Capillary Velocity Research Articles

Acute insertion effects of penetrating cortical microelectrodes imaged with quantitative optical coherence angiography

.The vascular response during cortical microelectrode insertion was measured with amplitude decorrelation-based quantitative optical coherence angiography (OCA). Four different shank-style microelectrode configurations were inserted in murine motor cortex beneath a surgically implanted window in discrete steps while OCA images were collected and processed for angiography and flowmetry. Quantitative measurements included tissue displacement (measured by optical flow), perfused capillary density, and capillary flow velocity. The primary effect of insertion was mechanical perturbation, the effects of which included tissue displacement, arteriolar rupture, and compression of a branch of the anterior cerebral artery causing a global decrease in flow. Other effects observed included local flow drop-out in the region immediately surrounding the microelectrode. The mean basal capillary network velocity for all animals was 0.23 () and 0.18 () for capillaries from 100 to and 300 to , respectively. Upon insertion, the 2-shank electrode arrays caused a decrease in capillary flow density and velocity, while the results from other configurations were not different from controls. The proximity to large vessels appears to play a larger role than the array configuration. These results can guide neurosurgeons and electrode designers to minimize trauma and ischemia during microelectrode insertion.

Effect of salvianolic acid B on TNF-α induced cerebral microcirculatory changes in a micro-invasive mouse model

PurposeTo investigate the effects of salvianolic acid B (SAB) on tumor necrosis factor α (TNF-α) induced alterations of cerebral microcirculation with a bone-abrading model. MethodsThe influences of craniotomy model and bone-abrading model on cerebral microcirculation were compared. The bone-abrading method was used to detect the effects of intracerebroventricular application of 40 μg/kg·bw TNF-α on cerebral venular leakage of fluorescein isothiocyanate (FITC)-albulmin and the rolling and adhesion of leukocytes on venules with fluorescence tracer rhodamine 6G. The therapeutical effects of SAB on TNF-α induced microcirculatory alteration were observed, with continuous intravenous injection of 5 mg/kg·h SAB starting at 20 min before or 20 min after TNF-α administration, respectively. The expressions of CD11b/CD18 and CD62L in leukocytes were measured with flow cytometry. Immunohistochemical staining was also used to detect E-selectin and ICAM-1 expression in endothelial cells. ResultsCompared with craniotomy method, the bone-abrading method preserved a higher erythrocyte velocity in cerebral venules and more opening capillaries. TNF-α intervention only caused responses of vascular hyperpermeability and leukocyte rolling on venular walls, without leukocyte adhesion and other hemodynamic changes. Pre- or post-SAB treatment attenuated those responses and suppressed the enhanced expressions of CD11b/CD18 and CD62L in leukocytes and E-selectin and ICAM-1 in endothelial cells induced by TNF-α. ConclusionsThe pre- and post-applications of SAB during TNF-α stimulation could suppress adhesive molecular expression and subsequently attenuate the increase of cerebral vascular permeability and leukocyte rolling.

Improvement of Impaired Cerebral Microcirculation Using Rheological Modulation by Drag-Reducing Polymers.

Nanomolar intravascular concentrations of drag-reducing polymers (DRP) have been shown to improve hemodynamics and survival in animal models of ischemic myocardium and limb, but the effects of DRP on the cerebral microcirculation have not yet been studied. We recently demonstrated that DRP enhance microvascular flow in normal rat brain and hypothesized that it would restore impaired microvascular perfusion and improve outcomes after focal ischemia and traumatic brain injury (TBI). We studied the effects of DRP (high molecular weight polyethylene oxide, 4000 kDa, i.v. at 2 μg/mL of blood) on microcirculation of the rat brain: (1) after permanent middle cerebral artery occlusion (pMCAO); and (2) after TBI induced by fluid percussion. Using in vivo two-photon laser scanning microscopy (2PLSM) over the parietal cortex of anesthetized rats we showed that both pMCAO and TBI resulted in progressive decrease in microvascular circulation, leading to tissue hypoxia (NADH increase) and increased blood brain barrier (BBB) degradation. DRP, injected post insult, increased blood volume flow in arterioles and red blood cell (RBC) flow velocity in capillaries mitigating capillary stasis, tissue hypoxia and BBB degradation, which improved neuronal survival (Fluoro-Jade B, 24 h) and neurologic outcome (Rotarod, 1 week). Improved microvascular perfusion by DRP may be effective in the treatment of ischemic stroke and TBI.

Quantitative imaging of microvascular blood flow networks in deep cortical layers by 1310 nm μODT.

There is growing interest in new neuroimage techniques that permit not only high-resolution quantification of cerebral blood flow velocity (CBFv) in capillaries, but also a large field of view to map the CBFv network dynamics. Such image capabilities are of great importance for decoding the functional difference across multiple cortical layers under stimuli. To tackle the limitation of optical penetration depth, we present a new ultrahigh-resolution optical coherence Doppler tomography (μODT) system at 1310 nm and compare it with a prior 800 nm μODT system for mouse brain 3D CBFv imaging. We show that the new 1310 nm μODT allows for dramatically increased depth (∼4 times) of quantitative CBFv imaging to 1.4 mm, thus covering the full thickness of the mouse cortex (i.e., layers I-VI). Interestingly, we show that such a unique 3D CBFv imaging capability allows identification of microcirculatory redistribution across different cortical layers resulting from repeated cocaine exposures.

Investigation of poly(styrene-divinylbenzene-vinylsulfonic acid) as retentive and electroosmotic flow generating phase in open-tubular electrochromatography

In this work, a new sulfonated polystyrene based porous layer was synthesized on the wall of a capillary by a single step in situ polymerization process. To obtain a capillary suited for electrochromatography, vinylsulfonic acid (VSA) was, next to divinylbenzene (DVB), copolymerized to induce charges for the electroosmotic flow (EOF) generation. The VSA ratio in the monomer mixture and the polymerization time were optimized while the chromatographic characteristics of the obtained open tubular columns were investigated in electrochromatography. To allow unambiguous study of only chromatographic processes, evaluations were performed with a mixture of sufficiently retained and electrophoretically neutral parabens. Comparison of SEM pictures and chromatograms revealed that the polymerization time had a great influence on the polymer layer morphology and on the chromatographic performance. An increase in the VSA ratio, led to an increase in the mobile phase velocity but simultaneously lowered paraben retention. The novel optimized stationary phase could generate a stable and significant electro-osmotic flow (EOF) of 1.1mm/s over a wide pH range which could be produced in a reproducible manner. Minimal plate heights of 10μm, equivalent to the capillary internal diameter, were obtained. The open-tubular character of this optimized porous layer column allowed successful analyses at elevated temperature, resulting in a maximum efficiency of 85,500 plates for a 75cm capillary and linear velocities up to 1.4mm/s. Finally, a thermal gradient was successfully applied, leading to artificial sharpened peaks with a peak capacity of 55 in a 20min time span.

Abstract 219: Activity-Dependent Capillary Hyperemia in The Brain Is Not Regulated by Pericytes

Activity-dependent increases in blood flow comprise the basis for functional brain imaging and are considered a hallmark of normal brain function. The central dogma of blood flow regulation states that flow changes effected by arteriolar tone drive functional hyperemia and that the capillary bed is a passive conduit for hyperemia resulting from upstream vasodilation. Recent evidence has begun to challenge this convention in cerebral blood flow control and suggests that pericytes may dilate capillaries during functional hyperemia, but whether pericytes can regulate flow of individual red blood cells (RBCs) through capillaries during sensory stimulation is unknown. Using high-speed two-photon microscopy in a live mouse model, we document that increases in RBC flow velocity and RBC flux through capillaries were detected within 1.0 second after sensory stimulation, and that the observed activity-evoked capillary hyperemia did not depend on the presence of a pericyte. We further report that local application of vasorelaxants shown to relax pericytes ex vivo did not alter resting RBC velocity in capillaries in vivo and did not affect sensory stimulation-evoked capillary RBC velocity increases. These findings support the hypothesis that cerebral capillary hyperemia occurs rapidly after sensory input, but fail to provide evidence for dynamic pericyte-dependent regulation of capillary functional hyperemia during brain activation. These results provide novel insight into the fundamental mechanisms underlying brain capillary blood flow regulation and have significant implications for targeting the disruption of cerebral microvascular blood flow characteristic of ischemic and hemorrhagic strokes.

Rapid manufacture of modifiable 2.5-dimensional (2.5D) microstructures for capillary force-driven fluidic velocity control

2.5D multilevel microchannel as thin as 500 μm is fabricated through multi-layer-tape lithography. Capillary force-driven flow velocity increases from 0.03 μL s−1 to 0.39 μL s−1 as multilevel microchannel height increases from 100 μm to 400 μm.

Dynamics of Collapse of Free Surface Bubbles

We experimentally study the collapse of cavities formedby bubbles of different radius R at the free surface of five different fluids. The tangential and normal velocities of the disturbance front on the bubble surface were measured andshown that the tangential velocities scale as the capillary velocity (σ/ρR)1/2. The total time for the completion of cavity collapse was measured and shown to scale as capillary time scale R3/2/(σ/ρ)1/2. We hence infer thatthe cavity collapse is dominated by surface tension and inertia with viscosity not playing a role in the regime of our investigation. Such a behavior of cavity dynamics is different from the behavior of jet velocity discussed by Sangeeth et.al.[9] wherein the jet velocity showed a clear viscous cut off. The rate of change of cavity volume was found to be constant with time, the implications of which needs to be investigated further.

Effects of radiographic contrast media on the micromorphology of the junctional complex of erythrocytes visualized by immunocytology.

Effects of radiographic contrast media (RCM) application were demonstrated in vitro and in vivo where the injection of RCM into the A. axillaris of patients with coronary artery disease was followed by a significant and RCM-dependent decrease of erythrocyte velocity in downstream skin capillaries. Another study in pigs revealed that the deceleration of erythrocytes coincided with a significant reduction of the oxygen partial pressure in the myocardium—supplied by the left coronary artery—after the administration of RCM into this artery. Further reports showed RCM dependent alterations of erythrocytes like echinocyte formation and exocytosis, sequestration of actin or band 3 and the buckling of endothelial cells coinciding with a formation of interendothelial fenestrations leading to areas devoid of endothelial cells. Key to morphological alterations of erythrocytes is the membrane cytoskeleton, which is linked to the band 3 in the erythrocyte membrane via the junctional complex. Fundamental observations regarding the cell biological and biochemical aspects of the structure and function of the cell membrane and the membrane cytoskeleton of erythrocytes have been reported. This review focuses on recent results gained, e.g., by advanced confocal laser scanning microscopy of different double-stained structural elements of the erythrocyte membrane cytoskeleton.

High-speed video analysis for kink formation in a bond wire looping

• An experimental study on bond wire looping by using high-speed video analysis was presented. • The video data shows that capillary velocity, trajectory position and the position of kinks. • The tool’s transverse move in its zigzag motion phase is a necessary step to create kinks. • Capillary nozzle applies small and localized moment to the segment of fresh wire to create a new kink. • The residual curvature of kinks would be major target for wire looping design.

In Vivo Two‐photon Fluorescence Microscopy Reveals Disturbed Cerebral Capillary Blood Flow and Increased Susceptibility to Ischemic Insults in Diabetic Mice

Diabetes mellitus increases the risk of stroke, but the mechanisms are unclear. The present study tested the hypothesis that diabetes mellitus disturbs the brain microcirculation and increases the susceptibility to cerebral damage in a middle cerebral artery occlusion (MCAO) model of ischemia. Diabetes was induced by streptozocin in mice expressing green fluorescent protein in endothelial cells (Tie2-GFP mice). Four weeks later, they were subjected to transient (20min) MCAO. In vivo blood flow was measured by two-photon laser-scanning microscopy (TPLSM) in cerebral arteries, veins, and capillaries. There was a significant decrease in red blood cell (RBC) velocity in capillaries in diabetic mice as assessed by TPLSM, yet the regional cerebral blood flow, as assessed by laser Doppler flowmetry, was maintained. Brain capillary flow developed turbulence after MCAO only in diabetic mice. These mice sustained increased neurological deficits after MCAO which were accompanied by an exaggerated degradation of tight junction proteins and blunted CaMKII phosphorylation in cerebral tissues indicating disruption of the blood-brain barrier and disturbed cognitive potential. Diabetic mice are more susceptible to disturbances of cerebral capillary blood flow which may predispose them to neurovascular defects following ischemia.

Visualization experiments on extrudate swell behavior at the microscale

Extrudate swell exerts a significant impact on the shape and dimensional accuracy of extruded products. It is one of the important factors to be considered when designing the extrusion die and controlling the quality of products. The die swell ratio (B) is used to evaluate the degree of extrudate swell. In this article, comparative experiments were performed in order to simulate and observe in a precise fashion the extrudate swell behavior of carboxymethyl cellulose solution at a microscale by means of a visualization device. We chose micro dies capillaries where the inner diameter was in the range of 0.1–0.5 mm. The effects of capillary geometry, entrance velocity, and shear rate (shear stress) on extrudate swell were investigated. The results indicated that shear rate (shear stress) increases and the value of B is enhanced with decreasing capillary diameter under the same capillary entrance velocity. At different entrance velocities, the die swell behavior from 0.3- to 0.5-mm-diameter capillaries was similar to that of conventional ones, and the value of B increased with increasing shear rate. Additionally, the extrudate swell from the 0.2-mm-diameter capillaries revealed a decline, whereas that from the 0.1-mm-diameter capillaries first diminished and then increased concomitantly with rising shear rate. We expect that this was due to wall slip that occurred analytically in our micro channel.

Физическое представление и расчет начала кипения в пульсационной тепловой трубе

LED development is accompanied by the need to ensure a constructive solution for the thermal conditions problem. For this purpose one can use pulsating heat pipes (PHP), that operate more efficiently after the start of heat carrier boiling. This article describes the physical representation and formula that allows determining the boiling point, which is a lower bound of the PHP effective operating range. It is shown that the main factors influencing the required heat flow are driving capillary pressure and velocity of the vapor bubble. The formula was obtained for the closed PHP made of the copper with water as a heat carrier. Information about this heat flux can be used for further design of cooling systems for heat-sensitive elements, such as LED for promising lighting devices.

Abstract 93: In Vivo Two-photon Fluorescence Microscopy Reveals Disturbed Cerebral Capillary Blood Flow and Increased Susceptibility to Ischemic Insults in Diabetic Mice

Background: Diabetes imposes an increased risk of microvascular complications. The present study aims to evaluate if diabetes and its disturbances in brain blood microcirculation increases the susceptibility to brain ischemic insults. Methods and Results: Diabetes was induced by streptozocin in mice expressing green fluorescent protein in endothelial cells (Tie2-GFP mice). Four weeks later the diabetic mice were subjected to transient (20 min) middle cerebral artery occlusion (MCAO). In vivo two-photon laser scanning microscopy (TPLSM) was applied to the brains of the mice, and blood flow was estimated in arteries, capillaries and veins in diabetic and control mice after the MCAO. We found a significant decrease in red blood cell (RBC) velocity in capillaries in diabetic mice (0.93 ± 0.11 mm/s, P <0.001 versus control mice). Despite this no significant changes in regional blood flow was observed by simultaneously performed laser-Doppler flowmetry. Notably, we observed that a further decline in RBC velocity (0.62 ± 0.07 mm/s, P <0.001 versus diabetic or ischemic mice) and capillary volume flux [(2.29 ± 0.27) × 10 -5 μl/s, P <0.001 versus diabetic or ischemic mice] in diabetic-MCAO mice, indicating diabetes-aggravated brain ischemia-induced disturbance in cerebral capillary blood flow. Furthermore, our intravital TPLSM data demonstrated that brain capillary flow was more turbulent in diabetic-MCAO mice than in the other groups. Diabetic-MCAO mice also exhibited increased neurological deficit (3.36 ± 0.23, P <0.01 versus MCAO mice), which was accompanied by exaggerated degradation of tight junction proteins and blunted CaMKII phosphorylation. Conclusions: The present data indicate that diabetic mice are more susceptible to disturbances of cerebral capillary blood flow and neurovascular defects during ischemic conditions.

Analytical Model of Capillary Suction Velocity of a Pipe with Multiple Sizes

Absorption of water in concrete is often described by simple linear water uptake vs. square-root-of-time law. This model based on the classical capillary model derived from the Hagen-Poiseuille’ flow which travel on a single pipe dimension. However, in cement-like material concrete, the pore structure is complex, including for example, variable pore radius and complicated topological changes. In this work, an analytical velocity model of Hagen Poiseuille’s flow on a pipe with multiply sizes is constructed. This model takes the pipe geometry as described by two sets of parameters α_i and β_i;i=1,2…,N into account. In addition, a numerical study of other flow models using Navier Stokes and Stokes models has been conducted. The analytical model is in good agreement with the numerical models at a series of different pipe geometry sizes.

Potassium‐induced cortical spreading depression bilaterally suppresses the electroencephalogram but only ipsilaterally affects red blood cell velocity in intraparenchymal capillaries

Cortical spreading depression (CSD) is a repetitive, propagating profile of mass depolarization of neuronal and glial cells, followed by sustained suppression of spontaneous neuronal activity. We have reported a long-lasting suppressive effect on red blood cell (RBC) velocities in intraparenchymal capillaries. Here, to test the hypothesis that the prolonged decrease of RBC velocity in capillaries is due to suppression of neuronal activity, we measured CSD-elicited changes in the electroencephalogram (EEG) as an index of neuronal activity. In isoflurane-anesthetized rats, DC potential, EEG, partial pressure of oxygen (PO₂), and cerebral blood flow (CBF) were simultaneously recorded in the temporo-parietal region. The velocities of fluorescently labeled RBCs were evaluated by high-speed camera laser scanning confocal fluorescence microscopy with our original software, KEIO-IS2. Transient deflection of DC potential and PO₂ and increase of CBF were repeatedly detected only in the ipsilateral hemisphere following topical KCl application. On the other hand, the relative spectral power of EEG was reduced bilaterally, showing the lowest value at 5 min after KCl application, when the other parameters had already returned to the baseline after the passage of CSD. Mean RBC velocity in capillaries was slightly but significantly reduced during and after passage of CSD in the ipsilateral hemisphere but did not change in the contralateral hemisphere in the same rats. We suggest that mass depolarization of neuronal and glial cells might transiently decelerate RBCs in nearby capillaries, but the sustained reduction of ipsilateral RBC velocity might be a result of the prolonged effect of CSD, not of neuronal suppression alone.

Feasibility of capillary velocity assessment by statistical means using dual‐beam spectral‐domain Optical Coherence Tomography: a preliminary study

The assessment of vascular dynamics has been shown to yield both qualitative and quantitative metrics and thus play a pivotal role in the diagnosis and prognosis of various diseases, which may manifest as microcirculatory irregularities. Optical Coherence Tomography (OCT) is an established imaging modality which utilises the principle of optical interferometry to distinguish between spatial changes in refractive index and thus formulate a multi-dimensional representation of a specimen in vivo. Nonetheless, difficulties remain in obtaining accurate data (morphological and/or transient) in an environment which is subject to such large biological variability. In an effort to address the issue of angular dependence as with Doppler based analysis, a dual-beam Spectral-domain OCT system for quasi-simultaneous specimen scanning is described. A statistical based method of phase correlation is outlined which is capable of quantifying velocity values in addition to the ability to discern bidirectionality, without the necessity of angular computation.

Capillary leveling of stepped films with inhomogeneous molecular mobility

A homogeneous thin polymer film with a stepped height profile levels due to the presence of Laplace pressure gradients. Here we report on studies of polymeric samples with precisely controlled, spatially inhomogeneous molecular weight distributions. The viscosity of a polymer melt strongly depends on the chain length distribution; thus, we learn about thin-film hydrodynamics with viscosity gradients. These gradients are achieved by stacking two films with different molecular weights atop one another. After a sufficient time these samples can be well described as having one dimensional viscosity gradients in the plane of the film, with a uniform viscosity normal to the film. We develop a hydrodynamic model that accurately predicts the shape of the experimentally observed self-similar profiles. The model allows for the extraction of a capillary velocity, the ratio of the surface tension and the viscosity, in the system. The results are in excellent agreement with capillary velocity measurements of uniform mono- and bi-disperse stepped films and are consistent with bulk polymer rheology.

Renal macro- and microcirculation autoregulatory capacity during early sepsis and norepinephrine infusion in rats

IntroductionThe relationships between systemic hemodynamics and renal blood flow and renal microcirculation are poorly known in sepsis. Norepinephrine (NE) infusion may add another level of complexity.MethodsVentilated and anesthetized rats were submitted to various mean arterial pressure (MAP) steps by blood removal, in presence and absence of sepsis and/or NE. Renal blood flow (RBF) and blood velocity (Vm) in renal cortical capillaries (using Sidestream Dark Field Imaging) were measured. Data were analyzed using linear mixed models enabling us to display the effects of both the considered explanatory variables and their interactions.ResultsPositive correlations were found between MAP and RBF. Sepsis had no independent impact on RBF whereas norepinephrine decreased RBF, regardless of the presence of sepsis. The relationship between MAP and RBF was weaker above a MAP of 100 mmHg as opposed to below 100 mmHg, with RBF displaying a relative "plateau" above this threshold. Sepsis and NE impacted carotid blood flow (CBF) differently compared to RBF, demonstrating organ specificity. A positive relationship was observed between MAP and Vm. Sepsis increased Vm while nNE decreased Vm irrespective of MAP. Sepsis was associated with an increase in serum creatinine determined at the end of the experiments, which was prevented by NE infusion.ConclusionIn our model, sepsis at an early phase did not impact RBF over a large range of MAP. NE elicited a renal vasoconstrictive effect. Autoregulation of RBF appeared conserved in sepsis. Conversely, sepsis was associated with "hypervelocity" of blood flow in cortical peritubular capillaries reversed by NE infusion.

Microcirculation in hypertensive patients

Regardless of the mechanisms that initiate the increase in blood pressure, functional and structural changes in the systemic vasculature are the final result of long-standing hypertension. These changes can occur in the macro- but also in the microvasculature. The supply of the tissues with oxygen, nutrients, and metabolites occurs almost exclusively in the microcirculation (which comprises resistance arterioles, capillaries and venules), and an adequate perfusion via the microcirculatory network is essential for the integrity of tissue and organ function. This review focuses on results from clinical studies in hypertensive patients, which have been performed in close cooperation with different clinical groups over the last three decades. Intravital microscopy was used to study skin microcirculation, microcatheters for the analysis of skeletal muscle microcirculation, the slit lamp for conjunctival microcirculation and the laser scanning ophthalmoscope for the measurement of the retinal capillary network. The first changes of the normal microcirculation can be found in about 93% of patients with essential hypertension, long before organ dysfunctions become clinically manifest. The earliest disorders were found in skin capillaries and thereafter in the retina and the skeletal muscle. In general, the disorders in the different areas were clearly correlated. While capillary rarefaction occurred mainly in the retina and the conjunctiva bulbi, in skin capillaries morphological changes were rare. A significant decrease of capillary erythrocyte velocities under resting conditions together with a marked damping of the postischemic hyperemia was found, both correlating with the duration of hypertension or WHO stage or the fundus hypertonicus stage. Also the mean oxygen tension in the skeletal muscle was correlated with the state of the disease. These data show that the microcirculatory disorders in hypertension are systemic and are hallmarks of the long-term complications of hypertension. There is now a large body of evidence that microvascular changes occur very early and may be important in their pathogenesis and progression.