualize peripheral arteries. The choice of the appropriate instrumental method is guided by the clinical presentation. The main role of capillaroscopy is to provide differential diagnosis between primary and secondary RP. In rheumatology, capillaroscopic changes in systemic sclerosis have been recently defined as diagnostic. The appearance of abnormal capillaroscopic pattern inherits high positive predictive value for the development of a connective tissue disease that is higher than the predictive value of antinuclear antibodies. In cases of abrupt onset of peripheral ischaemia, clinical signs of critical ischaemia, unilateral or lower limb involvement, Doppler ultrasound and angiography are indicated. The most common causes for such clinical picture that may be referred to rheumatologic consultation are the antiphospholipid syndrome, mimickers of vasculitides such as atherosclerosis with cholesterol emboli, and neoplasms.

Effects of altitude and exercise on pulmonary capillary integrity: evidence for subclinical high-altitude pulmonary edema.

PubMed

Eldridge, Marlowe W; Braun, Ruedi K; Yoneda, Ken Y; Walby, William F

2006-03-01

Strenuous exercise may be a significant contributing factor for development of high-altitude pulmonary edema, particularly at low or moderate altitudes. Thus we investigated the effects of heavy cycle ergometer exercise (90% maximal effort) under hypoxic conditions in which the combined effects of a marked increase in pulmonary blood flow and nonuniform hypoxic pulmonary vasoconstriction could add significantly to augment the mechanical stress on the pulmonary microcirculation. We postulated that intense exercise at altitude would result in an augmented permeability edema. We recruited eight endurance athletes and examined their bronchoalveolar lavage fluid (BALF) for red blood cells (RBCs), protein, inflammatory cells, and soluble mediators at 2 and 26 h after intense exercise under normoxic and hypoxic conditions. After heavy exercise, under all conditions, the athletes developed a permeability edema with high BALF RBC and protein concentrations in the absence of inflammation. We found that exercise at altitude (3,810 m) caused significantly greater leakage of RBCs [9.2 (SD 3.1)x10(4) cells/ml] into the alveolar space than that seen with normoxic exercise [5.4 (SD 1.2)x10(4) cells/ml]. At altitude, the 26-h postexercise BALF revealed significantly higher RBC and protein concentrations, suggesting an ongoing capillary leak. Interestingly, the BALF profiles following exercise at altitude are similar to that of early high-altitude pulmonary edema. These findings suggest that pulmonary capillary disruption occurs with intense exercise in healthy humans and that hypoxia augments the mechanical stresses on the pulmonary microcirculation.

Effects of n-3 polyunsaturated fatty acids and vitamin E on colonic mucosal leukotriene generation, lipid peroxidation, and microcirculation in rats with experimental colitis.

PubMed

Shimizu, T; Igarashi, J; Ohtuka, Y; Oguchi, S; Kaneko, K; Yamashiro, Y

2001-01-01

We investigated the effect of n-3 polyunsaturated fatty acids (PUFAs) on mucosal levels of leukotrienes (LTs) and lipid peroxide (LPO), and on mucosal microcirculation, in rats with experimental colitis induced by dextran sulfate sodium (DSS). We fed Wistar rats a perilla oil-enriched diet containing alpha-linolenic acid (63.2% of total fatty acids) with various doses of vitamin E for 4 weeks, with 4% DSS added to the drinking water during the last week. Control rats were fed a diet produced from soybean oil containing alpha-linolenic acid (5.1% of total fatty acids). Colonic mucosal blood flow was measured with a laser Doppler flowmeter. The mucosal level of arachidonic acid was significantly lower and that of eicosapentaenoic acid was significantly higher in the experimental group. The mucosal level of LPO in the experimental group fed a trace or ordinary dose of vitamin E was significantly higher than that of the controls. The production of LTB(4) and LTC(4) from the colonic mucosa in the experimental group was significantly lower than that in controls. However, only the experimental group fed a vitamin E dose 4-fold higher than that given to the controls showed a significant increase in mucosal blood flow. These results suggest that n-3 PUFAs increase mucosal blood flow by inhibiting LT production when there is sufficient vitamin E to inhibit lipid peroxidation in rats with experimental colitis. Copyright 2001 S. Karger AG, Basel

Activation of GLP-1 receptors on vascular smooth muscle cells reduces the autoregulatory response in afferent arterioles and increases renal blood flow.

PubMed

Jensen, Elisa P; Poulsen, Steen S; Kissow, Hannelouise; Holstein-Rathlou, Niels-Henrik; Deacon, Carolyn F; Jensen, Boye L; Holst, Jens J; Sorensen, Charlotte M

2015-04-15

Glucagon-like peptide (GLP)-1 has a range of extrapancreatic effects, including renal effects. The mechanisms are poorly understood, but GLP-1 receptors have been identified in the kidney. However, the exact cellular localization of the renal receptors is poorly described. The aim of the present study was to localize renal GLP-1 receptors and describe GLP-1-mediated effects on the renal vasculature. We hypothesized that renal GLP-1 receptors are located in the renal microcirculation and that activation of these affects renal autoregulation and increases renal blood flow. In vivo autoradiography using (125)I-labeled GLP-1, (125)I-labeled exendin-4 (GLP-1 analog), and (125)I-labeled exendin 9-39 (GLP-1 receptor antagonist) was performed in rodents to localize specific GLP-1 receptor binding. GLP-1-mediated effects on blood pressure, renal blood flow (RBF), heart rate, renin secretion, urinary flow rate, and Na(+) and K(+) excretion were investigated in anesthetized rats. Effects of GLP-1 on afferent arterioles were investigated in isolated mouse kidneys. Specific binding of (125)I-labeled GLP-1, (125)I-labeled exendin-4, and (125)I-labeled exendin 9-39 was observed in the renal vasculature, including afferent arterioles. Infusion of GLP-1 increased blood pressure, RBF, and urinary flow rate significantly in rats. Heart rate and plasma renin concentrations were unchanged. Exendin 9-39 inhibited the increase in RBF. In isolated murine kidneys, GLP-1 and exendin-4 significantly reduced the autoregulatory response of afferent arterioles in response to stepwise increases in pressure. We conclude that GLP-1 receptors are located in the renal vasculature, including afferent arterioles. Activation of these receptors reduces the autoregulatory response of afferent arterioles to acute pressure increases and increases RBF in normotensive rats. Copyright © 2015 the American Physiological Society.

Ambient Air Pollution Exaggerates Adipose Inflammation and Insulin Resistance in a Mouse Model of Diet-Induced Obesity

PubMed Central

Sun, Qinghua; Yue, Peibin; Deiuliis, Jeffrey A.; Lumeng, Carey N.; Kampfrath, Thomas; Mikolaj, Michael B.; Cai, Ying; Ostrowski, Michael C.; Lu, Bo; Parthasarathy, Sampath; Brook, Robert D.; Moffatt-Bruce, Susan D.; Chen, Lung Chi; Rajagopalan, Sanjay

2009-01-01

Background There is a strong link between urbanization and type 2 diabetes mellitus. Although a multitude of mechanisms have been proposed, there are no studies evaluating the impact of ambient air pollutants and the propensity to develop type 2 diabetes mellitus. We hypothesized that exposure to ambient fine particulate matter (<2.5 μm; PM2.5) exaggerates diet-induced insulin resistance, adipose inflammation, and visceral adiposity. Methods and Results Male C57BL/6 mice were fed high-fat chow for 10 weeks and randomly assigned to concentrated ambient PM2.5 or filtered air (n=14 per group) for 24 weeks. PM2.5-exposed C57BL/6 mice exhibited marked whole-body insulin resistance, systemic inflammation, and an increase in visceral adiposity. PM2.5 exposure induced signaling abnormalities characteristic of insulin resistance, including decreased Akt and endothelial nitric oxide synthase phosphorylation in the endothelium and increased protein kinase C expression. These abnormalilties were associated with abnormalities in vascular relaxation to insulin and acetylcholine. PM2.5 increased adipose tissue macrophages (F4/80+ cells) in visceral fat expressing higher levels of tumor necrosis factor-α/interleukin-6 and lower interleukin-10/N-acetyl-galactosamine specific lectin 1. To test the impact of PM2.5 in eliciting direct monocyte infiltration into fat, we rendered FVBN mice expressing yellow fluorescent protein (YFP) under control of a monocyte-specific promoter (c-fms, c-fmsYFP) diabetic over 10 weeks and then exposed these mice to PM2.5 or saline intratracheally. PM2.5 induced YFP cell accumulation in visceral fat and potentiated YFP cell adhesion in the microcirculation. Conclusion PM2.5 exposure exaggerates insulin resistance and visceral inflammation/adiposity. These findings provide a new link between air pollution and type 2 diabetes mellitus. PMID:19153269

Tissue culture on a chip: Developmental biology applications of self-organized capillary networks in microfluidic devices.

PubMed

Miura, Takashi; Yokokawa, Ryuji

2016-08-01

Organ culture systems are used to elucidate the mechanisms of pattern formation in developmental biology. Various organ culture techniques have been used, but the lack of microcirculation in such cultures impedes the long-term maintenance of larger tissues. Recent advances in microfluidic devices now enable us to utilize self-organized perfusable capillary networks in organ cultures. In this review, we will overview past approaches to organ culture and current technical advances in microfluidic devices, and discuss possible applications of microfluidics towards the study of developmental biology. © 2016 Japanese Society of Developmental Biologists.

The Impact of Negative Pressure Wound Therapy on Orthopaedic Infection.

PubMed

Webb, Lawrence X

2017-04-01

By hastening the resolution of edema and improving local microcirculation, topical negative pressure wound therapy (TNP) aids the establishment of early wound coverage. Its use in the setting of type III open fractures is reviewed. The author's initial use of TNP for closed surgical incisions and how it morphed its way into being applied to closed surgical wounds with heightened likelihood for infection is presented. Several case studies are presented to illustrate the role and the technique for management of acute or subacute infections involving bone and implant. Copyright © 2017 Elsevier Inc. All rights reserved.

Bronchial blood supply after lung transplantation without bronchial artery revascularization.

PubMed

Nicolls, Mark R; Zamora, Martin R

2010-10-01

This review discusses how the bronchial artery circulation is interrupted following lung transplantation and what may be the long-term complications of compromising systemic blood flow to allograft airways. Preclinical and clinical studies have shown that the loss of airway microcirculations is highly associated with the development of airway hypoxia and an increased susceptibility to chronic rejection. The bronchial artery circulation has been highly conserved through evolution. Current evidence suggests that the failure to routinely perform bronchial artery revascularization at the time of lung transplantation may predispose patients to develop the bronchiolitis obliterans syndrome.

Fat embolism syndrome

PubMed Central

Kwiatt, Michael E.; Seamon, Mark J.

2013-01-01

Fat embolism syndrome (FES) is an ill-defined clinical entity that arises from the systemic manifestations of fat emboli within the microcirculation. Embolized fat within capillary beds cause direct tissue damage as well as induce a systemic inflammatory response resulting in pulmonary, cutaneous, neurological, and retinal symptoms. This is most commonly seen following orthopedic trauma; however, patients with many clinical conditions including bone marrow transplant, pancreatitis, and following liposuction. No definitive diagnostic criteria or tests have been developed, making the diagnosis of FES difficult. While treatment for FES is largely supportive, early operative fixation of long bone fractures decreases the likelihood of a patient developing FES. PMID:23724388

Fat embolism syndrome.

PubMed

Kwiatt, Michael E; Seamon, Mark J

2013-01-01

Fat embolism syndrome (FES) is an ill-defined clinical entity that arises from the systemic manifestations of fat emboli within the microcirculation. Embolized fat within capillary beds cause direct tissue damage as well as induce a systemic inflammatory response resulting in pulmonary, cutaneous, neurological, and retinal symptoms. This is most commonly seen following orthopedic trauma; however, patients with many clinical conditions including bone marrow transplant, pancreatitis, and following liposuction. No definitive diagnostic criteria or tests have been developed, making the diagnosis of FES difficult. While treatment for FES is largely supportive, early operative fixation of long bone fractures decreases the likelihood of a patient developing FES.

Feasibility of Human Skin Grafts on An Isolated But Accessible Vascular Supply on Athymic Rats As a System to Study Percutaneous Penetration and Cutaneous Injury

DTIC Science & Technology

1986-06-01

percutaneous toxicity, microcirculation of skin, nude rat 20. A.LSTICIACT (Carfrguje .r r *fd It n~e"ary7 d dn"fI b , block nyrnbor) ~Te bjctve of this researc...significant differences. An..iysis of the blood flow to the flap as a function of flap age , as well as the effect of cyclosporine, demonstrated that the...particular flap on a week to week basis. This was not related to administration of cyclosporine, body temperature, or age of the flap. The variability